Selection indices for quality evaluation in wheat breeding.

PubMed

Branlard, G; Pierre, J; Rousset, M

1992-06-01

From multilocation trials involving 125 cultivars of wheat of mainly French and European origin four tests - protein content, Pelshenke, modified Zeleny and the mixograph - were used to establish six selection indices. Three of these indices - IW1, IW2 and IW3 - were calculated in order to evaluate the genetic potentiality of the lines for dough strength as given by the Chopin alveograph. The indices IV1, IV2 and IV3 were established to evaluate loaf volume as measured by the French bread-making standard. A quality index IQ was calculated from the allelic effects of the high-molecular-weight (HMW) subunits of glutenin from 195 cultivars assessed by the Chopin alveograph and the Pelshenke test. Comparison of the relative efficiency of each of the six indices to the individual tests revealed the superiority of the indices over one or several technological parameters. The six selection indices and the quality index were compared using 30 very diverse F4 lines. Their ability to retain the good quality lines is discussed in particular.

Decline in Frozen Section Diagnosis for Axillary Sentinel Lymph Nodes as a Result of the American College of Surgeons Oncology Group Z0011 Trial.

PubMed

Bishop, Julie Anne; Sun, Jihong; Ajkay, Nicolas; Sanders, Mary Ann G

2016-08-01

-Results of the American College of Surgeons Oncology Group Z0011 trial showed that patients with early-stage breast cancer and limited sentinel node metastasis treated with breast conservation and systemic therapy did not benefit from axillary lymph node dissection. Subsequently, most pathology departments have likely seen a decrease in frozen section diagnosis of sentinel lymph nodes. -To determine the effect of the Z0011 trial on pathology practice and to examine the utility of intraoperative sentinel lymph node evaluation for this subset of patients. -Pathology reports from cases of primary breast cancer that met Z0011 clinical criteria and were initially treated with lumpectomy and sentinel lymph node biopsy from 2009 to 2015 were collected. Clinicopathologic data were recorded. -Sentinel lymph node biopsies sent for frozen section diagnosis occurred in 22 of 22 cases (100%) in 2009 and 15 of 22 cases (68%) in 2010 during the pre-Z0011 years, and in 3 of 151 cases (2%) collected in 2011 through 2015, considered to be post-Z0011 years. Of the 151 post-Z0011 cases, 28 (19%) had sentinel lymph nodes with metastasis, and 147 (97%) were spared axillary lymph node dissection. -Following Z0011, intraoperative sentinel lymph node evaluation has significantly decreased at our institution. Prior to surgery, all patients had clinically node-negative disease. After sentinel lymph node evaluation, 97% (147 of 151) of the patients were spared axillary lymph node dissection. Therefore, routine frozen section diagnosis for sentinel lymph node biopsies can be avoided in these patients.

Books for Summer Reading.

ERIC Educational Resources Information Center

Phi Delta Kappan, 1991

1991-01-01

To help replenish educators' supply of ideas, "Kappan" editors suggest several books for summer reading, including many noncurrent titles not specifically on education such as Peter Novick's "That Noble Dream," Joy Kogawa's "Obasan," Zora Neale Hurston's "Their Eyes Were Watching God," Kate Chopin's "The Awakening," Willa Cather's "My Antonia,"…

The Double Opposing Z-Plasty Plus or Minus Buccal Flap Approach for Repair of Cleft Palate: A Review of 505 Consecutive Cases.

PubMed

Mann, Robert J; Martin, Matthew D; Eichhorn, Mitchell G; Neaman, Keith C; Sierzant, Charles G; Polley, John W; Girotto, John A

2017-03-01

Standard methods of cleft palate repair rely on existing palatal tissue to achieve closure. These procedures often require relaxing incisions, causing scars and growth restriction, and may result in insufficient palatal length and suboptimal positioning of the velar musculature. The Furlow double opposing Z-plasty improves palatal length and repositions the velar musculature; however, relaxing incisions may still be needed. The addition of buccal flaps to the Furlow repair obviates the need for relaxing incisions and allows the Furlow repair to be used in wide clefts. A retrospective review was performed on 505 patients; all patients were treated with the double opposing Z-plasty plus or minus buccal flap approach. Outcomes included nasal resonance, secondary speech surgery, and postoperative complications. A comparison was made between patients treated with double opposing Z-plasty alone and those treated with double opposing Z-plasty plus buccal flaps. The average nasal resonance score was 1.38 and was equivalent in both the double opposing Z-plasty alone and with buccal flap groups, despite significantly more wide clefts in the buccal flap group (56 percent versus 8 percent). The secondary surgery rate for velopharyngeal insufficiency was 6.6 percent and the fistula rate was 6.1 percent. The large fistula rate (>2 mm) was 2.7 percent. The double opposing Z-plasty plus or minus buccal flap approach is a useful alternative to standard palate repairs. Speech outcomes were excellent, even in wider clefts, and postoperative complications were minimal. Buccal flaps allow the benefits of the Furlow repair to be applied to any size cleft, without the need for relaxing incisions. Therapeutic, III.

How Can Music Seem to Be Emotional?

ERIC Educational Resources Information Center

Price, Kingsley

2004-01-01

Within music heard, there are two distinguishable factors. The first is the relation of the music to its seeming emotionality-the relation, for example, of the wedding march to its joyfulness. The second is that seeming emotionality itself-the sorrowfulness, for example, of the second movement of the Chopin Sonata. The author looks for an answer…

Joint Data Assimilation and Parameter Calibration in on-line groundwater modelling using Sequential Monte Carlo techniques

NASA Astrophysics Data System (ADS)

Ramgraber, M.; Schirmer, M.

2017-12-01

As computational power grows and wireless sensor networks find their way into common practice, it becomes increasingly feasible to pursue on-line numerical groundwater modelling. The reconciliation of model predictions with sensor measurements often necessitates the application of Sequential Monte Carlo (SMC) techniques, most prominently represented by the Ensemble Kalman Filter. In the pursuit of on-line predictions it seems advantageous to transcend the scope of pure data assimilation and incorporate on-line parameter calibration as well. Unfortunately, the interplay between shifting model parameters and transient states is non-trivial. Several recent publications (e.g. Chopin et al., 2013, Kantas et al., 2015) in the field of statistics discuss potential algorithms addressing this issue. However, most of these are computationally intractable for on-line application. In this study, we investigate to what extent compromises between mathematical rigour and computational restrictions can be made within the framework of on-line numerical modelling of groundwater. Preliminary studies are conducted in a synthetic setting, with the goal of transferring the conclusions drawn into application in a real-world setting. To this end, a wireless sensor network has been established in the valley aquifer around Fehraltorf, characterized by a highly dynamic groundwater system and located about 20 km to the East of Zürich, Switzerland. By providing continuous probabilistic estimates of the state and parameter distribution, a steady base for branched-off predictive scenario modelling could be established, providing water authorities with advanced tools for assessing the impact of groundwater management practices. Chopin, N., Jacob, P.E. and Papaspiliopoulos, O. (2013): SMC2: an efficient algorithm for sequential analysis of state space models. Journal of the Royal Statistical Society: Series B (Statistical Methodology), 75 (3), p. 397-426. Kantas, N., Doucet, A., Singh, S.S., Maciejowski, J., and Chopin, N. (2015): On Particle Methods for Parameter Estimation in State-Space Models. Statistical Science, 30 (3), p. 328.-351.

Limited predictive value of achieving beneficial plasma (Z)-endoxifen threshold level by CYP2D6 genotyping in tamoxifen-treated Polish women with breast cancer.

PubMed

Hennig, Ewa E; Piatkowska, Magdalena; Karczmarski, Jakub; Goryca, Krzysztof; Brewczynska, Elzbieta; Jazwiec, Radoslaw; Kluska, Anna; Omiotek, Robert; Paziewska, Agnieszka; Dadlez, Michal; Ostrowski, Jerzy

2015-08-01

Tamoxifen, the most frequently used drug for treating estrogen receptor-positive breast cancer, must be converted into active metabolites to exert its therapeutic efficacy, mainly through CYP2D6 enzymes. The objective of this study was to investigate the impact of CYP2D6 polymorphisms on (Z)-endoxifen-directed tamoxifen metabolism and to assess the usefulness of CYP2D6 genotyping for identifying patients who are likely to have insufficient (Z)-endoxifen concentrations to benefit from standard therapy. Blood samples from 279 Polish women with breast cancer receiving tamoxifen 20 mg daily were analyzed for CYP2D6 genotype and drug metabolite concentration. Steady-state plasma levels of tamoxifen and its 14 metabolites were measured by using the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. In nearly 60 % of patients, including over 30 % of patients with fully functional CYP2D6, (Z)-endoxifen concentration was below the predefined threshold of therapeutic efficacy. The most frequently observed CYP2D6 genotype was EM/PM (34.8 %), among which 83.5 % of patients had a combination of wild-type and *4 alleles. Plasma concentration of five metabolites was significantly correlated with CYP2D6 genotype. For the first time, we identified an association between decreased (E/Z)-4-OH-N-desmethyl-tamoxifen-β-D-glucuronide levels (r (2) = 0.23; p < 10(-16)) and increased CYP2D6 functional impairment. The strongest correlation was observed for (Z)-endoxifen, whose concentration was significantly lower in groups of patients carrying at least one CYP2D6 null allele, compared with EM/EM patients. The CYP2D6 genotype accounted for plasma level variability of (Z)-endoxifen by 27 % (p < 10(-16)) and for the variability of metabolic ratio indicating (Z)-endoxifen-directed metabolism of tamoxifen by 51 % (p < 10(-43)). The majority of breast cancer patients in Poland may not achieve a therapeutic level of (Z)-endoxifen upon receiving a standard dose of tamoxifen. This finding emphasizes the limited value of CYP2D6 genotyping in routine clinical practice for identifying patients who might not benefit from the therapy. In its place, direct monitoring of plasma steady-state (Z)-endoxifen concentration should be performed to personalize and optimize the treatment.

The effect of age at surgery and compensatory articulation on speech outcome in submucous cleft palate patients treated with double-opposing Z-plasty: A 10-year experience.

PubMed

Baek, Rong-Min; Kim, Baek-Kyu; Jeong, Jae Hoon; Ahn, Taeseon; Park, Mikyong; Han, Jihyeon

2017-05-01

Submucous cleft palate is a congenital deformity that may present as velopharyngeal insufficiency. The degree of anatomical abnormality varies widely among patients and does not predict severity of symptom. We present our 10-year experience treating submucous cleft palate patients with double opposing z-plasty and explore the effect of age at surgery and compensatory articulation on speech. Preoperative assessment included intraoral examination, nasoendoscopy, and perceptual speech evaluation. Age, gap size, and severity of hypernasality were assessed to determine the timing and type of surgery. A retrospective study of 74 submucous cleft palate patients undergoing double-opposing z-plasty from 2005 to 2016 by a single surgeon (Baek RM) was conducted. Double opposing z-plasty was modified to fully release all abnormal insertions of the levator veli palatini muscle. Postoperative velopharyngeal function was measured and statistical analyses were performed. The ages of patients at surgery ranged from 11 months to 19 years. Postoperatively 87 percent of the patients achieved velopharyngeal competency and 13 percent had remaining mild hypernasality. Age was a significant factor in predicting speech outcome, and patients receiving surgery prior to the age of 5.5 years had a higher normalization rate. Compensatory articulation did not have an impact on postoperative hypernasality. There were no cases of postoperative hyponasality or airway problems. Satisfactory speech outcome was achieved with the authors' protocol and modification of the double-opposing z-plasty. A comprehensive assessment of patient age, intraoral findings, severity of hypernasality, and gap size, is necessary for proper treatment of submucous cleft palate patients. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Kickoffs and Metaphors: Selecting a First Story for the Modern Fiction Course.

ERIC Educational Resources Information Center

Cioe, Paul

2001-01-01

Discusses the importance of the selection of a first short story in a modern fiction class. Proposes that compact stories about memorable protagonists in familiar settings can engage students' interests in first class meetings. Outlines two examples of such stories: Jim Shepard's "Ida" and Kate Chopin's "The Story of an Hour." (PM)

Evaluation of cardiac function in a group of small for gestational age school-age children treated with growth hormone.

PubMed

Aurensanz Clemente, Esther; Ayerza Casas, Ariadna; Samper Villagrasa, Pilar; Ruiz Frontera, Pablo; Bueno Lozano, Gloria

2017-02-09

Small for gestational age (SGA) patients have an increased risk of developing a cardiovascular pathology, as well as a metabolic syndrome. Our objective is to evaluate the cardiac morphology and function of SGA children treated with growth hormone (GH), identifying changes that could potentially have long-term consequences. We selected 23 SGA school-age patients and 23 healthy children. We measured their weight, height, blood pressure and heart rate. Using transthoracic echocardiography, we evaluated cardiac chamber size, ascending and abdominal aortic diameter as well as the systolic and diastolic function of both ventricles. SGA children have a higher systolic and diastolic blood pressure (P<.05) without significant changes in their heart rate. They also have a thicker interventricular septum (SGA Z-score 1.57 vs. 0.89; P=.026) and a worse right ventricular systolic function, with a lower TAPSE (SGA Z-score -0.98 vs. 0.95; P=.000), as well as a lower blood flow rate in the pulmonary artery (SGA 0.85m/s vs. 0.97m/s; P=.045). No significant difference was observed in the patients' left ventricular function. SGA patients' ascending aortic diameter was greater (SGA Z-score -1.09 vs. -1.93; P=.026), whereas the systolic abdominal aortic diameter was smaller (SGA Z-score-0.89 vs. -0.19; P=.015). We found functional and morphological cardiac changes in SGA school-age patients treated with GH. It is important to follow-up this patient group in order to determine if these changes contribute to an increased cardiac morbidity in adulthood. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Differences in body mass index z-scores and weight status in a Dutch pediatric psychiatric population with and without use of second-generation antipsychotics.

PubMed

de Hoogd, Sjoerd; Overbeek, Wieske A; Heerdink, Eibert R; Correll, Christoph U; de Graeff, Elisabeth R; Staal, Wouter G

2012-04-01

Weight gain and metabolic adverse effects of second-generation antipsychotics (SGAs) have become a major concern, particularly in youth. However, the specific contribution of SGAs versus other medications or the underlying illness is unclear. In a chart review study of psychiatric outpatients aged ≤ 18 years treated with SGAs and psychiatric controls without lifetime SGA, use body mass index (BMI) z-scores between patients and controls were compared in the entire sample, patients without co-medications, diagnostic subgroups, and age subgroups. In patients with follow-up data, weight z-score change was calculated. Altogether, 592 Caucasian patients aged 4-18 (mean: 10.0) years with a psychiatric diagnosis were included. BMI z-scores in 96 youth treated with SGAs for 9.0 ± 6.1 months were significantly higher than in 496 patients without lifetime SGA use (0.81 ± 1.1 vs. 0.05 ± 1.2; p<0.0001). BMI z-score differences remained significant in all age groups <16 years old. In sub-analyses, results remained the same after eliminating patients on any co-medication (0.82 ± 1.2 vs. 0.23 ± 1.2; p<0.0001) and in patients with (0.75 ± 1.2 vs. 0.17 ± 1.1, p<0.0001) or without autism spectrum disorders (1.1 ± 1.0 vs. -0.02 ± 1.2, p<0.0001). Significantly more SGA-treated youth were obese (27.1% vs. 9.5%, odds ratio [OR]: 3.55, 95% confidence interval [CI]:2.07-6.08) or overweight (21.9% vs. 8.3%, OR: 3.11, 95%CI: 1.75-5.52). In 24 patients (92.3% antipsychotic-naïve) with 6.6 months follow-up, weight z-score increased significantly from -0.17 ± 1.5 to 0.25 ± 1.4 (p<0.0001) with 12.5% transitioning to overweight or obese status. These data show robust and significant differences in sex- and age-adjusted body weight and weight status in young pediatric Caucasian samples with and without use of SGAs independent of Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) (American Psychiatric Association 2000 ) diagnosis and nonantipsychotic medications. Weight status and metabolic effects of SGAs require careful attention, especially in youth.

A microcosm of musical expression: II. Quantitative analysis of pianists' dynamics in the initial measures of Chopin's Etude in E major.

PubMed

Repp, B H

1999-03-01

Patterns of expressive dynamics were measured in bars 1-5 of 115 commercially recorded performances of Chopin's Etude in E major, op. 10, No. 3. The grand average pattern (or dynamic profile) was representative of many performances and highly similar to the average dynamic profile of a group of advanced student performances, which suggests a widely shared central norm of expressive dynamics. The individual dynamic profiles were subjected to principal components analysis, which yielded Varimax-rotated components, each representing a different, nonstandard dynamic profile associated with a small subset of performances. Most performances had dynamic patterns resembling a mixture of several components, and no clustering of of performances into distinct groups was apparent. Some weak relationships of dynamic profiles with sociocultural variables were found, most notably a tendency of female pianists to exhibit a greater dynamic range in the melody. Within the melody, there were no significant relationships between expressive timing [Repp, J. Acoust. Soc. Am. 104, 1085-1100 (1998)] and expressive dynamics. These two important dimensions seemed to be controlled independently at this local level and thus offer the artist many degrees of freedom in giving a melody expressive shape.

A microcosm of musical expression. III. Contributions of timing and dynamics to the aesthetic impression of pianists' performances of the initial measures of Chopin's Etude in E major.

PubMed

Repp, B H

1999-07-01

Four judges repeatedly assessed the overall aesthetic quality of more than 100 recorded performances of the opening of Chopin's Etude in E major on a 10-point scale. The judgments, which exhibited reasonable reliability and modest intercorrelations, were entered into regression analyses with 16 independent variables derived from earlier objective analyses of the expressive timing and dynamics of the performances [Repp, J. Acoust. Soc. Am. 104, 1085-1100 (1998); 105, 1972-1988 (1999)]. Only between 9% and 18% of the variance in the judges' ratings was accounted for. By contrast, timing variables accounted for 53% of the variance in one judge's ratings of synthesized performances that varied in timing only and mimicked the timing patterns of the original performances. These results indicate, first, that the aesthetic impression of the original recordings rested primarily on aspects other than those measured (such as texture, tone, or aspects of timing and dynamics that eluded the earlier analyses) and, second, that very different patterns of timing and dynamics are aesthetically acceptable for the same music, provided that other, aesthetically more crucial performance aspects are present.

Brain-derived neurotrophic factor levels under chronic natalizumab treatment in multiple sclerosis. A preliminary report.

PubMed

Văcăraş, Vitalie; Major, Zoltán Zsigmond; Buzoianu, Anca Dana

Our main purpose was to investigate if the chronic treatment with the disease-modifying drug natalizumab shows quantifiable effect on BDNF levels in multiple sclerosis patients. BDNF plasma concentration was evaluated using enzyme-linked immunosorbent assay in healthy individuals, not treated multiple sclerosis patients and patients treated with natalizumab. Multiple sclerosis patients have a significantly lower amount of peripheral BDNF than healthy individuals. Patients treated with natalizumab have significantly higher BDNF levels than not treated patients. Chronic natalizumab treatment is associated with significantly increased plasma BDNF concentration in multiple sclerosis. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Contributions of procoagulants and anticoagulants to the international normalized ratio and thrombin generation assay in patients treated with warfarin: potential role of protein Z as a powerful determinant of coagulation assays.

PubMed

Choi, Qute; Kim, Ji-Eun; Hyun, Jungwon; Han, Kyou-Sup; Kim, Hyun Kyung

2013-07-01

The effects of warfarin are measured with the international normalized ratio (INR). However, the thrombin generation assay (TGA) may offer more information about global coagulation. We analyzed the monitoring performance of the TGA and INR and investigated the impact of procoagulants (fibrinogen, factor (F)II, FVII, FIX, and FX) and anticoagulants (proteins C, S, and Z) on them. The TGA was performed on a calibrated automated thrombogram, producing lag time, endogenous thrombin potential (ETP), and peak thrombin in 239 patients treated with warfarin. Pro- and anticoagulant levels were also measured. The INR was significantly and inversely correlated with ETP. The therapeutic range of ETP comparable to an INR range of 2.0-3.0 was 290.1-494.6. ETP showed comparable performance to the INR as a warfarin-monitoring parameter with respect to clinical complication rate. The median levels of FII, FVII, FIX, and FX and proteins C and Z tended to decrease gradually with increasing anticoagulation intensity according to the INR or ETP. Of note, protein Z levels decreased dramatically with increasing anticoagulation status. INRs were significantly determined by FII, FVII, and protein Z. ETP was significantly dependent on FVII, and proteins C and Z concentration. Protein Z significantly reduced the total amount of thrombin generation and prolonged PT value in vitro. The INR and ETP exhibit similar efficacy for warfarin monitoring according to the clinical complication rate. Protein Z is considered to be a significant determinant of INR and ETP in patients on warfarin therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Clinical evaluation of preadjusted appliance based on Chinese normal occlusion].

PubMed

Chen, Lin; Gao, Xue-Mei; Zeng, Xiang-Long

2008-02-01

To evaluate the effect of the preadjusted appliance (Z1 appliance) based on Chinese normal occlusion. Thirty non-extraction patients were treated with Z1 appliance. No wire bending was made during treatment. The results of these 30 cases had been evaluated by five senior orthodontists. Models were analysed quantitatively to testify and evaluate the efficiency of the appliance. The average score for post-treatment models was 91.2 (total score was 100). The model measurements indicated that average projective distance on occlusal plane between proximal contact points of adjacent teeth was less than 0.3 mm, which demonstrated good alignment. The prominence of crowns was almost coincident with the data of Chinese normal occlusion. For the average tip of most teeth, there was no statistical difference between the study group and the normal control group. The crown torque variation tendency from anterior to posterior was similar to that in the subjects with normal occlusion. However, the cases treated with Z1 appliance achieved more negative torque in the lower posterior segment. The result of the non-extraction patients treated with Z1 appliance was quite satisfied. Wire bending could be reduced during treatment. It was necessary to adjust the crown torque values for lower posterior teeth.

Isolated olecranon fractures in children affected by osteogenesis imperfecta type I treated with single screw or tension band wiring system: Outcomes and pitfalls in relation to bone mineral density.

PubMed

Persiani, Pietro; Ranaldi, Filippo M; Graci, Jole; De Cristo, Claudia; Zambrano, Anna; D'Eufemia, Patrizia; Martini, Lorena; Villani, Ciro

2017-05-01

The purpose of this study is to compare the results of 2 techniques, tension band wiring (TBW) and fixation with screws, in olecranon fractures in children affected with osteogenesis imperfecta (OI) type I. Between 2010 and 2014, 21 olecranon fractures in 18 children with OI (average age: 12 years old) were treated surgically. Ten patients were treated with the screw fixation and 11 with TBW. A total of 65% of olecranon fractures occurred as a result of a spontaneous avulsion of the olecranon during the contraction of the triceps muscle. The average follow-up was 36 months. Among the children treated with 1 screw, 5 patients needed a surgical revision with TBW due to a mobilization of the screw. In this group, the satisfactory results were 50%. In patients treated with TBW, the satisfactory results were 100% of the cases. The average Z-score, the last one recorded in the patients before the trauma, was -2.53 in patients treated with screw fixation and -2.04 in those treated with TBW. TBW represents the safest surgical treatment for patients suffering from OI type I, as it helps to prevent the rigidity of the elbow through an earlier recovery of the range of motion, and there was no loosening of the implant. In analyzing the average Z-score before any fracture, the fixation with screws has an increased risk of failure in combination with low bone mineral density.

The Genetics and Evolution of Human Skin Color: The Case of Desiree's Baby

ERIC Educational Resources Information Center

Schneider, Patricia

2004-01-01

This case explores the genetics and evolution of skin color, using a short story by Kate Chopin called "Desiree's Baby" as a starting point. Students read the story and discuss a series of questions probing the genetics of the family in the tale. Students then read an article about the evolution of skin color and write an essay analyzing the…

A simple and effective procedure for treating burn contractures: releasing incision and quadra Z technique.

PubMed

Sen, Cenk; Karacalar, Ahmet; Agir, Hakan; Dinar, Serkan; Isil, Eda; Iscen, Deniz

2007-03-01

Burn contractures particularly involving the joints are challenging problems which might cause severe functional impairments. Many surgical techniques have been described for use, however, an ideal method yet to be found. Releasing incision is the most common and effective way to release the wide and severe contractures but it has some drawbacks. We propose a releasing incision technique combined with four Z plasty incisions to overcome the disadvantages of traditional releasing incision technique. We successfully used our releasing incision and quadra Z technique on seven consecutive patients with burn contractures between 2003 and 2005. We modified the classical releasing incision technique by adding four Z plasties; two of them with a common base on each corner of the incision line. In this technique, limitation of the webbing following the incision is made possible by the transposed flaps and unnecessary lateral extension of the incision and the defect was avoided, i.e. maximum release gain with minimal defect was provided. Satisfactory results were achieved in seven patients treated with this technique due to significant burn contractures between 2003 and 2005 with no significant complication. We propose this technique is suitable in all patients with severe burn contractures who require releasing incision and grafting.

Stair-shaped Achilles tendon lengthening in continuity - A new method to treat equinus deformity in patients with spastic cerebral palsy.

PubMed

Li, Zhengxun; Zhang, Ning; Wang, Yang; Cao, Songhua; Huang, Zheng; Hu, Yong

2017-10-27

Equinus of the ankle is a common deformity in spastic cerebral palsy. Achilles tendon lengthening is one of the effective options for the treatment of equinus deformity. In the study, a new stair-shaped Achilles tendon lengthening (ATL) procedure that preserves of the tendon continuity was performed in 28 tendons with equinus deformity (20 patients, mean age=10.5±2.6 years). The results were compared with a group of patients treated with the Z-lengthening procedure. During the latest follow-up visit, the American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot scale score was much higher in the stair-shaped ATL group than in the Z-lengthening group (p<0.05). The two groups showed similar surgical correction angle after ATL(37.2±3.5° for stair-shaped ATL and 36.1±4.5° for Z-lengthening). During the latest follow-up visit, the correction angle in the Z-lengthening group decreased to 21.6±4.3°, which was lower than in the stair-shaped ATL group (29.0±3.1°; p<0.05). In addition, the data regarding the time required by each patient before being able to start rehabilitation and walking as well as gaining better stability for running indicated that the stair-shaped ATL group recovered significantly quicker than the Z-lengthening group. The stair-shaped ATL procedure resulted in a successful correction of the equinus deformity in spastic cerebral palsy, with the advantage of preserving a degree of continuity without a complete section of the tendon. This confers greater antigravity stability and quicker recovery in patients. Copyright © 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

A Peri-Intubation Intervention to Reduce Oral Flora and VAP

DTIC Science & Technology

2008-11-25

potentially pathogenic bacteria in dental plaque provides a nidus of infection for microorganisms that have been shown to be responsible for the...Chopin, 1998; Garrouste et al., 1997). Growth of potentially pathogenic bacteria in dental plaque provides a nidus of infection for...silent epidemic” of dental and oral disease (U.S. Department of Health and Human Services, 2000). Among those who suffer the worst oral health are

A microcosm of musical expression. I. Quantitative analysis of pianists' timing in the initial measures of Chopin's Etude in E major.

PubMed

Repp, B H

1998-08-01

Patterns of expressive timing were measured in bars 1-5 of 115 commercially recorded performances of Chopin's Etude in E major, op. 10, No. 3. These patterns were subjected to principal components analysis, which suggested at least four independent "timing strategies": (1) major ritards at the ends of melodic gestures; (2) acceleration within some of these gestures, without final ritards; (3) extreme lengthening of the initial downbeat; and (4) ritards between as well as within melodic gestures. Strategies 1 and 4 respond in different ways to the melodic-rhythmic grouping structure of the music, and strategy 3 merely represents a local emphasis. Strategy 2 is the one most difficult to rationalize; it does not seem to represent an alternative structural interpretation of the music but rather an alternative gestural shaping. Each individual pianist's timing pattern could be described as a weighted combination of these four strategies plus idiosyncratic variation. A wide variety of combinations was represented, and no two individual patterns were exactly the same. In addition, there was a wide range of basic tempi and of degrees of tempo modulation. There were no strong relationships between any of these variables and sociocultural characteristics of the artists, although some weak trends were observed.

Wheat flour dough Alveograph characteristics predicted by Mixolab regression models.

PubMed

Codină, Georgiana Gabriela; Mironeasa, Silvia; Mironeasa, Costel; Popa, Ciprian N; Tamba-Berehoiu, Radiana

2012-02-01

In Romania, the Alveograph is the most used device to evaluate the rheological properties of wheat flour dough, but lately the Mixolab device has begun to play an important role in the breadmaking industry. These two instruments are based on different principles but there are some correlations that can be found between the parameters determined by the Mixolab and the rheological properties of wheat dough measured with the Alveograph. Statistical analysis on 80 wheat flour samples using the backward stepwise multiple regression method showed that Mixolab values using the ‘Chopin S’ protocol (40 samples) and ‘Chopin + ’ protocol (40 samples) can be used to elaborate predictive models for estimating the value of the rheological properties of wheat dough: baking strength (W), dough tenacity (P) and extensibility (L). The correlation analysis confirmed significant findings (P < 0.05 and P < 0.01) between the parameters of wheat dough studied by the Mixolab and its rheological properties measured with the Alveograph. A number of six predictive linear equations were obtained. Linear regression models gave multiple regression coefficients with R²(adjusted) > 0.70 for P, R²(adjusted) > 0.70 for W and R²(adjusted) > 0.38 for L, at a 95% confidence interval. Copyright © 2011 Society of Chemical Industry.

Evaluation of bone mineral density in children receiving carbamazepine or valproate monotherapy.

PubMed

Chou, I-Jun; Lin, Kuang-Lin; Wang, Huei-Shyong; Wang, Chao-Jan

2007-01-01

Antiepileptic drugs have been shown to be associated with a lowering of bone mineral density in childhood and adolescence, which are critical periods of skeletal mineralization. A lower peak bone mass attained at the end of adolescence is associated with greater involutional osteoporosis and risk for fracture in the elderly. Our purpose was to evaluate the effects of carbamazepine and valproate monotherapy on bone mineral density in children in Taiwan. From November 1995 to April 2005, forty-two children with uncomplicated epilepsy, who were treated with either carbamazepine (n=21) or valproate (n=21) monotherapy for more than 6 months, were enrolled in this study. All subjects were 5 to 18 years of age, seizure-free for 5 months or more, with normal daily activity, and normal diet. Lumbar bone mineral density of L1 to L4 was measured by dual-energy X-ray absorptiometry. The mean serum levels of carbamazepine and valproate were 5.12 +/- 2.15 mcg/ml and 49.61 +/- 20.84 mcg/ml, respectively. Treatment durations were 37.05 +/- 31.11 months and 22.86 +/- 18.84 months, respectively. The serum levels of calcium and phosphate in both groups were within therapeutic range. The serum level of alkaline phosphatase was significantly higher in the carbamazepine group (264.71 +/- 66.91, U/L) than in the valproate group (179.48 +/- 79.37, U/L). Three patients (140%) had bone mineral density Z-score of -2.0 or lower in the carbamazepine-treated group, but none in the valproate-treated group (p=0.232). Comparing the Z-score in carbamazapine- and valproate-monotherapy children, 7 (33%) had Z-score of -1.5 or lower in the carbamazepine-treated group, and none in the valporate-treated group had Z-score of -1.5 or lower (p=0.009). Four (57%) patients in the 7 carbamazepine-treated children with Z-score of -1.5 or lower had serum drug level lower than therapeutic range. Children receiving carbarmazepine monotherapy had increased frequency of lower bone density than children receiving valproate monotherapy.

Anterior Z-plate and titanic mesh fixation for acute burst thoracolumbar fracture.

PubMed

Xu, Jian-Guang; Zeng, Bing-Fang; Zhou, Wei; Kong, Wei-Qing; Fu, Yi-Shan; Zhao, Bi-Zeng; Zhang, Tao; Lian, Xiao-Feng

2011-04-01

A retrospective study. To evaluate the clinical outcome, effectiveness, and security of the surgical management of acute thoracolumbar burst fracture with corpectomy, titanic mesh autograft, and Z-plate fixation by anterior approach. Many surgical methods were adopted to treat acute burst thoracolumbar fracture. But the optimal surgical management remains controversial. A retrospective review of a consecutive series of 48 patients with thoracolumbar burst fracture treated with anterior corpectomy, titanic mesh autograft, and Z-plate internal fixation was carried out. Preoperative clinical and radiographic data of all cases were originally collected. Surgical indications were motor neurologic deficit and thoracolumbar column instability. Twenty-two patients (45.8%) with acute thoracolumbar burst fractures presented with a neurologic deficit. The postoperative recovery of neural function, restoration of anterior cortex collapse, kyphotic angle, and spinal canal compromise were observed. The preoperative kyphotic angle was improved to a mean of 5.6°, radiographic height restored to 95.8% of the adjacent normal levels, and canal compromise was 0%. None of the patients had neurologic deterioration. Mean follow-up time was 32.4 months (range, 24-47 months). All 22 patients with neurologic deficit demonstrated at least one Frankel grade improvement on final observation, with 16 (73%) patients had accomplished complete neurologic recovery. Forty-six (96%) patients reported minimal or no pain at final follow-up observation, and 40 (83%) patients who had been working before injury returned to original work. The authors considered spinal cord decompression with anterior corpectomy and stability reconstruction with titanic mesh autograft and Z-plate fixation at same time in one incision as an effective technique for unstable thoracolumbar burst fracture with and without neurologic deficit.

6R-tetrahydrobiopterin treated PKU patients below 4 years of age: Physical outcomes, nutrition and genotype.

PubMed

Aldámiz-Echevarría, Luis; Bueno, María A; Couce, María L; Lage, Sergio; Dalmau, Jaime; Vitoria, Isidro; Llarena, Marta; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Ruiz, María A; Peña-Quintana, Luis; González, David; Sánchez-Valverde, Felix

2015-05-01

Phenylalanine-restricted diets have proven effective in treating phenylketonuria. However, such diets have occasionally been reported to hinder normal development. Our study aimed to assess whether treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin might prevent growth retardation later in life. We conducted a longitudinal retrospective study which examined anthropometric characteristics of phenylketonuric patients on 6R-tetrahydrobiopterin therapy (22 subjects), and compared them with a group of phenylketonuric patients on protein-restricted diets (44 subjects). Nutritional issues were also considered. We further explored possible relationships between mutations in the PAH gene, BH4 responsiveness and growth outcome. No significant growth improvements were observed in either the group on 6R-tetrahydrobiopterin treatment (height Z-score: initial= -0.57 ± 1.54; final=-0.52 ± 1.29; BMI Z-score: initial=0.17 ± 1.05; final=0.18 ± 1.00) or the diet-only group (height Z-score: initial=-0.92 ± 0.96; final= -0.78 ± 1.08; BMI Z-score: initial=0.17 ± 0.97; final=-0.07 ± 1.03) over the 1-year observation period. Furthermore, we found no significant differences (p>0.05) between the two groups at any of the time points considered (0, 6 and 12 months). Patients on 6R-tetrahydrobiopterin increased their phenylalanine intake (from 49.1 [25.6-60.3] to 56.5 [39.8-68.3] mgkg(-1)day(-1)) and natural protein intake (from 1.0 [0.8-1.7] to 1.5 [1.0-1.8] g kg(-1)day(-1)), and some patients managed to adopt normal diets. Higher phenylalanine and natural protein intakes were positively correlated with better physical outcomes in the diet-only group (p<0.05). No correlation was found between patient genotype and physical outcomes, results being similar regardless of the nutritional approach used. We did not detect any side effects due to 6R-tetrahydrobiopterin administration. Our study indicates that treating 0-4-year-old phenylketonuric patients with 6R-tetrahydrobiopterin is safe. However, poor developmental outcomes were observed, despite increasing the intake of natural proteins. Genotype could be a valid predictor of tetrahydrobiopterin-responsiveness, since patients who carried the same genotype responded similarly to the 6R-tetrahydrobiopterin loading test. On the other hand, harbouring 6R-tetrahydrobiopterin responsive genotypes did not predispose patients to better physical outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

Near East/South Asia Report, No. 2754

DTIC Science & Technology

1983-05-17

more surprising was what these "battles" revealed about .. the basic conflicts between the two parties of the unholy alliance. How did tourism change...first week of last June after an official visit to Tehran by the minister of information and tourism . Both parties agreed to an exchange of tourists... music accompanying the reports: Chopin’s funeral march, deceives practically no one because Iranians listen to foreign radio stations in order to

A multicenter, retrospective chart review study comparing index therapy change rates in open-angle glaucoma or ocular hypertension patients newly treated with latanoprost or travoprost-Z monotherapy.

PubMed

Fain, Joel M; Kotak, Sameer; Mardekian, Jack; Bacharach, Jason; Edward, Deepak P; Rauchman, Steven; Brevetti, Teresa; Fox, Janet L; Lovelace, Cherie

2011-06-13

Because latanoprost and the original formulation of travoprost that included benzalkonium chloride (BAK) have been shown to be similar with regard to tolerability, we compared initial topical intraocular pressure (IOP)-lowering medication change rates in patients newly treated with latanoprost or travoprost-Z monotherapy. At 14 clinical practice sites, medical records were abstracted for patients with a diagnosis of open-angle glaucoma or ocular hypertension and who were ≥40 years of age, had a baseline and at least one follow-up visit, and had no prior history of ocular prostaglandin use. Data regarding demographics, ocular/systemic medical histories, clinical variables, therapy initiations and reasons for changes, adverse events, and resource utilization were recorded from randomly chosen eligible charts. Primary outcomes were rates of and reasons for changing from the initial therapy within six months and across the full study period (1000 days). Data from 900 medical charts (latanoprost, 632; travoprost-Z, 268) were included. For both cohorts, average follow-up was >1 year. Cohorts were similar with regard to age (median ~67 years), gender distribution (>50% female), and diagnosis (~80% with open-angle glaucoma). Within six months, rates of index therapy change for latanoprost versus travoprost-Z were 21.2% (134/632) and 28.7% (77/268), respectively (p = 0.0148); across the full study period, rates were 34.5% (218/632) and 45.2% (121/268), respectively (p = 0.0026). Among those who changed their index therapy, insufficient IOP control was the most commonly reported reason followed by adverse events; hyperemia was the most commonly reported adverse event at index therapy change. In this "real world" study of changes in therapy in patients prescribed initial monotherapy with latanoprost with BAK or travoprost-Z with SofZia, medication changes were common in both treatment groups but statistically significantly more frequent with travoprost-Z.

Growing Up After Critical Illness: Verbal, Visual-Spatial, and Working Memory Problems in Neonatal Extracorporeal Membrane Oxygenation Survivors.

PubMed

Madderom, Marlous J; Schiller, Raisa M; Gischler, Saskia J; van Heijst, Arno F J; Tibboel, Dick; Aarsen, Femke K; IJsselstijn, Hanneke

2016-06-01

To assess neuropsychologic outcome in 17- and 18-year-old neonatal extracorporeal membrane oxygenation survivors. A prospective longitudinal follow-up study. Follow-up program at the Erasmus MC-Sophia Children's Hospital in Rotterdam, The Netherlands. Thirty adolescents 17 or 18 years old, treated between 1991 and 1997, underwent neuropsychologic assessment. None. Attention, memory, executive functioning, visual-spatial functions, social-emotional functioning, and behavior were assessed with validated instruments, and data were compared with reference data. Included predictors for analysis of adverse outcome were diagnosis, age at start extracorporeal membrane oxygenation, convulsions, and use of antiepileptics. Adolescents' performance (expressed as mean [SD] z score) was significantly lower than the norm on short-term and long-term verbal memory (z score = -1.40 [1.58], p = 0.016; z score = -1.54 [1.67], p = 0.010, respectively), visual-spatial memory (z score = -1.65 [1.37], p = 0.008; z score = -1.70 [1.23], p = 0.008, respectively), and working memory (32% vs 9% in the norm population). Parents reported more problems for their children regarding organization of materials (z score = -0.60 [0.90]; p = 0.03) and behavior evaluation (z score = -0.53 [0.88]; p = 0.05) on a questionnaire. Patients reported more withdrawn/depressed behavior (z score = -0.47 [0.54]; p = 0.02), somatic complaints (z score = -0.43 [0.48]; p = 0.03), and social problems (z score = -0.41 [0.46]; p = 0.04). Patients reported more positive feelings of self-esteem and an average health status. Adolescents treated with neonatal extracorporeal membrane oxygenation are at risk of verbal, visual-spatial, and working memory problems. Future research should focus on 1) the longitudinal outcome of specific neuropsychologic skills in adolescence and adulthood; 2) identifying risk factors of neuropsychologic dysfunction; 3) evaluating to what extent "severity of illness" is responsible for acquired brain injury; and 4) effects of timely cognitive rehabilitation.

CAAPM: Computer-Aided Admissible Probability Measurement on PLATO IV

DTIC Science & Technology

1976-03-01

counterpoint 2. The "Emperor Concerto11 for piano and orchestra was composed by: a. Frederic Chopin b. Franz Liszt *c. Ludwig van Beethoven 3. The...impressionistic 7. "The Night Watch" was painted by: a. Franz Hals b. Titian *c. Rembrandt van Rijn ~-37- ART 2 B. The French artist who used the...accompaniment, was: a. Franz Schubert *b. Charles Gounod c. Gabriel Faure 7. Which composer wrote a symphony depicting the emotional stress of a

Cerebral blood flow and freezing of gait in Parkinson's disease.

PubMed

Imamura, K; Okayasu, N; Nagatsu, T

2012-09-01

We investigated the relationship between freezing of gait (FOG) severity in Parkinson's disease (PD) and regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) and evaluated the effect of selegiline therapy. We evaluated 54 patients with PD (FOG positive: 21 patients, and FOG negative: 33 patients) with N-isopropyl-p-[I-123] iodoamphetamine ((123) I-IMP) SPECT and the Unified Parkinson's Disease Rating Scale (UPDRS) part III, Mini-Mental State Examination (MMSE), and Beck Depression Inventory. [Correction added on 18 April 2012, after online publication: In the preceding statement, 55 instead of 54 patients with PD were evaluated, and FOG negative consisted of 34 instead of 33 patients] Furthermore, we examined rCBF in FOG-negative patients treated with levodopa with or without selegiline. Z-values of bilateral Brodmann areas (BA) 10 and 11 and left BA32 showed significant increases in the FOG-positive group compared with the FOG-negative group. [Correction added on 18 April 2012, after online publication: In the preceding statement, Z-values was changed to Z-scores] There were significantly positive correlations between Z-values of these areas and FOG score, especially on both sides of BA11. [Correction added on 18 April 2012, after online publication: In the preceding statement, Z-values was changed to Z-scores] An increase in Z-values in bilateral BA10 and 11 and left BA32 in the levodopa-selegiline treatment group after 1 year was significantly inhibited compared with the levodopa treatment group. [Correction added on 18 April 2012, after online publication: In the preceding statement, left BA32 was changed to right BA32, and Z-values was changed to Z-scores] There was a close relationship between FOG severity in PD and an increase in rCBF in BA 10, 11 and 32. Furthermore, selegiline's FOG prevention effect may be related to maintaining rCBF in these same areas. © 2012 John Wiley & Sons A/S.

Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial.

PubMed

Giuliano, Armando E; Ballman, Karla V; McCall, Linda; Beitsch, Peter D; Brennan, Meghan B; Kelemen, Pond R; Ollila, David W; Hansen, Nora M; Whitworth, Pat W; Blumencranz, Peter W; Leitch, A Marilyn; Saha, Sukamal; Hunt, Kelly K; Morrow, Monica

2017-09-12

The results of the American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial were first reported in 2005 with a median follow-up of 6.3 years. Longer follow-up was necessary because the majority of the patients had estrogen receptor-positive tumors that may recur later in the disease course (the ACOSOG is now part of the Alliance for Clinical Trials in Oncology). To determine whether the 10-year overall survival of patients with sentinel lymph node metastases treated with breast-conserving therapy and sentinel lymph node dissection (SLND) alone without axillary lymph node dissection (ALND) is noninferior to that of women treated with axillary dissection. The ACOSOG Z0011 phase 3 randomized clinical trial enrolled patients from May 1999 to December 2004 at 115 sites (both academic and community medical centers). The last date of follow-up was September 29, 2015, in the ACOSOG Z0011 (Alliance) trial. Eligible patients were women with clinical T1 or T2 invasive breast cancer, no palpable axillary adenopathy, and 1 or 2 sentinel lymph nodes containing metastases. All patients had planned lumpectomy, planned tangential whole-breast irradiation, and adjuvant systemic therapy. Third-field radiation was prohibited. The primary outcome was overall survival with a noninferiority hazard ratio (HR) margin of 1.3. The secondary outcome was disease-free survival. Among 891 women who were randomized (median age, 55 years), 856 (96%) completed the trial (446 in the SLND alone group and 445 in the ALND group). At a median follow-up of 9.3 years (interquartile range, 6.93-10.34 years), the 10-year overall survival was 86.3% in the SLND alone group and 83.6% in the ALND group (HR, 0.85 [1-sided 95% CI, 0-1.16]; noninferiority P = .02). The 10-year disease-free survival was 80.2% in the SLND alone group and 78.2% in the ALND group (HR, 0.85 [95% CI, 0.62-1.17]; P = .32). Between year 5 and year 10, 1 regional recurrence was seen in the SLND alone group vs none in the ALND group. Ten-year regional recurrence did not differ significantly between the 2 groups. Among women with T1 or T2 invasive primary breast cancer, no palpable axillary adenopathy, and 1 or 2 sentinel lymph nodes containing metastases, 10-year overall survival for patients treated with sentinel lymph node dissection alone was noninferior to overall survival for those treated with axillary lymph node dissection. These findings do not support routine use of axillary lymph node dissection in this patient population based on 10-year outcomes. clinicaltrials.gov Identifier: NCT00003855.

Total error shift patterns for daily CT on rails image-guided radiotherapy to the prostate bed

PubMed Central

2011-01-01

Background To evaluate the daily total error shift patterns on post-prostatectomy patients undergoing image guided radiotherapy (IGRT) with a diagnostic quality computer tomography (CT) on rails system. Methods A total of 17 consecutive post-prostatectomy patients receiving adjuvant or salvage IMRT using CT-on-rails IGRT were analyzed. The prostate bed's daily total error shifts were evaluated for a total of 661 CT scans. Results In the right-left, cranial-caudal, and posterior-anterior directions, 11.5%, 9.2%, and 6.5% of the 661 scans required no position adjustments; 75.3%, 66.1%, and 56.8% required a shift of 1 - 5 mm; 11.5%, 20.9%, and 31.2% required a shift of 6 - 10 mm; and 1.7%, 3.8%, and 5.5% required a shift of more than 10 mm, respectively. There was evidence of correlation between the x and y, x and z, and y and z axes in 3, 3, and 3 of 17 patients, respectively. Univariate (ANOVA) analysis showed that the total error pattern was random in the x, y, and z axis for 10, 5, and 2 of 17 patients, respectively, and systematic for the rest. Multivariate (MANOVA) analysis showed that the (x,y), (x,z), (y,z), and (x, y, z) total error pattern was random in 5, 1, 1, and 1 of 17 patients, respectively, and systematic for the rest. Conclusions The overall daily total error shift pattern for these 17 patients simulated with an empty bladder, and treated with CT on rails IGRT was predominantly systematic. Despite this, the temporal vector trends showed complex behaviors and unpredictable changes in magnitude and direction. These findings highlight the importance of using daily IGRT in post-prostatectomy patients. PMID:22024279

Dilation of the ascending aorta after balloon valvuloplasty for aortic stenosis during infancy and childhood.

PubMed

McElhinney, Doff B; Lacro, Ronald V; Gauvreau, Kimberlee; O'Brien, Cheryl M; Yaroglu Kazanci, Selcen; Vogel, Melanie; Emani, Sitaram; Brown, David W

2012-09-01

Dilation of the ascending aorta (AA) is common in patients with a bicuspid aortic valve. The natural history of the aortic root and AA and the risk factors for dilation have not been characterized in patients with congenital aortic stenosis (AS) treated with balloon valvuloplasty during childhood. The present study was performed to determine the prevalence of aortic dilation in patients with congenital AS before and up to 20 years after balloon valvuloplasty performed during childhood. In patients who underwent balloon valvuloplasty for AS at age ≤ 18 years from 1984 to 2005, the aortic diameter measurements before intervention and at 5-year intervals afterward were recorded and the Z scores calculated. Among 156 patients (median age 1.5 years at valvuloplasty), the AA Z scores were significantly larger than normal before intervention (median Z score 1.5) and at all follow-up points (all p <0.001). Using mixed modeling, with time as a categorical variable (before intervention, 5-year window, 10-year window, and so forth), the mean AA Z score was greater at all postvalvuloplasty points than before the intervention, with mean Z score increases of 1.20 at 5 years and 2.11 at 20 years (p <0.001). Moderate or greater aortic regurgitation early after valvuloplasty was associated with greater AA Z scores than mild or less aortic regurgitation, with a progressive difference over time. More significant residual AS after valvuloplasty was associated with lower AA Z scores over time. In conclusion, AA dilation is common in children with congenital AS and continues to progress over many years after balloon valvuloplasty. Copyright © 2012 Elsevier Inc. All rights reserved.

Radiation Field Design in the ACOSOG Z0011 (Alliance) Trial

PubMed Central

Jagsi, Reshma; Chadha, Manjeet; Moni, Janaki; Ballman, Karla; Laurie, Fran; Buchholz, Thomas A.; Giuliano, Armando; Haffty, Bruce G.

2014-01-01

Purpose ACOSOG Z0011 established that axillary lymph node dissection (ALND) is unnecessary in patients with breast cancer with one to two positive sentinel lymph nodes (SLNs) who undergo lumpectomy, radiotherapy (RT), and systemic therapy. We sought to ascertain RT coverage of the regional nodes in that trial. Methods We evaluated case report forms completed 18 months after enrollment. From 2012 to 2013, we collected all available detailed RT records for central review. Results Among 605 patients with completed case report forms, 89% received whole-breast RT. Of these, 89 (15%) were recorded as also receiving treatment to the supraclavicular region. Detailed RT records were obtained for 228 patients, of whom 185 (81.1%) received tangent-only treatment. Among 142 with sufficient records to evaluate tangent height, high tangents (cranial tangent border ≤ 2 cm from humeral head) were used in 50% of patients (33 of 66) randomly assigned to ALND and 52.6% (40 of 76) randomly assigned to SLND. Of the 228 patients with records reviewed, 43 (18.9%) received directed regional nodal RT using ≥ three fields: 22 in the ALND arm and 21 in the SLND arm. Those receiving directed nodal RT had greater nodal involvement (P < .001) than those who did not. Overall, there was no significant difference between treatment arms in the use of protocol-prohibited nodal fields. Conclusion Most patients treated in Z0011 received tangential RT alone, and some received no RT at all. Some patients received directed nodal irradiation via a third field. Further research is necessary to determine the optimal RT approach in patients with low-volume axillary disease treated with SLND alone. PMID:25135994

Decreased occipital lobe metabolism by FDG-PET/CT

PubMed Central

Solnes, Lilja; Nalluri, Abhinav; Cohen, Jesse; Jones, Krystyna M.; Zan, Elcin; Javadi, Mehrbod S.; Venkatesan, Arun

2017-01-01

Objective: To compare brain metabolism patterns on fluorodeoxyglucose (FDG)-PET/CT in anti–NMDA receptor and other definite autoimmune encephalitis (AE) and to assess how these patterns differ between anti–NMDA receptor neurologic disability groups. Methods: Retrospective review of clinical data and initial dedicated brain FDG-PET/CT studies for neurology inpatients with definite AE, per published consensus criteria, treated at a single academic medical center over a 10-year period. Z-score maps of FDG-PET/CT were made using 3-dimensional stereotactic surface projections in comparison to age group–matched controls. Brain region mean Z scores with magnitudes ≥2.00 were interpreted as significant. Comparisons were made between anti–NMDA receptor and other definite AE patients as well as among patients with anti–NMDA receptor based on modified Rankin Scale (mRS) scores at the time of FDG-PET/CT. Results: The medial occipital lobes were markedly hypometabolic in 6 of 8 patients with anti–NMDA receptor encephalitis and as a group (Z = −4.02, interquartile range [IQR] 2.14) relative to those with definite AE (Z = −2.32, 1.46; p = 0.004). Among patients with anti–NMDA receptor encephalitis, the lateral and medial occipital lobes were markedly hypometabolic for patients with mRS 4–5 (lateral occipital lobe Z = −3.69, IQR 1; medial occipital lobe Z = −4.08, 1) compared with those with mRS 0–3 (lateral occipital lobe Z = −0.83, 2; p < 0.0005; medial occipital lobe Z = −1.07, 2; p = 0.001). Conclusions: Marked medial occipital lobe hypometabolism by dedicated brain FDG-PET/CT may serve as an early biomarker for discriminating anti–NMDA receptor encephalitis from other AE. Resolution of lateral and medial occipital hypometabolism may correlate with improved neurologic status in anti–NMDA receptor encephalitis. PMID:29159205

Ultraviolet mutagenesis in a plasmid vector replicated in lymphoid cells from patient with the melanoma-prone disorder dysplastic nevus syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seetharam, S.; Waters, H.L.; Seidman, M.M.

The hereditary dysplastic nevus syndrome (DNS) is an autosomal dominant disorder in which affected individuals have increased numbers of dysplastic (premalignant) nevi and a greater than 100-fold increased risk of developing cutaneous melanoma. Epstein-Barr virus-transformed lymphoblastoid cell lines from patients with hereditary DNS have been shown to be hypermutable to UV radiation. To examine the mechanism involved in this UV hypermutability, we used a shuttle vector plasmid, pZ189, which carries a 160-base pair marker gene, supF, and can replicate in human cells. pZ189 was treated with UV radiation and transfected into DNS6BE, a lymphoblastoid cell line from a patient withmore » hereditary DNS. Plasmid survival after UV was similar with the DNS6BE line and with a lymphoblastoid cell line from a normal donor. Plasmid mutation frequency was greater with the DNS line in accord with the DNS cellular hypermutability. Base sequence analysis was performed on 69 mutated plasmids recovered from the DNS line. There were significantly more plasmids with single base substitution mutations (P less than 0.01) in comparison to UV-treated plasmids passed through normal fibroblasts. pZ189 hypermutability and an increased frequency of single base substitutions was previously found with a cell line from a melanoma-prone xeroderma pigmentosum patient. These differences may be related to the increased melanoma susceptibility in both DNS and xeroderma pigmentosum.« less

Selective perturbation of in vivo linear energy transfer using high- Z vaginal applicators for Cf-252 brachytherapy

NASA Astrophysics Data System (ADS)

Rivard, M. J.; Evans, K. E.; Leal, L. C.; Kirk, B. L.

2004-01-01

Californium-252 ( 252Cf) brachytherapy sources emit both neutrons and photons, and have the potential to vastly improve the current standard-of-practice for brachytherapy. While hydrogenous materials readily attenuate the 252Cf fission energy neutrons, high- Z materials are utilized to attenuate the 252Cf gamma-rays. These differences in shielding materials may be exploited when treating with a vaginal applicator to possibly improve patient survival through perturbation of the in vivo linear energy transfer radiation.

A stepwise protocol for the treatment of refractory gastroesophageal reflux-induced chronic cough

PubMed Central

Xu, Xianghuai; Lv, Hanjing; Yu, Li; Chen, Qiang; Liang, Siwei

2016-01-01

Background Refractory gastroesophageal reflux-induced chronic cough (GERC) is difficult to manage. The purpose of the study is to evaluate the efficacy of a novel stepwise protocol for treating this condition. Methods A total of 103 consecutive patients with suspected refractory reflux-induced chronic cough failing to a standard anti-reflux therapy were treated with a stepwise therapy. Treatment commences with high-dose omeprazole and, if necessary, is escalated to subsequent sequential treatment with ranitidine and finally baclofen. The primary end-point was overall cough resolution, and the secondary end-point was cough resolution after each treatment step. Results High-dose omeprazole eliminated or improved cough in 28.1% of patients (n=29). Further stepwise of treatment with the addition of ranitide yielded a favorable response in an additional 12.6% (n=13) of patients, and subsequent escalation to baclofen provoked response in another 36.9% (n=38) of patients. Overall, this stepwise protocol was successful in 77.6% (n=80) of patients. The diurnal cough symptom score fell from 3 [1] to 1 [0] (Z=6.316, P=0.000), and the nocturnal cough symptom score decreased from 1 [1] to 0 [1] (Z=–4.511, P=0.000), with a corresponding reduction in the Gastroesophageal Reflux Diagnostic Questionnaire score from 8.6±1.7 to 6.8±0.7 (t=3.612, P=0.000). Conversely, the cough threshold C2 to capsaicin was increased from 0.49 (0.49) µmol/L to 1.95 (2.92) µmol/L (Z=–5.892, P=0.000), and the cough threshold C5 was increased from 1.95 (2.92) µmol/L to 7.8 (5.85) µmol/L (Z=–5.171, P=0.000). Conclusions Sequential stepwise anti-reflux therapy is a useful therapeutic strategy for refractory reflux-induced chronic cough. PMID:26904227

Submolecular recognition of the C-terminal domain of the heavy chain of botulinum neurotoxin type A by T cells from toxin-treated cervical dystonia patients.

PubMed

Oshima, Minako; Deitiker, Philip; Jankovic, Joseph; Aoki, K Roger; Atassi, M Zouhair

2016-04-01

We determined the T-cell proliferative responses of the peripheral blood lymphocytes (PBL) from 25 botulinum neurotoxin (BoNT)-treated patients to 31 overlapping synthetic peptides encompassing the C-terminal half (residues 855-1296) of BoNT/A heavy chain. Responses of PBL to HC peptides varied among patients. Samples from 14 patients treated solely with BoNT/A recognized 2-13 (average 6.4) peptides/sample at Z>3.0 level. Six peptide regions representing residues 855-873, 1023-1041, 1051-1069, 1093-1111, 1135-1153 and 1247-1265 were frequently recognized by 36-57% of these PBLs. Influence of treatment parameters on T-cell recognition of the peptides was also investigated. Copyright © 2015 Elsevier GmbH. All rights reserved.

Z-plasty of the flexor hallucis longus tendon at tarsal tunnel for checkrein deformity.

PubMed

Lee, Jae Hoon; Kim, Young Jun; Baek, Jong Hun; Kim, Dong Hee

2016-12-01

To review the outcome of Z-plasty of the flexor hallucis longus (FHL) tendon at the tarsal tunnel for checkrein deformity in 8 patients. Records of 6 males and 2 females aged 14 to 67 (mean, 39.5) years who underwent Z-plasty (lengthening) of the FHL tendon at the tarsal tunnel for checkrein deformity in the first and second toes by a single surgeon were reviewed. All patients had undergone 3 months of conservative treatment. The mean time from injury to surgical treatment was 8.4 (range, 5-12) months. All patients had associated injuries including distal tibiofibular fracture (n=6), distal fibular fracture (n=1), and crush injury aroundthe ankle (n=1); they were treated with intramedullary nailing (n=6), long leg splinting (n=1), and short leg splinting (n=1). After a mean follow-up of 3.4 (range, 1-7) years, the FHL tendon was lengthened by a mean of 1.7 (range, 1.6-1.8) cm, and the mean American Orthopedic Foot and Ankle Society hallux score increased from 59 (range, 52-67) to 89 (range, 80-90). No patient had recurrence, nerve injury, or tarsal tunnel syndrome, although one patient had sensory disturbance of the posterior tibial nerve in the forefoot, which resolved spontaneously at week 2. Z-plasty of the FHL tendon at the tarsal tunnel is a viable option for correction of checkrein deformity.

Cueing musical emotions: An empirical analysis of 24-piece sets by Bach and Chopin documents parallels with emotional speech.

PubMed

Poon, Matthew; Schutz, Michael

2015-01-01

Acoustic cues such as pitch height and timing are effective at communicating emotion in both music and speech. Numerous experiments altering musical passages have shown that higher and faster melodies generally sound "happier" than lower and slower melodies, findings consistent with corpus analyses of emotional speech. However, equivalent corpus analyses of complex time-varying cues in music are less common, due in part to the challenges of assembling an appropriate corpus. Here, we describe a novel, score-based exploration of the use of pitch height and timing in a set of "balanced" major and minor key compositions. Our analysis included all 24 Preludes and 24 Fugues from Bach's Well-Tempered Clavier (book 1), as well as all 24 of Chopin's Preludes for piano. These three sets are balanced with respect to both modality (major/minor) and key chroma ("A," "B," "C," etc.). Consistent with predictions derived from speech, we found major-key (nominally "happy") pieces to be two semitones higher in pitch height and 29% faster than minor-key (nominally "sad") pieces. This demonstrates that our balanced corpus of major and minor key pieces uses low-level acoustic cues for emotion in a manner consistent with speech. A series of post hoc analyses illustrate interesting trade-offs, with sets featuring greater emphasis on timing distinctions between modalities exhibiting the least pitch distinction, and vice-versa. We discuss these findings in the broader context of speech-music research, as well as recent scholarship exploring the historical evolution of cue use in Western music.

Global grey matter volume in adult bipolar patients with and without lithium treatment: A meta-analysis.

PubMed

Sun, Yue Ran; Herrmann, Nathan; Scott, Christopher J M; Black, Sandra E; Khan, Maisha M; Lanctôt, Krista L

2018-01-01

The goal of this meta-analysis was to quantitatively summarize the evidence available on the differences in grey matter volume between lithium-treated and lithium-free bipolar patients. A systematic search was conducted in Cochrane Central, Embase, MEDLINE, and PsycINFO databases for original peer-reviewed journal articles that reported on global grey matter volume in lithium-medicated and lithium-free bipolar patients. Standard mean difference and Hedges' g were used to calculate effect size in a random-effects model. Risk of publication bias was assessed using Egger's test and quality of evidence was assessed using standard criteria. There were 15 studies with a total of 854 patients (368 lithium-medicated, 486 lithium-free) included in the meta-analysis. Global grey matter volume was significantly larger in lithium-treated bipolar patients compared to lithium-free patients (SMD: 0.17, 95% CI: 0.01-0.33; z = 2.11, p = 0.035). Additionally, there was a difference in global grey matter volume between groups in studies that employed semi-automated segmentation methods (SMD: 0.66, 95% CI: 0.01-1.31; z = 1.99, p = 0.047), but no significant difference in studies that used fully-automated segmentation. No publication bias was detected (bias coefficient = - 0.65, p = 0.46). Variability in imaging methods and lack of high-quality evidence limits the interpretation of the findings. Results suggest that lithium-treated patients have a greater global grey matter volume than those who were lithium-free. Further study of the relationship between lithium and grey matter volume may elucidate the therapeutic potential of lithium in conditions characterized by abnormal changes in brain structure. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Growth Suppression and Therapy Sensitization of Breast Cancer

DTIC Science & Technology

1999-07-01

northern analysis, the same membrane was hybridized successively with JNKI probe, JNK2 probe and the G3PDH probe. Figure 10. A549 cells were treated with the...90 0 00 z SO E 40 04. z 20 to JNK2 Oligonucleotide n* 47 JNK1AS TREATED 2 JNlK2AS TREATED. 0) c a 0 mRNA mRNA JNK1 J&,I ~R JNK1 JNK2 JNK2 G3PDH SI... G3PDH 48 iil vý 0 z z Z O! zz C13~ A.LOR 496 Reference #28 PREFERENTIAL PLATINATION OF AN ACTIVATED CELLULAR PROMOTER BY CIS-DIAMMINEDICHLOROPLATINUM

Treatment of Unicameral Bone Cysts of the Calcaneus: A Systematic Review.

PubMed

Levy, David M; Gross, Christopher E; Garras, David N

2015-01-01

The calcaneus is the most common tarsal affected by unicameral bone cysts (UBCs); however, the treatment of calcaneal UBCs remains controversial. The purpose of the present systematic review was to evaluate the treatment modalities for calcaneal UBCs. A systematic review was performed using clinical studies of calcaneal UBCs with a minimum of 1 year of follow-up and level I to IV evidence. Ten studies with 171 patients (181 cysts) were selected. Heel pain and radiographic cyst consolidation were the primary outcomes. A series of Z tests were used to compare the outcomes in the nonoperative and operative groups, cannulated screw and bone augmentation groups, and autografting and allografting groups. All patients treated with open curettage and bone augmentation had significant improvements in heel pain (p < .001). Only 1.1% ± 1.0% of the cysts treated conservatively had healed on radiographs compared with 93.0% ± 13.0% of the cysts after surgery (p < .001). A greater percentage of patients treated with bone augmentation had preoperative heel pain and resolution of that pain than did patients treated with cannulated screws (p < .001). Autografting had a significantly greater percentage of radiographic cyst consolidation than did allografting (97.4% ± 11.1% versus 85.1% ± 15.8%, p < .001, Z = 3.5). Objective outcomes data on calcaneal UBCs are relatively sparse. The results of the present review suggest that open curettage with autograft bone augmentation is the most effective procedure. We would encourage future comparative clinical studies to elucidate differences in UBC treatment modalities. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Evaluation of the Effect of Hévíz Mud in Patients with Hand Osteoarthritis: A Randomized, Controlled, Single-Blind Follow-Up Study.

PubMed

Gyarmati, Noémi; Kulisch, Ágota; Németh, András; Bergmann, Annamária; Horváth, József; Mándó, Zsuzsanna; Matán, Ágnes; Szakál, Erika; Sasné Péter, Tímea; Szántó, Dóra; Bender, Tamás

2017-03-01

Heat therapy is one of the most popular non-pharmacological treatments for osteoarthritis of the hand. To investigate the therapeutic and chemical effects of Hévíz mud on patients with hand osteoarthritis. We randomly assigned 47 patients with mild-to-moderate hand osteoarthritis to two groups. Patients in group 1 (n=23) received Hévíz mud applied directly to both hands, whereas patients in group 2 (n=24) also received mud to both hands, but nylon gloves separated the skin from the mud. Patients in both groups underwent five 20 minute treatment sessions per week for 3 weeks. The temperature of the mud was 42°C. Outcome measures were Visual Analogue Scale (VAS) scores, hand grip strength, the number of swollen and tender joints of the hand, the duration of morning joint stiffness, Health Assessment Questionnaire score, and EuroQoL Group 5-Dimension Self-Report Questionnaire score. The study parameters were evaluated at baseline, immediately after treatment, and after 16 weeks. Both groups showed improvement in nearly all assessed parameters at the end of treatment and at 16 weeks from the start of treatment. At the week 16 follow-up visit, the patient group directly treated with mud showed significantly better improvement in VAS for II and IV parameters and in swollen joint count in both hands compared to the nylon glove-mud group. Hévíz mud therapy significantly improved objective and subjective parameters in patients with hand osteoarthritis and had a beneficial effect on the patients' quality of life. Further studies are required to evaluate the chemical effects of the mud.

Treatment of Bartter syndrome. Unsolved issue.

PubMed

Nascimento, Carla Lessa Pena; Garcia, Cecilia Lopes; Schvartsman, Benita Galassi Soares; Vaisbich, Maria Helena

2014-01-01

To describe the results of a long-term follow-up of Bartter syndrome patients treated with different drugs. Patients were diagnosed according to clinical and laboratory data. Treatment protocol was potassium supplementation, sodium, spironolactone, and non-steroidal anti-inflammatory drug. Patients who developed proteinuria were converted to angiotensin conversion enzyme inhibitor. The variables evaluated for each drug were Z-score for weight and stature, proteinuria, creatinine clearance, gastrointestinal complaints, amount of potassium supplementation, serum potassium and bicarbonate levels, and findings of upper digestive endoscopy. 20 patients were included. Follow-up was 10.1 ± 5.2 years. 17 patients received indomethacin for 5.9 ± 5.3 years; 19 received celecoxib, median of 35 months; and five received enalapril, median of 23 months. During indomethacin, a statistically significant increase was observed in the Z-score for stature and weight, without a change in the creatinine clearance. Seven of 17 patients had gastrointestinal symptoms, and upper digestive endoscopy evidenced gastritis in three patients and gastric ulcer in four patients. During celecoxib use, a significant increase was detected in the Z-score for stature and weight and a reduction of hyperfiltration; seven patients presented gastrointestinal symptoms, and upper digestive endoscopy evidenced mild gastritis in three. During enalapril use, no significant changes were observed in the Z-score for stature, weight and creatinine clearance. The conversion to enalapril resulted in a significant reduction in proteinuria. The authors suggest starting the treatment with celecoxib, and replacing by ACEi if necessary, monitoring the renal function. The safety and efficacy of celecoxib need to be assessed in larger controlled studies. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Effect of Larvae Treated with Mixed Biopesticide Bacillus thuringiensis - Abamectin on Sex Pheromone Communication System in Cotton Bollworm, Helicoverpa armigera

PubMed Central

Shen, Li-Ze; Chen, Peng-Zhou; Xu, Zhi-Hong; Deng, Jian-Yu; Harris, Marvin-K; Wanna, Ruchuon; Wang, Fu-Min; Zhou, Guo-Xin; Yao, Zhang-Liang

2013-01-01

Third instar larvae of the cotton bollworm (Helicoverpa armigera) were reared with artificial diet containing a Bacillus thuringiensis - abamectin (BtA) biopesticide mixture that resulted in 20% mortality (LD20). The adult male survivors from larvae treated with BtA exhibited a higher percentage of “orientation” than control males but lower percentages of “approaching” and “landing” in wind tunnel bioassays. Adult female survivors from larvae treated with BtA produced higher sex pheromone titers and displayed a lower calling percentage than control females. The ratio of Z-11-hexadecenal (Z11–16:Ald) and Z-9-hexadecenal (Z9–16:Ald) in BtA-treated females changed and coefficients of variation (CV) of Z11–16:Ald and Z9–16:Ald were expanded compared to control females. The peak circadian calling time of BtA-treated females occurred later than that of control females. In mating choice experiment, both control males and BtA-treated males preferred to mate with control females and a portion of the Bt-A treated males did not mate whereas all control males did. Our Data support that treatment of larvae with BtA had an effect on the sex pheromone communication system in surviving H.armigera moths that may contribute to assortative mating. PMID:23874751

Effect of carbamezapine and valproic acid on bone mineral density, IGF-I and IGFBP-3.

PubMed

Kumandas, Sefer; Koklu, Esad; Gümüs, Hakan; Koklu, Selmin; Kurtoglu, Selim; Karakukcu, Musa; Keskin, Mehmet

2006-04-01

To examine the effect of carbamezapine and valproate on bone mineral density (BMD), IGF-I and IGFBP-3 levels in children. The effects of at least 2 years valproic acid and carbamazepine therapy on BMD were evaluated in a cross-sectional and retrospective study. All children were ambulatory, prepubertal, and had normal activity and nutritionally adequate diets. Ambulatory epileptic patients were divided into two groups. Thirty-three patients (group 1; 17 boys, 16 girls; mean age: 8.8 +/- 2.0 years) were treated with valproic acid and 33 patients were treated with carbamazepine (group 2; 20 boys, 13 girls; mean age: 9.7 +/- 1.6 years). The control group consisted of 22 healthy children (13 boys, 9 girls; mean age: 8.9 +/- 2.3 years), who were age- and sex-matched with the patient groups. Children with metabolic bone disease, growth and neurological impairment, signs of malnutrition, or any chronic disease were excluded from the study. BMD values at lumbar spine in both the carbamazepine (-1.69 +/- 0.85 mean L1-4 BMD z-scores, mean 35.5 +/- 12.8 months treatment, and 19,478.6 +/- 6,301.3 mg/kg cumulative dose) and valproic acid (-1.28 +/- 0.80 mean L1-4 BMD z-scores, mean 33.7 +/- 15.0 months treatment, and 22,852.4 +/- 12,477.4 mg/kg cumulative dose) groups were significantly lower than that of the control group (-0.23 +/- 0.87 mean L1-4 BMD z-score). Serum ALP and PTH levels were significantly higher in the carbamazepine-treated group (65.4 +/- 21.1 pg/ml, 767 +/- 267 U/l, respectively) than those of the valproic acid-treated (39.1 +/- 12.8 pg/ml, 561 +/- 166 U/l, respectively) and control groups (36.3 +/- 4.9 pg/ml, 487 +/- 82 U/l, respectively). Serum 25-hydroxyvitamin D of the carbamazepine-treated group (9.8 +/- 3.2 microg/l) was significantly lower than the other groups (15.1 +/- 3.5, 16.6 +/- 4.7 microg/l, respectively). There were eight and 13 patients with plasma intact PTH above reference values in groups 1 and 2, respectively. Valproic acid and carbamazepine therapy results in a hyperparathyroid state and altered vitamin D metabolism, respectively. BMD values at lumbar spine were significantly reduced in both carbamezapine and valproic acid treated groups. Valproic acid and carbamazepine therapy do not change IGF-I and IGFBP-3 levels. Altering the hepatic conversion of vitamin D may be the mechanism of carbamazepine-associated reduction in BMD, but the mechanism of decreased BMD in valproate therapy remains unclear.

Outcome of Split Thickness Skin Grafting and Multiple Z-Plasties in Postburn Contractures of Groin and Perineum: A 15-Year Experience

PubMed Central

Sajad, Wani; Hamid, Raashid

2014-01-01

Background. Groin and perineal burn contracture is a rare postburn sequel. Such postburn contractures causes distressing symptoms to the patients and in the management of these contractures, both functional and cosmetic appearance should be the primary concern. Aims. To study the outcome of surgical treatment (STSG and multiple Z-plasties) in postburn contractures of groin and perineum. Material and Methods. We conducted a study of 49 patients, with postburn groin and perineal contractures. Release of contracture with split thickness skin grafting (STSG) was done in 44 (89.79%) patients and release of contracture and closure by multiple Z-plasties was done in 5 (10.21%) patients. Results. Satisfactory functional and cosmetic outcome was seen in 44 (89.79%) patients. Minor secondary contractures of the graft were seen in 3 (6.81%) patients who were managed by physiotherapy and partial recurrence of the contracture in 4 (8.16%) patients required secondary surgery. Conclusion. We conclude that postburn contractures of the groin and perineum can be successfully treated with release of contracture followed by STSG with satisfactory functional and cosmetic results. Long term measures like regular physiotherapy, use of pressure garments, and messaging with emollient creams should not be neglected and should be instituted postoperatively to prevent secondary contractures of the graft and recurrence of the contracture. PMID:24967100

Outcome of split thickness skin grafting and multiple z-plasties in postburn contractures of groin and perineum: a 15-year experience.

PubMed

Sajad, Wani; Hamid, Raashid

2014-01-01

Background. Groin and perineal burn contracture is a rare postburn sequel. Such postburn contractures causes distressing symptoms to the patients and in the management of these contractures, both functional and cosmetic appearance should be the primary concern. Aims. To study the outcome of surgical treatment (STSG and multiple Z-plasties) in postburn contractures of groin and perineum. Material and Methods. We conducted a study of 49 patients, with postburn groin and perineal contractures. Release of contracture with split thickness skin grafting (STSG) was done in 44 (89.79%) patients and release of contracture and closure by multiple Z-plasties was done in 5 (10.21%) patients. Results. Satisfactory functional and cosmetic outcome was seen in 44 (89.79%) patients. Minor secondary contractures of the graft were seen in 3 (6.81%) patients who were managed by physiotherapy and partial recurrence of the contracture in 4 (8.16%) patients required secondary surgery. Conclusion. We conclude that postburn contractures of the groin and perineum can be successfully treated with release of contracture followed by STSG with satisfactory functional and cosmetic results. Long term measures like regular physiotherapy, use of pressure garments, and messaging with emollient creams should not be neglected and should be instituted postoperatively to prevent secondary contractures of the graft and recurrence of the contracture.

Relationship of Posttreatment Decentering and Cognitive Reactivity to Relapse in Major Depression

ERIC Educational Resources Information Center

Fresco, David M.; Segal, Zindel V.; Buis, Tom; Kennedy, Sydney

2007-01-01

Z. V. Segal et al. (2006) demonstrated that depressed patients treated to remission through either antidepressant medication (ADM) or cognitive-behavioral therapy (CBT), but who evidenced mood-linked increases in dysfunctional thinking, showed elevated rates of relapse over 18 months. The current study sought to evaluate whether treatment response…

Zingiber officinale Roscoe ameliorates anticancer antibiotic doxorubicin-induced acute cardiotoxicity in rat.

PubMed

Ajith, Thekkuttuparambil Ananthanarayanan; Hema, Unnikrishnan; Aswathi, Sreedharan

2016-07-01

Oxidative stress (OS) has been suggested in the cardiotoxicity induced by anticancer antibiotic doxorubicin (DXN). The cardioprotective effects of aqueous ethanol extract of Zingiber officinale was evaluated against DXN-induced acute cardiac damage in rat. The results of the study demonstrated that Z. officinale significantly and dose dependently protected the cardiotoxicity induced by DXN. The activities of serum glutamate oxaloacetate transaminase and serum lactate dehydrogenase activity in the DXN alone treated group of animals were significantly (p<0.01) elevated when compared to normal animals. The activities were reduced in the Z. officinale (200 and 400 mg/kg, p.o) plus DXN treated groups. The cardiac malondialdehyde was elevated in the DXN alone treated group and declined significantly in the Z. officinale (400 mg/kg) plus DXN treated group. The results concluded that aqueous ethanol extract of Z. officinale ameliorated DXN-induced cardiotoxicity. The protection can be ascribed to the free radical scavenging activity of Z. officinale. This protective effect may suggest the adjuvant role of Z. officinale against OS induced by cancer chemotherapeutants, which warrant further research. © 2016 Old City Publishing, Inc.

The cost of antidepressant overdose.

PubMed

D'Mello, D A; Finkbeiner, D S; Kocher, K N

1995-11-01

Ninety percent of suicide attempts referred to a general hospital are by self-poisoning. Among women, drug overdose is the commonest means of suicide. In a retrospective naturalistic review of 200 patients who were treated in the Critical Care Unit of a general hospital following medication overdose, 12% were antidepressant overdoses. The mean duration of hospital stay for overdose with tricyclic antidepressants (TCA) was more than double that for overdose with selective serotonin reuptake inhibitors (SSRI) (7 vs 3 days; z = 2.20, p < 0.05). The dollar cost of hospital treatment for patients who overdosed on TCAs was four times greater than that for patients who overdosed on SSRIs ($22,923 vs $5,379; z = 2.30, p < 0.05). The tricyclic compounds clearly have a price advantage over more recently introduced antidepressant agents fluoxetine, sertraline, paroxetine, venlafaxine, and bupropion. The apparent cost advantage of prescribing a less expensive drug may be nullified by the cost associated with adverse consequences.

The Effect of Growing Rod Treatment on Hemoglobin and Hematocrit Levels in Early-onset Scoliosis.

PubMed

Barrett, Kody K; Lee, Christopher; Myung, Karen; Johnston, Charles; Shah, Suken A; Akbarnia, Behrooz A; Skaggs, David L

2016-09-01

This study examines preoperative hemoglobin (Hgb) and hematocrit (Hct) levels in a group of early-onset scoliosis (EOS) patients and the effect of distraction-based growing rods (GRs) on these levels. Children with EOS are at risk for respiratory insufficiency and chronic hypoxemia. Increased Hgb and Hct levels have been identified as surrogate markers for chronic hypoxemia. A study of patients who underwent VEPTR surgery showed a significant decrease in Hgb levels following surgery. Data were retrospectively collected on 66 EOS patients without confounding respiratory issues or oxygen dependence who were treated with GRs at 5 institutions. Average age at initial surgery was 5.5 years. Patients were followed for a minimum of 2 years (average 3.7 y). Preoperative and postoperative Hgb and Hct levels were converted to Z-scores based on age-adjusted mean blood indices and were compared using a paired t test. The prevalence of elevated Hgb and Hct levels (Z-score >2) preoperatively was 15% (10/66) and 19% (12/64), respectively. The average Hgb Z-score decreased from 0.20 to -0.31 (P=0.005) 6 to 24 months following surgery and the Hct Z-score decreased from 0.31 to -0.28 (P=0.002) 6 to 24 months following surgery. Following distraction-based GR treatment of children with EOS there was a significant decrease in both their Hgb and Hct. This is a physiological marker of decreased hypoxemia and improved pulmonary function. Level III-therapeutic study.

Tamoxifen dose and serum concentrations of tamoxifen and six of its metabolites in routine clinical outpatient care.

PubMed

Jager, N G L; Rosing, H; Schellens, J H M; Linn, S C; Beijnen, J H

2014-02-01

A sensitive and selective HPLC-MS/MS assay was used to analyze steady-state serum concentrations of tamoxifen, N-desmethyltamoxifen (E)-endoxifen, (Z)-endoxifen, N-desmethyl-4'-hydroxytamoxifen, 4-hydroxytamoxifen, and 4'-hydroxytamoxifen to support therapeutic drug monitoring (TDM) in patients treated with tamoxifen according to standard of care. When the (Z)-endoxifen serum concentration was below the predefined therapeutic threshold concentration of 5.9 ng/mL, the clinician was advised to increase the tamoxifen dose and to collect another serum sample. Paired serum samples from patients at one dose level at different time points during the tamoxifen treatment were used to assess the intra-patient variability. A total of 251 serum samples were analyzed, obtained from 205 patients. Of these patients, 197 used 20 mg tamoxifen per day and 8 patients used 10 mg/day. There was wide variability in tamoxifen and metabolite concentrations within the dosing groups. The threshold concentration for (Z)-endoxifen was reached in one patient (12 %) in the 10 mg group, in 153 patients (78 %) in the 20 mg group, and in 26 (96 %) of the patients who received a dose increase to 30 or 40 mg/day. Dose increase from 20 to 30 or 40 mg per day resulted in a significant increase in the mean serum concentrations of all analytes (p < 0.001). The mean intra-patient variability was between 10 and 20 % for all analytes. These results support the suitability of TDM for optimizing the tamoxifen treatment. It is shown that tamoxifen dose is related to (Z)-endoxifen exposure and increasing this dose leads to a higher serum concentration of tamoxifen and its metabolites. The low intra-patient variability suggests that only one serum sample is needed for TDM, making this a relatively noninvasive way to optimize the patient's treatment.

Theta EEG source localization using LORETA in partial epilepsy patients with and without medication.

PubMed

Clemens, B; Bessenyei, M; Fekete, I; Puskás, S; Kondákor, I; Tóth, M; Hollódy, K

2010-06-01

To investigate and localize the sources of spontaneous, scalp-recorded theta activity in patients with partial epilepsy (PE). Nine patients with beginning, untreated PE (Group 1), 31 patients with already treated PE (Group 2), and 14 healthy persons were investigated by means of spectral analysis and LORETA, low resolution electromagnetic tomography (1 Hz very narrow band analysis, age-adjusted, Z-scored values). The frequency of main interest was 4-8 Hz. Group analysis: Group 1 displayed bilateral theta maxima in the temporal theta area (TTA), parietal theta area (PTA), and frontal theta area (FTA). In Group 2, theta activity increased all over the scalp as compared to the normative mean (Z=0) and also to Group 1. Maximum activity was found in the TTA, PTA, and FTA. However, in the PTA and FTA the centers of the abnormality shifted towards the medial cortex. Individual analysis: all the patients showed preferential activation (maximum Z-values) within one of the three theta areas. EEG activity in the theta band is increased in anatomically meaningful patterns in PE patients, which differs from the anatomical distribution of theta in healthy persons. The findings contribute to our understanding of the sources of theta rhythms and the pathophysiology of PE. Copyright 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Treatment of Pediatric Graves' Disease Is Associated with Excessive Weight Gain

PubMed Central

van Veenendaal, Nicole R.

2011-01-01

Context: Little information is available about changes in body weight and body mass index in children before, during, and after treatment for Graves' disease (GD). Objective: Our objective was to examine changes in body weight after treatment for GD in children as related to clinical features. Design: The medical records of 43 pediatric patients with GD [35 girls and eight boys, aged 4.0–18.5 (mean 10.9) yr] were examined. Patients were included if clinical data were available for 1 yr before and after the diagnosis of GD. Main Outcome Measures: Weight, height, body mass index (BMI) z-scores, and thyroid hormone levels were assessed. Results: Overall, patients presented with an average BMI z-score of −0.02 ± 1.05 that was not different from the normal population (P = 0.921) or their premorbid values (P = 0.07). However, in the subset of patients who were initially overweight or obese in the premorbid state, the BMI decreased significantly during the development of hyperthyroidism (P < 0.05). After initiation of treatment, patients gained significant amounts of weight over the first 6 months leading to elevated BMI z-scores (P < 0.0001), and elevations in BMI persisted in about 25% of the patients. Conclusion: Excessive weight gain within 6 months of treatment is seen in children treated for GD, and the gain in weight can persist. PMID:21849528

[Comparative study of proximal femoral shortening after the third generation of Gamma nail versus proximal femoral nail anti-rotation in treatment of intertrochanteric fracture].

PubMed

Hou, Yu; Yao, Qi; Zhang, Gen'ai; Ding, Lixiang

2018-03-01

To explore the difference of the proximal femoral shortening (PFS) between the third generation of Gamma nail (TGN) and the proximal femoral nail anti-rotation (PFNA) in treating intertrochanteric fracture of femur. The clinical data of 158 patients with intertrochanteric fracture of femur who were treated with TGN internal fixation or PFNA internal fixation between January 2014 and December 2015 were retrospectively analysed. The patients were divided into TGN group (69 cases) and PFNA group (89 cases) according to surgical operation. There was no significant difference in gender, age, bone mineral density, causes of injury, AO/Association for the Study of Internal Fixation (AO/ASIF) classification, accompanied disease, and the time from injury to operation between 2 groups ( P >0.05). The result of fracture reduction was divided into 3 types: positive medial cortex support, neutral position cortex support, and negative medial cortex support according to the method of Chang et al . At 18 months postoperatively, bilateral hip anteroposterior X-ray films were taken to measure horizontal PFS values (marked as X), vertical PFS values (marked as Y), and calculate the total PFS values (marked as Z). The PFS values were divided into 4 grades according to the criteria (≤1.0 mm, 1.0-4.9 mm, 5.0-9.9 mm, and ≥10.0 mm), and the constituent ratio was calculated and compared between 2 groups. The X, Y, and Z values and the collodiaphyseal angles of 2 groups at 18 months postoperatively were compared. The X, Y, and Z values of 2 groups of patients with failed fixation and normal healing within 18 months after operation were recorded and compared. The X, Y, and Z values of 2 groups of the patients with different cortex support types were also compared. There were 34 cases of positive medial cortex support, 30 cases of neutral position cortex support, and 5 cases of negative medial cortex support in TGN group, and there were 45, 33, and 11 cases in PFNA group respectively, showing no significant difference between 2 groups ( Z =-1.06, P =0.29). All patients were followed up 18 months after operation. At 18 months after operation, the constituent ratios of PFS values (X, Y, Z) had significant differences between 2 groups ( P <0.05). The patients of shortening of 1.0-4.9 mm and 5.0-9.9 mm were obviously more in TGN group than in PFNA group; the patients of shortening of ≥10.0 mm were obviously more in PFNA group than in TGN group. There were significant differences in X, Y, and Z values between 2 groups ( P <0.05), but no significant difference of the collodiaphysial angle was found between 2 groups ( t =0.47, P =0.64). Six cases of internal fixation failed in TGN group and PFNA group respectively within 3 months after operation, and there was no significant difference of X, Y, and Z values between failed fixation and normal healing patients within 2 groups ( P >0.05). When the reposition effect was the positive medial cortex support, the X, Y, and Z values were significantly lower in TGN group than in PFNA group ( P <0.05); but no significant difference was found between 2 groups when the reposition effect was the neutral position cortex support or negative medial cortex support ( P >0.05). At 18 months after operation, the X, Y, and Z values of the negative medial cortex support patients were significantly higher than those of the positive medial cortex support or the neutral position cortex support patients within 2 groups ( P <0.05). PFS is a common complication of the intertrochanteric fracture of the femur after internal fixation. During operation, the selection of internal fixation should be based on the results of intraoperative reduction. TGN should be applied to reduce PFS if positive medial cortex support happened.

Gianturco-Rösch Z stents in tracheobronchial stenoses.

PubMed

Petersen, B D; Uchida, B T; Barton, R E; Keller, F S; Rösch, J

1995-01-01

To evaluate expandable metallic Gianturco-Rösch Z (GRZ) stents for treatment of benign and malignant tracheobronchial stenoses. Six patients, ages 45-73 years, were treated for severe dyspnea with placement of GRZ stents. Three patients had benign tracheal lesions (one tracheomalacia, two postoperative) and received uncovered GRZ stents. Three patients had malignant stenoses at the level of the carina; one received an uncovered stent and the other two received silicone-covered GRZ stents. Two patients with benign lesions responded well to stent placement. One was asymptomatic for a year and then was lost to follow-up; the other improved substantially but died of end-stage lung disease 5 months after stent placement. A third patient with a benign high tracheal lesion did poorly; symptoms recurred secondary to inferior migration of a stent, which was removed surgically at 4 months. All patients with malignant lesions improved symptomatically after stent placement and remained without significant dyspnea until death (from 1 to 6 months). Expandable GRZ stents are promising devices for treatment of benign lesions and offer effective palliation of malignant tracheobronchial stenoses.

Exercise physiology and its role in disease prevention and in rehabilitation.

PubMed

Astrand, P O

1987-05-01

It is an impressive fact that many musicians can perform perfectly at an advanced age. Arthur Rubenstein played very demanding compositions of Chopin at the age of 88 and Andre Segovia at the age of 91 is still giving concerts on the classical guitar. Apparently, through practice very demanding neuromuscular activities can be maintained at advanced ages. Yet hours of daily "training" are behind these achievements. This review discusses some of the general aspects of training and their effects on function and health. As an overall goal it is more important to add life to years rather than add years to life.

Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia.

PubMed

Davila, Marco L; Riviere, Isabelle; Wang, Xiuyan; Bartido, Shirley; Park, Jae; Curran, Kevin; Chung, Stephen S; Stefanski, Jolanta; Borquez-Ojeda, Oriana; Olszewska, Malgorzata; Qu, Jinrong; Wasielewska, Teresa; He, Qing; Fink, Mitsu; Shinglot, Himaly; Youssif, Maher; Satter, Mark; Wang, Yongzeng; Hosey, James; Quintanilla, Hilda; Halton, Elizabeth; Bernal, Yvette; Bouhassira, Diana C G; Arcila, Maria E; Gonen, Mithat; Roboz, Gail J; Maslak, Peter; Douer, Dan; Frattini, Mark G; Giralt, Sergio; Sadelain, Michel; Brentjens, Renier

2014-02-19

We report on 16 patients with relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL) that we treated with autologous T cells expressing the 19-28z chimeric antigen receptor (CAR) specific to the CD19 antigen. The overall complete response rate was 88%, which allowed us to transition most of these patients to a standard-of-care allogeneic hematopoietic stem cell transplant (allo-SCT). This therapy was as effective in high-risk patients with Philadelphia chromosome-positive (Ph(+)) disease as in those with relapsed disease after previous allo-SCT. Through systematic analysis of clinical data and serum cytokine levels over the first 21 days after T cell infusion, we have defined diagnostic criteria for a severe cytokine release syndrome (sCRS), with the goal of better identifying the subset of patients who will likely require therapeutic intervention with corticosteroids or interleukin-6 receptor blockade to curb the sCRS. Additionally, we found that serum C-reactive protein, a readily available laboratory study, can serve as a reliable indicator for the severity of the CRS. Together, our data provide strong support for conducting a multicenter phase 2 study to further evaluate 19-28z CAR T cells in B-ALL and a road map for patient management at centers now contemplating the use of CAR T cell therapy.

Treatment of Post-Stent Gastroesophageal Reflux by Anti-Reflux Z-Stent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davies, Roger Philip; Kew, Jacqueline; Byrne, Peter D.

2000-11-15

Severe symptoms of heartburn and retrosternal pain consistent with gastro-esophageal reflux (GER) developed in a patient following placement of a conventional self-expanding 16-24-mm-diameter x 12-cm-long esophageal stent across the gastroesophageal junction to treat an obstructing esophageal carcinoma. A second 18-mm-diameter x 10-cm-long esophageal stent with anti-reflux valve was deployed coaxially and reduced symptomatic GER immediately. Improvement was sustained at 4-month follow-up. An anti-reflux stent can be successfully used to treat significant symptomatic GER after conventional stenting.

Spontaneous recovery of bone mass after cure of endogenous hypercortisolism.

PubMed

Randazzo, Maria Elena; Grossrubatscher, Erika; Dalino Ciaramella, Paolo; Vanzulli, Angelo; Loli, Paola

2012-06-01

Patients with Cushing's syndrome (CS) develop osteopenia-osteoporosis. The present study evaluates the recovery of bone mass within 2 years after remission of hypercortisolism and in long term follow up, an issue rarely addressed. Twenty patients (6M, 14F, 3 post-menopausal, 15-64 years old), 15 with Cushing's disease, 2 with ectopic ACTH syndrome, 3 with ACTH-independent CS were studied. BMD, T and Z scores at lumbar spine and proximal femur were assessed by dual-energy X-ray absorptiometry before and 7-33 months after treatment of hypercortisolism. Five patients were treated with bisphosphonates. Four patients had hypogonadism and 4 GH-deficiency. At baseline all patients showed osteopenia/osteoporosis and the spine appeared more damaged than the femur; femur BMD was positively related with body mass index (BMI). No correlations were observed between spine and femur bone parameters and duration of disease or severity of hypercortisolism. Bone parameters did not differ in patients with or without GH or other pituitary deficiencies. After cure of hypercortisolism a significant improvement in spine BMD, Z and T scores and in femur Z and T scores was observed with normalization in 3 patients; there was no significant difference in percent improvement between femur and spine. The increase in bone parameters at spine and femur was independent from values at baseline. The percent increase in spine T and Z scores was positively related with time elapsed since cure. Bisphosphonates did not influence the recovery of bone mineralization. In long term follow up, after a median period of 7 years a further improvement in bone density was observed in 100% of patients at spine and in 9/11 at femur, although 8/11 patients still had femoral and/or vertebral T score in the range of osteopenia/osteoporosis. Spontaneous improvement of osteoporosis after cure of hypercortisolism occurs both at spine and femur, is independent from basal conditions and not affected by bisphosphonates. The improvement at spine depends on time since cure.

Clinical and Microbiological Aspects of β-Lactam Resistance in Staphylococcus lugdunensis

PubMed Central

McHardy, Ian H.; Veltman, Jennifer; Hindler, Janet; Bruxvoort, Katia; Carvalho, Marissa M.

2016-01-01

ABSTRACT Antimicrobial susceptibility results from broth microdilution MIC testing of 993 Staphylococcus lugdunensis isolates recovered from patients at a tertiary care medical center from 2008 to 2015 were reviewed. Ninety-two oxacillin-susceptible isolates were selected to assess the accuracy of penicillin MIC testing, the penicillin disk diffusion test, and three β-lactamase tests, including the cefoxitin-induced nitrocefin test, penicillin cloverleaf assay, and penicillin disk zone edge test. The results of all phenotypic tests were compared to the results of blaZ PCR. The medical records of 62 patients from whom S. lugdunensis was isolated, including 31 penicillin-susceptible and 31 penicillin-resistant strains, were retrospectively reviewed to evaluate the clinical significance of S. lugdunensis isolation, the antimicrobial agents prescribed, if any, and the clinical outcome. MIC testing revealed that 517/993 (52.1%) isolates were susceptible to penicillin and 946/993 (95.3%) were susceptible to oxacillin. The induced nitrocefin test was 100% sensitive and specific for the detection of β-lactamase compared to the blaZ PCR results, whereas the penicillin disk zone edge and cloverleaf tests showed sensitivities of 100% but specificities of only 9.1% and 89.1%, respectively. The penicillin MIC test had 100% categorical agreement with blaZ PCR, while penicillin disk diffusion yielded one major error. Only 3/31 patients with penicillin-susceptible isolates were treated with a penicillin family antimicrobial. The majority of cases were treated with other β-lactams, trimethoprim-sulfamethoxazole, or vancomycin. These data indicate that nearly all isolates of S. lugdunensis are susceptible to narrow-spectrum antimicrobial agents. Clinical laboratories in areas with resistance levels similar to those described here can help promote the use of these agents versus vancomycin by effectively designing their antimicrobial susceptibility reports to convey this message. PMID:27927926

Clinical and Microbiological Aspects of β-Lactam Resistance in Staphylococcus lugdunensis.

PubMed

McHardy, Ian H; Veltman, Jennifer; Hindler, Janet; Bruxvoort, Katia; Carvalho, Marissa M; Humphries, Romney M

2017-02-01

Antimicrobial susceptibility results from broth microdilution MIC testing of 993 Staphylococcus lugdunensis isolates recovered from patients at a tertiary care medical center from 2008 to 2015 were reviewed. Ninety-two oxacillin-susceptible isolates were selected to assess the accuracy of penicillin MIC testing, the penicillin disk diffusion test, and three β-lactamase tests, including the cefoxitin-induced nitrocefin test, penicillin cloverleaf assay, and penicillin disk zone edge test. The results of all phenotypic tests were compared to the results of blaZ PCR. The medical records of 62 patients from whom S. lugdunensis was isolated, including 31 penicillin-susceptible and 31 penicillin-resistant strains, were retrospectively reviewed to evaluate the clinical significance of S. lugdunensis isolation, the antimicrobial agents prescribed, if any, and the clinical outcome. MIC testing revealed that 517/993 (52.1%) isolates were susceptible to penicillin and 946/993 (95.3%) were susceptible to oxacillin. The induced nitrocefin test was 100% sensitive and specific for the detection of β-lactamase compared to the blaZ PCR results, whereas the penicillin disk zone edge and cloverleaf tests showed sensitivities of 100% but specificities of only 9.1% and 89.1%, respectively. The penicillin MIC test had 100% categorical agreement with blaZ PCR, while penicillin disk diffusion yielded one major error. Only 3/31 patients with penicillin-susceptible isolates were treated with a penicillin family antimicrobial. The majority of cases were treated with other β-lactams, trimethoprim-sulfamethoxazole, or vancomycin. These data indicate that nearly all isolates of S. lugdunensis are susceptible to narrow-spectrum antimicrobial agents. Clinical laboratories in areas with resistance levels similar to those described here can help promote the use of these agents versus vancomycin by effectively designing their antimicrobial susceptibility reports to convey this message. Copyright © 2017 American Society for Microbiology.

The effects of copper-histidine therapy on brain metabolism in a patient with Menkes disease: a proton magnetic resonance spectroscopic study.

PubMed

Munakata, Mitsutoshi; Sakamoto, Osamu; Kitamura, Taro; Ishitobi, Mamiko; Yokoyama, Hiroyuki; Haginoya, Kazuhiro; Togashi, Noriko; Tamura, Hajime; Higano, Shuichi; Takahashi, Shoki; Ohura, Toshihiro; Kobayashi, Yasuko; Onuma, Akira; Iinuma, Kazuie

2005-06-01

We report on metabolic changes in the brain of a boy with Menkes disease. He was treated with parenteral copper (Cu)-histidine supplementation, from 5 months of age, and assessed with proton magnetic resonance spectroscopy ((1)H-MRS). The single-voxel (1)H-MRS before treatment revealed an accumulation of lactate and a reduced N-acetyl aspartate (NAA)/total creatine (tCr) ratio with a z-score of -3.0. During treatment, the lactate signal faded away, whereas the NAA signal gradually increased to a z-score of -1.5 at 120 days of treatment. The choline/tCr ratio did not deviate much initially (z-score +0.5), but the ratio increased markedly during treatment (z-score +4.8). Consequently, the Cu-histidine therapy initiated after the critical period still improved the neuronal metabolism, suggesting that some Cu was delivered to neurons. Nevertheless, the brain atrophy, impaired myelination, and severe neurological symptoms were not ameliorated.

Velopharyngeal Dysfunction Evaluation and Treatment.

PubMed

Meier, Jeremy D; Muntz, Harlan R

2016-11-01

Velopharyngeal dysfunction (VPD) can significantly impair a child's quality of life and may have lasting consequences if inadequately treated. This article reviews the work-up and management options for patients with VPD. An accurate perceptual speech analysis, nasometry, and nasal endoscopy are helpful to appropriately evaluate patients with VPD. Treatment options include nonsurgical management with speech therapy or a speech bulb and surgical approaches including double-opposing Z-plasty, sphincter pharyngoplasty, pharyngeal flap, or posterior wall augmentation. Copyright © 2016 Elsevier Inc. All rights reserved.

Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer

ClinicalTrials.gov

2018-06-11

Estrogen Receptor Positive; HER2/Neu Negative; Recurrent Breast Carcinoma; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IV Breast Cancer AJCC v6 and v7

Impact of mometasone furoate nasal spray on individual ocular symptoms of allergic rhinitis: a meta-analysis.

PubMed

Bielory, L; Chun, Y; Bielory, B P; Canonica, G W

2011-05-01

Intranasal corticosteroids (INSs) are a mainstay of treatment of allergic rhinitis (AR) nasal symptoms. The INS mometasone furoate nasal spray (MFNS) has well-documented efficacy and safety for the treatment and prophylaxis of nasal symptoms of seasonal AR (SAR) and for the treatment of nasal symptoms of perennial AR (PAR). Increasing interest has focused on whether INSs, including MFNS, may have beneficial effects on the ocular symptoms frequently associated with AR. We performed a meta-analysis of 10 randomized, placebo-controlled trials of the efficacy of MFNS 200 mcg daily in relieving ocular allergy symptoms, including itching/burning, redness, and tearing/watering in both SAR and PAR. Four PAR studies and six SAR studies are included in the analysis. A fixed-effect inverse variance model was used to calculate weighted mean differences, 95% confidence intervals (CIs) for each comparison, and a combined overall treatment effect (Z) with P-value. In both analyses of SAR and PAR studies, including 3132 patients, all individual ocular symptoms were reduced in patients treated with MFNS. Overall treatment effect was significant for all three individual ocular symptoms in the SAR studies (Z = 9.18 for tearing, Z = 10.15 for itching, and Z = 8.88 for redness; P < 0.00001 for all) and in the PAR studies (Z = 5.94, P < 0.00001 for tearing; Z = 2.43, P = 0.02 for itching; and Z = 2.42, P = 0.02 for redness). Our findings add to the growing body of literature supporting the positive class effect of INSs, including MFNS, on ocular symptoms associated with SAR and PAR. © 2011 John Wiley & Sons A/S.

Attention-Deficit/Hyperactivity Disorder Drugs and Growth: An Italian Prospective Observational Study

PubMed Central

Germinario, Elena A.P.; Arcieri, Romano; Bonati, Maurizio; Zuddas, Alessandro; Masi, Gabriele; Vella, Stefano; Chiarotti, Flavia

2013-01-01

Abstract Objective This study was conducted to assess the long-term effect of methylphenidate (MPH) or atomoxetine (ATX) on growth in attention-deficit/hyperactivity disorder (ADHD) drug-naïve children. Design The study was an observational, post-marketing, fourth phase study. Methods Data on height and weight were collected at baseline and every 6 months up to 24 months. Results Both ATX and MPH lead to decreased height gain (assessed by means of z-scores); the effect was significantly higher for ATX than for MPH. At any time, height z-score decrease in the ATX group was higher than the corresponding decrease observed in the MPH group, but the difference was significantly relevant only during the first year of treatment. An increment of average weight was observed both in patients treated with MPH and in those treated with ATX. However, using Tanner's percentile, a subset of patients showed a degree of growth lower than expected. This negative effect was significantly higher for ATX than for MPH. Conclusions We conclude that ADHD drugs show a negative effect on linear growth in children in middle term. Such effect appears more evident for ATX than for MPH. PMID:24024538

[Cost-benefit analysis of cranial computed tomography in mild traumatic brain injury--appropriate depiction within the G-DRG system?].

PubMed

Garving, C; Weber, C D; Poßelt, S; Pishnamaz, M; Pape, H C; Dienstknecht, T

2014-06-01

The treatment of patients with mild head injury is related to a continuous lack of finances. The current investigation summarises radiological costs of patients from a level I trauma centre and discusses the indication for CT scanning within the G-DRG system. The study includes all patients who underwent a CCT scan in 2011. Diagnosis, length of stay and cost data were recorded for every patient. Finally, frequent diagnosis groups were summarised to clusters (Basis-DRG/MDC 21A). A total of 380 patients was treated. Within the largest group (G-DRG B80Z) the costs for a CCT already took up one quarter of the total proceedings. In combination with the high cost for monitoring patients with mild head injuries this causes an ongoing lack of finances. In spite of the often necessary CCT investigation in mild head injuries, the earnings do not cover the costs of the patients. To improve the situation clear guidelines for CCT scanning should be provided and the reimbursement in particular in the diagnosis group of the G-DRG B80Z has to be improved. Georg Thieme Verlag KG Stuttgart · New York.

Synergistic effect of apoptosis and necroptosis inhibitors in cisplatin-induced nephrotoxicity.

PubMed

Tristão, Vivian Regina; Pessoa, Edson A; Nakamichi, Renata; Reis, Luciana A; Batista, Marcelo Costa; Durão Junior, Marcelino de Souza; Monte, Júlio Cesar Martins

2016-01-01

Necroptosis is a nonapoptotic cell death pathway. We aim to study the effect of necrostatin-1 (a specific necroptosis inhibitor) in cisplatin-induced injury. We analyzed the effect of the combined use of inhibitors of apoptosis (z-vad) and necroptosis (necrostatin-1) in acute kidney injury by cisplatin in human proximal tubule cells. Our results showed moderate effectiveness in cytoprotection after treatment with z-vad. But the concomitant use of inhibitors (z-vad and necrostatin-1) presented synergistic and additive protection. The present study analyzed the caspase-3 activity and we observed a significant decrease in the group treated with z-vad and cisplatin. However we did not observe changes in the group treated with both inhibitors (z-vad and necrostatin-1) and cisplatin. Thus, demonstrating that necroptosis is a caspase-independent mechanism. We also analyzed the effect of necrostatin-1 in vivo model. C57BL/6 mice were treated with cisplatin and/or inhibitors. The concomitant use of inhibitors (z-vad and necrostatin-1) recovered renal function and decreased levels of urinary Ngal. Additionally, we analyzed the expression of RIP-1, a specific marker for necroptosis. In animals treated with cisplatin and z-VAD levels of RIP-1 were higher. This result reinforces that necroptosis occurs only in conditions where apoptosis was blocked. However, the use of both inhibitors (z-vad and necrostatin-1) provided additional protection. In conclusion, our study has a significant potential to show in vitro and in vivo protection obtained by necrostatin-1. Therefore, our results suggest that necroptosis may be an important mechanism of cell death after kidney injury.

N-terminal pro-brain natriuretic peptide in acute Kawasaki disease correlates with coronary artery involvement.

PubMed

Adjagba, Philippe M; Desjardins, Laurent; Fournier, Anne; Spigelblatt, Linda; Montigny, Martine; Dahdah, Nagib

2015-10-01

We have lately documented the importance of N-terminal pro-brain natriuretic peptide in aiding the diagnosis of Kawasaki disease. We sought to investigate the potential value of N-terminal pro-brain natriuretic peptide pertaining to the prediction of coronary artery dilatation (Z-score>2.5) and/or of resistance to intravenous immunoglobulin therapy. We hypothesised that increased serum N-terminal pro-brain natriuretic peptide level correlates with increased coronary artery dilatation and/or resistance to intravenous immunoglobulin. We carried out a prospective study involving newly diagnosed patients treated with 2 g/kg intravenous immunoglobulin within 5-10 days of onset of fever. Echocardiography was performed in all patients at onset, then weekly for 3 weeks, then at month 2, and month 3. Coronary arteries were measured at each visit, and coronary artery Z-score was calculated. All the patients had N-terminal pro-brain natriuretic peptide serum level measured at onset, and the Z-score calculated. There were 109 patients enrolled at 6.58±2.82 days of fever, age 3.79±2.92 years. High N-terminal pro-brain natriuretic peptide level was associated with coronary artery dilatation at onset in 22.2 versus 5.6% for normal N-terminal pro-brain natriuretic peptide levels (odds ratio 4.8 [95% confidence interval 1.05-22.4]; p=0.031). This was predictive of cumulative coronary artery dilatation for the first 3 months (p=0.04-0.02), but not during convalescence at 2-3 months (odds ratio 1.28 [95% confidence interval 0.23-7.3]; p=non-significant). Elevated N-terminal pro-brain natriuretic peptide levels did not predict intravenous immunoglobulin resistance, 15.3 versus 13.5% (p=1). Elevated N-terminal pro-brain natriuretic peptide level correlates with acute coronary artery dilatation in treated Kawasaki disease, but not with intravenous immunoglobulin resistance.

Relationship between final height and health outcomes in adults with congenital adrenal hyperplasia: United Kingdom congenital adrenal hyperplasia adult study executive (CaHASE).

PubMed

Han, T S; Conway, G S; Willis, D S; Krone, N; Rees, D A; Stimson, R H; Arlt, W; Walker, B R; Ross, R J

2014-08-01

Treatment of congenital adrenal hyperplasia (CAH) in childhood focuses on growth and development and adult final height (FH) is a measure of effective treatment. We hypothesized that shorter adults will have more severe underlying disease and worse health outcomes. This was a cross-sectional analysis of 199 adults with CAH. FH and quality of life were expressed as z-scores adjusted for midparental target height or UK population height. FH correlated inversely with age (men, r = -0.38; women, r = -0.26, P < .01). Men and women had z-scores adjusted for midparental target height of -2 and -1, respectively, and both groups had UK population height z-scores of -1 below the UK population (P < .01). In women, FH was shorter in non-salt-wasting than salt-wasting classic CAH (P < .05) and in moderately affected genotype group B women than either more severely affected groups null and A (P < .01) or the mildest group C (P < .001). Short stature and a higher prevalence of hypertension were observed in classic CAH patients diagnosed late (after 1 y) compared with those diagnosed early and in women treated with glucocorticoid only compared with those treated with both glucocorticoids and mineralocorticoids (P < .05). FH did not associate with insulin sensitivity, lipid profile, adiposity, or quality of life. Adult CAH patients remain short, although height prognosis has improved over time. The shortest adults are those diagnosed late with moderate severity CAH and are at increased risk of adult hypertension; we hypothesize that these patients are exposed in childhood to high androgens and/or excessive glucocorticoids with potential programming of hypertension. Another possibility is inadequate mineralocorticoid treatment early in life in the late-diagnosed patient group. Prospective studies are now required to examine these hypotheses.

Editor’s message: Groundwater modeling fantasies - Part 2, down to earth

USGS Publications Warehouse

Voss, Clifford I.

2011-01-01

Simplicity is the final achievement. After one has played a vast quantity of notes and more notes, it is simplicity that emerges as the crowning reward of art. (Frédéric Chopin, a musician and composer, quoted in If Not God, Then What? by Fost 2007)Despite the dubious developments discussed in part 1 of this Editor’s Message (Voss 2011), groundwater modeling really does represent the state of the art in hydrogeology, and groundwater modeling is in fact one of our most powerful tools for enhancing hydrogeologic understanding and for informing management of subsurface resources, at least when in the hands of competent hydrologists.

The effect of testosterone on cardiometabolic risk factors in atorvastatin-treated men with late-onset hypogonadism.

PubMed

Krysiak, Robert; Gilowski, Wojciech; Okopień, Bogusław

2016-02-01

By reducing LDL cholesterol levels, statins may decrease androgen production. This study was aimed at investigating whether testosterone treatment has an impact on cardiometabolic risk factors in statin-treated men with late-onset hypogonadism (LOH). The study included 31 men with LOH who had been treated for at least 6 months with atorvastatin (20-40mg daily). On the basis of patient preference, atorvastatin-treated patients were divided into two matched groups of patients: receiving intramuscular testosterone enanthate (100mg weekly, n=16) and not treated with this hormone (n=15). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were assessed before and after 4 months of therapy. Compared with the control age-, weight, and lipid-matched statin-naïve subjects with LOH (n=12), atorvastatin-treated patients were characterized by decreased levels of testosterone, hsCRP, and homocysteine. In patients not receiving testosterone therapy, plasma lipids, glucose homeostasis markers, as well as plasma levels of the investigated risk factors remained at the similar levels throughout the whole period of atorvastatin treatment. In atorvastatin-naïve patients, testosterone increased its plasma levels and decreased HDL cholesterol. Apart from an increase in testosterone levels, if administered to atorvastatin-treated subjects with LOH, testosterone reduced plasma levels of LDL cholesterol, uric acid, hsCRP, homocysteine, and fibrinogen, as well as improved insulin sensitivity. Our study may suggest the clinical benefits associated with combination therapy with a statin and testosterone in elderly men with LOH. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Abnormal ultraviolet mutagenic spectrum in plasmid DNA replicated in cultured fibroblasts from a patient with the skin cancer-prone disease, xeroderma pigmentosum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seetharam, S.; Protic-Sabljic, M.; Seidman, M.M.

1987-12-01

A shuttle vector plasmid, pZ189, was utilized to assess the types of mutations that cells from a patient with xeroderma pigmentosum, complementation group D, introduce into ultraviolet (UV) damaged, replicating DNA. Patients with xeroderma pigmentosum have clinical and cellular UV hypersensitivity, increased frequency of sun-induced skin cancer, and deficient DNA repair. In comparison to UV-treated pZ189 replicated in DNA repair-proficient cells, there were fewer surviving plasmids, a higher frequency of plasmids with mutations, fewer plasmids with two or more mutations in the marker gene, and a new mutagenic hotspot. The major type of base substitution mutation was the G:C tomore » A:T transition with both cell lines. These results, together with similar findings published earlier with cells from a xeroderma pigmentosum patient in complementation group A, suggest that isolated G:C to A:T somatic mutations may be particularly important in generation of human skin cancer by UV radiation.« less

[François Girardot (1773-1831) the surgeon of Light - Cavalrymen Regiment of Napoleon I Guard].

PubMed

Witczak, W

1996-01-01

The paper is the first wider biographic study presentif life and activity of François Girardot (1773-1831), a French physician, a surgeon of Polish light-cavalrymen regiment of Napoleon I guard for many years; since 1816 permanently domiciled in the Congress Kingdom of Poland, in Warsaw and Opinogóra, as a family doctor of Krasińskis family. There are his relations with Poland recalled, started in 1798 already, there are shown some famous patients of Girardot - Klementyna Hoffman of Tańskis, Zygmunt Krasiński and Fryderyk Chopin. There is also the attention drawn to his medical activity among poor population of Warsaw. The fact is underlined, that Girardot as the only physician was made by Napoleon the baron of Empire at the battle field (Craonne, 7th March, 1814), directly after injury, the effect of which there was an amputation of leg. It is also indicated, that despite unquestionable military merits, confirmed by numerous awards and the title of baron granted, and also medical merits of Girardot, he is still remaining a personage not well known to the historians of Napoleonic period.

Clinical efficacy of Spasmofen® suppository in the emergency treatment of renal colic: a randomized, double-blind, double-dummy comparative trial.

PubMed

Yakoot, Mostafa; Salem, Amel; Yousef, Sameh; Helmy, Sherine

2014-01-01

Renal colic is typically characterized by the sudden onset of severe pain radiating from the flank to the groin and its acute management in emergency departments essentially aims at rapid pain relief. Spasmofen(®) is a brand of Amriya Pharmaceutical Industries in the form of rectal suppositories containing ketoprofen 100 mg and hyoscine butylbromide 10 mg. This combination is intended for the rapid relief of severe colicky pain in the renal system, hepatobiliary system, or gastrointestinal tract. This trial aims to compare a single-dose of Spasmofen rectal suppository to a single intravenous (IV) ketorolac tromethamine 30 mg/2 mL dose in patients with acute renal colic. A total of 80 eligible consecutive patients presenting to the emergency departments of two medical centers with acute renal colic were included in the study. Eligible patients who signed the informed consent were randomly assigned into two treatment groups: an experimental group (Spasmofen group) who received one Spasmofen rectal suppository plus an IV injection of 2 mL of normal saline solution; and a control group (ketorolac group) who received one ketorolac 30 mg/2 mL ampoule IV plus one placebo suppository. Treatment success, defined as a change in the verbal rating score from severe or moderate pain to none or mild at 60 minutes after the dose, was compared between groups using the chi-square/Fisher's exact test. Percentage reductions in visual pain analog scale (VPAS) scores at 15 and 60 minutes after the dose were compared between groups using the Z-test for proportions. Successful treatment at 60 minutes occurred in 35 of 40 (87.5%) of Spasmofen-treated patients and in 33 of 40 (82.5%) of ketorolac-treated patients. The difference was not statistically significant by Fisher's exact test (P=0.755). The mean percentage reduction of VPAS after 15 minutes was 61.82% in the Spasmofen-treated group and 64.76% in the ketorolac-treated group. The difference was also not statistically significant by the Z-test for proportions (P=0.795). Sixty minutes after being treated, Spasmofen was associated with a statistically significant greater reduction in VPAS (mean% reduction =92.36%) than ketorolac (75.06%; P=0.0466). Single-dose Spasmofen rectal suppository might be a safe and effective first-aid treatment for the emergency department relief of acute renal colic.

Trans-nipple double Z-plasty for benign periareolar disease with inverted nipple.

PubMed

Lee, Jeeyeon; Lee, Seokwon; Bae, Youngtae

2013-04-01

Various surgical procedures have been reported for correction of inverted nipples. The authors herein report a new procedure, "the trans-nipple double Z-plasty," for correction of inverted nipples combined with periareolar disease requiring excision. From July 2010 to June 2012, 11 unilateral inverted nipples with other benign periareolar diseases were treated with this technique. A midline incision and 5-mm Z-incisions were designed on the nipple-areola complex toward the direction of the combined breast disease. After removal of combined benign disease through the trans-nipple double Z-plasty incision, the defect was filled with surrounding breast tissue, and the inverted nipple was corrected. One case of partial necrosis improved with conservative treatment. No recurrence was reported during the follow-up period. Five patients each assessed the cosmetic result as excellent and good. The trans-nipple double Z-plasty is an easy and useful technique for simultaneous management of periareolar disease with an inverted nipple. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Debio 0507 primarily forms diaminocyclohexane-Pt-d(GpG) and -d(ApG) DNA adducts in HCT116 cells

PubMed Central

King, C. L.; Ramachandran, S.; Collins, L.; Swenberg, J. A.; deKrafft, K. E.; Lin, W.; Cicurel, L.; Barbier, M.

2013-01-01

Purpose To characterize the cellular action mechanism of Debio 0507, we compared the major DNA adducts formed by Debio 0507- and oxaliplatin-treated HCT116 human colon carcinoma cells by a combination of inductively coupled plasma mass spectrometry (ICP-MS) and ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS). Methods HCT116 cells were treated with IC50 doses of Debio 0507 or oxaliplatin for 3 days. Total cellular Pt–DNA adducts were determined by ICP-MS. The DNA was digested, and the major Pt–DNA adducts formed by both drugs were characterized by UPLC/MS/MS essentially as described previously for cisplatin (Baskerville-Abraham et al. in Chem Res Toxicol 22:905–912, 2009). Results The Pt level/deoxynucleotide was 7.4/104 for DNA from Debio 0507-treated cells and 5.5/104 for oxaliplatin-treated cells following a 3-day treatment at the IC50 for each drug. UPLC-MS/MS in the positive ion mode confirmed the major Pt–DNA adducts formed by both drugs were dach-Pt-d(GpG) (904.2 m/z → 610 m/z and 904.2 m/z → 459 m/z) and dach-Pt-d(ApG) (888.2 m/z → 594 m/z and 888.2 m/z → 459 m/z). Conclusions These data show that the major DNA adducts formed by Debio 0507 are the dach-Pt-d(GpG) and dach-Pt-d(ApG) adducts and at equitoxic doses Debio 0507 and oxaliplatin form similar levels of dach-Pt-d(GpG) and dach-Pt-d(ApG) adducts. This suggests that the action mechanisms of Debio 0507 and oxaliplatin are similar at a cellular level. PMID:21968950

Efficacy of Zingiber officinale ethanol extract on the viability, embryogenesis and infectivity of Toxocara canis eggs.

PubMed

El-Sayed, Nagwa Mostafa

2017-12-01

This study evaluated the effect of Zingiber officinal e ( Z. officinal e) ethanol extract on the viability, embryogenesis and infectivity Toxocara canis ( T. canis ) eggs. It was carried out both in vitro and in vivo. In the in vitro experiment, unembryonated T. canis eggs were incubated with 25, 50 and 100 mg/mL Z. officinal e extract at 25 °C for 6, 12, and 24 h to assess the effect of Z. officinal e on their viability and for two weeks to assess the effect of Z. officinal e on their embryogenesis. In vivo experiment was performed to assess the effect of Z. officinal e on infectivity of T. canis eggs. Treated embryonated eggs by Z. officinale extract at concentrations of 25, 50 and 100 mg/mL for 24 h were inoculated into mice and their livers were examined for the presence of T. canis larvae on the 7th day after infection and for histopathological evaluation at 14th day post-infection. Z. officinal e showed a significant ovicidal activity on T. canis eggs. The best effect was observed with 100 mg/mL concentration after 24 h with an efficacy of 98.2%. However, the treated eggs by 25, 50 mg/mL of Z. officinale extract after 24 h showed ovicidal activity by 59.22 and 82.5% respectively. Moreover, this extract effectively inhibited T. canis eggs embryogenesis by 99.64% and caused their degeneration at the concentration of 100 mg/mL after 2 weeks of treatment. However, the lower concentrations, 25 and 50 mg/mL inhibited embryogenesis by 51.19 and 78.57% respectively. The effect of Z. officinal e on the infectivity T. canis eggs was proven by the reduction of larvae recovery in the livers by 35.9, 62.8 and 89.5% in mice groups inoculated by Z. officinale treated eggs at concentrations of 25, 50 and 100 mg/mL respectively. Histopathologically, the liver tissues of mice infected with Z. officinale treated eggs at the concentration of 100 mg/mL appeared healthy with slight degenerative changes of hepatocytes, opposite to that recorded in the infected mice with treated eggs by the lower concentrations. In conclusion; Z. officinale extract possessed dose-dependent anti- T. canis activity on the viability, embryogenesis and infectivity of T. canis eggs.

Tuberculosis of hip in children: A retrospective analysis

PubMed Central

Moon, Myung-Sang; Kim, Sung-Soo; Lee, Sung-Rak; Moon, Young-Wan; Moon, Jeong-Lim; Moon, Seog-In

2012-01-01

Background: Tuberculosis (TB) of hip constitutes nearly 15% of all cases of osteoarticular tuberculosis. We report a retrospective study carried out on 43 children with hip TB. Materials and Methods: Forty-three children of TB hip treated between 1971 and 2000 were analysed. Twenty-four children of the early series were treated with streptomycin (S), isoniazid (H) and PAS (Pa) for 18 months (3HPaS, 15 HPa), while 19 children in the later series were treated with isoniazid (H), rifampicin (R) and ethambutol (E) or pyrazinamide (Z) for 12 months [(12 RHE(Z)]. Five out of 18 children with radiologically normal appearing type hip TB were treated with chemotherapy alone and 38 children were subjected to surgery; simple synovectomy alone in 31 hips, joint debridement in six hips, and proximal femoral varisation osteotomy in one. After surgery hips were immobilized in cast for one to three months according to the severity of the disease and patients pain tolerance, and then were mobilized under leg traction in bed gradually till pain subsided completely. Results: TB of hip healed with minimum sequelae in all children. In 18 Type one hip TB, normal hip (synovial form) anatomy was maintained, and in 25 patients with advanced lesions some defect in the femoral head and acetabulum was noticed, though painless good hip motion was maintained. Excellent to good results were obtained in 31 children (73.1%), fair in eight (18.6%), and poor in four (9.3%). In four patients with poor results, there was some residual morphological defect in the hip. None developed ankylosis of hip. Conclusion: We achieved good outcome with minimum sequelae in this series. The management goal should be aimed not only to heal the disease but also to maintain a painless mobile hip and anatomical cephalocotyloid relationship until maturity, and retard the development of secondary osteoarthritis. PMID:22448058

The Effect of 3 Versus 6 Years of Zoledronic Acid Treatment of Osteoporosis: A Randomized Extension to the HORIZON-Pivotal Fracture Trial (PFT)

PubMed Central

Black, Dennis M; Reid, Ian R; Boonen, Steven; Bucci-Rechtweg, Christina; Cauley, Jane A; Cosman, Felicia; Cummings, Steven R; Hue, Trisha F; Lippuner, Kurt; Lakatos, Peter; Leung, Ping Chung; Man, Zulema; Martinez, Ruvie Lou Maria; Tan, Monique; Ruzycky, Mary Ellen; Su, Guoqin; Eastell, Richard

2012-01-01

Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in postmenopausal women with osteoporosis. To investigate long-term effects of ZOL on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly–Pivotal Fracture Trial (HORIZON-PFT) was extended to 6 years. In this international, multicenter, double-blind, placebo-controlled extension trial, 1233 postmenopausal women who received ZOL for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD percentage change from year 3 to 6 in the intent-to-treat (ITT) population. Secondary endpoints included other BMD sites, fractures, biochemical bone turnover markers, and safety. In years 3 to 6, FN-BMD remained constant in Z6 and dropped slightly in Z3P3 (between-treatment difference = 1.04%; 95% confidence interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other BMD sites showed similar differences. Biochemical markers remained constant in Z6 but rose slightly in Z3P3, remaining well below pretreatment levels in both. New morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n = 30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not different. Significantly more Z6 patients had a transient increase in serum creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p = 0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose symptoms were similar in both groups. Reports of hypertension were significantly lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue therapy up to 3 years. However, vertebral fracture reductions suggest that those at high fracture risk, particularly vertebral fracture, may benefit by continued treatment. (ClinicalTrials.gov identifier: NCT00145327). © 2012 American Society for Bone and Mineral Research. PMID:22161728

Cytological diploidization of paleopolyploid genus Zea: Divergence between homoeologous chromosomes or activity of pairing regulator genes?

PubMed Central

2018-01-01

Cytological diploidization process is different in autopolyploid and allopolyploid species. Colchicine applied at the onset of meiosis suppresses the effect of pairing regulator genes resulting multivalents formation in bivalent-forming species. Colchicine treated maizes (4x = 2n = 20, AmAmBmBm) showed up to 5IV, suggesting pairing between chromosomes from genomes homoeologous Am and Bm. In untreated individuals of the alloautooctoploid Zea perennis (8x = 2n = 40, ApApAp´Ap´Bp1Bp1Bp2Bp2) the most frequent configuration was 5IV+10II (formed by A and B genomes, respectively). The colchicine treated Z. perennis show up to 10IV revealing higher affinity within genomes A and B, but any homology among them. These results suggest the presence of a paring regulator locus (PrZ) in maize and Z. perennis, whose expression is suppressed by colchicine. It could be postulated that in Z. perennis, PrZ would affect independently the genomes A and B, being relevant the threshold of homology, the fidelity of pairing in each genomes and the ploidy level. Cytological analysis of the treated hexaploid hybrids (6x = 2n = 30), with Z. perennis as a parental, strongly suggests that PrZ is less effective in only one doses. This conclusion was reinforced by the homoeologous pairing observed in untreated dihaploid maizes, which showed up to 5II. Meiotic behaviour of individuals treated with different doses of colchicine allowed to postulate that PrZ affect the homoeologous association by controlling entire genomes (Am or Bm) rather than individual chromosomes. Based on cytological and statistical results it is possible to propose that the cytological diploidization in Zea species occurs by restriction of pairing between homoeologous chromosomes or by genetical divergence of the homoeologous chromosomes, as was observed in untreated Z. mays ssp. parviglumis. These are independent but complementary systems and could be acting jointly in the same nucleus. PMID:29293518

Cytological diploidization of paleopolyploid genus Zea: Divergence between homoeologous chromosomes or activity of pairing regulator genes?

PubMed

Poggio, Lidia; González, Graciela Esther

2018-01-01

Cytological diploidization process is different in autopolyploid and allopolyploid species. Colchicine applied at the onset of meiosis suppresses the effect of pairing regulator genes resulting multivalents formation in bivalent-forming species. Colchicine treated maizes (4x = 2n = 20, AmAmBmBm) showed up to 5IV, suggesting pairing between chromosomes from genomes homoeologous Am and Bm. In untreated individuals of the alloautooctoploid Zea perennis (8x = 2n = 40, ApApAp´Ap´Bp1Bp1Bp2Bp2) the most frequent configuration was 5IV+10II (formed by A and B genomes, respectively). The colchicine treated Z. perennis show up to 10IV revealing higher affinity within genomes A and B, but any homology among them. These results suggest the presence of a paring regulator locus (PrZ) in maize and Z. perennis, whose expression is suppressed by colchicine. It could be postulated that in Z. perennis, PrZ would affect independently the genomes A and B, being relevant the threshold of homology, the fidelity of pairing in each genomes and the ploidy level. Cytological analysis of the treated hexaploid hybrids (6x = 2n = 30), with Z. perennis as a parental, strongly suggests that PrZ is less effective in only one doses. This conclusion was reinforced by the homoeologous pairing observed in untreated dihaploid maizes, which showed up to 5II. Meiotic behaviour of individuals treated with different doses of colchicine allowed to postulate that PrZ affect the homoeologous association by controlling entire genomes (Am or Bm) rather than individual chromosomes. Based on cytological and statistical results it is possible to propose that the cytological diploidization in Zea species occurs by restriction of pairing between homoeologous chromosomes or by genetical divergence of the homoeologous chromosomes, as was observed in untreated Z. mays ssp. parviglumis. These are independent but complementary systems and could be acting jointly in the same nucleus.

Resistance to intravenous immunoglobulin in children with Kawasaki disease

PubMed Central

Tremoulet, Adriana H.; Best, Brookie M.; Song, Sungchan; Wang, Susan; Corinaldesi, Elena; Eichenfield, Julia R.; Martin, Danielle D.; Newburger, Jane W.; Burns, Jane C.

2008-01-01

Objectives To explore the increased incidence of intravenous immunoglobulin (IVIG) resistance among San Diego County Kawasaki disease (KD) patients in 2006 and to evaluate a scoring system to predict IVIG-resistant patients with KD. Study design We performed a retrospective review of patients with KD treated within 10 days of fever onset. Using multivariate analysis, independent predictors of IVIG-resistance were combined into a scoring system. Results In 2006, 38.3 % of patients with KD in San Diego County were IVIG-resistant, a significant increase over previous years. IVIG-resistance was not associated with a particular brand or lot of IVIG. Resistant patients were diagnosed earlier, had higher % bands, and higher concentrations of C-reactive protein, alanine aminotransferase, and γ-glutamyl transferase (GGT). They also had lower platelet counts and age-adjusted hemoglobin (zHgb) concentrations and were more likely to have aneurysms (p=0.0008). A scoring system developed to predict IVIG-resistant patients using illness day, % bands, GGT, and zHgb, had a sensitivity of 73.3% and specificity of 61.9%. Conclusions An unexplained increase in IVIG-resistance was noted among patients with KD in San Diego County in 2006. Scoring systems based on demographic and laboratory data were insufficiently accurate to be clinically useful in our ethnically diverse population. PMID:18571548

Weight change during childhood acute lymphoblastic leukemia induction therapy predicts obesity: a report from the Children's Oncology Group.

PubMed

Withycombe, Janice S; Smith, Lynette M; Meza, Jane L; Merkle, Carrie; Faulkner, Melissa Spezia; Ritter, Leslie; Seibel, Nita L; Moore, Ki

2015-03-01

Obesity is a well documented problem associated with childhood acute lymphoblastic leukemia (ALL) with increasing body mass index often observed during therapy. This study aims to evaluate if weight gain, early in therapy, is predictive of obesity at the end of treatment. In this secondary analysis, data from 1,017 high-risk ALL patients previously treated on a Children's Oncology Group protocol (CCG study 1961) were reviewed. Logistic regression was used to examine whether change in BMI z-score at Induction or Delayed Intensification (DI) 1 were predictive of obesity at the end of therapy. The BMI z-score at the beginning of Induction and the change in BMI z-score during Induction were both significant predictors of obesity at the end of therapy. The change in BMI z-score during cycle 1 of DI was not found to be associated with obesity. It is well know that obesity at the beginning of therapy is predictive of obesity at the end of ALL therapy. The new, and more important, finding from this study is that even after adjusting for baseline weight, the increase in BMI z-scores during induction was an independent predictor of obesity at the end of therapy. Most researchers agree that prevention is the best form of treatment for obesity as it is difficult to reverse once it is present. This study suggests that monitoring weight trends during Induction may be useful in guiding healthcare practitioners in identifying which patients are at highest risk for obesity development so that early intervention may occur. © 2014 Wiley Periodicals, Inc.

Early treatment with laronidase improves clinical outcomes in patients with attenuated MPS I: a retrospective case series analysis of nine sibships.

PubMed

Al-Sannaa, Nouriya A; Bay, Luisa; Barbouth, Deborah S; Benhayoun, Youssef; Goizet, Cyril; Guelbert, Norberto; Jones, Simon A; Kyosen, Sandra Obikawa; Martins, Ana Maria; Phornphutkul, Chanika; Reig, Celia; Pleat, Rebecca; Fallet, Shari; Ivanovska Holder, Iva

2015-10-07

Enzyme replacement therapy (ERT) with laronidase, (recombinant human α-L-iduronidase; Aldurazyme) is the primary treatment option for patients with attenuated mucopolysaccharidosis type I (MPS I). This study examined the effect of early ERT on clinical manifestations. This multinational, retrospective case series abstracted data from records of 20 patients with Hurler-Scheie syndrome within nine sibships that included older siblings treated with laronidase after the development of significant clinical symptoms, and younger siblings treated before significant symptomatology. Median age at diagnosis was 5.6 and 0.5 years for older and younger siblings, respectively. Median age at ERT initiation was 7.9 and 1.9 years for older and younger siblings, respectively. Improvement or stabilization of somatic signs and symptoms was more notable in younger siblings. Organomegaly present at onset of ERT improved in the majority of both older and younger siblings. Analysis of physician-rated symptom severity demonstrated that cardiac, musculoskeletal, and cognitive symptoms, when absent or mild in younger siblings at ERT initiation, generally did not develop or progress. The majority of older siblings had height/length Z-scores greater than two standard deviations below the mean (less than -2) at both time points. In general, Z-scores for younger siblings were closer to the sex- and age-matched means at follow-up. These findings suggest early initiation of laronidase, prior to the onset of symptoms in patients with attenuated MPS I, can slow or prevent the development of severe clinical manifestations.

Necessity of hospitalization and stress testing in low risk chest pain patients.

PubMed

Beri, Neil; Marston, Nicholas A; Daniels, Lori B; Nowak, Richard M; Schreiber, Donald; Mueller, Christian; Jaffe, Allan; Diercks, Deborah B; Wettersten, Nicholas; DeFilippi, Christopher; Peacock, W Frank; Limkakeng, Alexander T; Anand, Inder; McCord, James; Hollander, Judd E; Wu, Alan H B; Apple, Fred S; Nagurney, John T; Berardi, Cecilia; Cannon, Chad M; Clopton, Paul; Neath, Sean-Xavier; Christenson, Robert H; Hogan, Christopher; Vilke, Gary; Maisel, Alan

2017-02-01

Copeptin is a marker of endogenous stress including early myocardial infarction(MI) and has value in early rule out of MI when used with cardiac troponin I(cTnI). The goal of this study was to demonstrate that patients with a normal electrocardiogram and cTnI<0.040μg/l and copeptin<14pmol/l at presentation and after 2 h may be candidates for early discharge with outpatient follow-up potentially including stress testing. This study uses data from the CHOPIN trial which enrolled 2071 patients with acute chest pain. Of those, 475 patients with normal electrocardiogram and normal cTnI(<0.040μg/l) and copeptin<14pmol/l at presentation and after 2 h were considered "low risk" and selected for further analysis. None of the 475 "low risk" patients were diagnosed with MI during the 180day follow-up period (including presentation). The negative predictive value of this strategy was 100% (95% confidence interval(CI):99.2%-100.0%). Furthermore no one died during follow up. 287 (60.4%) patients in the low risk group were hospitalized. In the "low risk" group, the only difference in outcomes (MI, death, revascularization, cardiac rehospitalization) was those hospitalized underwent revascularization more often (6.3%[95%CI:3.8%-9.7%] versus 0.5%[95%CI:0.0%-2.9%], p=.002). The hospitalized patients were tested significantly more via stress testing or angiogram (68.6%[95%CI:62.9%-74.0%] vs 22.9%[95%CI:17.1%-29.6%], p<.001). Those tested had less cardiac rehospitalizations during follow-up (1.7% vs 5.1%, p=.040). In conclusion, patients with a normal electrocardiogram, troponin and copeptin at presentation and after 2 h are at low risk for MI and death over 180days. These low risk patients may be candidates for early outpatient testing and cardiology follow-up thereby reducing hospitalization. Copyright © 2016 Elsevier Inc. All rights reserved.

Outcome of temporal lobe epilepsy surgery predicted by statistical parametric PET imaging.

PubMed

Wong, C Y; Geller, E B; Chen, E Q; MacIntyre, W J; Morris, H H; Raja, S; Saha, G B; Lüders, H O; Cook, S A; Go, R T

1996-07-01

PET is useful in the presurgical evaluation of temporal lobe epilepsy. The purpose of this retrospective study is to assess the clinical use of statistical parametric imaging in predicting surgical outcome. Interictal 18FDG-PET scans in 17 patients with surgically-treated temporal lobe epilepsy (Group A-13 seizure-free, group B = 4 not seizure-free at 6 mo) were transformed into statistical parametric imaging, with each pixel representing a z-score value by using the mean and s.d. of count distribution in each individual patient, for both visual and quantitative analysis. Mean z-scores were significantly more negative in anterolateral (AL) and mesial (M) regions on the operated side than the nonoperated side in group A (AL: p < 0.00005, M: p = 0.0097), but not in group B (AL: p = 0.46, M: p = 0.08). Statistical parametric imaging correctly lateralized 16 out of 17 patients. Only the AL region, however, was significant in predicting surgical outcome (F = 29.03, p < 0.00005). Using a cut-off z-score value of -1.5, statistical parametric imaging correctly classified 92% of temporal lobes from group A and 88% of those from Group B. The preliminary results indicate that statistical parametric imaging provides both clinically useful information for lateralization in temporal lobe epilepsy and a reliable predictive indicator of clinical outcome following surgical treatment.

Correlation Between the Responses to Growth Hormone (GH) Treatment During Childhood and Adulthood in a Monocentric Cohort of GH-Deficient Patients.

PubMed

Thilmany, Sarah; Mchirgui, Leila; Brunelle, Chloé; Beauloye, Véronique; Maiter, Dominique; Alexopoulou, Orsalia

2018-06-01

Our aim was to analyze a cohort of patients with childhood-onset growth hormone deficiency (GHD) to evaluate if there is some correlation between the response to GH treatment during childhood and adulthood, respectively. This was an observational retrospective monocentric cohort study of 47 patients treated with GH during childhood and adulthood. Changes in growth parameters during childhood were compared with the increase of IGF-I z-score and other indexes of GH response (body composition, lipid profile) after 1 year of treatment in adulthood. The only significant positive correlation was observed between final growth velocity during the last year of childhood GH treatment and increase in IGF-I z-score in GH-treated adults (r=0.592, p=< 0.01). No correlation was observed between growth-promoting effects of GH as child and metabolic changes induced by GH as adult. We also observed a negative correlation between weight at the end of childhood GH treatment and the IGF-I response during first year of treatment in adults (r=- 0.335, p <0.05). No significant positive correlation could be observed between the main parameters that evaluate response to GH treatment in children and adults. However, the final growth velocity, which may be considered as one of the main criteria of end of GH treatment in children, was identified as parameter that could predict future response to GH treatment in adulthood. © Georg Thieme Verlag KG Stuttgart · New York.

Zingiber officinale and Type 2 Diabetes Mellitus: Evidence from Experimental Studies.

PubMed

Akash, Muhammad Sajid Hamid; Rehman, Kanwal; Tariq, Muhammad; Chen, Shuqing

2015-01-01

Zingiber officinale is being used as diet-based therapy because of its wide therapeutic potential in type 2 diabetes mellitus (T2DM) and against diabetic complications by directly interacting with different molecular and cellular pathways that provoke the pathogenesis of T2DM. This article explores the overall beneficial effects of Z. officinale on T2DM and its associated complications. Along with elucidating the beneficial facts of Z. officinale, this article may also aid in understanding the molecular basis of its effects in T2DM. The mechanistic rationale for antidiabetic effects of Z. officinale includes the inhibition of several transcriptional pathways, lipid peroxidation, carbohydrate-metabolizing enzymes, and HMG-CoA reductase and the activation of antioxidant enzyme capacity and low-density lipoprotein receptors. Consequently, by targeting these pathways, Z. officinale shows its antidiabetic therapeutic effects by increasing insulin sensitivity/synthesis, protecting β-cells of pancreatic islets, reducing fat accumulation, decreasing oxidative stress, and increasing glucose uptake by the tissues. In addition to these effects, Z. officinale also exhibits protective effects against several diabetes-linked complications, notably nephropathy and diabetic cataract, by acting as an antioxidant and antiglycating agent. In conclusion, this work suggests that consumption of Z. officinale can help to treat T2DM and diabetic complications; nevertheless, patient counseling also is required as a guiding force for the success of diet-based therapy in T2DM.

Detection and quantification of 4-ABP adducts in DNA from bladder cancer patients.

PubMed

Zayas, Beatriz; Stillwell, Sara W; Wishnok, John S; Trudel, Laura J; Skipper, Paul; Yu, Mimi C; Tannenbaum, Steven R; Wogan, Gerald N

2007-02-01

We analyzed bladder DNA from 27 cancer patients for dG-C8-4-aminobiphenyl (dG-C8-ABP) adducts using the liquid chromatography tandem mass spectrometry method with a 700 attomol (1 adduct in 10(9) bases) detection limit. Hemoglobin (Hb) 4-aminobiphenyl (4-ABP) adduct levels were measured by gas chromatography-mass spectrometry. After isolation of dG-C8-ABP by immunoaffinity chromatography and further purification, deuterated (d9) dG-C8-ABP (MW=443 Da) was added to each sample. Structural evidence and adduct quantification were determined by selected reaction monitoring, based on the expected adduct ion [M+H+]+1, at m/z 435 with fragmentation to the product ion at m/z 319, and monitoring of the transition for the internal standard, m/z 444-->328. The method was validated by analysis of DNA (100 microg each) from calf thymus; livers from ABP-treated and untreated rats; human placentas; and TK6 lymphoblastoid cells. Adduct was detected at femtomol levels in DNA from livers of ABP-treated rats and calf thymus, but not in other controls. The method was applied to 41 DNA samples (200 microg each) from 27 human bladders; 28 from tumor and 14 from surrounding non-tumor tissue. Of 27 tissues analyzed, 44% (12) contained 5-80 dG-C8-ABP adducts per 10(9) bases; only 1 out of 27 (4%) contained adduct in both tumor and surrounding tissues. The Hb adduct was detected in samples from all patients, at levels of 12-1960 pg per gram Hb. There was no correlation between levels of DNA and Hb adducts. The presence of DNA adducts in 44% of the subjects and high levels of Hb adducts in these non-smokers indicate environmental sources of exposure to 4-ABP.

Axillary Ultrasound After Neoadjuvant Chemotherapy and Its Impact on Sentinel Lymph Node Surgery: Results From the American College of Surgeons Oncology Group Z1071 Trial (Alliance)

PubMed Central

Boughey, Judy C.; Ballman, Karla V.; Hunt, Kelly K.; McCall, Linda M.; Mittendorf, Elizabeth A.; Ahrendt, Gretchen M.; Wilke, Lee G.; Le-Petross, Huong T.

2015-01-01

Purpose The American College of Surgeons Oncology Group Z1071 trial reported a 12.6% false-negative rate (FNR) for sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in cN1 disease. Patients were not selected for surgery based on response, but a secondary end point was to determine whether axillary ultrasound (AUS) after NAC after fine-needle aspiration cytology can identify abnormal nodes and guide patient selection for SLN surgery. Patients and Methods Patients with T0-4, N1-2, M0 breast cancer underwent AUS after neoadjuvant chemotherapy. AUS images were centrally reviewed and classified as normal or suspicious lymph nodes. AUS findings were tested for association with pathologic nodal status and SLN FNR. The impact of AUS results to select patients for SLN surgery to reduce the FNR was assessed. Results Postchemotherapy AUS images were reviewed for 611 patients. One hundred thirty (71.8%) of 181 AUS-suspicious patients were node positive at surgery compared with 243 (56.5%) of 430 AUS-normal patients (P < .001). Patients with AUS-suspicious nodes had a greater number of positive nodes and greater metastasis size (P < .001). The SLN FNR was not different based on AUS results; however, using a strategy where only patients with normal AUS undergo SLN surgery would potentially reduce the FNR in Z1071 patients with ≥ two SLNs removed from 12.6% to 9.8% when preoperative AUS results are considered as part of SLN surgery. Conclusion AUS is recommended after chemotherapy to guide axillary surgery. An FNR of 9.8% with the combination of AUS and SLN surgery would be acceptable for the adoption of SLN surgery for women with node-positive breast cancer treated with neoadjuvant chemotherapy. PMID:25646192

Integration of Early Specialist Palliative Care in Cancer Care: Survey of Oncologists, Oncology Nurses, and Patients.

PubMed

Salins, Naveen; Patra, Lipika; Usha Rani, M R; Lohitashva, S O; Rao, Raghavendra; Ramanjulu, Raghavendra; Vallath, Nandini

2016-01-01

Palliative care is usually delivered late in the course of illness trajectory. This precludes patients on active disease modifying treatment from receiving the benefit of palliative care intervention. A survey was conducted to know the opinion of oncologists, oncology nurses, and patients about the role of early specialist palliative care in cancer. A nonrandomized descriptive cross-sectional study was conducted at a tertiary cancer care center in India. Thirty oncologists, sixty oncology nurses, and sixty patients were surveyed. Improvement in symptom control was appreciated by oncologists, oncology nurses, and patients with respect to pain (Z = -4.10, P = 0.001), (Z = -5.84, P = 0.001), (Z = -6.20, P = 0.001); nausea and vomiting (Z = -3.75, P = 0.001), (Z = -5.3, P = 0.001), (Z = -5.1, P = 0.001); constipation (Z = -3.29, P = 0.001), (Z = -4.96, P = 0.001), (Z = -4.49, P = 0.001); breathlessness (Z = -3.57, P = 0.001), (Z = -5.03, P = 0.001), (Z = -4.99, P = 0.001); and restlessness (Z = -3.68, P = 0.001), (Z = -5.23, P = 0.001), (Z = -3.22, P = 0.001). Improvement in end-of-life care management was appreciated by oncologists and oncology nurses with respect to communication of prognosis (Z = -4.04, P = 0.001), (Z = -5.20, P = 0.001); discussion on limitation of life-sustaining treatment (Z = -3.68, P = 0.001), (Z = -4.53, P = 0.001); end-of-life symptom management (Z = -4.17, P = 0.001), (Z = -4.59, P = 0.001); perimortem care (Z = -3.86, P = 0.001), (Z = -4.80, P = 0.001); and bereavement support (Z = -3-80, P = 0.001), (Z = -4.95, P = 0.001). Improvement in health-related communication was appreciated by oncologists, oncology nurses, and patients with respect to communicating health related information in a sensitive manner (Z = -3.74, P = 0.001), (Z = -5.47, P = 0.001), (Z = -6.12, P = 0.001); conducting family meeting (Z = -3.12, P = 0.002), (Z = -4.60, P = 0.001), (Z = -5.90, P = 0.001); discussing goals of care (Z = -3.43, P = 0.001), (Z = -5.49, P = 0.001), (Z = -5.61, P = 0.001); maintaining hope (Z = -3.22, P = 0.001), (Z = -4.85, P = 0.001), (Z = -5.61, P = 0.001); and resolution of conflict (Z = -3.56, P = 0.001), (Z = -5.29, P = 0.001), (Z = -5.28, P = 0.001). Patients appreciated improvement in continuity of care with respect to discharge planning (Z = -6.12, P = 0.001), optimal supply of essential symptom control medications on discharge (Z = -6.32, P = 0.001), follow-up plan (Z = -6.40, P = 0.001), after hours telephonic support (Z = -6.31, P = 0.001), and preferred place of care (Z = -6.28, P = 0.001). Oncologists, oncology nurses, and patients felt that integration of early specialist palliative care in cancer improves symptom control, end-of-life care, health-related communication, and continuity of care. The perceptions of benefit of the palliative care intervention in the components surveyed, differed among the three groups.

Integration of Early Specialist Palliative Care in Cancer Care: Survey of Oncologists, Oncology Nurses, and Patients

PubMed Central

Salins, Naveen; Patra, Lipika; Usha Rani, MR; Lohitashva, SO; Rao, Raghavendra; Ramanjulu, Raghavendra; Vallath, Nandini

2016-01-01

Introduction: Palliative care is usually delivered late in the course of illness trajectory. This precludes patients on active disease modifying treatment from receiving the benefit of palliative care intervention. A survey was conducted to know the opinion of oncologists, oncology nurses, and patients about the role of early specialist palliative care in cancer. Methods: A nonrandomized descriptive cross-sectional study was conducted at a tertiary cancer care center in India. Thirty oncologists, sixty oncology nurses, and sixty patients were surveyed. Results: Improvement in symptom control was appreciated by oncologists, oncology nurses, and patients with respect to pain (Z = −4.10, P = 0.001), (Z = −5.84, P = 0.001), (Z = −6.20, P = 0.001); nausea and vomiting (Z = −3.75, P = 0.001), (Z = −5.3, P = 0.001), (Z = −5.1, P = 0.001); constipation (Z = −3.29, P = 0.001), (Z = −4.96, P = 0.001), (Z = −4.49, P = 0.001); breathlessness (Z = −3.57, P = 0.001), (Z = −5.03, P = 0.001), (Z = −4.99, P = 0.001); and restlessness (Z = −3.68, P = 0.001), (Z = −5.23, P = 0.001), (Z = −3.22, P = 0.001). Improvement in end-of-life care management was appreciated by oncologists and oncology nurses with respect to communication of prognosis (Z = −4.04, P = 0.001), (Z = −5.20, P = 0.001); discussion on limitation of life-sustaining treatment (Z = −3.68, P = 0.001), (Z = −4.53, P = 0.001); end-of-life symptom management (Z = −4.17, P = 0.001), (Z = −4.59, P = 0.001); perimortem care (Z = −3.86, P = 0.001), (Z = −4.80, P = 0.001); and bereavement support (Z = −3-80, P = 0.001), (Z = −4.95, P = 0.001). Improvement in health-related communication was appreciated by oncologists, oncology nurses, and patients with respect to communicating health related information in a sensitive manner (Z = −3.74, P = 0.001), (Z = −5.47, P = 0.001), (Z = −6.12, P = 0.001); conducting family meeting (Z = −3.12, P = 0.002), (Z = −4.60, P = 0.001), (Z = −5.90, P = 0.001); discussing goals of care (Z = −3.43, P = 0.001), (Z = −5.49, P = 0.001), (Z = −5.61, P = 0.001); maintaining hope (Z = −3.22, P = 0.001), (Z = −4.85, P = 0.001), (Z = −5.61, P = 0.001); and resolution of conflict (Z = −3.56, P = 0.001), (Z = −5.29, P = 0.001), (Z = −5.28, P = 0.001). Patients appreciated improvement in continuity of care with respect to discharge planning (Z = −6.12, P = 0.001), optimal supply of essential symptom control medications on discharge (Z = −6.32, P = 0.001), follow-up plan (Z = −6.40, P = 0.001), after hours telephonic support (Z = −6.31, P = 0.001), and preferred place of care (Z = −6.28, P = 0.001). Conclusion: Oncologists, oncology nurses, and patients felt that integration of early specialist palliative care in cancer improves symptom control, end-of-life care, health-related communication, and continuity of care. The perceptions of benefit of the palliative care intervention in the components surveyed, differed among the three groups. PMID:27559253

Midline cervical cleft: a rare congenital anomaly.

PubMed

Renukaswamy, Gayathri Mandya; Soma, Marlene A; Hartley, Benjamin E J

2009-11-01

A midline cervical cleft (MCC) is a rare congenital anomaly due to failure of fusion of the first and second branchial arches during embryogenesis. It may present as a midline defect of the anterior neck skin with a skin projection or sinus, or as a subcutaneous fibrous cord. This report evaluates the clinical features and surgical management of an MCC. We analyzed a series of 4 patients with an MCC successfully treated at Great Ormond Street Hospital for Children in London. Three male patients and 1 female patient between 4 and 11 months of age were found to have an MCC. Each patient presented with an erythematous, fibrous band of tissue extending between the chin and the suprasternal notch. Treatment comprised surgical excision of the lesion and Z-plasty repair. We present the embryology, common clinical presentation, investigations, differential diagnosis, and histology, along with a literature review, of this uncommon malformation of the anterior neck. An MCC is a differential diagnosis to consider when assessing a child with a midline cervical lesion. Early surgical excision with Z-plasty repair of the soft tissue defect is the treatment of choice to prevent long-term complications.

Debio 0507 primarily forms diaminocyclohexane-Pt-d(GpG) and -d(ApG) DNA adducts in HCT116 cells.

PubMed

King, C L; Ramachandran, S; Chaney, S G; Collins, L; Swenberg, J A; DeKrafft, K E; Lin, W; Cicurel, L; Barbier, M

2012-03-01

To characterize the cellular action mechanism of Debio 0507, we compared the major DNA adducts formed by Debio 0507- and oxaliplatin-treated HCT116 human colon carcinoma cells by a combination of inductively coupled plasma mass spectrometry (ICP-MS) and ultraperformance liquid chromatography mass spectrometry (UPLC-MS/MS). HCT116 cells were treated with IC(50) doses of Debio 0507 or oxaliplatin for 3 days. Total cellular Pt-DNA adducts were determined by ICP-MS. The DNA was digested, and the major Pt-DNA adducts formed by both drugs were characterized by UPLC/MS/MS essentially as described previously for cisplatin (Baskerville-Abraham et al. in Chem Res Toxicol 22:905-912, 2009). The Pt level/deoxynucleotide was 7.4/10(4) for DNA from Debio 0507-treated cells and 5.5/10(4) for oxaliplatin-treated cells following a 3-day treatment at the IC(50) for each drug. UPLC-MS/MS in the positive ion mode confirmed the major Pt-DNA adducts formed by both drugs were dach-Pt-d(GpG) (904.2 m/z → 610 m/z and 904.2 m/z → 459 m/z) and dach-Pt-d(ApG) (888.2 m/z → 594 m/z and 888.2 m/z → 459 m/z). These data show that the major DNA adducts formed by Debio 0507 are the dach-Pt-d(GpG) and dach-Pt-d(ApG) adducts and at equitoxic doses Debio 0507 and oxaliplatin form similar levels of dach-Pt-d(GpG) and dach-Pt-d(ApG) adducts. This suggests that the action mechanisms of Debio 0507 and oxaliplatin are similar at a cellular level.

Current and developing therapies for the treatment of multi drug resistant tuberculosis (MDR-TB) in India.

PubMed

Muniyandi, Malaisamy; Ramachandran, Rajeswari

2017-09-01

India accounts for 25% of the global burden of MDR-TB. In 2016, the India's Revised National TB Control Programme reported a success rate of 46% among 19,298 MDR-TB patients treated under the programme. This suboptimal treatment outcome warrants an urgent need for newer drugs and newer regimens in the treatment of MDR-TB. India requires new shorter, cheap, safe and effective anti-TB regimen to treat MDR-TB. Areas covered: We used different search strategies to obtain relevant literature from PubMed, on Indian experiences of developing therapies for the treatment of MDR-TB. Further information from the Central TB Division Government of India on programmatic management of resistant TB was collected. Expert opinion: In 2016 WHO recommended a shorter MDR-TB regimen of 9-12 months (4-6 Km-Mfx-Pto-Cfz-Z-Hhigh-dose-E /5 Mfx-Cfz-Z-E) may be used instead of longer regimens. Currently, conducting trials involving newer drugs such as bedaquiline, have been proposed. The regimen will be of a shorter duration containing isoniazid, prothionamide, bedaquiline, levofloxacin, ciprofloxacin, ethambutol and pyrazinamide (STREAM regimen). To successfully treat MDR-TB one requires new classes of antibiotic and newer diagnostic tests. This represents an enormous financial and technical challenge to the programme managers and policy makers.

Axillary Ultrasound After Neoadjuvant Chemotherapy and Its Impact on Sentinel Lymph Node Surgery: Results From the American College of Surgeons Oncology Group Z1071 Trial (Alliance).

PubMed

Boughey, Judy C; Ballman, Karla V; Hunt, Kelly K; McCall, Linda M; Mittendorf, Elizabeth A; Ahrendt, Gretchen M; Wilke, Lee G; Le-Petross, Huong T

2015-10-20

The American College of Surgeons Oncology Group Z1071 trial reported a 12.6% false-negative rate (FNR) for sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in cN1 disease. Patients were not selected for surgery based on response, but a secondary end point was to determine whether axillary ultrasound (AUS) after NAC after fine-needle aspiration cytology can identify abnormal nodes and guide patient selection for SLN surgery. Patients with T0-4, N1-2, M0 breast cancer underwent AUS after neoadjuvant chemotherapy. AUS images were centrally reviewed and classified as normal or suspicious lymph nodes. AUS findings were tested for association with pathologic nodal status and SLN FNR. The impact of AUS results to select patients for SLN surgery to reduce the FNR was assessed. Postchemotherapy AUS images were reviewed for 611 patients. One hundred thirty (71.8%) of 181 AUS-suspicious patients were node positive at surgery compared with 243 (56.5%) of 430 AUS-normal patients (P < .001). Patients with AUS-suspicious nodes had a greater number of positive nodes and greater metastasis size (P < .001). The SLN FNR was not different based on AUS results; however, using a strategy where only patients with normal AUS undergo SLN surgery would potentially reduce the FNR in Z1071 patients with ≥ two SLNs removed from 12.6% to 9.8% when preoperative AUS results are considered as part of SLN surgery. AUS is recommended after chemotherapy to guide axillary surgery. An FNR of 9.8% with the combination of AUS and SLN surgery would be acceptable for the adoption of SLN surgery for women with node-positive breast cancer treated with neoadjuvant chemotherapy. © 2015 by American Society of Clinical Oncology.

Quantitative EEG and Current Source Density Analysis of Combined Antiepileptic Drugs and Dopaminergic Agents in Genetic Epilepsy: Two Case Studies.

PubMed

Emory, Hamlin; Wells, Christopher; Mizrahi, Neptune

2015-07-01

Two adolescent females with absence epilepsy were classified, one as attention deficit and the other as bipolar disorder. Physical and cognitive exams identified hypotension, bradycardia, and cognitive dysfunction. Their initial electroencephalograms (EEGs) were considered slightly slow, but within normal limits. Quantitative EEG (QEEG) data included relative theta excess and low alpha mean frequencies. A combined treatment of antiepileptic drugs with a catecholamine agonist/reuptake inhibitor was sequentially used. Both patients' physical and cognitive functions improved and they have remained seizure free. The clinical outcomes were correlated with statistically significant changes in QEEG measures toward normal Z-scores in both anterior and posterior regions. In addition, low resolution electromagnetic tomography (LORETA) Z-scored source correlation analyses of the initial and treated QEEG data showed normalized patterns, supporting a neuroanatomic resolution. This study presents preliminary evidence for a neurophysiologic approach to patients with absence epilepsy and comorbid disorders and may provide a method for further research. © EEG and Clinical Neuroscience Society (ECNS) 2014.

Analysis of point mutations in an ultraviolet-irradiated shuttle vector plasmid propagated in cells from Japanese xeroderma pigmentosum patients in complementation groups A and F

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yagi, T.; Tatsumi-Miyajima, J.; Sato, M.

1991-06-15

To assess the contribution to mutagenesis by human DNA repair defects, a UV-treated shuttle vector plasmid, pZ189, was passed through fibroblasts derived from Japanese xeroderma pigmentosum (XP) patients in two different DNA repair complementation groups (A and F). Patients with XP have clinical and cellular UV hypersensitivity, increased frequency of skin cancer, and defects in DNA repair. The XP DNA repair defects represented by complementation groups A (XP-A) and F (XP-F) are more common in Japan than in Europe or the United States. In comparison to results with DNA repair-proficient human cells (W138-VA13), UV-treated pZ189 passed through the XP-A (XP2OS(SV))more » or XP-F (XP2YO(SV)) cells showed fewer surviving plasmids (XP-A less than XP-F) and a higher frequency of mutated plasmids (XP-A greater than XP-F). Base sequence analysis of more than 200 mutated plasmids showed the major type of base substitution mutation to be the G:C----A:T transition with all three cell lines. The XP-A and XP-F cells revealed a higher frequency of G:C----A:T transitions and a lower frequency of transversions among plasmids with single or tandem mutations and a lower frequency of plasmids with multiple point mutations compared to the normal line. The spectrum of mutations in pZ189 with the XP-A cells was similar to that with the XP-F cells. Seventy-six to 91% of the single base substitution mutations occurred at G:C base pairs in which the 5{prime}-neighboring base of the cytosine was thymine or cytosine. These studies indicate that the DNA repair defects in Japanese XP patients in complementation groups A and F result in different frequencies of plasmid survival and mutagenesis but in similar types of mutagenic abnormalities despite marked differences in clinical features.« less

Effects of an Antagonistic Analog of Growth Hormone-Releasing Hormone on Endometriosis in a Mouse Model and In Vitro.

PubMed

Köster, Frank; Jin, Li; Shen, Yuanming; Schally, Andrew V; Cai, Ren-Zhi; Block, Norman L; Hornung, Daniela; Marschner, Gabriele; Rody, Achim; Engel, Jörg B; Finas, Dominique

2017-11-01

Endometriosis is a benign gynecologic disorder causing dysmenorrhea, pelvic pain, and subfertility. Receptors for the growth hormone-releasing hormone (GHRH) were found in endometriotic tissues. Antagonists of GHRH have been used to inhibit the growth of endometriotic endometrial stromal cells. In this study, the GHRH receptor splice variant (SV) 1 was detected in human endometrial tissue samples by Western blots and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The highest messenger RNA (mRNA) and protein levels of SV1 were found in eutopic endometrium from patients with endometriosis compared to ectopic endometriotic tissues and endometrium from normal patients. The highest expression for GHRH mRNA was found by qRT-PCR in ectopic endometriosis lesions. In an in vivo mouse model with human endometrial explants from patients with endometriosis, 10 μg MIA-602 per day resulted in significantly smaller human endometrial xenotransplants after 4 weeks compared to mice treated with vehicle. The endometrial tissues expressed SV1 before and after xenotransplantation. The proliferation of endometrial stromal cells as well as the endometriosis cell lines 12-Z and 49-Z was decreased by exposure to 1 μM MIA-602 after 72 hours. The protein levels of epithelial growth factor receptors in 12-Z and 49-Z cell lines were reduced 48 and 72 hours after the administration of 1 μM MIA-602. MIA-602 decreased the activation of the MAP-kinases ERK-1/2. Our study demonstrates the presence of SV1 receptor as a target for treatment with GHRH antagonist in endometriosis. Endometrial tissues respond to MIA-602 with inhibition of proliferation in vitro and in vivo. The use of MIA-602 could be an effective supplement to the treatment strategies in endometriosis.

Evaluation of the Correlation Coefficient of Polyethylene Glycol Treated and Direct Prolactin Results and Comparability with Different Assay System Results.

PubMed

Pal, Shyamali

2017-12-01

The presence of Macro prolactin is a significant cause of elevated prolactin resulting in misdiagnosis in all automated systems. Poly ethylene glycol (PEG) pretreatment is the preventive process but such process includes the probability of loss of a fraction of bioactive prolactin. Surprisingly, PEG treated EQAS & IQAS samples in Cobas e 411 are found out to be correlating with direct results of at least 3 immunoassay systems and treated and untreated Cobas e 411 results are comparable by a correlation coefficient. Comparison of EQAS, IQAS and patient samples were done to find out the trueness of such correlation factor. Study with patient's results have established the correlation coefficient is valid for very small concentration of prolactin also. EQAS, IQAS and 150 patient samples were treated with PEG and prolactin results of treated and untreated samples obtained from Roche Cobas e 411. 25 patient's results (treated) were compared with direct results in Advia Centaur, Architect I & Access2 systems. Correlation coefficient was obtained from trend line of the treated and untreated results. Two tailed p-value obtained from regression coefficient(r) and sample size. The correlation coefficient is in the range (0.761-0.771). Reverse correlation range is (1.289-1.301). r value of two sets of calculated results were 0.995. Two tailed p- value is zero approving dismissal of null hypothesis. The z-score of EQAS does not always assure authenticity of resultsPEG precipitation is correlated by the factor 0.761 even in very small concentrationsAbbreviationsGFCgel filtration chromatographyPEGpolyethylene glycolEQASexternal quality assurance systemM-PRLmacro prolactinPRLprolactinECLIAelectro-chemiluminescence immunoassayCLIAclinical laboratory improvement amendmentsIQASinternal quality assurance systemrregression coefficient.

Peripheral mRNA expression of pluripotency markers in bipolar disorder and the effect of long-term lithium treatment.

PubMed

Ferensztajn-Rochowiak, Ewa; Tarnowski, Maciej; Samochowiec, Jerzy; Michalak, Michal; Ratajczak, Mariusz Z; Rybakowski, Janusz K

2016-10-01

The aim was to evaluate the peripheral mRNA expression of pluripotency master transcriptional factors such as octamer-binding transcription factor 4 (Oct4), sex-determining region Y-box 2 (Sox2) and homeobox protein Nanog, in patients with bipolar disorder (BD), and the effect of long-term lithium treatment. Fifteen BD patients (aged 53±7years) not treated with lithium, with duration of illness>10years, 15 BD patients (aged 55±6years) treated with lithium for 8-40 years (mean 16years) and 15 control subjects (aged 50±5years) were included. Assessment of the mRNA levels of pluripotency markers (Oct-4, Sox 2 and Nanog) was performed, using the Real-time quantitative reverse transcription PCR (RQ-PCR) procedure, and the number of CD34+ very small embryonic-like stem cells (VSELs) was measured by flow cytometric analysis. In those BD patients not treated with lithium the expression of all three pluripotency genes was significantly higher than that in the control subjects. Oct-4, Sox2 and Nanog also positively correlated with the number of CD34+ VSELs/[ul] in this group. In the lithium-treated patients the mRNA levels of Nanog were significantly higher than in the control individuals and correlated with the number and % of CD34+ VSELs. The overexpression of the pluripotency master transcriptional factors in patients with a long duration of BD not treated with lithium, may contribute to the pathogenesis of the illness and make them potential biological markers of BD. Long-term lithium treatment may attenuate these excessive regenerative processes, especially in relation to the transcription factors Oct-4 and Sox2. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Outcomes of different Class II treatments : Comparisons using the American Board of Orthodontics Model Grading System.

PubMed

Akinci Cansunar, Hatice; Uysal, Tancan

2016-07-01

The aim of this study was to evaluate the clinical outcomes of three different Class II treatment modalities followed by fixed orthodontic therapy, using the American Board of Orthodontics Model Grading System (ABO-MGS). As a retrospective study, files of patients treated at postgraduate orthodontic  clinics in different cities in Turkey was randomly selected. From 1684 posttreatment records, 669 patients were divided into three groups: 269 patients treated with extraction of two upper premolars, 198 patients treated with cervical headgear, and 202 patients treated with functional appliances. All the cases were evaluated by one researcher using ABO-MGS. The χ (2), Z test, and multivariate analysis of variance were used for statistical evaluation (p < 0.05). No significant differences were found among the groups in buccolingual inclination, overjet, occlusal relationship, and root angulation. However, there were significant differences in alignment, marginal ridge height, occlusal contact, interproximal contact measurements, and overall MGS average scores. The mean treatment time between the extraction and functional appliance groups was significantly different (p = 0.017). According to total ABO-MGS scores, headgear treatment had better results than functional appliances. The headgear group had better tooth alignment than the extraction group. Headgear treatment resulted in better occlusal contacts than the functional appliances and had lower average scores for interproximal contact measurements. Functional appliances had the worst average scores for marginal ridge height. Finally, the functional appliance group had the longest treatment times.

[LenSx® femto-LASIK, FEMTO LDV Z4® femto-LASIK, and PRK : Comparison of refractive results and an analysis of complications].

PubMed

Pahlitzsch, T; Pahlitzsch, M-L; Sumarni, U; Pahlitzsch, M

2017-10-30

The aim of this study is to evaluate three refractive procedures: LenSx® (Alcon, Fort Worth, TX, USA) femto-laser in situ keratomileusis (LASIK), FEMTO LDV Z4® (Ziemer, Port, Switzerland) femto-LASIK, and photorefractive keratectomy (PRK) in terms of refractive outcome, perioperative complications, pain, and patient satisfaction. Data of 168 eyes (myopic n = 84) were included in this retrospective study. Of these, 54 eyes (n = 27, 33.85 ± 7.64 years) were treated with LenSx® femto-LASIK, 60 eyes (n = 30, 35.03 ± 7.46 years) with FEMTO LDV Z4® femto-LASIK, and 54 eyes (n = 27, 33.24 ± 8.52 years) with PRK. Photoablation was induced by a MEL80 Excimerlaser (Zeiss, Oberkochen, Germany). The corrected (V sc ) and uncorrected (V cc ) distance subjective visual acuity, corneal topography (Pentacam® HR; Wetzlar, Germany), and objective astigmatism (ARK-760A Refractometer ; Nidek, Fremont, CA, USA) were measured preoperatively, and 1 day, 1 week, 1 month, and 3 months postoperatively. Subjective pain (verbal rating scale) and patient satisfaction were also recorded. Subjective V sc showed significantly better results in both femto-LASIK cohorts compared to PRK (p < 0.05) 1 day and 1 week postoperatively. There was no significant difference between the groups in terms of spherical equivalent and astigmatism 3 months postoperatively. The LenSx® femto-LASIK caused flap complications. The highest patient satisfaction results were shown in the LDV Z4® group, followed by the LenSx® and PRK cohorts (p = 0.072). LDV Z4® femto-LASIK showed the lowest pain score 1 day postoperatively (p < 0.001). There was no significant correlation between target refraction and preoperative corneal thickness and astigmatism. Femtosecond laser-assisted LASIK is an effective procedure enabling rapid rehabilitation of visual acuity with low postoperative pain compared to PRK. There is no difference between the three techniques regarding refractive outcome after 3 months follow-up. LDV Z4® femto-LASIK can be recommended, if available, due to its low intraoperative complication rate and higher patient satisfaction compared to LenSx® femto-LASIK.

Patterns of Local-Regional Management Following Neoadjuvant Chemotherapy in Breast Cancer: Results From ACOSOG Z1071 (Alliance)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haffty, Bruce G., E-mail: hafftybg@cinj.rutgers.edu; McCall, Linda M.; Ballman, Karla V.

2016-03-01

Purpose: American College of Surgeons Oncology Group Z1071 was a prospective trial evaluating the false negative rate of sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in breast cancer patients with initial node-positive disease. Radiation therapy (RT) decisions were made at the discretion of treating physicians, providing an opportunity to evaluate variability in practice patterns following NAC. Methods and Materials: Of 756 patients enrolled from July 2009 to June 2011, 685 met all eligibility requirements. Surgical approach, RT, and radiation field design were analyzed based on presenting clinical and pathologic factors. Results: Of 401 node-positive patients, mastectomy was performed inmore » 148 (36.9%), mastectomy with immediate reconstruction in 107 (26.7%), and breast-conserving surgery (BCS) in 146 patients (36.4%). Of the 284 pathologically node-negative patients, mastectomy was performed in 84 (29.6%), mastectomy with immediate reconstruction in 69 (24.3%), and BCS in 131 patients (46.1%). Bilateral mastectomy rates were higher in women undergoing reconstruction than in those without (66.5% vs 32.2%, respectively, P<.0001). Use of internal mammary RT was low (7.8%-11.2%) and did not differ between surgical approaches. Supraclavicular RT rate ranged from 46.6% to 52.2% and did not differ between surgical approaches but was omitted in 193 or 408 node-positive patients (47.3%). Rate of axillary RT was more frequent in patients who remained node-positive (P=.002). However, 22% of patients who converted to node-negative still received axillary RT. Post-mastectomy RT was more frequently omitted after reconstruction than mastectomy (23.9% vs 12.1%, respectively, P=.002) and was omitted in 19 of 107 patients (17.8%) with residual node-positive disease in the reconstruction group. Conclusions: Most clinically node-positive patients treated with NAC undergoing mastectomy receive RT. RT is less common in patients undergoing reconstruction. There is wide variability in RT fields. These practice patterns conflict with expert recommendations and ongoing trial guidelines. There is a significant need for greater uniformity and guidelines regarding RT following NAC.« less

Efficacy of oseltamivir-zanamivir combination compared to each monotherapy for seasonal influenza: a randomized placebo-controlled trial.

PubMed

Duval, Xavier; van der Werf, Sylvie; Blanchon, Thierry; Mosnier, Anne; Bouscambert-Duchamp, Maude; Tibi, Annick; Enouf, Vincent; Charlois-Ou, Cécile; Vincent, Corine; Andreoletti, Laurent; Tubach, Florence; Lina, Bruno; Mentré, France; Leport, Catherine

2010-11-02

Neuraminidase inhibitors are thought to be efficacious in reducing the time to alleviation of symptoms in outpatients with seasonal influenza. The objective of this study was to compare the short-term virological efficacy of oseltamivir-zanamivir combination versus each monotherapy plus placebo. We conducted a randomized placebo-controlled trial with 145 general practitioners throughout France during the 2008-2009 seasonal influenza epidemic. Patients, general practitioners, and outcome assessors were all blinded to treatment assignment. Adult outpatients presenting influenza-like illness for less than 36 hours and a positive influenza A rapid test diagnosis were randomized to oseltamivir 75 mg orally twice daily plus zanamivir 10 mg by inhalation twice daily (OZ), oseltamivir plus inhaled placebo (O), or zanamivir plus oral placebo (Z). Treatment efficacy was assessed virologically according to the proportion of patients with nasal influenza reverse transcription (RT)-PCR below 200 copies genome equivalent (cgeq)/µl at day 2 (primary outcome), and clinically to the time to alleviation of symptoms until day 14. Overall 541 patients (of the 900 planned) were included (OZ,  =192; O, n=176; Z, n=173), 49% male, mean age 39 years. In the intention-to-treat analysis conducted in the 447 patients with RT-PCR-confirmed influenza A, 46%, 59%, and 34% in OZ (n=157), O (n=141), and Z (n=149) arms had RT-PCR<200 cgeq/µl (-13.0%, 95% confidence interval [CI] -23.1 to -2.9, p=0.025; +12.3%, 95% CI 2.39-22.2, p=0.028 for OZ/O and OZ/Z comparisons). Mean day 0 to day 2 viral load decrease was 2.14, 2.49, and 1.68 log(10) cgeq/µl (p=0.060, p=0.016 for OZ/O and OZ/Z). Median time to alleviation of symptoms was 4.0, 3.0, and 4.0 days (+1.0, 95% CI 0.0-4.0, p=0.018; +0.0, 95% CI -3.0 to 3.0, p=0.960 for OZ/O and OZ/Z). Four severe adverse events were observed. Nausea and/or vomiting tended to be more frequent in the combination arm (OZ, n=13; O, n=4; and Z, n=5 patients, respectively). In adults with seasonal influenza A mainly H3N2 virus infection, the oseltamivir-zanamivir combination appeared less effective than oseltamivir monotherapy, and not significantly more effective than zanamivir monotherapy. Despite the theoretical potential for the reduction of the emergence of antiviral resistance, the lower effectiveness of this combination calls for caution in its use in clinical practice. www.ClinicalTrials.govNCT00799760.

Thiopurines are negatively associated with anthropometric parameters in pediatric Crohn’s disease

PubMed Central

Gupta, Neera; Lustig, Robert H; Chao, Cewin; Vittinghoff, Eric; Andrews, Howard; Leu, Cheng-Shiun

2018-01-01

AIM To determine the distribution of anthropometric parameter (AP)-z-scores and characterize associations between medications/serum biomarkers and AP-z-scores in pediatric Crohn’s disease (CD). METHODS CD patients [< chronological age (CA) 21 years] were enrolled in a cross-sectional study. Descriptive statistics were generated for participants’ demographic characteristics and key variables of interest. Paired t-tests were used to compare AP-z-scores calculated based on CA (CA z-scores) and bone age (BA) (BA z-scores) for interpretation of AP’s. Linear regression was utilized to examine associations between medications and serum biomarkers with AP-z-scores calculated based on CA (n = 82) and BA (n = 49). We reported regression coefficients as well as their corresponding p-values and 95% confidence intervals. RESULTS Mean CA at the time of the study visit was 15.3 ± 3.5 (SD; range = 4.8-20.7) years. Mean triceps skinfold (P = 0.039), subscapular skinfold (P = 0.002) and mid-arm circumference (MAC) (P = 0.001) BA z-scores were higher than corresponding CA z-scores. Medications were positively associated with subscapular skinfold [adalimumab (P = 0.018) and methotrexate (P = 0.027)] and BMI CA z-scores [adalimumab (P = 0.029)]. Azathioprine/6-mercaptopurine were negatively associated with MAC (P = 0.045), subscapular skinfold (P = 0.014), weight (P = 0.002) and BMI (P = 0.013) CA z-scores. ESR, CRP, and WBC count were negatively associated, while albumin and IGF-1 BA z-scores were positively associated, with specific AP z-scores (P < 0.05). Mean height CA z-scores were higher in females, not males, treated with infliximab (P = 0.038). Hemoglobin (P = 0.018) was positively associated, while platelets (P = 0.005), ESR (P = 0.003) and CRP (P = 0.039) were negatively associated with height CA z-scores in males, not females. CONCLUSION Our results suggest poor efficacy of thiopurines and a possible sex difference in statural growth response to infliximab in pediatric CD. Prospective longitudinal studies are required. PMID:29760546

[Effect of acupuncture therapy on patients with low back pain: a Meta-analysis].

PubMed

Liang, Fei-fan; Chen, Wei-ye; Chen, Bo; Xu, Qin-guang; Zhan, Hong-sheng

2016-05-01

To systematically review the clinical efficacy of acupuncture on the patients with low back pain (LBP). Randomized controlled trials (RCTs) about pure acupuncture therapy versus other treatments in treating LBP were electronically searched in PubMed, CBM, EMbase, The Cochrane Library, CNKI, VIP and Wanfang Data from January 2004 to May 2014. The observed index on the results were the changed scores of VAS, ODI, JOA and RMDQ. Two reviewers independently screened the literatures according to the inclusion and exclusion criteria, as well as the extracted data, and assessed the methodological quality. The results of Meta-analysis was conducted by RevMan 5.2 software. Ten RCTs involved 751 patients were finally included. The results of Meta-analysis indicated that the role of pure acupuncture group in improving the VAS score was better than that of the control group, and the combined effect size was RR = -.32, 95% CI (-1.41, -1.22); Z=27.28, P<0.00001; the role of pure acupuncture group in improving the ODI score was better than that of the control group, and the combined effect size was RR = -5.07, 95% CI (-7.50, -2.65); Z=4.10, P<0.0001; the role of pure acupuncture group on improved JOA score was better than that of the control group and the combined effect size was RR=2.83, 95% CI (2.02, 3.63), Z=6.90, P<0.00001. The role of pure acupuncture group in improving the RMDQ score was better than that of the control group, and the combined effect size was RR = -2.80, 95% CI (-3.49, -2.11), Z=7.95, P<0.00001. The result of meta-analysis demonstrates that pure acupuncture may have a favorable effect on self-reported pain and functional limitations in LBP patients.

The efficacy of trimetazidine on stable angina pectoris: a meta-analysis of randomized clinical trials.

PubMed

Peng, Song; Zhao, Min; Wan, Jing; Fang, Qi; Fang, Dong; Li, Kaiyong

2014-12-20

This meta-analysis aimed to evaluate the efficacy of trimetazidine in combination with other anti-anginal drugs versus other anti-anginal drugs in the treatment of stable angina pectoris (SAP). Randomized controlled trials (RCTs) published in English and Chinese were retrieved from computerized databases: Embase, PubMed, and CNKI. Primary outcomes consist of clinical parameters (numbers of weekly angina attacks and nitroglycerin use) and ergometric parameters (time to 1mm ST-segment depression, and total work (in Mets) and exercise duration (in seconds) at peak exercise) in stable angina pectoris treated by trimetazidine or not. The quality of studies was evaluated using Jadad score. Data analysis of 13 studies was performed using Stata 12.0 software. Results showed that treatment of trimetazidine and other anti-anginal drugs was associated with a smaller weekly mean number of angina attacks (WMD=-0.95, 95%CI: -1.30 to -0.61, Z=5.39, P<0.001), fewer weekly nitroglycerin use (WMD=-0.98, 95%CI: -1.44 to -0.52, Z=4.19, P<0.001), longer time to 1mm ST-segment depression (WMD=0.30, 95%CI: 0.17 to 0.43, Z=4.46, P<0.001), higher total work (WMD=0.82, 95%CI: 0.44 to 1.20, Z=4.22, P<0.001) and longer exercise duration at peak exercise (WMD=49.81, 95%CI: 15.04 to 84.57, Z=6.38, P<0.001) than treatment of other anti-anginal drugs for stable angina pectoris. Sensitivity analysis was performed. Sub-group analysis showed that treatment duration was not a significant moderator and patients treated within 8 weeks and above 12 weeks had no difference in the outcomes addressed in this meta-analysis. No publish bias was detected. This meta-analysis confirms the efficacy of trimetazidine in the treatment of stable angina pectoris, in comparison with conventional antianginal agents, regardless of treatment duration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Molecular Epidemiology of Mutations in Antimicrobial Resistance Loci of Pseudomonas aeruginosa Isolates from Airways of Cystic Fibrosis Patients.

PubMed

Greipel, Leonie; Fischer, Sebastian; Klockgether, Jens; Dorda, Marie; Mielke, Samira; Wiehlmann, Lutz; Cramer, Nina; Tümmler, Burkhard

2016-11-01

The chronic airway infections with Pseudomonas aeruginosa in people with cystic fibrosis (CF) are treated with aerosolized antibiotics, oral fluoroquinolones, and/or intravenous combination therapy with aminoglycosides and β-lactam antibiotics. An international strain collection of 361 P. aeruginosa isolates from 258 CF patients seen at 30 CF clinics was examined for mutations in 17 antimicrobial susceptibility and resistance loci that had been identified as hot spots of mutation by genome sequencing of serial isolates from a single CF clinic. Combinatorial amplicon sequencing of pooled PCR products identified 1,112 sequence variants that were not present in the genomes of representative strains of the 20 most common clones of the global P. aeruginosa population. A high frequency of singular coding variants was seen in spuE, mexA, gyrA, rpoB, fusA1, mexZ, mexY, oprD, ampD, parR, parS, and envZ (amgS), reflecting the pressure upon P. aeruginosa in lungs of CF patients to generate novel protein variants. The proportion of nonneutral amino acid exchanges was high. Of the 17 loci, mexA, mexZ, and pagL were most frequently affected by independent stop mutations. Private and de novo mutations seem to play a pivotal role in the response of P. aeruginosa populations to the antimicrobial load and the individual CF host. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Meta-analysis of gender differences in residual stroke risk and major bleeding in patients with nonvalvular atrial fibrillation treated with oral anticoagulants.

PubMed

Pancholy, Samir B; Sharma, Parikshit S; Pancholy, Dipti S; Patel, Tejas M; Callans, David J; Marchlinski, Francis E

2014-02-01

Studies comparing gender-specific outcomes in patients with atrial fibrillation (AF) have reported conflicting results. Gender differences in cerebrovascular accident/systemic embolism (CVA/SE) or major bleeding outcomes with novel oral anticoagulant (NOAC) use are not known. The goal of this analysis was to perform a systematic review and meta-analysis evaluating gender differences in residual risk of CVA/SE and major bleeding outcomes in patients with nonvalvular AF treated with either warfarin or NOAC. Sixty-four randomized studies were identified using keywords "gender," "AF," and "CVA." Using the Preferred Reporting Items for Systemic Reviews and Meta-analysis method, 6 studies met criteria for inclusion in this meta-analysis. CVA/SE and major bleeding outcomes were separately analyzed in cohorts receiving warfarin and NOAC agents, comparing men with women. Women with AF taking warfarin were at a significantly greater residual risk of CVA/SE compared with men (odds ratio 1.279, 95% confidence interval 1.111 to 1.473, Z = -3.428, p = 0.001). No gender difference in residual risk of CVA/SE was noted in patients with AF receiving NOAC agents (odds ratio 1.146, 95% confidence interval 0.97 to 1.354, p = 0.109). Major bleeding was less frequent in women with AF treated with NOAC. In conclusion, women with AF treated with warfarin have a greater residual risk of CVA/SE and an equivalent major bleeding risk, whereas those treated with NOAC agents deemed superior to warfarin are at equivalent residual risk of CVA/SE and less major bleeding risk compared with men. These results suggest an increased net clinical benefit of NOAC agents compared with warfarin in treating women with AF. Copyright © 2014 Elsevier Inc. All rights reserved.

The differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach.

PubMed

Bannur, Z; Teh, L K; Hennesy, T; Rosli, W R W; Mohamad, N; Nasir, A; Ankathil, R; Zakaria, Z A; Baba, A; Salleh, M Z

2014-04-01

Acute lymphoblastic leukaemia (ALL) has posed challenges to the clinician due to variable patients' responses and late diagnosis. With the advance in metabolomics, early detection and personalised treatment are possible. Metabolomic profile of 21 ALL patients treated with 6-mercaptopurine and 10 healthy volunteers were analysed using liquid chromatography/mass spectrometry quadrupole-time of flight (LC/MS Q-TOF). Principal components analysis (PCA), recursive analysis, clustering and pathway analysis were performed using MassHunter Qualitative and Mass Profiler Professional (MPP) software. Several metabolites were found to be expressed differently in patients treated with 6-mercaptopurine. Interestingly, 13 metabolites were significantly differently expressed [p-value <0.01 (unpaired t-test) and 2-fold change] in 19% of the patients who had relapses in their treatment. Down-regulated metabolites in relapsed patients were 1-tetrahexanoyl-2-(8-[3]-ladderane-octanyl)-sn-GPEtn, GPEtn (18:1(9Z)/0:0), GPCho(O-6:0/O-6:0), GPCho(O-2:0/O-1:0), methyl 8-[2-(2-formyl-vinyl)-3-hydroxy-5-oxo-cyclopentyl]-octanoate and plasma free amino acids (PFAA). Characterizing the subjects according to their ITPA 94C>A genotypes reveal differential expression of metabolites. Our research contributes to identification of metabolites that could be used to monitor disease progress of patients and allow targeted therapy for ALL at different stages, especially in preventing complication of relapse. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Effect of the 2013 AHA/ASA guidelines on TPA use in acute ischemic stroke at Assaf Harofeh Medical Center in Israel.

PubMed

Kimiagar, Itzhak; Kalmanovich-Avnery, Shani; Gonen, Ofer M; Sacagiu, Zvika; Shevtzov, Evelina; Levite, Ronen; Weinstein, Jochay; Bartal, Avigail; Aroesty, Rina; Bhonkar, Sarah; Tal, Sigal; Leonov, Youval; Blatt, Alex; Haitov, Zoya; Bar-Hayim, Samuel; Armon, Carmel

2016-10-15

Use of TPA to treat patients with acute ischemic stroke was introduced in Assaf Harofeh Medical Center (AHMC) in Israel in November 2007 initially with strict adherence to the inclusion/exclusion criteria of the pivotal NINDS TPA studies published in 1995. The treatment window was expanded in 2010 to 4.5h following the results of ECASS-III. Application of the 2013 AHA/ASA Guidelines resulted in further expanded inclusion and relaxed exclusion criteria. A retrospective chart review was conducted of patients who received TPA at AHMC to evaluate the additional impact of applying the 2013 guidelines. Number of patients treated, outcomes at discharge, and safety were compared between two periods: May 2011-January 2013 (the 21months preceding the 2013 Guidelines); and February 2013-October 2014 (the 21months after publication of the 2013 Guidelines). Statistical analysis was done using z-tests for differences between proportions, and t-tests to compare means. 63 patients were treated during the immediate pre-2013 Guideline period (36/year, or approximately 5% of patients with ischemic stroke), and 105 during the post-2013 Guidelines period (60/year, approximately 8.3% of patients with ischemic stroke) (p<0.001). During the two periods, respectively: discharges home were 22(34%) and 55(52%) (p<0.05); facility discharges were 29(46%) and 33(31%); and inter-hospital transfers were 6(9%), and 11(10% of treated patients). Most transfers were for endovascular treatment. Total treatment-related symptomatic bleeds in the two periods, respectively, was: 4(6%) and 4(4%), and the number of in-hospital deaths was 6 (9%) and 6 (6%) (unchanged). Application of the 2013 AHA/ASA Guidelines resulted in a 64% increase in the number of acute ischemic stroke patients treated with TPA at AHMC with no worsening of aggregate outcomes and no increase in bleeds or deaths. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of metabolic syndrome with growing epidemic syndrome Z in terms of risk factors and gender differences.

PubMed

Uyar, Meral; Davutoğlu, Vedat; Aydın, Neriman; Filiz, Ayten

2013-05-01

The aim of this study is to compare metabolic syndrome with syndrome Z growing epidemic in terms of risk factors, demographic variables, and gender differences in our large cohort at southeastern area in Turkey. Data of patients admitted to sleep clinic in University of Gaziantep from January 2006 to January 2011 were retrospectively evaluated. ATP III and JNC 7 were used for defining metabolic syndrome and hypertension. Data of 761 patients were evaluated. Hypertension, diabetes mellitus, coronary artery disease, pulmonary hypertension, and left ventricular hypertrophy were more common in patients with syndrome Z than in patients without metabolic syndrome. Age, waist/neck circumferences, BMI, triglyceride, glucose, and Epworth sleepiness scale score were detected higher, whereas the minimum oxygen saturation during sleep was lower in patients with syndrome Z. Metabolic syndrome was more common in sleep apneic subjects than in controls (58 versus 30 %). Female sleep apneics showed higher rate of metabolic syndrome than those of males (74 versus 52 %). Hypertension, diabetes mellitus, coronary artery disease, and left ventricular hypertrophy were detected higher in males with syndrome Z than in males without metabolic syndrome. Snoring and excessive daytime sleepiness were detected higher in females with syndrome Z than in females without metabolic syndrome. Systemic/pulmonary hypertension, diabetes mellitus, and left ventricular hypertrophy were more common in females with syndrome Z than in females without metabolic syndrome. Complaints of headache and systemic/pulmonary hypertension were more common among females than males with syndrome Z. Female syndrome Z patients had lower minimum oxygen saturation than male patients with syndrome Z. Metabolic syndrome in sleep apneic patients is more prevalent than in controls. All metabolic syndrome parameters were significantly different among obstructive sleep apneic patients with respect to gender with more severe coronary risk factors in males.

Use of modified Sandwich-graft technique to preserve hypogastric artery in EVAR treatment of complex aortic aneurysm anatomy.

PubMed

Mosquera Arochena, N; Rodríguez Feijoo, G; Carballo Fernandez, C; Molina Herrero, F; Fernandez Lebrato, R; Barrios Castro, A; Garcia Fernandez, I

2011-10-01

Since the introduction of the first endoprosthetic devices, continuous development in techniques and implants has occurred, such as the introduction of a stent graft with branches designed to preserve antegrade flow in the hypogastric artery, a stent-graft designed to treat extreme neck angulation and iliac tortuosity, as well as "Sandwich" and "Chimney" techniques used to maintain perfusion in branch vessels originating in the region to be treated. This paper describes how the Sandwich-Graft technique was adapted, as described by Lobato et al., employing the Aorfix™ system (Lombard Medical) and the Viabahn™ (W.L.Gore) to preserve hypogastric flow in cases with extreme neck angulation and iliac tortuosity. The study included four patients treated from April 2010 until November 2010 with the modified Sandwich technique. All patients eligible for this approach were considered unfit for open repair and were not suitable for an iliac branch graft (Z-BIS Zenith™ Cook Medical). A bifurcated endograft was implanted with specific, in-situ, branching to the target hypogastric artery and achieved clinical and technical success, in all the patients. After a 11-month follow-up in two cases and a six-month follow-up in the other two, clinical results were successful. All patients were endoleak-free, had patent hypogastric branches and had shrinking or stable aneurysms. The initial experience shows that the Sandwich technique with the Aorfix™ stent-graft demonstrated to be effective in endovascular repair of abdominal aortic aneurysms in patients with aortoiliac anatomy hostile to preserving hypogastric artery patency. This graft allows a broader group of patients to be treated with endovascular repair without potential complications of hypogastric artery occlusion; however, further studies are needed to evaluate long-term results in larger numbers of patients.

[Clinical application of alendronate for osteoporosis/osteopenia secondary to hyperthyroidism].

PubMed

Yang, Li-Juan; Shen, Fei-Xia; Zheng, Jing-Chen; Zhang, Hai-Ling

2012-02-01

To evaluate the efficacy and safety of alendronate for the treatment of osteoporosis/osteopenia secondary to hyperthyroidism. From April 2008 to November 2009, 27 patients with hyperthyroidism with osteoporosis/ osteopenia measured by dual energy X-ray absorptiometry (DXA) were included in this study, and then they were randomly divided into two groups (group A and group B) by simple random sampling. Group A consisted of 14 patients treated with antithyroid drug and caltrate D, the antithyroid drug change with thyroid function, and caltrate D 600 mg per day. Group B consisted of 13 patients treated with antithyroid drug, caltrate D and alendronate, antithyroid drug and caltrate D the same as group A, and alendronate 70 mg weekly. Meanwhile, 21 healthy voluntary adults were chosen as control group. And compared with the control group which was treated with nothing. Followed-up for one year, the bone mineral density (including T-score, Z-score, BMD) in lumbar spine (LS), femoral neck (FN) and distal radius (DR) and general information, were compared before and after treatment. BMD at FN and DR were significantly higher at 12 months after treatment than at the baseline in group A (P = 0.000); T-score, Z-score, and BMD at the LS, FN and DR were all significantly higher at 12 months after treatment than at the baseline in group B (P < 0.05), but these data could not arrive to normal level. In group A, the percentage increased in BMD at the LS, FN, and DR were (4.34 +/- 10.5)%, (3.21 +/- 1.38)%, (1.95 +/- 0.44)%, respectively, at 12 months after treatment. In group B, the percentage increased in BMD at the LS, FN, and DR were (6.10 +/- 8.12)%, (4.10 +/- 5.64)%, (3.10 +/- 3.23)%, respectively, at 12 months after treatment. There was significant difference in the rate of increase between two groups (P < 0.05). AKP decreased, weight, BMI increased, and thyroid function decreased, after treatment than those before in both of the two groups. (P < 0.05). Alendronate can significantly increase BMD in treating patients with hyperthyroidism and osteoporosis/osteopenia. Compared with anti-thyroid drugs alone, treatment with alendronate can obtain more clinical effect and also very safety.

What is next after transfer of care from hospital to home for stroke patients? Evaluation of a community stroke care service based in a primary care clinic

PubMed Central

Aziz, Aznida Firzah Abdul; Aziz, Noor Azah Abd; Nordin, Nor Azlin Mohd; Ali, Mohd Fairuz; Sulong, Saperi; Aljunid, Syed Mohamed

2013-01-01

Context: Poststroke care in developing countries is inundated with poor concordance and scarce specialist stroke care providers. A primary care-driven health service is an option to ensure optimal care to poststroke patients residing at home in the community. Aims: We assessed outcomes of a pilot long-term stroke care clinic which combined secondary prevention and rehabilitation at community level. Settings and Design: A prospective observational study of stroke patients treated between 2008 and 2010 at a primary care teaching facility. Subjects and Methods: Analysis of patients was done at initial contact and at 1-year post treatment. Clinical outcomes included stroke risk factor(s) control, depression according to Patient Health Questionnaire (PHQ9), and level of independence using Barthel Index (BI). Statistical Analysis Used: Differences in means between baseline and post treatment were compared using paired t-tests or Wilcoxon-signed rank test. Significance level was set at 0.05. Results: Ninety-one patients were analyzed. Their mean age was 62.9 [standard deviation (SD) 10.9] years, mean stroke episodes were 1.30 (SD 0.5). The median interval between acute stroke and first contact with the clinic 4.0 (interquartile range 9.0) months. Mean systolic blood pressure decreased by 9.7 mmHg (t = 2.79, P = 0.007), while mean diastolic blood pressure remained unchanged at 80mmHg (z = 1.87, P = 0.06). Neurorehabilitation treatment was given to 84.6% of the patients. Median BI increased from 81 (range: 2−100) to 90.5 (range: 27−100) (Z = 2.34, P = 0.01). Median PHQ9 scores decreased from 4.0 (range: 0−22) to 3.0 (range: 0−19) though the change was not significant (Z= −0.744, P = 0.457). Conclusions: Primary care-driven long-term stroke care services yield favorable outcomes for blood pressure control and functional level. PMID:24347948

[Effects of functional training combined with self-made hand flexing training band in treatment of scar contracture after burn injury of dorsal hand].

PubMed

Zhu, C; Yi, N; Shi, M N; Liang, Y Y; Zhou, Y B; Dang, R; Qi, Z S; Zhao, H Y

2017-07-20

Objective: To observe the effects of functional training combined with self-made hand flexing training band in treatment of scar contracture after burn injury of dorsal hand. Methods: Forty-six patients with scar contracture after deep partial-thickness or full-thickness burn injury of dorsal hand hospitalized in our department from March 2013 to February 2015 were divided into routine training group (RT, n =18) and comprehensive training group (CT, n =28) according to their willingness. Two weeks after the wounds were healed, patients in group RT were treated with functional training of hands and self-made pressure gloves, while patients in group CT were treated with self-made hand flexing training band (consisting of nylon strap, flexing band, and velcro) on the basis of those in group RT. All patients were treated for 3 months. Before and after treatment, scar condition of affected hands was assessed with Vancouver Scar Scale (VSS). The range of motion of joints of affected hands was measured by Total Active Movement (TAM) Scale. The function of affected hands was evaluated by Carroll Upper Extremity Function Test. Data were processed with t test, chi-square test, and Mann-Whitney U test. Results: (1) The score of VSS in patients of group RT was (10.0±1.9) points before treatment and (4.4±1.4) points after treatment, with the improved score of (5.6±1.0) points. The score of VSS in patients of group CT was (10.5±1.8) points before treatment and (4.6±1.4) points after treatment, with the improved score of (5.9±1.2) points. There was no statistically significant difference in the improved score of patients between the two groups ( t =0.834, P >0.05). The score of VSS in patients of groups RT and CT after treatment was significantly lower than that before treatment (with t values respectively 14.014 and 10.003, P values below 0.01). (2) Before treatment, the ratios of excellent and good results according to TAM were 2/9 in patients of group RT and 3/14 in group CT, with no statistical differences between them ( χ (2)=2.140, P >0.05). After treatment, the ratio of excellent and good results according to TAM in patients of group CT (6/7) was higher than that in group RT (5/9, χ (2)=0.023, P =0.038). The ratios of excellent and good results according to TAM in patients of groups RT and CT after treatment were significantly higher than those before treatment (with Z values respectively -2.023 and -4.780, P values below 0.05). (3) The improved score of hand function in patients of group CT was (26±12) points, which was higher than (15±7) points in group RT ( t =3.278, P =0.002). The score of hand function in patients of groups RT and CT after treatment was significantly higher than that before treatment (with t values respectively 2.628 and 6.125, P values below 0.05). There were no significant differences in grades of hand function of patients between the two groups before treatment ( Z =-0.286, P >0.05). After treatment, the grade of hand function in patients of group CT was higher than that in group RT( Z =-1.993, P =0.046). The grades of hand function in patients of groups RT and CT after treatment were significantly higher than those before treatment (with Z values respectively -2.717 and -4.998, P values below 0.01). Conclusions: For patients with scar contracture after burn injury of dorsal hand, early functional training combined with hand flexing training band can improve the range of motion of hand joints and functional recovery of hand, and the result was better than functional training alone.

Effect Size Analyses of Souvenaid in Patients with Alzheimer's Disease.

PubMed

Cummings, Jeffrey; Scheltens, Philip; McKeith, Ian; Blesa, Rafael; Harrison, John E; Bertolucci, Paulo H F; Rockwood, Kenneth; Wilkinson, David; Wijker, Wouter; Bennett, David A; Shah, Raj C

2017-01-01

Souvenaid® (uridine monophosphate, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium), was developed to support the formation and function of neuronal membranes. To determine effect sizes observed in clinical trials of Souvenaid and to calculate the number needed to treat to show benefit or harm. Data from all three reported randomized controlled trials of Souvenaid in Alzheimer's disease (AD) dementia (Souvenir I, Souvenir II, and S-Connect) and an open-label extension study were included in analyses of effect size for cognitive, functional, and behavioral outcomes. Effect size was determined by calculating Cohen's d statistic (or Cramér's V method for nominal data), number needed to treat and number needed to harm. Statistical calculations were performed for the intent-to-treat populations. In patients with mild AD, effect sizes were 0.21 (95% confidence intervals: -0.06, 0.49) for the primary outcome in Souvenir II (neuropsychological test battery memory z-score) and 0.20 (0.10, 0.34) for the co-primary outcome of Souvenir I (Wechsler memory scale delayed recall). No effect was shown on cognition in patients with mild-to-moderate AD (S-Connect). The number needed to treat (6 and 21 for Souvenir I and II, respectively) and high number needed to harm values indicate a favorable harm:benefit ratio for Souvenaid versus control in patients with mild AD. The favorable safety profile and impact on outcome measures converge to corroborate the putative mode of action and demonstrate that Souvenaid can achieve clinically detectable effects in patients with early AD.

Interpositional arthroplasty versus reconstruction arthroplasty for temporomandibular joint ankylosis: A systematic review and meta-analysis.

PubMed

Ma, Junli; Jiang, Hua; Liang, Limin

2015-09-01

Interpositional arthroplasty (IA) and reconstruction arthroplasty (RA) are widely used in treating temporomandibular joint ankylosis (TMJA). But the reported clinical outcomes are controversial, the debate over which one is better remains. The Pubmed, EMBASE, OVID EBM Reviews, and Web of science were searched up to Oct 11 2014 without limitation on year, language. Only randomized controlled trials and observational cohort studies with a follow-up of at least 12 months were included. A total of 8 retrospective cohort studies with 234 patients with TMJA were included in metaanalysis. Pooled analysis showed no significant differences in reankylosis (RD: -0.00; 95% CI: -0.08, 0.07; Z=0.06; P =0.95; I(2) =0%), and maximum incisal opening (MD=0.99; 95% CI: -1.43, 3.4, Z=0.8, p=0.42; I(2) =74%) between the IA and RA groups. IA and RA could produce similar outcomes in treating TMJA regarding to rankylosis and maximum incisal opening. Other postoperative complications, such as overgrowth of cartilage, malocclusion and the status of facial development should be evaluated more thoroughly. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Anthropometric Measures After Fontan Procedure: Implications for Suboptimal Functional Outcome

PubMed Central

Cohen, Meryl S.; Zak, Victor; Atz, Andrew M.; Printz, Beth F.; Pinto, Nelangi; Lambert, Linda; Pemberton, Victoria; Li, Jennifer S.; Margossian, Renee; Dunbar-Masterson, Carolyn; McCrindle, Brian W.

2010-01-01

Background Abnormal height and adiposity are observed after the Fontan operation. These abnormalities may be associated with worse functional outcome. Methods We analyzed data from the NHLBI Pediatric Heart Network cross-sectional study of Fontan patients. Groups were defined by height (z-score < −1.5 or ≥ −1.5) and body mass index (BMI z-score ≤ −1.5 or −1.5 to 1.5 or ≥ 1.5). Associations of anthropometric measures with measurements from clinical testing (exercise, echocardiography, MRI) were determined adjusting for demographics, anatomy, and pre-Fontan status. Relationships between anthropometric measures and functional health status (FHS) were assessed using the Child Health Questionnaire. Results Mean age of the cohort (n=544) was 11.9±3.4 years. Lower height-z patients (n=124, 23%) were more likely to have pre-Fontan atrioventricular valve regurgitation (p=0.029), as well as orthopedic and developmental problems (both p<0.001). Lower height-z patients also had lower physical and psychosocial FHS summary scores (both p <0.01). Higher BMI-z patients (n=45, 8%) and lower BMI-z patients (n=53, 10%) did not have worse FHS compared to midrange BMI-z patients (n=446, 82%). However, higher BMI-z patients had higher ventricular mass-to-volume ratio (p =0.03) and lower % predicted maximum work (p=0.004) compared to midrange and lower BMI-z patients. Conclusions Abnormal anthropometry is common in Fontan patients. Shorter stature is associated with poorer FHS and non-cardiac problems. Increased adiposity is associated with more ventricular hypertrophy and poorer exercise performance, which may have significant long-term implications in this at-risk population. PMID:21146663

Prolonged exposure therapy for the treatment of patients diagnosed with psychogenic non-epileptic seizures (PNES) and post-traumatic stress disorder (PTSD).

PubMed

Myers, Lorna; Vaidya-Mathur, Urmi; Lancman, Marcelo

2017-01-01

Although there is general consensus that psychogenic non-epileptic seizures (PNES) are treated with psychotherapy, the effectiveness of most psychotherapeutic modalities remains understudied. In this treatment series of 16 patients dually diagnosed with PNES and post-traumatic stress disorder (PTSD), we evaluated the effect of prolonged exposure therapy (PE) on reduction of PNES. Secondary measures included Beck Depression Inventory (BDI-II) and Post-Traumatic Disorder Diagnostic Scale (PDS). Subjects diagnosed with video EEG-confirmed PNES and PTSD confirmed through neuropsychological testing and clinical interview were treated with traditional PE psychotherapy with certain modifications for the PNES. Treatment was conducted over the course of 12-15 weekly sessions. Seizure frequency was noted in each session by examining the patients' seizure logs, and mood and PTSD symptomatology was assessed at baseline and on the final session. Eighteen subjects enrolled, and 16 (88.8%) completed the course of treatment. Thirteen of the 16 (81.25%) therapy completers reported no seizures by their final PE session, and the other three reported a decline in seizure frequency (Z=-3.233, p=0.001). Mean scores on scales of depression (M=-13.56, SD=12.27; t (15)=-4.420, p<0,001) and PTSD symptoms (M=-17.1875, SD=13.01; t (15)=-5.281, p<0.001) showed significant improvement from baseline to final session. Longitudinal seizure follow up in 14 patients revealed that gains made on the final session were maintained at follow-up (Z=-1.069 p=0.285). Prolonged exposure therapy for patients dually diagnosed with PNES and PTSD reduced the number of PNES and improved mood and post traumatic symptomatology. Follow-up revealed that gains made in seizure control on the last day of treatment were maintained over time. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Coupled Mode Formalism: Connecting Phasor, Matrix, and Geometrical Approaches

DTIC Science & Technology

2014-05-30

the Poincare sphere in classical optics, and was generalized to incoherent light as the Stokes and Mueller approach [4]. The Stokes description reduces...to the Poincare sphere description when one treats monochromatic light, and we restrict ourselves to this case. Background There are several...waves, cast as plane waves of the form g(z, t) = f(z − vt) = Aej(ω t −k z) , (1) namely a sinusoidal wave travelling in the positive z direction at phase

Composing Music with Complex Networks

NASA Astrophysics Data System (ADS)

Liu, Xiaofan; Tse, Chi K.; Small, Michael

In this paper we study the network structure in music and attempt to compose music artificially. Networks are constructed with nodes and edges corresponding to musical notes and their co-occurrences. We analyze sample compositions from Bach, Mozart, Chopin, as well as other types of music including Chinese pop music. We observe remarkably similar properties in all networks constructed from the selected compositions. Power-law exponents of degree distributions, mean degrees, clustering coefficients, mean geodesic distances, etc. are reported. With the network constructed, music can be created by using a biased random walk algorithm, which begins with a randomly chosen note and selects the subsequent notes according to a simple set of rules that compares the weights of the edges, weights of the nodes, and/or the degrees of nodes. The newly created music from complex networks will be played in the presentation.

Complex network approach to classifying classical piano compositions

NASA Astrophysics Data System (ADS)

Xin, Chen; Zhang, Huishu; Huang, Jiping

2016-10-01

Complex network has been regarded as a useful tool handling systems with vague interactions. Hence, numerous applications have arised. In this paper we construct complex networks for 770 classical piano compositions of Mozart, Beethoven and Chopin based on musical note pitches and lengths. We find prominent distinctions among network edges of different composers. Some stylized facts can be explained by such parameters of network structures and topologies. Further, we propose two classification methods for music styles and genres according to the discovered distinctions. These methods are easy to implement and the results are sound. This work suggests that complex network could be a decent way to analyze the characteristics of musical notes, since it could provide a deep view into understanding of the relationships among notes in musical compositions and evidence for classification of different composers, styles and genres of music.

Endobiliary stent: marker for patient alignment in image-guided radiotherapy in pancreatic and periampullary cancers.

PubMed

Shukla, Pragya; Engineer, Reena; Chopra, Supriya; Shrivastava, Shyam Kishore

2013-12-01

The aim of this study was to analyse the possibility of using stent in pretreatment megavoltage computed tomography (MVCT) images with respect to that on planning kilovoltage computed tomography as tumour surrogate during matching for daily registration in cases of pancreatic and periampullary cancer treated on a TomoTherapy Hi-Art system. Planning CT and pretreatment MVCT of the first and then after every three fractions were transferred to a FocalSim workstation for ten patients. Planning CT of each patient was independently fused with each of the seven MVCT images of that patient. The stent was contoured on all of the eight images for each patient. The difference between the three co-ordinates of centre of mass (CM) of the stent on the planning CT and seven MVCT images was found. The difference between CM of the liver and stents on the planning CT as well as on the MVCT for all seven fractions was also calculated. The mean of these differences across all patients was calculated and analysed. The mean difference in planning and MVCT CMs for stents in the X, Y and Z directions was 0.13 cm (±0.4), 0.16 cm (±2.2) and 0.35 cm (±0.7), respectively. Average difference between CM of the liver and stent on the planning CT in the X, Y and Z directions was found to be 1.832 cm (±1.64), 5.34 cm (±1.33) and 0.54 cm (±0.26), respectively. Average difference between CM of the liver and CM of stent on the MVCT for that day in the X, Y and Z directions was found to be 1.93 cm (±1.5), 4.6 cm (±1.03) and 0.654 cm (±0.35), respectively. Endobiliary stents are stable tumour localisation surrogates and can be used to correct for interfraction target motion.

Proteins associated with EGFR-TKIs resistance in patients with non-small cell lung cancer revealed by mass spectrometry.

PubMed

Yang, Shaoyu; Chen, Xueqin; Pan, Yuelong; Yu, Jiekai; Li, Xin; Ma, Shenglin

2016-11-01

The present study aimed to identify potential serum biomarkers for predicting the clinical outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‑TKIs). A total of 61 samples were collected and analyzed using the integrated approach of magnetic bead‑based weak cation exchange chromatography and matrix‑assisted laser desorption/ionization‑time of flight‑mass spectrometry. The Zhejiang University Protein Chip Data Analysis system was used to identify the protein spectra of patients that are resistant and sensitive to EGFR‑TKIs. Furthermore, a support vector machine was used to construct a predictive model with high accuracy. The model was trained using 46 samples and tested with the remaining 15 samples. In addition, the ExPASy Bioinformatics Resource Portal was used to search potential candidate proteins for peaks in the predictive model. Seven mass/charge (m/z) peaks at 3,264, 9,156, 9,172, 3,964, 9,451, 4,295 and 3,983 Da, were identified as significantly different peaks between the EGFR‑TKIs sensitive and resistant groups. A predictive model was generated with three protein peaks at 3,264, 9,451 and 4,295 Da (m/z). This three‑peak model was capable of distinguishing EGFR‑TKIs resistant patients from sensitive patients with a specificity of 80% and a sensitivity of 80.77%. Furthermore, in a blind test, this model exhibited a high specificity (80%) and a high sensitivity (90%). Apelin, TYRO protein tyrosine kinase‑binding protein and big endothelin‑1 may be potential candidates for the proteins identified with an m/z of 3,264, 9,451 and 4,295 Da, respectively. The predictive model used in the present study may provide an improved understanding of the pathogenesis of NSCLC, and may provide insights for the development of TKI treatment plans tailored to specific patients.

Multiple point mutations in a shuttle vector propagated in human cells: evidence for an error-prone DNA polymerase activity.

PubMed

Seidman, M M; Bredberg, A; Seetharam, S; Kraemer, K H

1987-07-01

Mutagenesis was studied at the DNA-sequence level in human fibroblast and lymphoid cells by use of a shuttle vector plasmid, pZ189, containing a suppressor tRNA marker gene. In a series of experiments, 62 plasmids were recovered that had two to six base substitutions in the 160-base-pair marker gene. Approximately 20-30% of the mutant plasmids that were recovered after passing ultraviolet-treated pZ189 through a repair-proficient human fibroblast line contained these multiple mutations. In contrast, passage of ultraviolet-treated pZ189 through an excision-repair-deficient (xeroderma pigmentosum) line yielded only 2% multiple base substitution mutants. Introducing a single-strand nick in otherwise unmodified pZ189 adjacent to the marker, followed by passage through the xeroderma pigmentosum cells, resulted in about 66% multiple base substitution mutants. The multiple mutations were found in a 160-base-pair region containing the marker gene but were rarely found in an adjacent 170-base-pair region. Passing ultraviolet-treated or nicked pZ189 through a repair-proficient human B-cell line also yielded multiple base substitution mutations in 20-33% of the mutant plasmids. An explanation for these multiple mutations is that they were generated by an error-prone polymerase while filling gaps. These mutations share many of the properties displayed by mutations in the immunoglobulin hypervariable regions.

4-Hydroxydocosahexaenoic acid, a potent peroxisome proliferator-activated receptor {gamma} agonist alleviates the symptoms of DSS-induced colitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamamoto, Keiko; Ninomiya, Yuichi; Iseki, Mioko

2008-03-14

(5E,7Z,10Z,13Z,16Z,19Z)-4-Hydroxy-5,7,10,13,16,19-docosahexaenoic acid (4-OHDHA) is a potential agonist of peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) and antidiabetic agent as has been previously reported. As PPAR{gamma} agonists may also have anti-inflammatory functions, in this study, we investigated whether 4-OHDHA has an inhibitory effect on expression of inflammatory genes in vitro and whether 4-OHDHA could relieve the symptoms of dextran sodium sulfate (DSS)-induced colitis in a murine model of inflammatory bowel disease. 4-OHDHA inhibited production of nitric oxide and expression of a subset of inflammatory genes including inducible nitric oxide synthase (Nos2/iNOS) and interleukin 6 (Il6) by lipopolysaccharide (LPS)-activated macrophages. In addition, 4-OHDHA-treated mice whenmore » compared to control mice not receiving treatment recovered better from the weight loss caused by DSS-induced colitis. Changes in disease activity index (DAI) of 4-OHDHA-treated mice were also more favorable than for control mice and were comparable with mice treated with a typical anti-inflammatory-drug, 5-aminosalichylic acid (5-ASA). These results suggest that 4-OHDHA has potentially clinically useful anti-inflammatory effects mediated by suppression of inflammatory gene expression.« less

Analysis of Geometric Shifts and Proper Setup-Margin in Prostate Cancer Patients Treated With Pelvic Intensity-Modulated Radiotherapy Using Endorectal Ballooning and Daily Enema for Prostate Immobilization.

PubMed

Jeong, Songmi; Lee, Jong Hoon; Chung, Mi Joo; Lee, Sea Won; Lee, Jeong Won; Kang, Dae Gyu; Kim, Sung Hwan

2016-01-01

We evaluate geometric shifts of daily setup for evaluating the appropriateness of treatment and determining proper margins for the planning target volume (PTV) in prostate cancer patients.We analyzed 1200 sets of pretreatment megavoltage-CT scans that were acquired from 40 patients with intermediate to high-risk prostate cancer. They received whole pelvic intensity-modulated radiotherapy (IMRT). They underwent daily endorectal ballooning and enema to limit intrapelvic organ movement. The mean and standard deviation (SD) of daily translational shifts in right-to-left (X), anterior-to-posterior (Y), and superior-to-inferior (Z) were evaluated for systemic and random error.The mean ± SD of systemic error (Σ) in X, Y, Z, and roll was 2.21 ± 3.42 mm, -0.67 ± 2.27 mm, 1.05 ± 2.87 mm, and -0.43 ± 0.89°, respectively. The mean ± SD of random error (δ) was 1.95 ± 1.60 mm in X, 1.02 ± 0.50 mm in Y, 1.01 ± 0.48 mm in Z, and 0.37 ± 0.15° in roll. The calculated proper PTV margins that cover >95% of the target on average were 8.20 (X), 5.25 (Y), and 6.45 (Z) mm. Mean systemic geometrical shifts of IMRT were not statistically different in all transitional and three-dimensional shifts from early to late weeks. There was no grade 3 or higher gastrointestinal or genitourianry toxicity.The whole pelvic IMRT technique is a feasible and effective modality that limits intrapelvic organ motion and reduces setup uncertainties. Proper margins for the PTV can be determined by using geometric shifts data.

Analysis of Geometric Shifts and Proper Setup-Margin in Prostate Cancer Patients Treated With Pelvic Intensity-Modulated Radiotherapy Using Endorectal Ballooning and Daily Enema for Prostate Immobilization

PubMed Central

Jeong, Songmi; Lee, Jong Hoon; Chung, Mi Joo; Lee, Sea Won; Lee, Jeong Won; Kang, Dae Gyu; Kim, Sung Hwan

2016-01-01

Abstract We evaluate geometric shifts of daily setup for evaluating the appropriateness of treatment and determining proper margins for the planning target volume (PTV) in prostate cancer patients. We analyzed 1200 sets of pretreatment megavoltage-CT scans that were acquired from 40 patients with intermediate to high-risk prostate cancer. They received whole pelvic intensity-modulated radiotherapy (IMRT). They underwent daily endorectal ballooning and enema to limit intrapelvic organ movement. The mean and standard deviation (SD) of daily translational shifts in right-to-left (X), anterior-to-posterior (Y), and superior-to-inferior (Z) were evaluated for systemic and random error. The mean ± SD of systemic error (Σ) in X, Y, Z, and roll was 2.21 ± 3.42 mm, −0.67 ± 2.27 mm, 1.05 ± 2.87 mm, and −0.43 ± 0.89°, respectively. The mean ± SD of random error (δ) was 1.95 ± 1.60 mm in X, 1.02 ± 0.50 mm in Y, 1.01 ± 0.48 mm in Z, and 0.37 ± 0.15° in roll. The calculated proper PTV margins that cover >95% of the target on average were 8.20 (X), 5.25 (Y), and 6.45 (Z) mm. Mean systemic geometrical shifts of IMRT were not statistically different in all transitional and three-dimensional shifts from early to late weeks. There was no grade 3 or higher gastrointestinal or genitourianry toxicity. The whole pelvic IMRT technique is a feasible and effective modality that limits intrapelvic organ motion and reduces setup uncertainties. Proper margins for the PTV can be determined by using geometric shifts data. PMID:26765418

Surgical Management of Localized Scleroderma.

PubMed

Lee, Jae Hyun; Lim, Soo Yeon; Lee, Jang Hyun; Ahn, Hee Chang

2017-09-01

Localized scleroderma is characterized by a thickening of the skin from excessive collagen deposits. It is not a fatal disease, but quality of life can be adversely affected due to changes in skin appearance, joint contractures, and, rarely, serious deformities of the face and extremities. We present six cases of localized scleroderma in face from our surgical practice. We reviewed six localized scleroderma cases that were initially treated with medication and then received follow-up surgery between April 2003 and February 2015. Six patients had facial lesions. These cases presented with linear dermal sclerosis on the forehead, oval subcutaneous and dermal depression in the cheek. En coup de sabre (n=4), and oval-shaped lesion of the face (n=2) were successfully treated. Surgical methods included resection with or without Z-plasty (n=3), fat graft (n=1), dermofat graft (n=1), and adipofascial free flap (n=1). Deformities of the affected parts were surgically corrected without reoccurrence. We retrospectively reviewed six cases of localized scleroderma that were successfully treated with surgery. And we propose an algorithm for selecting the best surgical approach for individual localized scleroderma cases. Although our cases were limited in number and long-term follow-up will be necessary, we suggest that surgical management should be considered as an option for treating scleroderma patients.

Oral choline decreases brain purine levels in lithium-treated subjects with rapid-cycling bipolar disorder: a double-blind trial using proton and lithium magnetic resonance spectroscopy.

PubMed

Lyoo, In Kyoon; Demopulos, Christina M; Hirashima, Fuyuki; Ahn, Kyung Heup; Renshaw, Perry F

2003-08-01

Oral choline administration has been reported to increase brain phosphatidylcholine levels. As phospholipid synthesis for maintaining membrane integrity in mammalian brain cells consumes approximately 10-15% of the total adenosine triphosphate (ATP) pool, an increased availability of brain choline may lead to an increase in ATP consumption. Given reports of genetic studies, which suggest mitochondrial dysfunction, and phosphorus (31P) magnetic resonance spectroscopy (MRS) studies, which report dysfunction in high-energy phosphate metabolism in patients with bipolar disorder, the current study is designed to evaluate the role of oral choline supplementation in modifying high-energy phosphate metabolism in subjects with bipolar disorder. Eight lithium-treated patients with DSM-IV bipolar disorder, rapid cycling type were randomly assigned to 50 mg/kg/day of choline bitartrate or placebo for 12 weeks. Brain purine, choline and lithium levels were assessed using 1H- and 7Li-MRS. Patients received four to six MRS scans, at baseline and weeks 2, 3, 5, 8, 10 and 12 of treatment (n = 40 scans). Patients were assessed using the Clinical Global Impression Scale (CGIS), the Young Mania Rating Scale (YRMS) and the Hamilton Depression Rating Scale (HDRS) at each MRS scan. There were no significant differences in change-from-baseline measures of CGIS, YMRS, and HDRS, brain choline/creatine ratios, and brain lithium levels over a 12-week assessment period between the choline and placebo groups or within each group. However, the choline treatment group showed a significant decrease in purine metabolite ratios from baseline (purine/n-acetyl aspartate: coef = -0.08, z = -2.17, df = 22, p = 0.030; purine/choline: coef = -0.12, z = -1.97, df = 22, p = 0.049) compared to the placebo group, controlling for brain lithium level changes. Brain lithium level change was not a significant predictor of purine ratios. The current study reports that oral choline supplementation resulted in a significant decrease in brain purine levels over a 12-week treatment period in lithium-treated patients with DSM-IV bipolar disorder, rapid-cycling type, which may be related to the anti-manic effects of adjuvant choline. This result is consistent with mitochondrial dysfunction in bipolar disorder inadequately meeting the demand for increased ATP production as exogenous oral choline administration increases membrane phospholipid synthesis.

Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function.

PubMed

Liu, Xiaoli; Pachori, Alok S; Ward, Christopher A; Davis, J Paul; Gnecchi, Massimiliano; Kong, Deling; Zhang, Lunan; Murduck, Jared; Yet, Shaw-Fang; Perrella, Mark A; Pratt, Richard E; Dzau, Victor J; Melo, Luis G

2006-02-01

We reported previously that predelivery of the anti-oxidant gene heme oxygenase-1 (HO-1) to the heart by adeno associated virus (AAV) markedly reduces injury after acute myocardial infarction (MI). However, the effect of HO-1 gene delivery on postinfarction recovery has not been investigated. In the current study, we assessed the effect of HO-1 gene delivery on post-MI left ventricle (LV) remodeling and function using echocardiographic imaging and histomorphometric approaches. Two groups of Sprague-Dawley rats were injected with 4 x 10(11) particles of AAV-LacZ (control) or AAV-hHO-1 in the LV wall. Eight wk after gene transfer, the animals were subjected to 30 min of ischemia by ligation of left anterior descending artery (LAD) followed by reperfusion. Echocardiographic measurements were obtained in a blinded fashion prior and at 1.5 and 3 months after I/R. Ejection fraction (EF) was reduced by 13% and 40% in the HO-1 and LacZ groups, respectively at 1.5 months after MI. Three months after MI, EF recovered fully in the HO-1, but only partially in the LacZ-treated animals. Post-MI LV dimensions were markedly increased and the anterior wall was markedly thinned in the LacZ-treated animals compared with the HO-1-treated animals. Significant myocardial scarring and fibrosis were observed in the LacZ-group in association with elevated levels of interstitial collagen I and III and MMP-2 activity. Post-MI myofibroblast accumulation was reduced in the HO-1-treated animals, and retroviral overexpression of HO-1 reduced proliferation of isolated cardiac fibroblasts. Our data indicate that rAAV-HO-1 gene transfer markedly reduces fibrosis and ventricular remodeling and restores LV function and chamber dimensions after myocardial infarction.

Anthropometric characteristics and nutrition in a cohort of PAH-deficient patients.

PubMed

Aldámiz-Echevarría, Luis; Bueno, María A; Couce, María L; Lage, Sergio; Dalmau, Jaime; Vitoria, Isidro; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Peña-Quintana, Luis; Ruiz, María A; González, David; Sánchez-Valverde, Felix

2014-08-01

Treating phenylketonuria based upon strict vegetarian diets has occasionally been found to hamper physical development, some patients presenting with growth retardation and malnutrition. In addition, some researchers have reported an association between higher protein intakes and attaining better developmental outcomes, although it remains unclear which protein fraction (natural or synthetic) has the greatest influence on growth. The present study aimed to evaluate anthropometric characteristics and nutrition in a cohort of patients with phenylketonuria and mild-hyperphenylalaninaemia from birth to adulthood. We conducted a retrospective longitudinal study comparing anthropometric characteristics (weight, height, body mass index, and growth rate) in our patients and healthy subjects, with the measurements expressed as z-scores. Nutritional issues were also considered. Data were collected every 6 months from birth to 18 years of age. Growth impairment was observed in phenylketonuric patients. Specifically, there were two well-differentiated periods throughout which height fell well below z-score = 0: from birth to two years of age, and on reaching adulthood. We also found height and weight to be positively correlated with phenylalanine intake. No growth retardation was seen in the patients with mild-hyperphenylalaninaemia. Phenylketonuric patients showed growth impairment in the early stages, with higher phenylalanine intakes being associated with attaining better developmental outcomes in this period. Therefore, prescribing very stringent diets in the early years might predispose phenylketonuric patients to retarded growth later in life, with growth outcomes in adulthood being well below the 50th percentile for healthy subjects. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

SU-E-J-248: Comparative Study of Two Image Registration for Image-Guided Radiation Therapy in Esophageal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shang, K; Wang, J; Liu, D

2014-06-01

Purpose: Image-guided radiation therapy (IGRT) is one of the major treatment of esophageal cancer. Gray value registration and bone registration are two kinds of image registration, the purpose of this work is to compare which one is more suitable for esophageal cancer patients. Methods: Twenty three esophageal patients were treated by Elekta Synergy, CBCT images were acquired and automatically registered to planning kilovoltage CT scans according to gray value or bone registration. The setup errors were measured in the X, Y and Z axis, respectively. Two kinds of setup errors were analysed by matching T test statistical method. Results: Fourmore » hundred and five groups of CBCT images were available and the systematic and random setup errors (cm) in X, Y, Z directions were 0.35, 0.63, 0.29 and 0.31, 0.53, 0.21 with gray value registration, while 0.37, 0.64, 0.26 and 0.32, 0.55, 0.20 with bone registration, respectively. Compared with bone registration and gray value registration, the setup errors in X and Z axis have significant differences. In Y axis, both measurement comparison results of T value is 0.256 (P value > 0.05); In X axis, the T value is 5.287(P value < 0.05); In Z axis, the T value is −5.138 (P value < 0.05). Conclusion: Gray value registration is recommended in image-guided radiotherapy for esophageal cancer and the other thoracic tumors. Manual registration could be applied when it is necessary. Bone registration is more suitable for the head tumor and pelvic tumor department where composed of redundant interconnected and immobile bone tissue.« less

Macronutrient Regulation of Ghrelin and Peptide YY in Pediatric Obesity and Prader-Willi Syndrome

PubMed Central

Balikcioglu, Metin; Muehlbauer, Michael J.; Purnell, Jonathan Q.; Broadhurst, David; Freemark, Michael; Haqq, Andrea M.

2015-01-01

Background: The roles of macronutrients and GH in the regulation of food intake in pediatric obesity and Prader-Willi Syndrome (PWS) are poorly understood. Objective: We compared effects of high-carbohydrate (HC) and high-fat (HF) meals and GH therapy on ghrelin, insulin, peptide YY (PYY), and insulin sensitivity in children with PWS and body mass index (BMI) –matched obese controls (OCs). Methods: In a randomized, crossover study, 14 PWS (median, 11.35 y; BMI z score [BMI-z], 2.15) and 14 OCs (median, 11.97 y; BMI-z, 2.35) received isocaloric breakfast meals (HC or HF) on separate days. Blood samples were drawn at baseline and every 30 minutes for 4 hours. Mixed linear models were adjusted for age, sex, and BMI-z. Results: Relative to OCs, children with PWS had lower fasting insulin and higher fasting ghrelin and ghrelin/PYY. Ghrelin levels were higher in PWS across all postprandial time points (P < .0001). Carbohydrate was more potent than fat in suppressing ghrelin levels in PWS (P = .028); HC and HF were equipotent in OCs but less potent than in PWS (P = .011). The increase in PYY following HF was attenuated in PWS (P = .037); thus, postprandial ghrelin/PYY remained higher throughout. A lesser increase in insulin and lesser decrease in ghrelin were observed in GH-treated PWS patients than in untreated patients; PYY responses were comparable. Conclusion: Children with PWS have fasting and postprandial hyperghrelinemia and an attenuated PYY response to fat, yielding a high ghrelin/PYY ratio. GH therapy in PWS is associated with increased insulin sensitivity and lesser postprandial suppression of ghrelin. The ratio Ghrelin/PYY may be a novel marker of orexigenic drive. PMID:26259133

Macronutrient Regulation of Ghrelin and Peptide YY in Pediatric Obesity and Prader-Willi Syndrome.

PubMed

Gumus Balikcioglu, Pinar; Balikcioglu, Metin; Muehlbauer, Michael J; Purnell, Jonathan Q; Broadhurst, David; Freemark, Michael; Haqq, Andrea M

2015-10-01

The roles of macronutrients and GH in the regulation of food intake in pediatric obesity and Prader-Willi Syndrome (PWS) are poorly understood. We compared effects of high-carbohydrate (HC) and high-fat (HF) meals and GH therapy on ghrelin, insulin, peptide YY (PYY), and insulin sensitivity in children with PWS and body mass index (BMI) -matched obese controls (OCs). In a randomized, crossover study, 14 PWS (median, 11.35 y; BMI z score [BMI-z], 2.15) and 14 OCs (median, 11.97 y; BMI-z, 2.35) received isocaloric breakfast meals (HC or HF) on separate days. Blood samples were drawn at baseline and every 30 minutes for 4 hours. Mixed linear models were adjusted for age, sex, and BMI-z. Relative to OCs, children with PWS had lower fasting insulin and higher fasting ghrelin and ghrelin/PYY. Ghrelin levels were higher in PWS across all postprandial time points (P < .0001). Carbohydrate was more potent than fat in suppressing ghrelin levels in PWS (P = .028); HC and HF were equipotent in OCs but less potent than in PWS (P = .011). The increase in PYY following HF was attenuated in PWS (P = .037); thus, postprandial ghrelin/PYY remained higher throughout. A lesser increase in insulin and lesser decrease in ghrelin were observed in GH-treated PWS patients than in untreated patients; PYY responses were comparable. Children with PWS have fasting and postprandial hyperghrelinemia and an attenuated PYY response to fat, yielding a high ghrelin/PYY ratio. GH therapy in PWS is associated with increased insulin sensitivity and lesser postprandial suppression of ghrelin. The ratio Ghrelin/PYY may be a novel marker of orexigenic drive.

Effect Size Analyses of Souvenaid in Patients with Alzheimer’s Disease

PubMed Central

Cummings, Jeffrey; Scheltens, Philip; McKeith, Ian; Blesa, Rafael; Harrison, John E.; Bertolucci, Paulo H.F.; Rockwood, Kenneth; Wilkinson, David; Wijker, Wouter; Bennett, David A.; Shah, Raj C.

2016-01-01

Background: Souvenaid® (uridine monophosphate, docosahexaenoic acid, eicosapentaenoic acid, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium), was developed to support the formation and function of neuronal membranes. Objective: To determine effect sizes observed in clinical trials of Souvenaid and to calculate the number needed to treat to show benefit or harm. Methods: Data from all three reported randomized controlled trials of Souvenaid in Alzheimer’s disease (AD) dementia (Souvenir I, Souvenir II, and S-Connect) and an open-label extension study were included in analyses of effect size for cognitive, functional, and behavioral outcomes. Effect size was determined by calculating Cohen’s d statistic (or Cramér’s V method for nominal data), number needed to treat and number needed to harm. Statistical calculations were performed for the intent-to-treat populations. Results: In patients with mild AD, effect sizes were 0.21 (95% confidence intervals: –0.06, 0.49) for the primary outcome in Souvenir II (neuropsychological test battery memory z-score) and 0.20 (0.10, 0.34) for the co-primary outcome of Souvenir I (Wechsler memory scale delayed recall). No effect was shown on cognition in patients with mild-to-moderate AD (S-Connect). The number needed to treat (6 and 21 for Souvenir I and II, respectively) and high number needed to harm values indicate a favorable harm:benefit ratio for Souvenaid versus control in patients with mild AD. Conclusions: The favorable safety profile and impact on outcome measures converge to corroborate the putative mode of action and demonstrate that Souvenaid can achieve clinically detectable effects in patients with early AD. PMID:27767993

Broadly Applicable Nanowafer Drug Delivery System for Treating Eye Injuries

DTIC Science & Technology

2015-09-01

Eyedrops in the Treatment of Dry Eye in Sjögren Syndrome . Eur. J. Ophthalmol. 2013, 23, 368–376. 23. Acharya, G.; Shin, C. S.; McDermott, M.; Mishra, H...J.E. Buring, M.R. Dana, Prevalence of dry eye syndrome among US women, Am J. Ophthalmol. 136 (2003) 318–326. [7] M.A. Lemp, Advances in...surface of patients with dry eye syndrome , Invest. Ophthalmol. Vis. Sci. 51 (2010) 643–650. [43] D.T. Jones, D. Monroy, Z. Ji, S.S. Atherton, S.C

Restricted ultraviolet mutational spectrum in a shuttle vector propagated in xeroderma pigmentosum cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bredberg, A.; Kraemer, K.H.; Seidman, M.M.

1986-11-01

A shuttle vector plasmid, pZ189, carrying a bacterial suppressor tRNA marker gene, was treated with ultraviolet radiation and propagated in cultured skin cells from a patient with the skin-cancer-prone, DNA repair-deficient disease xeroderma pigmentosum and in repair-proficient cells. After replication in the human cells, progeny plasmids were purified. Plasmid survival and mutations inactivating the marker gene were scored by transforming an indicator strain of Escherichia coli carrying a suppressible amber mutation in the beta-galactosidase gene. Plasmid survival in the xeroderma pigmentosum cells was less than that of pZ189 harvested from repair-proficient human cells. The point-mutation frequency in the 150-base-pair tRNAmore » marker gene increased up to 100-fold with ultraviolet dose. Sequence analysis of 150 mutant plasmids revealed that mutations were infrequent at potential thymine-thymine dimer sites. Ninety-three percent of the mutant plasmids from the xeroderma pigmentosum cells showed G X C----A X T transitions, compared to 73% in the normal cells (P less than 0.002). There were significantly fewer transversions (P less than 0.002) (especially G X C----T X A) and multiple base substitutions (P less than 0.00001) than when pZ189 was passaged in repair-proficient cells. The subset of mutational changes that are common to ultraviolet-treated plasmids propagated in both repair-proficient and xeroderma pigmentosum skin cells may be associated with the development of ultraviolet-induced skin cancer in humans.« less

Classification of Airflow Limitation Based on z-Score Underestimates Mortality in Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Tejero, Elena; Prats, Eva; Casitas, Raquel; Galera, Raúl; Pardo, Paloma; Gavilán, Adelaida; Martínez-Cerón, Elisabet; Cubillos-Zapata, Carolina; Del Peso, Luis; García-Río, Francisco

2017-08-01

Global Lung Function Initiative recommends reporting lung function measures as z-score, and a classification of airflow limitation (AL) based on this parameter has recently been proposed. To evaluate the prognostic capacity of the AL classifications based on z-score or percentage predicted of FEV 1 in patients with chronic obstructive pulmonary disease (COPD). A cohort of 2,614 patients with COPD recruited outside the hospital setting was examined after a mean (± SD) of 57 ± 13 months of follow-up, totaling 10,322 person-years. All-cause mortality was analyzed, evaluating the predictive capacity of several AL staging systems. Based on Global Initiative for Chronic Obstructive Lung Disease guidelines, 461 patients (17.6%) had mild, 1,452 (55.5%) moderate, 590 (22.6%) severe, and 111 (4.2%) very severe AL. According to z-score classification, 66.3% of patients remained with the same severity, whereas 23.7% worsened and 10.0% improved. Unlike other staging systems, patients with severe AL according to z-score had higher mortality than those with very severe AL (increase of risk by 5.2 and 3.9 times compared with mild AL, respectively). The predictive capacity for 5-year survival was slightly higher for FEV 1 expressed as percentage of predicted than as z-score (area under the curve: 0.714-0.760 vs. 0.649-0.708, respectively). A severity-dependent relationship between AL grades by z-score and mortality was only detected in patients younger than age 60 years. In patients with COPD, the AL classification based on z-score predicts worse mortality than those based on percentage of predicted. It is possible that the z-score underestimates AL severity in patients older than 60 years of age with severe functional impairment.

[Central blood pressure and vascular damage].

PubMed

Pérez-Lahiguera, Francisco; Rodilla, Enrique; Costa, José Antonio; Pascual, José María

2015-07-20

The aim of this study was to assess the relationship between central blood pressure and vascular damage. This cross-sectional study involved 393 never treated hypertensive patients (166 women). Clinical blood pressure (BP), 24h blood pressure (BP24h) and central blood pressure (CBP) were measured. Vascular organ damage (VOD) was assessed by calculating the albumin/creatinine ratio (ACR), wave pulse pressure velocity and echocardiographic left ventricular mass index (LVMI). Patients with VOD had higher values of BP, BP24h, and CBP than patients without ACR. When comparing several systolic BP, systolic BP24h had a higher linear correlation with CBP (Z Steiger test: 2.26; P=.02) and LVMI (Z Steiger test: 3.23; P=.01) than PAC. In a multiple regression analysis corrected by age, sex and metabolic syndrome, all pressures were related with VOD but systolic BP24h showed the highest correlation. In a logistic regression analysis, having the highest tercile of systolic BP24h was the stronger predictor of VOD (multivariate odds ratio: 3.4; CI 95%: 2.5-5.5, P=.001). CBP does not have more correlation with VOD than other measurements of peripheral BP. Systolic BP24h is the BP measurement that best predicts VOD. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Hepatic-targeted RNA interference provides robust and persistent knockdown of alpha-1 antitrypsin levels in ZZ patients.

PubMed

Turner, Alice M; Stolk, Jan; Bals, Robert; Lickliter, Jason D; Hamilton, James; Christianson, Dawn R; Given, Bruce D; Burdon, Jonathan G; Loomba, Rohit; Stoller, James K; Teckman, Jeffery H

2018-03-21

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder causing pulmonary and liver disease. The PiZ mutation in AAT (SERPINA1) results in mis-folded AAT protein (Z-AAT) accumulating in hepatocytes, leading to fibrosis and cirrhosis. RNAi-based therapeutics silencing production of hepatic Z-AAT might benefit patients with AATD-associated liver disease. This study evaluated an RNAi therapeutic to silence production of AAT. Part A of this double-blind first-in-human study randomized 54 healthy volunteers (HVs) into single dose cohorts (two placebo: four active), receiving escalating doses of the investigational agent ARC-AAT from 0.38 to 8.0 mg/kg or placebo. Part B randomized 11 patients with PiZZ (homozygous for Z-AAT) genotype AATD, who received up to 4.0 mg/kg of ARC-AAT or placebo. Patients with baseline FibroScan® >11 kPa or forced expiratory volume in one second (FEV1) <60% were excluded. Assessments included safety, pharmacokinetics, and change in serum AAT concentrations. A total of 36 HVs received ARC-AAT and 18 received placebo (part A). Seven PiZZ individuals received ARC-AAT and four received placebo (part B). A dose response in serum AAT reduction was observed at doses ≥4 mg/kg with similar relative reductions in PiZZ patients and HVs at 4 mg/kg and a maximum reduction of 76.1% (HVs) vs. 78.8% (PiZZ) at this dose. The time it took for serum AAT to return to baseline was similar for HV and PiZZ. There were no notable differences between HV and PiZZ safety parameters. The study was terminated early because of toxicity findings related to the delivery vehicle (ARC-EX1) seen in a non-human primate study. PiZZ patients and HVs responded similarly to ARC-AAT. Deep and durable knockdown of hepatic AAT production based on observed reduction in serum AAT concentrations was demonstrated. Accumulation of abnormal proteins in the livers of patients with alpha-1 antitrypsin deficiency may lead to decreased liver function and potentially liver failure. Therapeutics targeting the production of these abnormal proteins may be used to prevent or treat liver disease in patients with alpha-1 antitrypsin deficiency. NCT02363946. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Efficacy and Safety of Botulinum Toxin Type A in Treating Patients of Advanced Age with Idiopathic Trigeminal Neuralgia

PubMed Central

Xu, Ying-Ying; Zhang, Qi-Lin

2018-01-01

Objective To assess the therapeutic efficacy and safety of botulinum toxin type A (BTX-A) for treating idiopathic trigeminal neuralgia (ITN) in patients ≥80 years old. Methods Selected patients (n=43) with ITN, recruited from the neurology clinic and inpatient department of the Second Affiliated Hospital of Soochow University between August 2008 and February 2014, were grouped by age, one subset (n=14) ≥80 years old and another (n=29) <60 years old. Each group scored similarly in degrees of pain registered by the visual analogue scale (VAS). Dosing, efficacy, and safety of BTX-A injections were compared by group. Results Mean dosages of BTX-A were 91.3 ± 25.6 U and 71.8 ± 33.1 U in older and younger patients, respectively (t=1.930,  p=0.061). The median of the VAS score in older patients at baseline (8.5) declined significantly at 1 month after treatment (4.5) (p=0.007), as did that of younger patients (8.0 and 5.0, resp.) (p=0.001). The median of the D values of the VAS scores did not differ significantly by group (older, 2.5; younger, 0; Z=−1.073, p=0.283). Two patients in each group developed minor transient side effects (p=0.825). Adverse reactions in both groups were mild, resolving spontaneously within 3 weeks. Conclusions BTX-A is effective and safe in treating patients of advanced age (≥80 years old) with ITN, at dosages comparable to those used in much younger counterparts (<60 years old). PMID:29849847

Methylation of subtelomeric repeat D4Z4 in peripheral blood leukocytes is associated with biochemical recurrence in localized prostate cancer patients.

PubMed

Han, Yuyan; Xu, Junfeng; Kim, Jeri; Wu, Xifeng; Gu, Jian

2017-08-01

Global DNA methylation may affect chromosome structure and genomic stability and is involved in carcinogenesis. In this study, we aimed to investigate whether methylation of pericentromeric repeat NBL2 and subtelomeric repeat D4Z4 in peripheral blood was associated with the aggressiveness of prostate cancer (PCa). We measured the methylation status of different CpG sites of NBL2 and D4Z4 in 795 PCa patients and compared their methylation levels among patients with different Gleason Score at diagnosis. We then analyzed the association of the NBL2 and D4Z4 methylation with the risk of biochemical recurrence (BCR) in patients receiving radical prostatectomy or radiotherapy using a multivariate Cox proportional hazards model. In addition, we used the Kaplan-Meier survival function and log-rank tests to assess BCR-free survival associated with D4Z4 methylation. There was no significant difference in methylation level of NBL2 and D4Z4 between clinically defined aggressive and non-aggressive PCa at diagnosis. However, the methylation of D4Z4 was associated with BCR, while the methylation of NBL2 was not. In tertile analysis, patients in the highest tertile of D4Z4 methylation had an increased risk of BCR (HR = 2.17, 95% CI 1.36-3.48) compared to patients in the lower tertiles after adjustment of age, body mass index, smoking status, pack year, D'Amico risk groups and treatments. Among the four CpG sites in this region, the association was mostly attributable to the methylation of the second CpG site of D4Z4. These data suggest that higher methylation in D4Z4 was associated with worse prognosis of localized PCa patients. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Stepped approach for prediction of syndrome Z in patients attending sleep clinic: a north Indian hospital-based study.

PubMed

Agrawal, Swastik; Sharma, Surendra Kumar; Sreenivas, Vishnubhatla; Lakshmy, Ramakrishnan; Mishra, Hemant K

2012-09-01

Syndrome Z is the occurrence of metabolic syndrome (MS) with obstructive sleep apnea. Knowledge of its risk factors is useful to screen patients requiring further evaluation for syndrome Z. Consecutive patients referred from sleep clinic undergoing polysomnography in the Sleep Laboratory of AIIMS Hospital, New Delhi were screened between June 2008 and May 2010, and 227 patients were recruited. Anthropometry, body composition analysis, blood pressure, fasting blood sugar, and lipid profile were measured. MS was defined using the National Cholesterol Education Program (adult treatment panel III) criteria, with Asian cutoff values for abdominal obesity. Prevalence of MS and syndrome Z was 74% and 65%, respectively. Age, percent body fat, excessive daytime sleepiness (EDS), and ΔSaO(2) (defined as difference between baseline and minimum SaO(2) during polysomnography) were independently associated with syndrome Z. Using a cutoff of 15% for level of desaturation, the stepped predictive score using these risk factors had sensitivity, specificity, positive predictive value, and negative predictive value of 75%, 73%, 84%, and 61%, respectively for the diagnosis of syndrome Z. It correctly characterized presence of syndrome Z 75% of the time and obviated need for detailed evaluation in 42% of the screened subjects. A large proportion of patients presenting to sleep clinics have MS and syndrome Z. Age, percent body fat, EDS, and ΔSaO(2) are independent risk factors for syndrome Z. A stepped predictive score using these parameters is cost-effective and useful in diagnosing syndrome Z in resource-limited settings.

Comparing aspheric ablation profile with standard corneal ablation for correction of myopia and myopic astigmatism, a contralateral eye study.

PubMed

Ghoreishi, Mohammad; Naderi Beni, Afsaneh; Naderi Beni, Zahra; Zandi, Alireza; Kianersi, Farzan

2017-12-01

The purpose of this study is to compare visual outcomes of myopic refractive surgery, using tissue saving (TS), a standard ablation profile by a Technolas 217z100, and aberration smart ablation (ASA), an aspheric algorithm by a MEL 80 excimer laser in two eyes of one patient. In this prospective interventional paired-eye controlled study, a total of 100 eyes of 50 participants with myopia with or without astigmatism underwent thin-flap Femto-LASIK, using a Femto LDV femtosecond laser (Ziemer Ophthalmic Systems AG, Port, Switzerland). For each patient, one eye was randomly treated with tissue-saving algorithm (TS group) by the Technolas 217z100 excimer laser and the other eye was treated with optimized smart ablation profile (ASA group) by the MEL 80 excimer laser. Outcome measures were uncorrected distance visual acuities (UDVAs), corrected distance visual acuities (CDVAs), manifest refraction, higher-order aberrations (HOAs), contrast sensitivity, and patient satisfaction 12 months after surgery. At 12 months postoperative, "45 subjects returned with mean" UDVA was - 0.02 ± 0.08 Logarithm of mean angle of resolution (LogMAR) for TS group and - 0.02 ± 0.09 LogMAR for ASA group (P = 0.91). Of the TS eyes, 42/45 (93.3%) and 32/45 (71.1%) were within ± 0.5 D and ± 0.25 D of target refraction, respectively, and of the ASA eyes, 41/45 (91.1%) and 30/45 (66.6%) were within ± 0.5 D and ± 0.25 D of target refraction, respectively. No statistically significant differences were observed between groups in HOAs changes and contrast sensitivity function. Aspheric and non-aspheric LASIKs using the two different excimer lasers provide similar results in myopic and myopic astigmatism patients.

Root resorption of maxillary incisors retracted with and without skeletal anchorage.

PubMed

Barros, Sérgio Estelita; Janson, Guilherme; Chiqueto, Kelly; Baldo, Vitor Oliveira; Baldo, Taiana Oliveira

2017-02-01

Our objective was to compare root resorption degree of the maxillary central incisors retracted with and without skeletal anchorage. This nonrandomized historical control study included 37 patients requiring maximum anterior retraction and treated with extraction of 2 maxillary premolars. Group 1 consisted of 22 patients (11 male, 11 female) in whom anterior retraction was performed without skeletal anchorage, and group 2 included 15 patients (3 male, 12 female) treated with skeletally anchored anterior retraction. Periapical radiographs were used to evaluate root resorption degree by a scoring system. The groups were compared regarding the resorption score and resorption degree distribution with the Mann-Whitney U test, chi-square test, and Z test on proportions. There was no statistically significant intergroup difference regarding root resorption, but the number of patients with severe and extreme root resorption degrees was significantly greater in group 2. Although the root resorption degree of the skeletal anchorage group was not significantly different from the group without skeletal anchorage, the number of patients with severe to extreme resorption in the first group was significantly greater. Therefore, careful clinical monitoring of skeletally anchored anterior retraction is needed, especially when there are known root resorption predisposing factors. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Growing Up with Type 1 Narcolepsy: Its Anthropometric and Endocrine Features

PubMed Central

Ponziani, Virginia; Gennari, Monia; Pizza, Fabio; Balsamo, Antonio; Bernardi, Filippo; Plazzi, Giuseppe

2016-01-01

Study Objectives: To evaluate the effect of type 1 narcolepsy (NT1) on anthropometric and endocrine features in childhood/adolescence, focusing on patterns and correlates of weight, pubertal development, and growth in treated and untreated patients. Methods: We collected anthropometric (height, weight, body mass index (BMI) z-scores), pubertal, metabolic, and endocrine data from 72 NT1 patients at diagnosis and all available premorbid anthropometric parameters of patients from their pediatric files (n = 30). New measurements at 1-y reassessment in patients undergoing different treatments were compared with baseline data. Results: We detected a high prevalence of overweight (29.2%), obesity (25%), metabolic syndrome (18.8%), and precocious puberty (16.1%), but no signs of linear growth alterations at diagnosis. According to anthropometric records, weight gain started soon after NT1 onset. At 1-y follow-up reassessment, sodium oxybate treatment was associated with a significant BMI z-score reduction (−1.29 ± 0.30, p < 0.0005) after adjusting for baseline age, sex, sleepiness, and BMI. Conclusions: NT1 onset in children/adolescents is associated with rapid weight gain up to overweight/obesity and precocious puberty without affecting growth. In our study, sodium oxybate treatment resulted in a significant weight reduction in NT1 overweight/obese patients at 1-y follow-up. Citation: Ponziani V, Gennari M, Pizza F, Balsamo A, Bernardi F, Plazzi G. Growing up with type 1 narcolepsy: its anthropometric and endocrine features. J Clin Sleep Med 2016;12(12):1649–1657. PMID:27707443

Z-drug for schizophrenia: A systematic review and meta-analysis.

PubMed

Kishi, Taro; Inada, Ken; Matsui, Yuki; Iwata, Nakao

2017-10-01

No systematic reviews and meta-analyses on the use of Z-drug for schizophrenia are available. Randomized, placebo-controlled, or non-pharmacological intervention-controlled trials published before 03/20/2017 were retrieved from major healthcare databases and clinical trial registries. A meta-analysis including only randomized, placebo-controlled trials was performed. Efficacy outcomes were measured as improvement in overall schizophrenia symptoms, total sleep time, and wake after sleep onset. Safety/acceptability outcomes were discontinuation rate and individual adverse events. Four trials [1 alpidem placebo-controlled study (n=66), 2 eszopiclone placebo-controlled studies (n=60), and 1 eszopiclone, shallow needling-controlled study (n=96)] were identified. The meta-analysis showed no significant differences in any outcome between pooled Z-drug and placebo treatment groups. For individual studies, alpidem was superior to placebo in improving the overall schizophrenia symptoms. One of the eszopiclone studies showed that eszopiclone was superior to placebo in improving the Insomnia Severity Index scores. Another eszopiclone study showed that eszopiclone did not differ from shallow needling therapy in improving both schizophrenia- and insomnia-related symptoms. Although this study failed to show significant benefits for the use of Z-drug in the treatment of schizophrenia, it showed that short-term use of eszopiclone is an acceptable method for treating persistent insomnia among these patients. Copyright © 2017 Elsevier B.V. All rights reserved.

People, clothing, music, and arousal as contextual retrieval cues in verbal memory.

PubMed

Standing, Lionel G; Bobbitt, Kristin E; Boisvert, Kathryn L; Dayholos, Kathy N; Gagnon, Anne M

2008-10-01

Four experiments (N = 164) on context-dependent memory were performed to explore the effects on verbal memory of incidental cues during the test session which replicated specific features of the learning session. These features involved (1) bystanders, (2) the clothing of the experimenter, (3) background music, and (4) the arousal level of the subject. Social contextual cues (bystanders or experimenter clothing) improved verbal recall or recognition. However, recall decreased when the contextual cue was a different stimulus taken from the same conceptual category (piano music by Chopin) that was heard during learning. Memory was unaffected by congruent internal cues, produced by the same physiological arousal level (low, moderate, or high heart rate) during the learning and test sessions. However, recall increased with the level of arousal across the three congruent conditions. The results emphasize the effectiveness as retrieval cues of stimuli which are socially salient, concrete, and external.

The role of ocean phenomenon in music compositions

NASA Astrophysics Data System (ADS)

Liu, Chi-Min

2016-04-01

This is a preliminarily interdisciplinary study for exploring the elements of ocean phenomenon appearing in some compositions of classical music. The so-called ocean phenomenon contain wave conditions, climate change, coastal landform, and other natural events around or over the sea. In some music compositions, it is apparent that natural phenomenon over the sea influence the composers' moods and the music pieces they composed. In this poster, some music compositions in the 19th and the early 20th centuries will be introduced to demonstrate the relation between ocean and music works. These works include Meeresstille by Schubert, Étude Op.25 No.12 by Chopin, Fingal's Cave Overture by Mendelssohn, Der Fliegende Holländer by Wagner and La Mer by Debussy. In addition, present idea may give a novel way for music teachers to elucidate the knowledge of ocean science in classes.

Individualization of radiotherapy in breast cancer patients: possible usefulness of a DNA damage assay to measure normal cell radiosensitivity.

PubMed

Ruiz de Almodóvar, José Mariano; Guirado, Damian; Isabel Núñez, María; López, Escarlata; Guerrero, Rosario; Valenzuela, María Teresa; Villalobos, Mercedes; del Moral, Rosario

2002-03-01

The purpose of this study was to determine whether the distribution of sensitivities in breast cancer patients, measured using a DNA damage assay on lymphocytes, is likely to provide sufficient discrimination to enable the reliable identification of patients with abnormal sensitivities. Radiosensitivity (x) was assessed in 226 samples of lymphocytes from unselected women with breast cancer and was quantified as the initial number of DNA double-strand breaks (dsb) induced per Gy and per DNA unit (200 Mbp). The existence of an inter-individual variation in the parameter (x) is described through the range (0.40-4.72 dsb/Gy/DNA unit) of values found, which have been fitted to the mathematical model defined by the log-normal distribution (mu = 0.42+/-0.03; sigma = 0.52+/-0.03; R(2)=0.9475). A total of 189 patients received radiotherapy after surgical treatment. Among them, we have detected 15 patients who developed severe skin reactions and we have compared their radiosensitivity values with the rest of patients treated. Our results suggest that DNA initial damage measured on lymphocytes offers an approach to predict the acute response of human normal tissues prior to radiotherapy. Values of x higher than 3.20 dsb/Gy/DNA unit theoretically should correspond to the highly radio-sensitive patients. Using the experimental results, we have calculated the strength of the test by means of the area under the receiver operator characteristic curves (A(Z)) to determine whether the radiosensitivity assay can discriminate between patients according to their radiation response. The value found (A(Z)=0.675+/-0.072) is indicative of a fair-poor discriminating capacity of the test to identify the patients with higher risk of developing a severe acute reaction during the radiotherapy treatment.

Quantitative calcaneal ultrasound parameters and bone mineral density at final height in girls treated with depot gonadotrophin-releasing hormone agonist for central precocious puberty or idiopathic short stature.

PubMed

Kapteijns-van Kordelaar, Simone; Noordam, Kees; Otten, Barto; van den Bergh, Joop

2003-11-01

To evaluate the effect of gonadotrophin-releasing hormone (GnRH) agonist treatment on bone quality at final height, we studied girls with central precocious puberty (CPP) and with idiopathic short stature (ISS). A total of 25 Caucasian girls were included: group A (n=14) with idiopathic CPP (mean age at start 7.4 years) and group B (n=11) with ISS (mean age at start 11.7 years). Treatment duration was 3.8 and 1.7 years respectively. The quantitative ultrasound parameters (QUS) broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the calcaneus (UBIS 3000 device). Lumbar spine bone mineral density (BMD; L2-L4) was measured by dual energy X-ray absorptiometry (DXA) (Hologic QDR1000). Measurements were performed at final height and expressed as Z-scores corrected for bone age. Mean Z-scores of QUS parameters, areal BMD and volumetric BMD (BMDvol) were above -1 in both groups (group A: BUA Z-score -0.21, SOS Z-score -0.29, BMD Z-score 0.02, BMDvol Z-score 0.05, group B: BUA Z-score -0.93, SOS Z-score -0.40, BMD Z-score -0.86, BMDvol Z-score -0.68), although mean Z-scores of BUA and areal BMD in group B were significantly different from zero (P=0.03 and P=0.02 respectively). Mean Z-score BMDvol was not significantly different from zero (P=0.05), we found no significant difference between the groups for BMDvol (P=0.13). Although quantitative ultrasound parameters parameters and bone mineral density were normal in girls with central precocious puberty at final height after gonadotrophin-releasing hormone agonist treatment, mean Z-score for broadband ultrasound attenuation and areal bone mineral density were significantly different from zero and mean Z-score for volumetric bone mineral density was (just) not significantly different from zero in idiopathic short stature girls with normal puberty treated with gonadotrophin-releasing hormone agonists. Therefore we cannot say that this treatment is safe in these girls with regard to bone health.

Protein Z G79A polymorphism in Turkish pediatriccerebral infarct patients.

PubMed

Öztürk, Ayşenur; Eğin, Yonca; Deda, Gülhis; Teber, Serap; Akar, Nejat

2008-09-05

Protein Z (PZ) plays an enhancer role in coagulation as an anticoagulant. This is the first study in which G79A polymorphism investigated in Turkish paediatric stroke patients. Ninety-one paediatric stroke patients with cerebral ischemia and 70 control subjects were analyzed for PZ G79A and also FVL, PT mutations. PZ 79 'A' allele in homozygous state was found in five patients (5,5%), while it was found only in one control subject (1,4%) and it was seemed as a risk factor for peadiatric ischemia [OR=3,94 (0,44-35,1)]. When patients and controls who had FVL and PT carriers were excluded, AA genotype carried a risk [OR=3,88 (0,41-36,5)]. Also plasma protein Z levels measured in 21 stroke patients and 52 controls. Plasma protein Z levels were not different between stroke patients (500,95 ngmL-1±158,35) and controls (447,34 ngmL-1±165,97). But the plasma levels of protein Z was decreased in patients with AA genotype. Our data showed that carrying 79 AA genotype could be a genetic risk factor for cerebral infarct in peadiatric patients.

A new approach to treat discontinuities in multi-layered soils

NASA Astrophysics Data System (ADS)

Berardi, Marco; Difonzo, Fabio; Caputo, Maria; Vurro, Michele; Lopez, Luciano

2017-04-01

The water infiltration into two (or more) layered soils can give rise to preferential flow paths at the interface between different soils. The deep understanding of this phenomenon can be of great interest in modeling different environmental problems in geosciences and hydrology. Flow through layered soils arises naturally in agriculture, and layered soils are also engineered as cover liners for landfills. In particular, the treatment of the soil discontinuity is of great interest from the modeling and the numerical point of view, and is still an open problem.% (see, for example, te{Matthews_et_al,Zha_vzj_2013,DeLuca_Cepeda_ASCE_2016}). Assuming to approximate the soils with different porous media, the governing equation for this phenomenon is Richards' equation, in the following form: {eq:different_Richards_1} C_1(ψ) partial ψ/partial t = partial /partial z [ K_1(ψ) ( partial ψ/partial z - 1 ) ], \\quad if \\quad z < \\overline{z}, C_2(ψ) partial ψ/partial t = partial /partial z [ K_2(ψ) ( partial ψ/partial z - 1 ) ], \\quad if \\quad z > \\overline{z}, where \\overline{z} is the spatial threshold that identifies the change in soil structure, and C1 C_2, K_1, K_2, the hydraulic functions that describe the upper and the lower soil, respectively. The ψ-based form is used, in this work. Here we have used the Filippov's theory in order to deal with discontinuous differential systems, and we handled opportunely the numerical discretization in order to treat the abovementioned system by means of this theory, letting the discontinuity depend on the state variable. The advantage of this technique is a better insight on the solution behavior on the discontinuity surface, and the no-need to average the hydraulic conductivity field on the threshold itself, as in the existing literature.

Africa's largest long-lasting insecticide-treated net producer: lessons from A to Z Textiles.

PubMed

Masum, Hassan; Shah, Ronak; Schroeder, Karl; Daar, Abdallah S; Singer, Peter A

2010-12-13

Field trials have demonstrated the efficacy of insecticide-treated nets, and the WHO has recently endorsed a shift toward Long-Lasting Insecticide Treated nets (LLINs) due to factors such as reduced distribution costs. However, the need for LLINs poses several challenges. Is it possible to manufacture LLINs in large quantities in the African continent, where malaria is most endemic? When production is located in low-income countries, what role is played by local funding and employment, scaling up manufacturing, and partnerships? What factors influence availability and pricing? A case study of A to Z Textiles was undertaken to answer the question of how large-scale production of LLINs can occur in a low income setting. One of the largest sources of bed nets for Africa, A to Z Textiles is Africa-based, and its Tanzanian operations have a production capacity of 30 million LLINs per year, along with full WHO recommendation for its nets. Our analysis is based on semi-structured interviews with key informants familiar with A to Z, site visits in Tanzania, and literature reviews.This paper discusses the history and current status of A to Z Textiles, identifies the factors that led to its success, and suggests policy considerations that could support similar initiatives in the future. Local funding, scaling up manufacturing, technology transfer, and partnerships all played important roles in A to Z's ascent, as did perceived benefits of local employment and capacity-building. Regulatory issues and procurement rules acted as barriers. A to Z cost-effectively manufactures high-quality LLINs where malaria is most endemic. With a production capacity of 30 million LLINs per year, and full WHOPES (WHO Pesticide Evaluation Scheme) certification, A to Z Textiles demonstrates how key health goods can be successfully produced in the low-income countries that use them. Its example may be instructive and of high interest to readers in the malaria community, especially in developing countries, and to those who wish to support or partner with efforts by developing countries to build their health innovation capacity.

Extended Daily Eye Patching Effective at Treating Stubborn Amblyopia in Children

MedlinePlus

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Discovery and identification of potential biomarkers of pediatric Acute Lymphoblastic Leukemia

PubMed Central

Shi, Linan; Zhang, Jun; Wu, Peng; Feng, Kai; Li, Jing; Xie, Zhensheng; Xue, Peng; Cai, Tanxi; Cui, Ziyou; Chen, Xiulan; Hou, Junjie; Zhang, Jianzhong; Yang, Fuquan

2009-01-01

Background Acute lymphoblastic leukemia (ALL) is a common form of cancer in children. Currently, bone marrow biopsy is used for diagnosis. Noninvasive biomarkers for the early diagnosis of pediatric ALL are urgently needed. The aim of this study was to discover potential protein biomarkers for pediatric ALL. Methods Ninety-four pediatric ALL patients and 84 controls were randomly divided into a "training" set (45 ALL patients, 34 healthy controls) and a test set (49 ALL patients, 30 healthy controls and 30 pediatric acute myeloid leukemia (AML) patients). Serum proteomic profiles were measured using surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy (SELDI-TOF-MS). A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by HPLC, identified by LC-MS/MS and validated using ProteinChip immunoassays. Results A total of 7 protein peaks (9290 m/z, 7769 m/z, 15110 m/z, 7564 m/z, 4469 m/z, 8937 m/z, 8137 m/z) were found with differential expression levels in the sera of pediatric ALL patients and controls using SELDI-TOF-MS and then analyzed by BPS to construct a classification model in the "training" set. The sensitivity and specificity of the model were found to be 91.8%, and 90.0%, respectively, in the test set. Two candidate protein peaks (7769 and 9290 m/z) were found to be down-regulated in ALL patients, where these were identified as platelet factor 4 (PF4) and pro-platelet basic protein precursor (PBP). Two other candidate protein peaks (8137 and 8937 m/z) were found up-regulated in the sera of ALL patients, and these were identified as fragments of the complement component 3a (C3a). Conclusion Platelet factor (PF4), connective tissue activating peptide III (CTAP-III) and two fragments of C3a may be potential protein biomarkers of pediatric ALL and used to distinguish pediatric ALL patients from healthy controls and pediatric AML patients. Further studies with additional populations or using pre-diagnostic sera are needed to confirm the importance of these findings as diagnostic markers of pediatric ALL. PMID:19291297

Extraction and identification of bioactive components in Sida cordata (Burm.f.) using gas chromatography-mass spectrometry.

PubMed

Ganesh, Mani; Mohankumar, Murugan

2017-09-01

Sida cordata (Burm.f.) is a pineal tropical plant in the family Malvaceae that is found throughout India and used to treat various diseases and ailments in many complementary and alternative medicine systems. This study identified the bioactive components present in whole-plant ethanol extracts of S . cordata using gas chromatography-mass spectrometry (GC-MS). Based on their retention times (RT) and mass-to-charge ratios (m/z), 29 bioactive compounds were identified: nonanoic acid, vitamin D 3 , 3-trifluroacetoxypentadecane, α-d-glucopyranoside, O-α-d-glucopyranosyl-(1.fwdarw.3)-α-d-fructofuranosyl,3,7,11,15-tetramethyl-2-hexadecan-1-ol, octadecanoic acid, ethyl ester, phytol, 9,12-octadecadienoic acid, methyl ester (E,E), 9,12,15-octadecadienoic acid, methyl ester (Z,Z,Z), oleic acid, 1,2-15,16-diepoxyhexadecane, 3-hexadecyloxycarbonyl-5-(2-hydroxyethyl)-4-methylimidazolium ion, methoxyacetic acid, 4-tetradecyl ester, 1,2-benzenedicarboxylic acid, mono (2-ethylhexyl) ester, 1-iodo-2-methylundecane, dodecane, 2,6,10-trimethyl-, 2-piperidinone-N-[4-bromo-n-butyl]-, squalene, octadecane-1-(ethenyloxy)-, Z,Z-2,5-pentadecadien-1-ol, 1-hexadecanol, 2-methyl-, spiro[androst-5ene-17,1'-cyclobutan]-2'-one-3-hydroxy-, (3a,17a)-, diethylene glycol monododecyl ether, vitamin E, cholestan-3-ol, 2-methylene-, (3a,5a)-, 2H-pyran, 2-(7-heptadecynyloxy)tetrahydro-, and cis -Z-α-bisabolene epoxide. The presence of various bioactive compounds justifies the use of this plant for treating various ailments by traditional practitioners.

Significant and continuous improvement in bone mineral density among type 1 Gaucher disease patients treated with velaglucerase alfa: 69-month experience, including dose reduction.

PubMed

Elstein, Deborah; Foldes, A Joseph; Zahrieh, David; Cohn, Gabriel M; Djordjevic, Maja; Brutaru, Costin; Zimran, Ari

2011-06-15

Since bone pathology is a major concern in type 1 Gaucher disease (GD1), we evaluated bone mineral density (BMD) in adults receiving velaglucerase alfa in the seminal Phase I/II and extension trial. Ten treatment-naïve symptomatic patients with GD1 (four men, six women; median age 35years, range 18-62years) were included; of these, four patients were receiving bisphosphonates at enrollment. Using WHO criteria to classify the lumbar spine (LS) and femoral neck (FN) BMD T-scores, respectively, one (10%) and four (40%) patients had osteoporosis; eight (80%) and five (50%) had osteopenia; and one each (10%) was in the normal range, at baseline. By Month 69, two LS and one FN osteopenic patients normalized and one FN osteoporotic patient became osteopenic; change was seen only in patients not receiving bisphosphonates. Significant improvements in BMD Z-scores were seen at the LS by Month 24 and at the FN by Month 33 and were continuous thereafter. In linear mixed models, Z-scores were significantly lower than the reference population at baseline and improved significantly with treatment (LS and FN both P<0.01); analysis of the subgroup of patients not receiving bisphosphonates showed similar results. In conclusion, in this small cohort, velaglucerase alfa was associated with clinically meaningful and statistically significant LS and FN BMD improvements as early as Month 24 (LS) and 33 (FN), despite dose reduction and significant baseline skeletal pathology. These results suggest that velaglucerase alfa may hold promise in the management of skeletal pathology associated with GD1. Copyright © 2011 Elsevier Inc. All rights reserved.

Contemporary adjuvant polymethyl methacrylate cementation optimally limits recurrence in primary giant cell tumor of bone patients compared to bone grafting: a systematic review and meta-analysis

PubMed Central

2013-01-01

Background Reports of recurrence following restructuring of primary giant cell tumor (GCT) defects using polymethyl methacrylate (PMMA) bone cementation or allogeneic bone graft with and without adjuvants for intralesional curettage vary widely. Systematic review and meta-analysis were conducted to investigate efficacy of PMMA bone cementation and allogeneic bone grafting following intralesional curettage for GCT. Methods Medline, EMBASE, Google Scholar, and Cochrane databases were searched for studies reporting GCT of bone treatment with PMMA cementation and/or bone grafting with or without adjuvant therapy following intralesional curettage of primary GCTs. Pooled risk ratios and 95% confidence intervals (CIs) for local recurrence risks were calculated by fixed-effects methods. Results Of 1,690 relevant titles, 6 eligible studies (1,293 patients) spanning March 2008 to December 2011 were identified in published data. Treatment outcomes of PMMA-only (n = 374), bone graft-only (n = 436), PMMA with or without adjuvant (PMMA + adjuvant; n = 594), and bone graft filling with or without adjuvant (bone graft + adjuvant; n = 699) were compared. Bone graft-only patients exhibited higher recurrence rates than PMMA-treated patients (RR 2.09, 95% CI (1.64, 2.66), Overall effect: Z = 6.00; P <0.001), and bone graft + adjuvant patients exhibited higher recurrence rates than PMMA + adjuvant patients (RR 1.66, 95% CI (1.21, 2.28), Overall effect: Z = 3.15, P = 0.002). Conclusions Local recurrence was minimal in PMMA cementation patients, suggesting that PMMA is preferable for routine clinical restructuring in eligible GCT patients. Relationships between tumor characteristics, other modern adjuvants, and recurrence require further exploration. PMID:23866921

Prevalence and associated factors of low bone mass in adults with systemic lupus erythematosus.

PubMed

Cramarossa, G; Urowitz, M B; Su, J; Gladman, D; Touma, Z

2017-04-01

Background Systemic lupus erythematosus (SLE) patients are often treated with glucocorticoids, which place them at risk of bone loss. Objectives The objectives of this article are to determine: (1) the prevalence of low bone mineral density (BMD) and factors associated with low BMD and (2) the prevalence of symptomatic fragility fractures in inception patients of the Toronto Lupus Cohort (TLC). Methods Prospectively collected data from the TLC (1996-2015) of inception patients' first BMD were analyzed. For pre-menopausal women/males <50 years, BMD 'below expected range for age' was defined by Z-score ≤ -2.0 SD. For post-menopausal women/males age 50 or older, osteoporosis was defined by T-score ≤ -2.5 SD and low bone mass by T-score between -1.0 and -2.5 SD. Patients' BMDs were defined as abnormal if Z-score ≤ -2.0 or T-score < -1.0 SD, and the remainder as normal. Descriptive analysis and logistic regression were employed. Results Of 1807 patients, 286 are inception patients with BMD results (mean age 37.9 ± 13.7 years); 88.8% are female. The overall prevalence of abnormal BMD is 31.5%. In pre-menopausal women ( n = 173), the prevalence of BMD below expected range is 17.3%. In post-menopausal women ( n = 81), the prevalence of osteoporosis and low BMD are 12.3% and 43.2%, respectively. Age and cumulative dose of glucocorticoids are statistically significantly associated with abnormal BMD in multivariate analysis. Of 769 inception patients from TLC, 11.1% experienced symptomatic fragility fractures (peripheral and vertebral) over the course of their disease. Conclusion The prevalence of low BMD is high in SLE patients, and is associated with older age and higher cumulative glucocorticoid dose.

Is increased uric acid a risk factor or a defensive response? The Campania Salute Network.

PubMed

Mancusi, C; Izzo, R; Ferrara, L A; Rozza, F; Losi, M A; Canciello, G; Pepe, M; de Luca, N; Trimarco, B; de Simone, G

2018-05-04

Circulating uric acid (UA) is positively associated with body mass index (BMI), blood glucose, blood pressure (BP), markers of inflammation, and altered lipid profile. UA has also anti-oxidative properties which might be beneficial for cardiovascular (CV) system. It is still debated whether or not UA is independently associated with increased CV morbidity and/or mortality. We studied prognostic impact of UA in 8833 hypertensive adults (mean age 53 ± 12 yrs, 3857 women) from the Campania Salute Network, without prevalent CV disease and more than stage 3 CKD. We calculated standardized UA Z-score, adjusted for age, sex, glomerular filtration rate, and BMI. Low and high UA and UA Z-score quartiles were compared to the 2 middle quartiles assumed to be "normal". Prevalence of obesity and diabetes was higher in low and high than in normal UA Z-score group (all p < 0.001). Systolic BP, left ventricular mass, carotid intima thickness were significantly higher and ejection fraction was reduced in the presence of high UA Z-score (all p < 0.001). Over 33-months average follow-up, incident major CV end-points (MACE) were not significantly different among low, normal and high UA or UA Z-score. In the latter analysis, however, incident MACE tended to be more frequent in the low than the high UA Z-score. Despite the results of multivariable analyses, the effect of less aggressive therapy in low UA Z-score cannot be excluded with certainty. In treated hypertensive patients, high levels of UA normalized for major biological determinants do not independently predict CV outcome. CLINICALTRIALS. NCT02211365. Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Metal transformation as a strategy for bacterial detoxification of heavy metals.

PubMed

Essa, Ashraf M M; Al Abboud, Mohamed A; Khatib, Sayeed I

2018-01-01

Microorganisms can modify the chemical and physical characters of metals leading to an alteration in their speciation, mobility, and toxicity. Aqueous heavy metals solutions (Hg, Cd, Pb, Ag, Cu, and Zn) were treated with the volatile metabolic products (VMPs) of Escherichia coli Z3 for 24 h using aerobic bioreactor. The effect of the metals treated with VMPs in comparison to the untreated metals on the growth of E. coli S1 and Staphylococcus aureus S2 (local isolates) was examined. Moreover, the toxic properties of the treated and untreated metals were monitored using minimum inhibitory concentration assay. A marked reduction of the treated metals toxicity was recorded in comparison to the untreated metals. Scanning electron microscopy and energy dispersive X-ray analysis revealed the formation of metal particles in the treated metal solutions. In addition to heavy metals at variable ratios, these particles consisted of carbon, oxygen, sulfur, nitrogen elements. The inhibition of metal toxicity was attributed to the existence of ammonia, hydrogen sulfide, and carbon dioxide in the VMPs of E. coli Z3 culture that might responsible for the transformation of soluble metal ions into metal complexes. This study clarified the capability of E. coli Z3 for indirect detoxification of heavy metals via the immobilization of metal ions into biologically unavailable species. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Copeptin helps in the early detection of patients with acute myocardial infarction: primary results of the CHOPIN trial (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction).

PubMed

Maisel, Alan; Mueller, Christian; Neath, Sean-Xavier; Christenson, Robert H; Morgenthaler, Nils G; McCord, James; Nowak, Richard M; Vilke, Gary; Daniels, Lori B; Hollander, Judd E; Apple, Fred S; Cannon, Chad; Nagurney, John T; Schreiber, Donald; deFilippi, Christopher; Hogan, Christopher; Diercks, Deborah B; Stein, John C; Headden, Gary; Limkakeng, Alexander T; Anand, Inder; Wu, Alan H B; Papassotiriou, Jana; Hartmann, Oliver; Ebmeyer, Stefan; Clopton, Paul; Jaffe, Allan S; Peacock, W Frank

2013-07-09

The goal of this study was to demonstrate that copeptin levels <14 pmol/L allow ruling out acute myocardial infarction (AMI) when used in combination with cardiac troponin I (cTnI) <99 th percentile and a nondiagnostic electrocardiogram at the time of presentation to the emergency department (ED). Copeptin is secreted from the pituitary early in the course of AMI. This was a 16-site study in 1,967 patients with chest pain presenting to an ED within 6 hours of pain onset. Baseline demographic characteristics and clinical data were collected prospectively. Copeptin levels and a contemporary sensitive cTnI (99 th percentile 40 ng/l; 10% coefficient of variation 0.03 μg/l) were measured in a core laboratory. Patients were followed up for 180 days. The primary outcome was diagnosis of AMI. Final diagnoses were adjudicated by 2 independent cardiologists blinded to copeptin results. AMI was the final diagnosis in 156 patients (7.9%). A negative copeptin and cTnI at baseline ruled out AMI for 58% of patients, with a negative predictive value of 99.2% (95% confidence interval: 98.5 to 99.6). AMIs not detected by the initial cTnI alone were picked up with copeptin >14 pmol/l in 23 (72%) of 32 patients. Non-ST-segment elevation myocardial infarctions undetected by cTnI at 0 h were detected with copeptin >14 pmol/l in 10 (53%) of 19 patients. Projected average time-to-decision could be reduced by 43% (from 3.0 h to 1.8 h) by the early rule out of 58% of patients. Both abnormal copeptin and cTnI were predictors of death at 180 days (p < 0.0001 for both; c index 0.784 and 0.800, respectively). Both were independent of age and each other and provided additional predictive value (all p < 0.0001). Adding copeptin to cTnI allowed safe rule out of AMI with a negative predictive value >99% in patients presenting with suspected acute coronary syndromes. This combination has the potential to rule out AMI in 58% of patients without serial blood draws. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

[Comparison of two kinds of artificial tears on the dry eye after phacoemulsification].

PubMed

You, R; Wang, J; Han, Y; Liu, L J; Wang, W Y

2017-06-11

Objective: To compare the curative effect of two different artificial tears on dry eye after phacoemulsification. Methods: Prospective randomized controlled clinical trial. From March to June in 2012, 102 patients (102 eyes) with age-related cataract were treated with phacoemulsification at Beijing Tongren Hospital, Capital University of Medical Sciences, and these eyes were randomly divided into blank group (group A ) 32 cases, treatment group 1 (group B) 35 cases and treatment group 2 (group C) 35 cases. Group A was treated with conventional antibiotics. Group B was sodium hyaluronate eye drop, group C was lipid-containing carbomer gel respectively. All patients finished a dry eye questionnaire called Ocular Surface Disease Index (OSDI), and Schimmer's test (SIt), break up time (BUT) and fluorescein staining (FL) tests were performed before surgery and at 7, 30 and 90 days after surgery respectively. Optometry were performed at 90 days after surgery. The χ(2) test was used to analyze the sex of the patients, and the age of the patients was analyzed by one-way ANOVA. Partial data in eye tests and in OSDI does not meet the normal distribution. Therefore, they were analyzed by Kruskal-Wallis H test. If significant difference existed, these data were then analyzed by independent sample Wilcoxon rank sum test. Results: Twelve patients were lost to visit within 3 months. A total of 90 patients were followed up for 90 days. The mean age of all patients was (69.5±9.5) years (46.0-89.0 years), 38 males and 64 females. There were 30 patients in Group A, group B and group C respectively. The prevalence of dry eye was 56. 7% (60/102). There was no significant difference among the three groups ( P> 0.05). OSDI questionnaire showed that OSDI score was significantly different among the three groups at 7, 30 and 90 days after operation ( H =9.89, 55.53, 45.43, P< 0.05). At 30 and 90 days after operation, the median OSDI scores were 12.50 and 10.42 in group C, respectively, which were better than those of group A scores 27.09 and 20. 8 ( Z=- 6.30, -5.94, P< 0.05), and were better than those of group B scores 17.71 and 13. 54 ( Z=- 3.40, -3.52, P< 0.05). At 90 days after operation, the median BUT of B and C treatment groups was 9. 00, which was better than that of group A (4.00). The difference was statistically significant ( H =21.51, P< 0.05), There was no significant difference between group B and group C ( Z=- 0.34, P> 0.05). Conclusion: The treatment of artificial tears with lipid composition in the early stage after phacoemulsification is beneficial to the improvement of postoperative symptoms and signs of dry eye. (Chin J Ophthalmol, 2017, 53: 445-450) .

Overdosing of benzodiazepines/Z-drugs and falls in older adults: Costs for the health system.

PubMed

Díaz-Gutiérrez, María José; Cengotitabengoa, Mónica Martínez; Bermúdez-Ampudia, Cristina; García, Sainza; López, Purificación; Martínez-Cengotitabengoa, Mayte; González-Pinto, Ana

2018-05-08

Benzodiazepines and Z drugs (BZD/Z drugs) are commonly used for the treatment of insomnia and anxiety in older adults for long periods of time. Given the physiological and metabolic characteristics of this group of patients, they are more prone to the adverse effects of these drugs which include falls. The recommendations for use of BZD/Z drugs include the need to adjust the dose and select those with a short half-life, to avoid adverse events, which as well as potentially affecting patient outcome, increase healthcare costs. In this study, we have evaluated the hospital-related costs associated with falls in older adults who use BZD/Z drugs at doses higher than recommended for this age group. We conducted a cross-sectional observational study assessing the BZD/Z drug prescriptions of older adults attending the emergency department after a fall. Cost analysis was performed for cases in which the prescriptions exceeded the maximum recommended dose for this age group. A total of 40.6% of the prescriptions recorded were higher than the defined daily dose in older adults (DDD olderadults ). Of the 57 patients who used BZD/Z drugs at higher-than-recommended doses, 53 experienced trauma and 33 required hospitalisation. The costs associated with emergency department services, tests performed and hospitalisation amounted to €1850/patient. Appropriate dosage of BZD/Z drugs in older adults could reduce both patient suffering and costs for the health system. Copyright © 2017. Published by Elsevier Inc.

Impaired vibrotactile sense in children and adolescents with type 1 diabetes - Signs of peripheral neuropathy.

PubMed

Ising, Erik; Dahlin, Lars B; Elding Larsson, Helena

2018-01-01

To investigate whether multi-frequency vibrometry can identify individuals with elevated vibration perception thresholds (VPTs), reflecting impaired vibrotactile sense, among children and adolescents with type 1 diabetes. In 72 pediatric patients with type 1 diabetes, VPTs were evaluated for seven frequencies on two sites of the hand, and five frequencies on two sites of the foot. Z-scores, based on previously collected reference data, were calculated. Perception to light touch was investigated using monofilaments. Subjects' characteristics were analyzed in comparison to normal and impaired vibrotactile sense. Subjects' median age, disease duration and age at disease onset were 12.8, 5.3 and 6.9 years, respectively. A total of 13 out of 72 (18%) subjects had impaired vibrotactile sense on at least one foot site. Impaired vibrotactile sense was more common among subjects treated with multiple daily insulin injections (MDI) compared to subjects treated with continuous subcutaneous insulin infusion (CSII) (p = 0.013). Age at disease onset was higher among subjects with impaired vibrotactile sense (p = 0.046). No significant correlations were found with gender, HbA1c or duration of diabetes. Impaired vibrotactile sense, mirroring diabetic peripheral neuropathy, was found in 1/5 of the children and adolescents in the study, and was more common in patients treated with MDI than in subjects treated with CSII.

Nutritional status of children with clinical conditions.

PubMed

Murphy, Alexia J; Hill, Rebecca J; Buntain, Helen; White, Melinda; Brookes, Denise; Davies, Peter S W

2017-06-01

Nutritional status is an important consideration in many pediatric clinical conditions. This paper aimed to examine and compare the nutritional status, represented by body cell mass (BCM), of children with cancer, Crohn's disease (CD), cystic fibrosis (CF) and anorexia nervosa (AN). Anthropometry was measured and BCM was calculated from whole body potassium-40 counting in 259 children being treated for clinical conditions (n = 66 cancer; n = 59 AN; n = 75 CF; n = 59 CD) and 108 healthy children. BCM was adjusted for height (BCMI) and expressed as a Z-score relative to laboratory reference data. The CD (-0.80 ± 1.61; p = 0.0001) and AN (-1.13 ± 0.99; p = 0.0001) groups had significantly lower BMI Z-score than the healthy control (0.13 ± 0.75), cancer (0.50 ± 1.40) and CF groups (-0.09 ± 0.95). The cancer (-1.16 ± 1.60; p = 0.0001), CD (-1.13 ± 1.36; p = 0.0001) and AN (-0.97 ± 1.18; p = 0.0001) groups had significantly reduced BCM compared to the healthy control (0.07 ± 0.93) and CF group (0.31 ± 1.08). According to BCMI Z-score, 42.4% of patients with cancer, 41.7% of the patients with CD, 27.1% of patients with AN, and 4.0% of patients with CF were considered malnourished. This study demonstrates that children undergoing treatment for clinical conditions may have alterations in BCM, independent of BMI. Children with cancer, CD and AN all had a high prevalence of malnutrition. Assessment of body composition, not just body size, is vital to understand nutritional status in children with clinical conditions. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

[Health needs of the diabetic user of primary care].

PubMed

Salinas-Martínez, A M; Muñoz-Moreno, F; Barraza de León, A R; Villarreal-Ríos, E; Núñez-Rocha, G M; Garza-Elizondo, M E

2001-01-01

To determine the extent and importance of unmet health needs of type 2 diabetic patients seen at primary care services. A cross-sectional study was conducted in 1999, among rural and urban patients of the Mexican Institute of Social Security, in Nuevo Leon, Mexico. The study population consisted of 256 subjects selected at random, diagnosed with type-II diabetes for at least two years. Data were obtained by interview and complemented with medical charts and provider interviews. Five health areas and four health determinants were evaluated, through Mexican Official Standards and American Diabetes Association standards of medical care for diabetic patients. Analysis consisted of descriptive statistics and estimation of z scores. Health needs were met in 49% of cases. A lower mean of health need satisfaction was found in rural regions as compared to urban regions (36.8% vs. 53.3%, p < .01). Nutrition was the most affected health area (z score = -6), followed by the physical exercise (z score = -1), the metabolic health area (z score = +1), the non-smoking health area (z score = +2), the prevention and early detection of complications health area (z score = +2), and the cognitive health area (z score = +3). The health determinant with the highest requirement corresponded to utilization (z score = -5), followed by resource availability (z score = -4), perceived health need (z score = +4), and access barriers (z score = +6). Health need measurement allows evaluating the effectiveness of existing interventions, in addition to identifying areas with higher unmet health needs. These findings facilitate analysis and decision-making to devise specific health policies and actions directed at improving the quality of care for diabetic patients. The English version of this paper is available at: http://www.insp.mx/salud/index.html

14S,21R-dihydroxy-docosahexaenoic acid treatment enhances mesenchymal stem cell amelioration of renal ischemia/reperfusion injury.

PubMed

Tian, Haibin; Lu, Yan; Shah, Shraddha P; Wang, Quansheng; Hong, Song

2012-05-01

Bone marrow mesenchymal stem cells (MSCs) have shown potential to improve treatment of renal failure. The prohealing functions of MSCs have been found to be enhanced by treatment with the lipid mediator, 14S,21R-dihydroxy-docosa4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21R-diHDHA). In this article, using a murine model of renal ischemia/reperfusion (I/R) injury, we found that treatment with 14S,21R-diHDHA enhanced MSC amelioration of renal I/R injury. Treated MSCs more efficiently inhibited I/R-induced elevation of serum creatinine levels, reduced renal tubular cell death, and inhibited infiltration of neutrophils, macrophages, and dendritic cells in kidneys. Conditioned medium from treated MSCs reduced the generation of tumor necrosis factor-α and reactive oxygen species by macrophages under I/R conditions. Infusion of treated MSCs more efficiently reduced I/R-damage to renal histological structures compared with untreated MSCs (injury score: 7.9±0.4 vs. 10.5±0.5). Treated MSCs were resistant to apoptosis in vivo when transplanted under capsules of I/R-injured kidneys (active caspase-3+ MSCs: 4.2%±2.8% vs. 11.7%±2.4% of control) and in vitro when cultured under I/R conditions. Treatment with 14S,21R-diHDHA promoted viability of MSCs through a mechanism involving activation of the phosphoinositide 3-kinase -Akt signaling pathway. Additionally, treatment of MSCs with 14S,21R-diHDHA promoted secretion of renotrophic hepatocyte growth factor and insulin growth factor-1. Similar results were obtained when 14S,21RdiHDHA was used to inhibit apoptosis of human MSCs (hMSCs) and to increase the generation of renotrophic cytokines from hMSCs. These findings provide a lead for new strategies in the treatment of acute kidney injury with MSCs.

Body mass index and waist circumference are not good surrogate indicators of adiposity in psychogeriatric patients.

PubMed

Camina Martín, M Alicia; De Mateo Silleras, Beatriz; Miján De La Torre, Alberto; Barrera Ortega, Sara; Domínguez Rodríguez, Luis; Redondo Del Río, M Paz

2016-01-01

to assess the utility of body mass index (BMI) and waist circumference (WC) as surrogate indicators of adiposity with respect to the total body fat estimated with bioimpedance analysis in psychogeriatric patients. Anthropometric and hand-to-foot bioimpedance measurements were performed according to standard procedures in a sample of 128 psychogeriatric patients (87 males, 41 females). WC cutoffs proposed by the International Diabetes Federation were used to define abdominal obesity. Z-scores of fat and fat-free mass indices (Z-FMI and Z-FFMI) were calculated. Males with WC values below the cutoff were normal weight, and showed normal levels of FM and low FFM (Z-FFMI below 1.5 SD). Males with WC values above the cutoff were overweight, showed high levels of FM (Z-FMI: 1.34 SD) and a slight depletion of FFM (Z-FFMI: -0.59 SD). In females with WC values below the cutoff, BMI was close to 20 kg/m(2) and both FM and FFM were depleted (Z-FMI: -0.7 SD; Z-FFMI: -1.76 SD). In females with WC above the cutoff, the average BMI was 25.6 kg/m(2) , Z-FMI was 0.48 SD, and Z-FFMI was -0.56 SD. Our results indicate that it is necessary to establish age and sex-specific BMI and WC cutoffs, and also highlight the importance of focusing on body composition analysis to ensure an accurate nutritional diagnosis in older-adults and in psychogeriatric patients. © 2015 Wiley Periodicals, Inc.

You look all right to me: compromised nutritional status in paediatric patients with ulcerative colitis.

PubMed

Hill, Rebecca J; Davies, Peter S W

2013-04-01

It is reported that malnutrition is not a feature of ulcerative colitis (UC). Body mass index (BMI) is frequently used clinically to indicate nutritional status; however, it is a proxy measure at best, and body cell mass (BCM) is a much more accurate representation. The present study aims to investigate BMI in patients with UC in relation to their BCM. A total of 18 patients (7M; 11F) had their nutritional status (BCM) measured using total body potassium⁴⁰ counting every 6 months to yield a total of 77 measurements. BCM measurements were adjusted for height and sex, and BMI was calculated as weight/height², with z scores determined for both parameters. Disease activity was determined using the Pediatric Ulcerative Colitis Activity Index. Mean (±SD) height, weight, BMI, and BCM z scores were 0.39 (0.96), 0.20 (1.08), -0.05 (1.18), and -0.74 (1.41), respectively. No correlation was found between BMI and BCM z scores, and these z scores were significantly different (P=0.02), particularly in the moderate/severe disease activity group (P=0.01). Mean BCM z scores were -0.69 (1.65) of a z score below BMI z scores. Furthermore, where BMI z scores showed no relation to disease activity and no differences between disease activity categories, BCM z scores were significantly negatively correlated (r=-0.32, P=0.01), with significantly lower scores found in the moderate/severe group (P=0.01). Simply calculating BMI in patients with UC does not give adequate information regarding nutritional status, and more accurate, yet easily accessible "bedside" techniques need to be determined to improve patient care.

Religion, Spirituality, and Physical Health in Cancer Patients: A Meta-Analysis

PubMed Central

Jim, Heather S.L.; Pustejovsky, James; Park, Crystal L.; Danhauer, Suzanne C.; Sherman, Allen C.; Fitchett, George; Merluzzi, Thomas V.; Munoz, Alexis R.; George, Login; Snyder, Mallory A.; Salsman, John M.

2015-01-01

Background Whereas religion/spirituality (R/S) is important in its own right for many cancer patients, a large body of research has examined whether R/S is also associated with better physical health outcomes. This literature has been characterized by heterogeneity in sample composition, measures of R/S, and measures of physical health. In an effort to synthesize previous findings, we conducted a meta-analysis of the relationship between R/S and patient-reported physical health in cancer patients. Methods A search of PubMed, PsycInfo, CINAHL, and Cochrane Library yielded 2,073 abstracts, which were independently evaluated by pairs of raters. Meta-analysis was conducted on 497 effect sizes from 101 unique samples encompassing over 32,000 adult cancer patients. R/S measures were categorized into affective, behavioral, cognitive, and ‘other’ dimensions. Physical health measures were categorized into physical well-being, functional well-being, and physical symptoms. Average estimated correlations (Fisher's z) were calculated using generalized estimating equations with robust variance estimation. Results Overall R/S was associated with overall physical health (z=.153, p<.001); this relationship was not moderated by sociodemographic or clinical variables. Affective R/S was associated with physical well-being (z=.167, p<.001), functional well-being (z=.343, p<.001), and physical symptoms (z=.282, p<.001). Cognitive R/S was associated with physical well-being (z=.079, p<.05) and functional well-being (z=.090, p<.01). ‘Other’ R/S was associated with functional well-being (z=.100, p<.05). Conclusions Results of the current meta-analysis suggest that greater R/S is associated with better patient-reported physical health. These results underscore the importance of attending to patients’ religious and spiritual needs as part of comprehensive cancer care. PMID:26258868

[Aortic root dilatation rate in pediatric patients with Marfan syndrome treated with losartan].

PubMed

Mariucci, Elisabetta; Guidarini, Marta; Donti, Andrea; Lovato, Luigi; Wischmeijer, Anita; Angeli, Emanuela; Gargiulo, Gaetano D; Picchio, Fernando M; Bonvicini, Marco

2015-12-01

Medical therapy with angiotensin II receptor blockers/angiotensin-converting enzyme inhibitors and/or beta-blockers was reported to reduce aortic root dilatation rates in pediatric patients with Marfan syndrome. No data are available in the literature on losartan effects after 3 years of therapy. The aim of our study was to establish whether losartan reduces aortic root dilatation rates in pediatric patients with Marfan syndrome in the mid and long term. This is a retrospective analysis of 38 pediatric patients with Marfan syndrome followed at the Marfan Clinic of S. Orsola-Malpighi Hospital of the University of Bologna (Italy). Aortic diameters were measured at sinuses of Valsalva and proximal ascending aorta with transthoracic echocardiography. After a mean follow-up of 4.5 ± 2.5 years (range 2-9 years), aortic root z score at sinuses of Valsalva and proximal ascending aorta remained stable. The average annual rate of change in aortic root z score was -0.1 ± 0.4 and 0 ± 0.3 at sinuses of Valsalva and proximal ascending aorta, respectively. The mean dose of losartan was 0.7 ± 0.3 mg/kg/day. Three patients were non-responders, probably because of late beginning or low dose of therapy. Eight patients underwent cardiac surgery (aortic root surgery in 5 and mitral valve repair in 3), all of them started losartan later in life. Despite the retrospective design of the study and the small sample size, a beneficial effect of losartan therapy was observed in pediatric patients with Marfan syndrome in the mid and long term. Late beginning or low doses of losartan can turn off the effects of therapy.

Timeliness of lung cancer care in Victoria: a retrospective cohort study.

PubMed

Evans, Sue M; Earnest, Arul; Bower, Wendy; Senthuren, Meera; McLaughlin, Peta; Stirling, Rob

2016-02-01

To assess factors associated with second-line delays in the management of patients diagnosed with lung cancer. A retrospective cohort study, conducted in six public and two private Victorian hospitals, of 1417 patients aged 18 years or more who were diagnosed between July 2011 and October 2014 with an incident case of lung cancer identified by International Classification of Diseases, 10th revision codes (C34.0-C34.9, Z85.1, Z85.2) on the basis of either a clinical or pathological diagnosis. Time intervals between referral, diagnosis and initial definitive management. The median time from referral to diagnosis was 15 days (interquartile range [IQR], 5-36); from diagnosis to initial definitive management, 30 days (IQR, 6-84); and from referral to initial definitive management, 53 days (IQR, 25-106). Factors that were significantly associated with delay between referral and initial definitive management include declining or not being referred to palliative care (hazard ratio [HR], v patients referred for palliation, 0.73; 95% CI, 0.62-0.86; P < 0.001), and being treated in a public hospital (HR, v patients managed in a private hospital, 0.55; 95% CI, 0.48-0.64; P < 0.001). The median time from referral to initial definitive management in public and private hospitals was 61 days (IQR, 35-118) and 30 days (IQR, 13-76) respectively; 48% of patients in public hospitals waited longer than the British National Health Service target of a maximum 62 days between referral and first definitive treatment. There are significant delays at various stages of the patient journey after referral for initial definitive management. Having a greater understanding of these delays will enable strategies to be developed that improve the timeliness of care for patients with lung cancer.

Prefrontal cortex activity during swallowing in dysphagia patients.

PubMed

Lee, Jun; Yamate, Chisato; Taira, Masato; Shinoda, Masamichi; Urata, Kentaro; Maruno, Mitsuru; Ito, Reio; Saito, Hiroto; Gionhaku, Nobuhito; Iinuma, Toshimitsu; Iwata, Koichi

2018-05-24

Prefrontal cortex activity is modulated by flavor and taste stimuli and changes during swallowing. We hypothesized that changes in the modulation of prefrontal cortex activity by flavor and taste were associated with swallowing movement and evaluated brain activity during swallowing in patients with dysphagia. To evaluate prefrontal cortex activity in dysphagia patients during swallowing, change in oxidized hemoglobin (z-score) was measured with near-infrared spectroscopy while dysphagia patients and healthy controls swallowed sweetened/unsweetened and flavored/unflavored jelly. Total z-scores were positive during swallowing of flavored/unsweetened jelly and negative during swallowing of unflavored/sweetened jelly in controls but negative during swallowing of sweetened/unsweetened and flavored/unflavored jelly in dysphagia patients. These findings suggest that taste and flavor during food swallowing are associated with positive and negative z-scores, respectively. Change in negative and positive z-scores may be useful in evaluating brain activity of dysphagia patients during swallowing of sweetened and unsweetened food.

Monitoring therapeutic response of human ovarian cancer to trastuzumab by SPECT imaging with (99m)Tc-peptide-Z(HER2:342).

PubMed

Zhang, Jingmian; Zhao, Xinming; Wang, Shijie; Wang, Na; Han, Jingya; Jia, Lizhuo; Ren, Xiuchun

2015-06-01

Patients with human epidermal growth factor receptor 2 (HER2)-positive cancer are candidates for treatment with the anti-HER2 antibody trastuzumab. How to systemically assess tumor HER2 expression and identifying appropriate use of anti-HER2 therapies by noninvasive imaging in vivo is an urgent issue. The purpose of this study was to evaluate SPECT imaging of (99m)Tc-Gly-(D)Ala-Gly-Gly-Z(HER2:342) ((99m)Tc-peptide-Z(HER2:342)) for monitoring therapeutic response to trastuzumab in nude mice bearing HER2-positive SKOV-3 xenografts. Nude mice bearing HER2-positive SKOV-3 xenografts were treated with trastuzumab (treatment group) or saline (control) with ten mice in each group. Mice in trastuzumab-treated group were given trastuzumab intraperiotoneally 4 mg/kg on day 1 and 2 mg/kg on day 8; Mice in control group were given physiological saline on day 1 and 8. Mice body weights and tumour volume were monitored every three days during treatment. In vivo SPECT imaging was performed in mice of the two groups using (99m)Tc-peptide-Z(HER2:342) before treatment, on day 8 and 15 after treatment. Radiolabeled probe uptake in tumours was measured as the ratio of radioactive counts in the tumour to that in the contralateral equivalent region (T/NT). After SPECT imaging on day 15, all the mice were euthanized, biodistribution studies of the SKOV-3 xenografts were carried out to validate the imaging results and HER2 expression of the transplanted tumours was analyzed by immunohistochemistry (IHC). Correlation analysis was performed between T/NT ratios acquired by in vivo SPECT imaging on day 15 and the HER2 level of tumours. In vitro cell binding capacity of (99m)Tc-Z(HER2:342) with SKOV-3 cells in the absence and presence of varying amount of trastuzumab were also conducted in the study. Twenty mice body weight in the two groups gradually increased during treatment, but there was no statistical difference (p > 0.05). Though volumes of SKOV-3 xenografts gradually increased in each group during the treatment, the transplanted tumours in trastuzumab-treated group had a slower growth than those in control group (p < 0.05). Compared with the baseline, the results of in vivo imaging showed that radionuclide accumulation in transplanted tumours reduced significantly in trastuzumab-treated group after treatment (p < 0.05), whereas the tumour accumulation in control group increased after treatment. Biodistribution studies demonstrated that the results corresponded well with in vivo imaging data. Immunohistochemical staining confirmed the significant reduction in tumor HER2 level upon trastuzumab treatment, and there was an obviously positive correlation between T/NT ratios and HER2 level of tumours with correlation coefficient rs = 0.919, p < 0.05. There was no significant significance in cell binding ratios between varying amount of trastuzumab and the absence of trastuzumab (p > 0.05). The early response to trastuzumab in mice bearing SKOV-3 xenografts was successfully monitored by SPECT imaging using (99m)Tc-peptide-Z(HER2:342). This approach may be valuable in monitoring the therapeutic response in HER 2-positive tumours under HER2-targeted therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical Predictors of Residual Sleep Apnea after Weight Loss Therapy in Obese Adolescents.

PubMed

Van Eyck, Annelies; De Guchtenaere, Ann; Van Gaal, Luc; De Backer, Wilfried; Verhulst, Stijn L; Van Hoorenbeeck, Kim

2018-05-01

To investigate clinical factors that could predict residual sleep-disordered breathing (SDB) after weight loss. Obese subjects between 10 and 19 years of age were recruited while entering an in-patient weight loss treatment program. All subjects underwent anthropometry and sleep screening using a portable device at baseline and after 4-6 months of therapy. Sleep and International Study of Asthma and Allergies in Childhood questionnaires were completed at baseline. A total of 339 patients were included. Median age was 15.4 years (10.1-19.1). Body mass index z score at baseline was 2.75 ± 0.42, and 35% of subjects were boys. SDB was present in 32%. After a mean decrease in body mass index z score of 32%, residual SDB was found in 20% of subjects with SDB at baseline. Subjects with more severe SDB (OR 1.18; CI 1.01-1.34; P = .02) and respiratory allergies (OR 7.85; CI 1.20-51.39; P = .03) were at higher risk of developing residual SDB, unlike age, sex, and anthropometric variables. Weight loss was successful for treating SDB in 80% of patients. More severe SDB and the presence of respiratory allergies at baseline were associated with a higher risk of residual SDB after weight loss. Copyright © 2017 Elsevier Inc. All rights reserved.

Pituitary iron and volume imaging in healthy controls.

PubMed

Noetzli, L J; Panigrahy, A; Hyderi, A; Dongelyan, A; Coates, T D; Wood, J C

2012-02-01

Patients with transfusional iron overload develop iron deposits in the pituitary gland, which are associated with volume loss and HH. The purpose of this study was to characterize R2 and volumetric data in a healthy population for diagnostic use in patients with transfusional iron overload. One hundred healthy controls without iron overload between the ages of 2 and 48 were recruited to have MR imaging of the brain to assess their pituitary R2 and volume. Pituitary R2 was assessed with a 8-echo spin-echo sequence, and pituitary volumes, by a 3D spoiled gradient-echo sequence with 1-mm(3) resolution. A 2-component continuous piecewise linear approximation was used for creating volumetric and R2 nomograms. Equations were generated from regression relationships for convenient z-score calculation. Pituitary R2 rose weakly with age (r(2) = 0.19, P < .0001). Anterior and total pituitary volumes increased steadily up to 18 years of age, after which volume slightly decreased. Females had larger pituitary glands, most likely representing their larger lactotroph population. From these data, a clinician can calculate the z scores for R2 and pituitary volume in patients with iron overload. Normal ranges are well-differentiated from values previously associated with endocrine disease in transfusional siderosis; this finding suggests that preclinical iron overload can be recognized and appropriately treated.

Hemocompatibility and cytocompatibility of pristine and plasma-treated silver-zeolite-chitosan composites

NASA Astrophysics Data System (ADS)

Taaca, Kathrina Lois M.; Vasquez, Magdaleno R.

2018-02-01

Silver-exchanged zeolite-chitosan (AgZ-Ch) composites with varying AgZ content were prepared by solvent casting and modified under argon (Ar) plasma excited by a 13.56 MHz radio frequency (RF) power source. Silver (Ag) was successfully incorporated in a natural zeolite host without losing its antibacterial activity against Escherichia coli and Staphylococcus aureus. The AgZ particles were incorporated into a chitosan matrix without making significant changes in the matrix structure. The composites also exhibited antibacterial sensitivity due to the inclusion of AgZ. Plasma treatment enhanced the surface wettability of polar and nonpolar test liquids of the composites. The average increase in total surface free energy after treatment was around 49% with the polar component having a significant change. Cytocompatibility tests showed at least 87% cell viability for pristine and plasma-treated composites comparable with supplemented RPMI as positive control. Hemocompatibility tests revealed that pristine composites does not promote hemolysis and the blood clotting ability is less than 10 min. Coupled with antibacterial property, the fabricated composites have promising biomedical applications.

Exhaled gases online measurements for esophageal cancer patients and healthy people by proton transfer reaction mass spectrometry.

PubMed

Zou, Xue; Zhou, Wenzhao; Lu, Yan; Shen, Chengyin; Hu, Zongtao; Wang, Hongzhi; Jiang, Haihe; Chu, Yannan

2016-11-01

Esophageal cancer is a prevalent malignancy. There is a considerable demand for developing a fast and noninvasive method to screen out the suspect esophageal cancer patients who may undergo further clinical diagnosis. The exhaled breathes from 29 esophageal cancer patients and 57 healthy people were directly measured using our home-made proton transfer reaction mass spectrometer (PTR-MS). Mann-Whitney U test and stepwise discriminant analysis were applied to identify the ions in the breath mass spectral data which can distinguish cancer cohort from healthy group. Receiver operating characteristics (ROC) analysis was also performed. Seven kinds of ions in the breath mass spectrum, viz., m/z 136, m/z 34, m/z 63, m/z 27, m/z 95, m/z 107 and m/z 45, have been found to distinguish between the esophageal cancer patients and healthy people with a sensitivity of 86.2% and a specificity of 89.5%, respectively. Compared with that from the healthy people, the breath mass spectra from esophageal cancer patients show that the mediant intensities of five kinds of ions were decrease and the rest two kinds of ions were increase. ROC analysis gave the area under the curve (AUC) of 0.943. This pilot study shows that the ionic characteristics of exhaled VOCs detected by PTR-MS may be used to differentiate between the esophageal cancer patients and the healthy people. Although the breath tests for more patients are needed to confirm such results, the present work indicates that the PTR-MS may be a promising method in the esophageal cancer screening. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Automated Text Messaging as an Adjunct to Cognitive Behavioral Therapy for Depression: A Clinical Trial.

PubMed

Aguilera, Adrian; Bruehlman-Senecal, Emma; Demasi, Orianna; Avila, Patricia

2017-05-08

Cognitive Behavioral Therapy (CBT) for depression is efficacious, but effectiveness is limited when implemented in low-income settings due to engagement difficulties including nonadherence with skill-building homework and early discontinuation of treatment. Automated messaging can be used in clinical settings to increase dosage of depression treatment and encourage sustained engagement with psychotherapy. The aim of this study was to test whether a text messaging adjunct (mood monitoring text messages, treatment-related text messages, and a clinician dashboard to display patient data) increases engagement and improves clinical outcomes in a group CBT treatment for depression. Specifically, we aim to assess whether the text messaging adjunct led to an increase in group therapy sessions attended, an increase in duration of therapy attended, and reductions in Patient Health Questionnaire-9 item (PHQ-9) symptoms compared with the control condition of standard group CBT in a sample of low-income Spanish speaking Latino patients. Patients in an outpatient behavioral health clinic were assigned to standard group CBT for depression (control condition; n=40) or the same treatment with the addition of a text messaging adjunct (n=45). The adjunct consisted of a daily mood monitoring message, a daily message reiterating the theme of that week's content, and medication and appointment reminders. Mood data and qualitative responses were sent to a Web-based platform (HealthySMS) for review by the therapist and displayed in session as a tool for teaching CBT skills. Intent-to-treat analyses on therapy attendance during 16 sessions of weekly therapy found that patients assigned to the text messaging adjunct stayed in therapy significantly longer (median of 13.5 weeks before dropping out) than patients assigned to the control condition (median of 3 weeks before dropping out; Wilcoxon-Mann-Whitney z=-2.21, P=.03). Patients assigned to the text messaging adjunct also generally attended more sessions (median=6 sessions) during this period than patients assigned to the control condition (median =2.5 sessions), but the effect was not significant (Wilcoxon-Mann-Whitney z=-1.65, P=.10). Both patients assigned to the text messaging adjunct (B=-.29, 95% CI -0.38 to -0.19, z=-5.80, P<.001) and patients assigned to the control conditions (B=-.20, 95% CI -0.32 to -0.07, z=-3.12, P=.002) experienced significant decreases in depressive symptom severity over the course of treatment; however, the conditions did not significantly differ in their degree of symptom reduction. This study provides support for automated text messaging as a tool to sustain engagement in CBT for depression over time. There were no differences in depression outcomes between conditions, but this may be influenced by low follow-up rates of patients who dropped out of treatment. ©Adrian Aguilera, Emma Bruehlman-Senecal, Orianna Demasi, Patricia Avila. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 08.05.2017.

Automated Text Messaging as an Adjunct to Cognitive Behavioral Therapy for Depression: A Clinical Trial

PubMed Central

Bruehlman-Senecal, Emma; Demasi, Orianna; Avila, Patricia

2017-01-01

Background Cognitive Behavioral Therapy (CBT) for depression is efficacious, but effectiveness is limited when implemented in low-income settings due to engagement difficulties including nonadherence with skill-building homework and early discontinuation of treatment. Automated messaging can be used in clinical settings to increase dosage of depression treatment and encourage sustained engagement with psychotherapy. Objectives The aim of this study was to test whether a text messaging adjunct (mood monitoring text messages, treatment-related text messages, and a clinician dashboard to display patient data) increases engagement and improves clinical outcomes in a group CBT treatment for depression. Specifically, we aim to assess whether the text messaging adjunct led to an increase in group therapy sessions attended, an increase in duration of therapy attended, and reductions in Patient Health Questionnaire-9 item (PHQ-9) symptoms compared with the control condition of standard group CBT in a sample of low-income Spanish speaking Latino patients. Methods Patients in an outpatient behavioral health clinic were assigned to standard group CBT for depression (control condition; n=40) or the same treatment with the addition of a text messaging adjunct (n=45). The adjunct consisted of a daily mood monitoring message, a daily message reiterating the theme of that week’s content, and medication and appointment reminders. Mood data and qualitative responses were sent to a Web-based platform (HealthySMS) for review by the therapist and displayed in session as a tool for teaching CBT skills. Results Intent-to-treat analyses on therapy attendance during 16 sessions of weekly therapy found that patients assigned to the text messaging adjunct stayed in therapy significantly longer (median of 13.5 weeks before dropping out) than patients assigned to the control condition (median of 3 weeks before dropping out; Wilcoxon-Mann-Whitney z=−2.21, P=.03). Patients assigned to the text messaging adjunct also generally attended more sessions (median=6 sessions) during this period than patients assigned to the control condition (median =2.5 sessions), but the effect was not significant (Wilcoxon-Mann-Whitney z=−1.65, P=.10). Both patients assigned to the text messaging adjunct (B=−.29, 95% CI −0.38 to −0.19, z=−5.80, P<.001) and patients assigned to the control conditions (B=−.20, 95% CI −0.32 to −0.07, z=−3.12, P=.002) experienced significant decreases in depressive symptom severity over the course of treatment; however, the conditions did not significantly differ in their degree of symptom reduction. Conclusions This study provides support for automated text messaging as a tool to sustain engagement in CBT for depression over time. There were no differences in depression outcomes between conditions, but this may be influenced by low follow-up rates of patients who dropped out of treatment. PMID:28483742

[INDIVIDUAL EVALUATION OF LORETA ABNORMALITIES IN IDIOPATHIC GENERALIZED EPILEPSY].

PubMed

Clemens, Béla; Puskás, Szilvia; Besenyei, Mónika; Kondákor, István; Hollódy, Katalin; Fogarasi, Andrós; Bense, Katalin; Emri, Miklós; Opposits Gábor; Kovács, Noémi Zsuzsanna; Fekete, István

2016-03-30

Contemporary neuroimaging methods disclosed structural and functional cerebral abnormalities in idiopathic generalized epilepsies (IGEs). However, individual electrical (EEG) abnormalities have not been evaluated yet in IGE patients. IGE patients were investigated in the drug-free condition and after 3-6 month of antiepileptic treatment. To estimate the reproducibility of qEEG variables a retrospective recruited cohort of IGE patients was investigated. 19-channel resting state EEG activity was recorded. For each patient a total of 2 minutes EEG activity was analyzed by LORETA (Low Resolution Electromagnetic Tomography). Raw LORETA values were Z-transformed and projected to a MRI template. Z-values outside within the [+3Z] to [-3Z] range were labelled as statistically abnormal. 1. In drug-free condition, 41-50% of IGE patients showed abnormal LORETA values. 2. Abnormal LORETA findings showed great inter-individual variability. 3. Most abnormal LORETA-findings were symmetrical. 4. Most maximum Z-values were localized to frontal or temporal cortex. 5. Succesfull treatment was mostly coupled with disappearence of LORETA-abnormality, persistent seizures were accompanied by persistent LORETA abnormality. 1. LORETA abnormalities detected in the untreated condition reflect seizure-generating property of the cortex in IGE patients. 2. Maximum LORETA-Z abnormalities were topographically congruent with structural abnormalities reported by other research groups. 3. LORETA might help to investigate drug effects at the whole-brain level.

Low D4Z4 copy number and gender difference in Korean patients with facioscapulohumeral muscular dystrophy type 1.

PubMed

Park, Hyung Jun; Hong, Ji-Man; Lee, Jung Hwan; Lee, Hyung Seok; Shin, Ha Young; Kim, Seung Min; Ki, Chang-Seok; Lee, Ji Hyun; Choi, Young-Chul

2015-11-01

The objective of this study was to investigate the clinical and genetic features of Korean patients with facioscapulohumeral muscular dystrophy type 1 (FSHD), and assessed the impact of molecular defects on phenotypic expression. We enrolled 104 FSHD patients from 87 unrelated Korean families with D4Z4 repeat array of less than 11 copies on 4q35. Sixty-one men and forty-three women were enrolled. Median D4Z4 copy number was 4 units and 99 (95%) Korean patients with FSHD carried 1-6 units. The median age at symptom onset was 13 [interquartile range: 8-17] years old. In 100 symptomatic patients, muscle weakness began in facial muscles in 58 patients, shoulder-girdle muscles in 37, and pelvic-girdle muscles in 5. Disease severity was significantly correlated with D4Z4 copy number. In addition, women were more severely affected than men even though there were no differences in age at examination or in D4Z4 copy number between the two genders. This gender difference among Korean patients was the opposite of analysis on individuals of European ancestry. In conclusion, the present study demonstrated the new diagnostic threshold for FSHD in Koreans based on the D4Z4 repeat array size distribution from 1 to 6 units and expanded the clinical spectrum. Copyright © 2015 Elsevier B.V. All rights reserved.

Therapeutic Effects of Sodium Hyaluronate on Ocular Surface Damage Induced by Benzalkonium Chloride Preserved Anti-glaucoma Medications

PubMed Central

Liu, Xing; Yu, Fen-Fen; Zhong, Yi-Min; Guo, Xin-Xing; Mao, Zhen

2015-01-01

Background: Long-term use of benzalkonium chloride (BAC)-preserved drugs is often associated with ocular surface toxicity. Ocular surface symptoms had a substantial impact on the glaucoma patients’ quality of life and compliance. This study aimed to investigate the effects of sodium hyaluronate (SH) on ocular surface toxicity induced by BAC-preserved anti-glaucoma medications treatment. Methods: Fifty-eight patients (101 eyes), who received topical BAC-preserved anti-glaucoma medications treatment and met the severe dry eye criteria, were included in the analysis. All patients were maintained the original topical anti-glaucoma treatment. In the SH-treated group (56 eyes), unpreserved 0.3% SH eye drops were administered with 3 times daily for 90 days. In the control group (55 eyes), phosphate-buffered saline were administered with 3 times daily for 90 days. Ocular Surface Disease Index (OSDI) questionnaire, break-up time (BUT) test, corneal fluorescein staining, corneal and conjunctival rose Bengal staining, Schirmer test, and conjunctiva impression cytology were performed sequentially on days 0 and 91. Results: Compared with the control group, SH-treated group showed decrease in OSDI scores (Kruskal-Wallis test: H = 38.668, P < 0.001), fluorescein and rose Bengal scores (Wilcoxon signed-ranks test: z = −3.843, P < 0.001, and z = −3.508, P < 0.001, respectively), increase in tear film BUT (t-test: t = −10.994, P < 0.001) and aqueous tear production (t-test: t = −10.328, P < 0.001) on day 91. The goblet cell density was increased (t-test: t = −9.981, P < 0.001), and the morphology of the conjunctival epithelium were also improved after SH treatment. Conclusions: SH significantly improved both symptoms and signs of ocular surface damage in patients with BAC-preserved anti-glaucoma medications treatment. SH could be proposed as a new attempt to reduce ocular surface toxicity, and alleviate symptoms of ocular surface damage in BAC-preserved anti-glaucoma medications treatment. PMID:26365960

Africa's largest long-lasting insecticide-treated net producer: lessons from A to Z Textiles

PubMed Central

2010-01-01

Background Field trials have demonstrated the efficacy of insecticide-treated nets, and the WHO has recently endorsed a shift toward Long-Lasting Insecticide Treated nets (LLINs) due to factors such as reduced distribution costs. However, the need for LLINs poses several challenges. Is it possible to manufacture LLINs in large quantities in the African continent, where malaria is most endemic? When production is located in low-income countries, what role is played by local funding and employment, scaling up manufacturing, and partnerships? What factors influence availability and pricing? Discussion A case study of A to Z Textiles was undertaken to answer the question of how large-scale production of LLINs can occur in a low income setting. One of the largest sources of bed nets for Africa, A to Z Textiles is Africa-based, and its Tanzanian operations have a production capacity of 30 million LLINs per year, along with full WHO recommendation for its nets. Our analysis is based on semi-structured interviews with key informants familiar with A to Z, site visits in Tanzania, and literature reviews. This paper discusses the history and current status of A to Z Textiles, identifies the factors that led to its success, and suggests policy considerations that could support similar initiatives in the future. Local funding, scaling up manufacturing, technology transfer, and partnerships all played important roles in A to Z’s ascent, as did perceived benefits of local employment and capacity-building. Regulatory issues and procurement rules acted as barriers. A to Z cost-effectively manufactures high-quality LLINs where malaria is most endemic. Summary With a production capacity of 30 million LLINs per year, and full WHOPES (WHO Pesticide Evaluation Scheme) certification, A to Z Textiles demonstrates how key health goods can be successfully produced in the low-income countries that use them. Its example may be instructive and of high interest to readers in the malaria community, especially in developing countries, and to those who wish to support or partner with efforts by developing countries to build their health innovation capacity. PMID:21144077

Predicting Coronary Artery Aneurysms in Kawasaki Disease at a North American Center: An Assessment of Baseline z Scores.

PubMed

Son, Mary Beth F; Gauvreau, Kimberlee; Kim, Susan; Tang, Alexander; Dedeoglu, Fatma; Fulton, David R; Lo, Mindy S; Baker, Annette L; Sundel, Robert P; Newburger, Jane W

2017-05-31

Accurate risk prediction of coronary artery aneurysms (CAAs) in North American children with Kawasaki disease remains a clinical challenge. We sought to determine the predictive utility of baseline coronary dimensions adjusted for body surface area ( z scores) for future CAAs in Kawasaki disease and explored the extent to which addition of established Japanese risk scores to baseline coronary artery z scores improved discrimination for CAA development. We explored the relationships of CAA with baseline z scores; with Kobayashi, Sano, Egami, and Harada risk scores; and with the combination of baseline z scores and risk scores. We defined CAA as a maximum z score (zMax) ≥2.5 of the left anterior descending or right coronary artery at 4 to 8 weeks of illness. Of 261 patients, 77 patients (29%) had a baseline zMax ≥2.0. CAAs occurred in 15 patients (6%). CAAs were strongly associated with baseline zMax ≥2.0 versus <2.0 (12 [16%] versus 3 [2%], respectively, P <0.001). Baseline zMax ≥2.0 had a C statistic of 0.77, good sensitivity (80%), and excellent negative predictive value (98%). None of the risk scores alone had adequate discrimination. When high-risk status per the Japanese risk scores was added to models containing baseline zMax ≥2.0, none were significantly better than baseline zMax ≥2.0 alone. In a North American center, baseline zMax ≥2.0 in children with Kawasaki disease demonstrated high predictive utility for later development of CAA. Future studies should validate the utility of our findings. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Which goal for fluid therapy during colorectal surgery is followed by the best outcome: near-maximal stroke volume or zero fluid balance?

PubMed

Brandstrup, B; Svendsen, P E; Rasmussen, M; Belhage, B; Rodt, S Å; Hansen, B; Møller, D R; Lundbech, L B; Andersen, N; Berg, V; Thomassen, N; Andersen, S T; Simonsen, L

2012-08-01

We aimed to investigate whether fluid therapy with a goal of near-maximal stroke volume (SV) guided by oesophageal Doppler (ED) monitoring result in a better outcome than that with a goal of maintaining bodyweight (BW) and zero fluid balance in patients undergoing colorectal surgery. In a double-blinded clinical multicentre trial, 150 patients undergoing elective colorectal surgery were randomized to receive fluid therapy after either the goal of near-maximal SV guided by ED (Doppler, D group) or the goal of zero balance and normal BW (Zero balance, Z group). Stratification for laparoscopic and open surgery was performed. The postoperative fluid therapy was similar in the two groups. The primary endpoint was postoperative complications defined and divided into subgroups by protocol. Analysis was performed by intention-to-treat. The follow-up was 30 days. The trial had 85% power to show a difference between the groups. The number of patients undergoing laparoscopic or open surgery and the patient characteristics were similar between the groups. No significant differences between the groups were found for overall, major, minor, cardiopulmonary, or tissue-healing complications (P-values: 0.79; 0.62; 0.97; 0.48; and 0.48, respectively). One patient died in each group. No significant difference was found for the length of hospital stay [median (range) Z: 5.00 (1-61) vs D: 5.00 (2-41); P=0.206]. Goal-directed fluid therapy to near-maximal SV guided by ED adds no extra value to the fluid therapy using zero balance and normal BW in patients undergoing elective colorectal surgery.

The effect of idursulfase on growth in patients with Hunter syndrome: data from the Hunter Outcome Survey (HOS).

PubMed

Jones, Simon A; Parini, Rossella; Harmatz, Paul; Giugliani, Roberto; Fang, Juanzhi; Mendelsohn, Nancy J

2013-05-01

Hunter syndrome (mucopolysaccharidosis type II) is a rare and life-limiting multisystemic disorder with an X-linked recessive pattern of inheritance. Short stature is a prominent feature of this condition. This analysis aimed to investigate the effects of enzyme replacement therapy with idursulfase on growth in patients enrolled in HOS - the Hunter Outcome Survey which is a multinational observational database. As of Jan 2012, height data before treatment were available for 567 of 740 males followed prospectively after HOS entry. Cross-sectional analysis showed that short stature became apparent after approximately 8 years of age; before this, height remained within the normal range. Age-corrected standardized height scores (z-scores) before and after treatment were assessed using piecewise regression model analysis in 133 patients (8-15 years of age at treatment start; data available on ≥ 1 occasion within +/-24 months of treatment start; growth hormone-treated patients excluded). Results showed that the slope after treatment (slope=-0.005) was significantly improved compared with before treatment (slope=-0.043) (difference=0.038, p=0.004). Analysis of covariates (age at treatment start, cognitive involvement, presence of puberty at the start of ERT, mutation type, functional classification), showed a significant influence on growth of mutation type (height deficit in terms of z-scores most pronounced in patients with deletions/large rearrangements/nonsense mutations, p<0.0001) and age (most pronounced in the 12-15-year group, p<0.0001). Cognitive involvement, pubertal status at the start of ERT and functional classification were not related to the growth deficit or response to treatment. In conclusion, the data showed an improvement in growth rate in patients with Hunter syndrome following idursulfase treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

Development and validation of an LC-MS/MS method for the determination of tigecycline in human plasma and cerebrospinal fluid and its application to a pharmacokinetic study.

PubMed

Mei, Shenghui; Luo, Xuying; Li, Xingang; Li, Qian; Huo, Jiping; Yang, Li; Zhu, Leting; Feng, Weixing; Zhou, Jianxin; Shi, Guangzhi; Zhao, Zhigang

2016-12-01

Tigecycline (TGC) is an important antibiotic in treating various drug-resistant bacteria. The dosage regimen for cerebral intraventricular TGC is still unknown. The aim of the study was to develop and validate liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for the determination of TGC in human plasma and cerebrospinal fluid (CSF) to obtain an applicable regimen. The ion transitions under ESI positive model were performed at m/z 586.3 > 513.2 and m/z 595.3 > 514.3 for TGC and d9-TGC internal standard (IS). For plasma and CSF samples, the calibration curve of TGC was linear within the ranges 25-2000 and 250-100,000 ng/mL; the IS normalized matrix effect was within the ranges 96.46-101.06% and 101.13-103.58%, respectively, for all. TGC was stable under all tested conditions. The patient received 1 mg intraventricular and 49 mg intravenous administration of TGC. The AUC 0-12 in plasma and CSF calculated according to our noncompartment model were 4713 and 23,0238 h ng/mL, respectively. Given our findings cerebral intraventricular TGC may be a choice for clinicians to treat drug-resistant Gram-negative bacterial-induced meningitis and the safety and efficacy of this administration route warrants further study. Copyright © 2016 John Wiley & Sons, Ltd.

Transcranial direct current stimulation (tDCS) and its influence on analgesics effectiveness in patients suffering from migraine headache.

PubMed

Przeklasa-Muszyńska, Anna; Kocot-Kępska, Magdalena; Dobrogowski, Jan; Wiatr, Maciej; Mika, Joanna

2017-08-01

Headache is one of the most common conditions troubling nearly 45% of the world's population. Migraine headache itself, being more common among women, affects 7-18% of people. As much as 20-30% of the population report accompanying aura and neurological symptoms. In many cases, migraine headache can be effectively treated with suitably selected pharmacotherapies which include drugs used in symptomatic treatment. Frequent occurrence of the condition is treated with prophylaxis, which often fails. Neuromodulating methods are part of the multidirectional treatment and they may be valuable complement to pharmacotherapy. Our study evaluates the impact of the transcranial direct current stimulation (tDCS) on the consumption of drugs and on pain conditions (frequency, duration, intensity). We recruited 50 patients with migraine headache (30 with aura, 20 without aura) refractory to pharmacological therapy. In 30 patients (18 with aura, 12 without aura) previous unsatisfactory treatment was supplemented with tDCS performed tenfold. 20 patients (12 with aura, 8 without aura) from a control group were treated with pharmacological methods The observation continued for 30 days after the stimulation. After tDCS, a reduction in the consumption of analgesics and triptans was reported. Additionally, we monitored pain intensity decrease during pain episodes, duration of episodes and the number of pain days. The subjective assessment of pain reduction in migraine patients encompassed 36-40% after tDCS much more effective in comparison to group with only pharmacotherapy (10-12.5%). The study suggests that tDCS may be safe and useful clinical tool in migraine prophylaxis and treatment. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Proton therapy for prostate cancer treatment employing online image guidance and an action level threshold.

PubMed

Vargas, Carlos; Falchook, Aaron; Indelicato, Daniel; Yeung, Anamaria; Henderson, Randall; Olivier, Kenneth; Keole, Sameer; Williams, Christopher; Li, Zuofeng; Palta, Jatinder

2009-04-01

The ability to determine the accuracy of the final prostate position within a determined action level threshold for image-guided proton therapy is unclear. Three thousand one hundred ten images for 20 consecutive patients treated in 1 of our 3 proton prostate protocols from February to May of 2007 were analyzed. Daily kV images and patient repositioning were performed employing an action-level threshold (ALT) of > or = 2.5 mm for each beam. Isocentric orthogonal x-rays were obtained, and prostate position was defined via 3 gold markers for each patient in the 3 axes. To achieve and confirm our action level threshold, an average of 2 x-rays sets (median 2; range, 0-4) was taken daily for each patient. Based on our ALT, we made no corrections in 8.7% (range, 0%-54%), 1 correction in 82% (41%-98%), and 2 to 3 corrections in 9% (0-27%). No patient needed 4 or more corrections. All patients were treated with a confirmed error of < 2.5 mm for every beam delivered. After all corrections, the mean and standard deviations were: anterior-posterior (z): 0.003 +/- 0.094 cm; superior-inferior (y): 0.028 +/- 0.073 cm; and right-left (x) -0.013 +/- 0.08 cm. It is feasible to limit all final prostate positions to less than 2.5 mm employing an action level image-guided radiation therapy (IGRT) process. The residual errors after corrections were very small.

Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)

PubMed Central

Hirst, Jennifer; Madeo, Marianna; Smets, Katrien; Edgar, James R.; Schols, Ludger; Li, Jun; Yarrow, Anna; Deconinck, Tine; Baets, Jonathan; Van Aken, Elisabeth; De Bleecker, Jan; Datiles, Manuel B.; Roda, Ricardo H.; Liepert, Joachim; Züchner, Stephan; Mariotti, Caterina; De Jonghe, Peter; Blackstone, Craig

2016-01-01

Objective: Biallelic mutations in the AP5Z1 gene encoding the AP-5 ζ subunit have been described in a small number of patients with hereditary spastic paraplegia (HSP) (SPG48); we sought to define genotype–phenotype correlations in patients with homozygous or compound heterozygous sequence variants predicted to be deleterious. Methods: We performed clinical, radiologic, and pathologic studies in 6 patients with biallelic mutations in AP5Z1. Results: In 4 of the 6 patients, there was complete loss of AP-5 ζ protein. Clinical features encompassed not only prominent spastic paraparesis but also sensory and motor neuropathy, ataxia, dystonia, myoclonus, and parkinsonism. Skin fibroblasts from affected patients tested positive for periodic acid Schiff and autofluorescent storage material, while electron microscopic analysis demonstrated lamellar storage material consistent with abnormal storage of lysosomal material. Conclusions: Our findings expand the spectrum of AP5Z1-associated neurodegenerative disorders and point to clinical and pathophysiologic overlap between autosomal recessive forms of HSP and lysosomal storage disorders. PMID:27606357

ACE Phenotyping as a Guide Toward Personalized Therapy With ACE Inhibitors.

PubMed

Danilov, Sergei M; Tovsky, Stan I; Schwartz, David E; Dull, Randal O

2017-07-01

Angiotensin-converting enzyme (ACE) inhibitors (ACEI) are widely used in the management of cardiovascular diseases but with significant interindividual variability in the patient's response. To investigate whether interindividual variability in the response to ACE inhibitors is explained by the "ACE phenotype"-for example, variability in plasma ACE concentration, activity, and conformation and/or the degree of ACE inhibition in each individual. The ACE phenotype was determined in plasma of 14 patients with hypertension treated chronically for 4 weeks with 40 mg enalapril (E) or 20 mg E + 16 mg candesartan (EC) and in 20 patients with hypertension treated acutely with a single dose (20 mg) of E with or without pretreatment with hydrochlorothiazide. The ACE phenotyping included (1) plasma ACE concentration; (2) ACE activity (with 2 substrates: Hip-His-Leu and Z-Phe-His-Leu and calculation of their ratio); (3) detection of ACE inhibitors in patient's blood (indicator of patient compliance) and the degree of ACE inhibition (ie, adherence); and (4) ACE conformation. Enalapril reduced systolic and diastolic blood pressure in most patients; however, 20% of patients were considered nonresponders. Chronic treatment results in 40% increase in serum ACE concentrations, with the exception of 1 patient. There was a trend toward better response to ACEI among patients who had a higher plasma ACE concentration. Due to the fact that "20% of patients do not respond to ACEI by blood pressure drop," the initial blood ACE level could not be a predictor of blood pressure reduction in an individual patient. However, ACE phenotyping provides important information about conformational and kinetic changes in ACE of individual patients, and this could be a reason for resistance to ACE inhibitors in some nonresponders.

Periorbital burns – a 6 year review of management and outcome.

PubMed

Fitzgerald O'Connor, Edmund; Frew, Q; Din, A; Pleat, J; Ashraff, S; Ghazi-Nouri, S; El-Muttardi, N; Philp, B; Dziewulski, P

2015-05-01

Periorbital burns are an infrequent but potentially devastating injury. This study aimed to elucidate the spectrum of such injuries presenting to a UK burns centre and the outcome achieved in the cases requiring periorbital reconstruction for the restoration of function and form. Patients admitted to a UK regional burns centre between January 2005 and January 2011 with periorbital burns were identified from the Patient Administration System (PAS), theatre logs and the International Burns Injury database (IBID). Multiple parameters were assessed using patient notes, ITU and hospital image databases. Over 6 years, 167 patients with facial burns requiring surgery were treated, including 103 patients with eyelid burns. The mean burn size was 33% total body surface area. The eyelid burn depth varied; 67% superficial partial thickness, 17% deep dermal and 16% full thickness. Two patients lost complete vision in one eye, one patient underwent amniotic membrane grafting. In total 16 patients required periorbital reconstruction to maintain eye closure, with 1.8 operations on average per patient. Acute surgery was required in 11 patients, whilst late intervention (>3 months) was needed in 5, 2 patients had both acute and delayed surgery. Of the 5 late intervention patients 4 were treated with full thickness skin grafts and 1 with a Z plasty. Average time for final reconstruction with delayed surgery was 4.5 months. The goal in management of periorbital burns is preservation of vision, prevention of future complications and restoration of an acceptable aesthetic outcome. Total visual loss is thankfully rare, but early ophthalmology intervention is vital given the evidence of corneal damage as a brief therapeutic window exists. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Cardiopulmonary Function, Exercise Capacity, and Echocardiography Finding of Pediatric Patients With Kawasaki Disease: An Observational Study.

PubMed

Tuan, Sheng-Hui; Li, Min-Hui; Hsu, Miao-Ju; Tsai, Yun-Jeng; Chen, Yin-Han; Liao, Tin-Yun; Lin, Ko-Long

2016-01-01

Coronary artery (CA) abnormalities influence exercise capacity (EC) of patients with Kawasaki disease (KD), and Z-score of CA is a well established method for detecting CA aneurysm. We studied the influence of KD on cardiopulmonary function and EC; meanwhile we analyzed echocardiographic findings of KD patients. We also assessed the correlation between CA Z-score and EC of KD patients to see if CA Z-score of KD patients could reflect EC during exercise.Sixty-three KD patients were recruited as KD group 1 from children (aged 5-18 y) who received transthoracic echocardiographic examinations and symptom-limited treadmill exercise test for regular follow-up of KD from January 2010 to October 2014 in 1 medical center. We then divided KD group 1 into KD group 2 (<5 y, n = 12) and KD group 3 (≥5 y, n = 51) according to time interval between KD onset to when patients received test. Control groups were matched by age, sex, and body mass index. Max-Z of CA was defined as the maximal Z-score of the proximal LCA or RCA by Dalliarre equation or Fuse calculator.All routine parameters measured during standard exercise test were similar between KD and control groups, except that peak rate pressure products (PRPPs) in KD group 1 to 3 were all lower than corresponding control groups significantly (P = 0.010, 0.020, and 0.049, respectively). PRPPs correlated with Max-Z of CA by both equations modest inversely (by Dallaire, P = 0.017, Spearman rho = -0.301; by Fuse, P = 0.014, Spearman rho = -0.309).Our study recruited larger number of KD patients and provided a newer data of EC of KD patients. Our finding suggests that after acute stage of KD, patients could maintain normal cardiorespiratory fitness. Therefore, we believe that it is important to promote cardiovascular health to KD patients and KD patients should exercise as normal peers. However, since KD patients might still have compromised coronary perfusion during exercise, it remains crucial to assess and monitor cardiovascular risk of KD patients. Max-Z of CA correlates with PRPP modest inversely and might be used as a follow-up indicator of CA reserve during exercise after acute stage of KD.

Cardiopulmonary Function, Exercise Capacity, and Echocardiography Finding of Pediatric Patients With Kawasaki Disease

PubMed Central

Tuan, Sheng-Hui; Li, Min-Hui; Hsu, Miao-Ju; Tsai, Yun-Jeng; Chen, Yin-Han; Liao, Tin-Yun; Lin, Ko-Long

2016-01-01

Abstract Coronary artery (CA) abnormalities influence exercise capacity (EC) of patients with Kawasaki disease (KD), and Z-score of CA is a well established method for detecting CA aneurysm. We studied the influence of KD on cardiopulmonary function and EC; meanwhile we analyzed echocardiographic findings of KD patients. We also assessed the correlation between CA Z-score and EC of KD patients to see if CA Z-score of KD patients could reflect EC during exercise. Sixty-three KD patients were recruited as KD group 1 from children (aged 5–18 y) who received transthoracic echocardiographic examinations and symptom-limited treadmill exercise test for regular follow-up of KD from January 2010 to October 2014 in 1 medical center. We then divided KD group 1 into KD group 2 (<5 y, n = 12) and KD group 3 (≥5 y, n = 51) according to time interval between KD onset to when patients received test. Control groups were matched by age, sex, and body mass index. Max-Z of CA was defined as the maximal Z-score of the proximal LCA or RCA by Dalliarre equation or Fuse calculator. All routine parameters measured during standard exercise test were similar between KD and control groups, except that peak rate pressure products (PRPPs) in KD group 1 to 3 were all lower than corresponding control groups significantly (P = 0.010, 0.020, and 0.049, respectively). PRPPs correlated with Max-Z of CA by both equations modest inversely (by Dallaire, P = 0.017, Spearman rho = −0.301; by Fuse, P = 0.014, Spearman rho = −0.309). Our study recruited larger number of KD patients and provided a newer data of EC of KD patients. Our finding suggests that after acute stage of KD, patients could maintain normal cardiorespiratory fitness. Therefore, we believe that it is important to promote cardiovascular health to KD patients and KD patients should exercise as normal peers. However, since KD patients might still have compromised coronary perfusion during exercise, it remains crucial to assess and monitor cardiovascular risk of KD patients. Max-Z of CA correlates with PRPP modest inversely and might be used as a follow-up indicator of CA reserve during exercise after acute stage of KD. PMID:26765431

Natural history of aortic root dilation through young adulthood in a hypermobile Ehlers-Danlos syndrome cohort.

PubMed

Ritter, Alyssa; Atzinger, Carrie; Hays, Brandon; James, Jeanne; Shikany, Amy; Neilson, Derek; Martin, Lisa; Weaver, Kathryn Nicole

2017-06-01

Hypermobile Ehlers-Danlos syndrome (hEDS) is a common inherited connective tissue disorder characterized by joint hypermobility. The natural history of aortic root dilation (AoD), a potential complication of EDS, has not been well characterized in this population. We describe the natural history of aortic root size in a large cohort of patients with hEDS. A cohort of 325 patients with HEDS was identified at Cincinnati Children's Hospital Medical Center (CCHMC), including 163 patients from a previous study. Medical records were reviewed and each participant's height, weight, and aortic dimensions from up to four echocardiograms were documented. Aortic root z-scores were calculated using two established formulas based on age (Boston or Devereux). Overall prevalence of AoD and prevalence by age were calculated and longitudinal regression was performed. The prevalence of AoD with a z-score ≥ 2.0 was 14.2% (46/325) and with a z-score of ≥3.0 was 5.5% (18/325). No significant increases in z-score were seen over time for patients with multiple echocardiograms. Participants under the age of 15 years had an average decline of 0.1 standard deviations (SDs)/year. No significant change was found after 15 of age. Between the ages of 15 and 21 years, Boston z-scores were 0.96 higher than Devereux z-scores. The nearly 1 z-score unit difference between formulas indicates caution prior to diagnosing AoD in patients with hEDS. In light of the low prevalence and lack of progression of AoD, routine echocardiograms may not be warranted for pediatric patients with hEDS. © 2017 Wiley Periodicals, Inc.

Duration of high-dose aspirin therapy does not affect long-term coronary artery outcomes in Kawasaki disease.

PubMed

Migally, Karl; Braunlin, Elizabeth A; Zhang, Lei; Binstadt, Bryce A

2018-05-02

BackgroundHigh-dose aspirin (HDA) is used with intravenous immunoglobulin (IVIg) in Kawasaki disease (KD). Practice regarding HDA varies, and it is unclear whether HDA duration affects the long-term course.MethodsWe retrospectively studied KD patients at our hospital for over 10 years. Patients were categorized as having received HDA for 0, 1-7, or >7 days. Primary outcome was the maximum coronary Z-score at diagnosis and follow-up; secondary outcomes included inflammatory markers.ResultsOne hundred and three patients had HDA duration documented, of which 35 patients had coronary artery abnormalities (CAAs) at diagnosis. There was no difference in demographics or inflammatory markers between the HDA groups, and no difference in HDA duration between patients with or without CAAs. Seventeen patients received no HDA; they had longer illness and defervescence duration before diagnosis, and were less likely to receive IVIg. For CAAs, multivariate regression revealed that HDA duration did not predict the coronary Z-score at 9-15 months. Higher Z-score at diagnosis was associated with higher Z-score at 9-15 months.ConclusionThe only factor associated with coronary Z-score at 9-15 months was the Z-score at diagnosis. At our institution, longer illness and defervescence duration and the lack of IVIg administration were associated with not administering HDA. HDA duration did not affect the clinically relevant outcomes, particularly CAA persistence.Pediatric Research advance online publication, 2 May 2018; doi:10.1038/pr.2018.44.

Risk factors for low bone mineral density in children and adolescents with inflammatory bowel disease.

PubMed

Lopes, Letícia Helena Caldas; Sdepanian, Vera Lucia; Szejnfeld, Vera Lúcia; de Morais, Mauro Batista; Fagundes-Neto, Ulysses

2008-10-01

To evaluate bone mineral density of the lumbar spine in children and adolescents with inflammatory bowel disease, and to identify the clinical risk factors associated with low bone mineral density. Bone mineral density of the lumbar spine was evaluated using dual-energy X-ray absorptiometry (DXA) in 40 patients with inflammatory bowel disease. Patients were 11.8 (SD = 4.1) years old and most of them were male (52.5%). Multiple linear regression analysis was performed to identify potential associations between bone mineral density Z-score and age, height-for-age Z-score, BMI Z-score, cumulative corticosteroid dose in milligrams and in milligrams per kilogram, disease duration, number of relapses, and calcium intake according to the dietary reference intake. Low bone mineral density (Z-score bellow -2) was observed in 25% of patients. Patients with Crohn's disease and ulcerative colitis had equivalent prevalence of low bone mineral density. Multiple linear regression models demonstrated that height-for-age Z-score, BMI Z-score, and cumulative corticosteroid dose in mg had independent effects on BMD, respectively, beta = 0.492 (P = 0.000), beta = 0.460 (P = 0.001), beta = - 0.014 (P = 0.000), and these effects remained significant after adjustments for disease duration, respectively, beta = 0.489 (P = 0.013), beta = 0.467 (P = 0.001), and beta = - 0.005 (P = 0.015). The model accounted for 54.6% of the variability of the BMD Z-score (adjusted R2 = 0.546). The prevalence of low bone mineral density in children and adolescents with inflammatory bowel disease is considerably high and independent risk factors associated with bone mineral density are corticosteroid cumulative dose in milligrams, height-for-age Z-score, and BMI Z-score.

[Molecular-biological properties of the rubella virus strains isolated in St. Petersburg].

PubMed

Buzitskaia, Zh V; Sirotkin, A K; Gudkova, T M; Prochukhanova, A P; Karpov, A V; Tsybalova, L M; Kiselev, O I

2012-01-01

In the surveillance of rubella in the northwest region of Russia samples of nasopharyngeal swabs from 37 patients with rubella, which were treated in the 442nd district military hospital named after Z.P. Solovyov in autumn 2007 were screened for the rubella virus using RK-13 cell line, 22 strains of rubella virus were isolated. Gene sequencing of E1 region of rubella virus isolates was carried out. Rubella virus strains isolated in St. Petersburg during the 2007 outbreak belonged to rubella virus genotype 1E. The morphogenesis of RK-13 cells with formation of replication complexes and enveloped virions of rubella virus was shown.

Prevalence and genetic diversity of torque teno virus in patients with systemic lupus erythematosus in a reference service in Mato Grosso do Sul.

PubMed

Costa, Márcio Reis da; Costa, Izaias Pereira da; Devalle, Sylvie; Castro, Ana Rita Coimbra Motta de; Freitas, Solange Zacalusni

2012-01-01

Recent studies on the torque teno virus (TTV), genus Anellovirus, have allowed formulating the hypothesis that TTV may trigger autoimmune rheumatic diseases or have some pathogenic role in them. To determine the frequency of TTV infection in patients with systemic lupus erythematosus (SLE), the genetic diversity of TTV, the correlation between TTV infection and SLE clinical manifestations, and SLE clinical course and serological profile. Serum samples were obtained from 46 SLE patients treated at the University-Affiliated Hospital of Campo Grande (NHU/FAMED/UFMS), Brazil. For controls, serum samples were obtained from 46 healthy volunteer blood donors. Viral DNA was extracted from samples using the QIAamp DNA Blood Mini Kit (QIAGEN, Hilden, Germany) and amplified using nested PCR. Positivity for TTV was found in 17 (37%) of SLE patients and in only seven (15.2%) of the controls (z test, P = 0.03). There was no correlation between TTV infection, SLE clinical manifestations, SLE clinical course, and the serological profile of the patients evaluated. Further studies on the presence of TTV in SLE patients are required.

Sequential Stenting for Extensive Malignant Airway Stenosis

PubMed Central

Takahama, Makoto; Nakajima, Ryu; Kimura, Michitaka; Tei, Keiko; Yamamoto, Ryoji

2014-01-01

Purpose: Malignant airway stenosis extending from the bronchial bifurcation to the lower lobar orifice was treated with airway stenting. We herein examine the effectiveness of airway stenting for extensive malignant airway stenosis. Methods: Twelve patients with extensive malignant airway stenosis underwent placement of a silicone Dumon Y stent (Novatech, La Ciotat, France) at the tracheal bifurcation and a metallic Spiral Z-stent (Medico’s Hirata, Osaka, Japan) at either distal side of the Y stent. We retrospectively analyzed the therapeutic efficacy of the sequential placement of these silicone and metallic stents in these 12 patients. Results: The primary disease was lung cancer in eight patients, breast cancer in two patients, tracheal cancer in one patient, and thyroid cancer in one patient. The median survival period after airway stent placement was 46 days. The Hugh–Jones classification and performance status improved in nine patients after airway stenting. One patient had prolonged hemoptysis and died of respiratory tract hemorrhage 15 days after the treatment. Conclusion: Because the initial disease was advanced and aggressive, the prognosis after sequential airway stent placement was significantly poor. However, because respiratory distress decreased after the treatment in most patients, this treatment may be acceptable for selected patients with extensive malignant airway stenosis. PMID:25273272

Novel Trisubstituted Benzimidazoles, Targeting Mtb FtsZ, As A New Class of Antitubercular Agents

PubMed Central

Kumar, Kunal; Awasthi, Divya; Lee, Seung-Yub; Zanardi, Ilaria; Ruzsicska, Bela; Knudson, Susan; Tonge, Peter J.; Slayden, Richard A.; Ojima, Iwao

2010-01-01

Libraries of novel trisubstituted benzimidazoles were created through rational drug design. A good number of these benzimidazoles exhibited promising MIC values in the range of 0.5-6 μg/mL (2-15 μM) for their antibacterial activity against Mtb H37Rv strain. Moreover, five of the lead compounds also exhibited excellent activity against clinical Mtb strains with different drug-resistance profiles. All lead compounds do not show appreciable cytotoxicity (IC50 >200 μM) against Vero cells, which inhibit Mtb FtsZ assembly in a dose dependent manner. The two lead compounds unexpectedly showed enhancement of the GTPase activity of Mtb FtsZ. The result strongly suggests that the increased GTPase activity destabilizes FtsZ assembly leading to efficient inhibition of FtsZ polymerization and filament formation. The TEM and SEM analyses of Mtb FtsZ and Mtb cells, respectively, treated with a lead compound strongly suggest that lead benzimidazoles have a novel mechanism of action on the inhibition of Mtb FtsZ assembly and Z-ring formation. PMID:21126020

Novel trisubstituted benzimidazoles, targeting Mtb FtsZ, as a new class of antitubercular agents.

PubMed

Kumar, Kunal; Awasthi, Divya; Lee, Seung-Yub; Zanardi, Ilaria; Ruzsicska, Bela; Knudson, Susan; Tonge, Peter J; Slayden, Richard A; Ojima, Iwao

2011-01-13

Libraries of novel trisubstituted benzimidazoles were created through rational drug design. A good number of these benzimidazoles exhibited promising MIC values in the range of 0.5-6 μg/mL (2-15 μM) for their antibacterial activity against Mtb H37Rv strain. Moreover, five of the lead compounds also exhibited excellent activity against clinical Mtb strains with different drug-resistance profiles. All lead compounds did not show appreciable cytotoxicity (IC(50) > 200 μM) against Vero cells, which inhibited Mtb FtsZ assembly in a dose dependent manner. The two lead compounds unexpectedly showed enhancement of the GTPase activity of Mtb FtsZ. The result strongly suggests that the increased GTPase activity destabilizes FtsZ assembly, leading to efficient inhibition of FtsZ polymerization and filament formation. The TEM and SEM analyses of Mtb FtsZ and Mtb cells, respectively, treated with a lead compound strongly suggest that lead benzimidazoles have a novel mechanism of action on the inhibition of Mtb FtsZ assembly and Z-ring formation.

Bioaccessibility, Cellular Uptake, and Transport of Astaxanthin Isomers and their Antioxidative Effects in Human Intestinal Epithelial Caco-2 Cells.

PubMed

Yang, Cheng; Zhang, Hua; Liu, Ronghua; Zhu, Honghui; Zhang, Lianfu; Tsao, Rong

2017-11-29

The bioaccessibility, bioavailability, and antioxidative activities of three astaxanthin geometric isomers were investigated using an in vitro digestion model and human intestinal Caco-2 cells. This study demonstrated that the trans-cis isomerization of all-E-astaxanthin and the cis-trans isomerization of Z-astaxanthins could happen both during in vitro gastrointestinal digestion and cellular uptake processes. 13Z-Astaxanthin showed higher bioaccessibility than 9Z- and all-E-astaxanthins during in vitro digestion, and 9Z-astaxanthin exhibited higher transport efficiency than all-E- and 13Z-astaxanthins. These might explain why 13Z- and 9Z-astaxanthins are found at higher concentrations in human plasma than all-E-astaxanthin in reported studies. All three astaxanthin isomers were effective in maintaining cellular redox homeostasis as seen in the antioxidant enzyme (CAT, SOD) activities ; 9Z- and 13Z- astaxanthins exhibited a higher protective effect than all-E-astaxanthin against oxidative stress as demonstrated by the lower cellular uptake of Z-astaxanthins and lower secretion and gene expression of the pro-inflammatory cytokine IL-8 in Caco-2 cells treated with H 2 O 2 . We conclude, for the first time, that Z-astaxanthin isomers may play a more important role in preventing oxidative stress induced intestinal diseases.

Evaluation of a Modified Pamidronate Protocol for the Treatment of Osteogenesis Imperfecta.

PubMed

Palomo, Telma; Andrade, Maria C; Peters, Barbara S E; Reis, Fernanda A; Carvalhaes, João Tomás A; Glorieux, Francis H; Rauch, Frank; Lazaretti-Castro, Marise

2016-01-01

Intravenous pamidronate is widely used to treat children with osteogenesis imperfecta (OI). In a well-studied protocol ('standard protocol'), pamidronate is given at a daily dose of 1 mg per kg body weight over 4 h on 3 successive days; infusion cycles are repeated every 4 months. Here, we evaluated renal safety of a simpler protocol for intravenous pamidronate infusions (2 mg per kg body weight given in a single infusion over 2 h, repeated every 4 months; 'modified protocol'). Results of 18 patients with OI types I, III, or IV treated with the modified protocol for 12 months were compared to 18 historic controls, treated with standard protocol. In the modified protocol, mild transient post-infusion increases in serum creatinine were found during each infusion but after 12 months serum creatinine remained similar from baseline [0.40 mg/dl (SD: 0.13)] to the end of the study [0.41 mg/dl (SD: 0.11)] (P = 0.79). The two protocols led to similar changes in serum creatinine during the first pamidronate infusion [modified protocol: +2% (SD: 21%); standard protocol: -3% (SD: 8%); P = 0.32]. Areal lumbar spine bone mineral density Z-scores increased from -2.7 (SD: 1.5) to -1.8 (SD: 1.4) with the modified protocol, and from -4.1 (SD: 1.4) to -3.1 (SD: 1.1) with standard protocol (P = 0.68 for group differences in bone density Z-score changes). The modified pamidronate protocol is safe and may have similar effects on bone density as the standard pamidronate protocol. More studies are needed with longer follow-up to prove anti-fracture efficacy.

A vigilant, hypoxia-regulated heme oxygenase-1 gene vector in the heart limits cardiac injury after ischemia-reperfusion in vivo.

PubMed

Tang, Yao Liang; Qian, Keping; Zhang, Y Clare; Shen, Leping; Phillips, M Ian

2005-12-01

The effect of a cardiac specific, hypoxia-regulated, human heme oxygenase-1 (hHO-1) vector to provide cardioprotection from ischemia-reperfusion injury was assessed. When myocardial ischemia and reperfusion is asymptomatic, the damaging effects are cumulative and patients miss timely treatment. A gene therapy approach that expresses therapeutic genes only when ischemia is experienced is a desirable strategy. We have developed a cardiac-specific, hypoxia-regulated gene therapy "vigilant vector'' system that amplifies cardioprotective gene expression. Vigilant hHO-1 plasmids, LacZ plasmids, or saline (n = 40 per group) were injected into mouse heart 2 days in advance of ischemia-reperfusion injury. Animals were exposed to 60 minutes of ischemia followed by 24 hours of reperfusion. For that term (24 hours) effects, the protein levels of HO-1, inflammatory responses, apoptosis, and infarct size were determined. For long-term (3 week) effects, the left ventricular remodeling and recovery of cardiac function were assessed. Ischemia-reperfusion resulted in a timely overexpression of HO-1 protein. Infarct size at 24 hours after ischemia-reperfusion was significantly reduced in the HO-1-treated animals compared with the LacZ-treated group or saline-treated group (P < .001). The reduction of infarct size was accompanied by a decrease in lipid peroxidant activity, inflammatory cell infiltration, and proapoptotic protein level in ischemia-reperfusion-injured myocardium. The long-term study demonstrated that timely, hypoxia-induced HO-1 overexpression is beneficial in conserving cardiac function and attenuating left ventricle remodelling. The vigilant HO-1 vector provides a protective therapy in the heart for reducing cellular damage during ischemia-reperfusion injury and preserving heart function.

Nitrous oxide reduction genetic potential from the microbial community of an intermittently aerated partial nitritation SBR treating mature landfill leachate.

PubMed

Gabarró, J; Hernández-Del Amo, E; Gich, F; Ruscalleda, M; Balaguer, M D; Colprim, J

2013-12-01

This study investigates the microbial community dynamics in an intermittently aerated partial nitritation (PN) SBR treating landfill leachate, with emphasis to the nosZ encoding gene. PN was successfully achieved and high effluent stability and suitability for a later anammox reactor was ensured. Anoxic feedings allowed denitrifying activity in the reactor. The influent composition influenced the mixed liquor suspended solids concentration leading to variations of specific operational rates. The bacterial community was low diverse due to the stringent conditions in the reactor, and was mostly enriched by members of Betaproteobacteria and Bacteroidetes as determined by 16S rRNA sequencing from excised DGGE melting types. The qPCR analysis for nitrogen cycle-related enzymes (amoA, nirS, nirK and nosZ) demonstrated high amoA enrichment but being nirS the most relatively abundant gene. nosZ was also enriched from the seed sludge. Linear correlation was found mostly between nirS and the organic specific rates. Finally, Bacteroidetes sequenced in this study by 16S rRNA DGGE were not sequenced for nosZ DGGE, indicating that not all denitrifiers deal with complete denitrification. However, nosZ encoding gene bacteria was found during the whole experiment indicating the genetic potential to reduce N2O. Copyright © 2013 Elsevier Ltd. All rights reserved.

Time - A Traveler's Guide

NASA Astrophysics Data System (ADS)

Pickover, Clifford A.

1999-09-01

"Bucky Fuller thought big," Wired magazine recently noted, "Arthur C. Clarke thinks big, but Cliff Pickover outdoes them both." In his newest book, Cliff Pickover outdoes even himself, probing a mystery that has baffled mystics, philosophers, and scientists throughout history--What is the nature of time?In Time: A Traveler's Guide , Pickover takes readers to the forefront of science as he illuminates the most mysterious phenomenon in the universe--time itself. Is time travel possible? Is time real? Does it flow in one direction only? Does it have a beginning and an end? What is eternity? Pickover's book offers a stimulating blend of Chopin, philosophy, Einstein, and modern physics, spiced with diverting side-trips to such topics as the history of clocks, the nature of free will, and the reason gold glitters. Numerous diagrams ensure readers will have no trouble following along.By the time we finish this book, we understand a wide variety of scientific concepts pertaining to time. And most important, we will understand that time travel is, indeed, possible.

The Difference Quantity of Urinary Peptides between Two Groups of Type 2 Diabetic Patients with or without Coronary Artery Disease

PubMed Central

Fu, Guangzhen; Hu, Mei; Chu, Lina; Zhang, Man

2015-01-01

Objectives. We aim to explore urinary biomarkers that could monitor CAD in type 2 diabetic patients. Materials and Methods. Urine samples from two groups, twenty-eight type 2 diabetic patients with coexisting CAD and thirty type 2 diabetic patients without CAD, were purified by MB-WCX and then analyzed by MALDI-TOF-MS. Subsequently, we compared the urinary peptide signatures of the two groups by use of ClinProTools2.1 and evaluated the potential ability of the differently expressed peptides to distinguish type 2 diabetic patients with coexisting CAD from type 2 diabetic patients without CAD by ROC analysis. Finally, the differently expressed peptides were identified by nanoliquid chromatography-tandem mass spectrometry. Results. There were six differently expressed peptides (m/z 1305.2, 1743.9, 2184.9, 2756.1, 3223.2, and 6196.1) between the two groups of subjects, and they were identified as fragments of isoform 1 of fibrinogen alpha chain precursor, prothrombin precursor, and interalpha-trypsin inhibitor heavy chain H4. The diagnostic efficacy of m/z 2756.1 and m/z 3223.2 was better than the other peptides. Area under ROC of the m/z 2756.1, and m/z 3223.2 was 0.98 and 0.93, respectively. Conclusions. These urinary peptides are potential urinary biomarkers for monitoring of type 2 diabetic patients with CAD. PMID:26089891

Liquid chromatography-electrospray mass spectrometry determination of carbamazepine, oxcarbazepine and eight of their metabolites in human plasma.

PubMed

Breton, Hélène; Cociglio, Marylène; Bressolle, Françoise; Peyriere, Hélène; Blayac, Jean Pierre; Hillaire-Buys, Dominique

2005-12-15

Carbamazepine (CBZ) and oxcarbazepine (OXCBZ) are both antiepileptic drugs, which are prescribed as first-line drugs for the treatment of partial and generalized tonic-clonic epileptic seizures. In this paper, a specific and sensitive liquid chromatography-electrospray ionization mass spectrometry method was described for the simultaneous determination of carbamazepine (CBZ), oxcarbazepine (OXCBZ) and eight of their metabolites [CBZ-10,11-epoxide (CBZ-EP), 10,11-dihydro-10,11-trans-dihydroxy-carbamazepine (DiOH-CBZ), 10-hydroxy-10,11-dihydroCBZ (10-OH-CBZ), 2-hydroxycarbamazepine (2-OH-CBZ), 3-hydroxycarbamazepine (3-OH-CBZ), iminostilbene (IM), acridone (AO) and acridine (AI)] in human plasma. The work-up procedure involved a simple precipitation with acetone. Separation of the analytes was achieved within 50 min using a Zorbax eclipse XD8 C8 analytical column. The mobile phase consisted of a mixture of acetonitrile-formate buffer (2 mM, pH 3). Detection was performed using a quadrupole mass spectrometer fitted with an electrospray ion source. Mass spectrometric data were acquired in single ion recording mode at m/z 237 for CBZ, m/z 180 for CBZ-EP and AI, m/z 236 for OXCBZ, m/z 237 for 10-OH-CBZ, m/z 253 for 2-OH-CBZ, 3-OH-CBZ and DiOH-CBZ, m/z 196 for AO and m/z 194 for IM. For all analytes, the drug/internal standard peak height ratios were linked via a quadratic relationship to plasma concentrations. The extraction recovery averaged 90% for CBZ, 80% for OXCBZ and was 80-105% for the metabolites. The lower limit of quantitation was 0.5mg/l for CBZ, 0.4 mg/l for OXCBZ and ranged from 0.02 to 0.3 mg/l for the metabolites. Precision ranged from 2 to 13% and accuracy was between 86 and 112%. This method was found suitable for the analysis of plasma samples collected during therapeutic drug monitoring of patients treated with CBZ or OXCBZ.

Arterial spin labeling-based Z-maps have high specificity and positive predictive value for neurodegenerative dementia compared to FDG-PET.

PubMed

Fällmar, David; Haller, Sven; Lilja, Johan; Danfors, Torsten; Kilander, Lena; Tolboom, Nelleke; Egger, Karl; Kellner, Elias; Croon, Philip M; Verfaillie, Sander C J; van Berckel, Bart N M; Ossenkoppele, Rik; Barkhof, Frederik; Larsson, Elna-Marie

2017-10-01

Cerebral perfusion analysis based on arterial spin labeling (ASL) MRI has been proposed as an alternative to FDG-PET in patients with neurodegenerative disease. Z-maps show normal distribution values relating an image to a database of controls. They are routinely used for FDG-PET to demonstrate disease-specific patterns of hypometabolism at the individual level. This study aimed to compare the performance of Z-maps based on ASL to FDG-PET. Data were combined from two separate sites, each cohort consisting of patients with Alzheimer's disease (n = 18 + 7), frontotemporal dementia (n = 12 + 8) and controls (n = 9 + 29). Subjects underwent pseudocontinuous ASL and FDG-PET. Z-maps were created for each subject and modality. Four experienced physicians visually assessed the 166 Z-maps in random order, blinded to modality and diagnosis. Discrimination of patients versus controls using ASL-based Z-maps yielded high specificity (84%) and positive predictive value (80%), but significantly lower sensitivity compared to FDG-PET-based Z-maps (53% vs. 96%, p < 0.001). Among true-positive cases, correct diagnoses were made in 76% (ASL) and 84% (FDG-PET) (p = 0.168). ASL-based Z-maps can be used for visual assessment of neurodegenerative dementia with high specificity and positive predictive value, but with inferior sensitivity compared to FDG-PET. • ASL-based Z-maps yielded high specificity and positive predictive value in neurodegenerative dementia. • ASL-based Z-maps had significantly lower sensitivity compared to FDG-PET-based Z-maps. • FDG-PET might be reserved for ASL-negative cases where clinical suspicion persists. • Findings were similar at two study sites.

Randomized Controlled Trial of a Cognitive-Behavioral Therapy Plus Hypnosis Intervention to Control Fatigue in Patients Undergoing Radiotherapy for Breast Cancer

PubMed Central

Montgomery, Guy H.; David, Daniel; Kangas, Maria; Green, Sheryl; Sucala, Madalina; Bovbjerg, Dana H.; Hallquist, Michael N.; Schnur, Julie B.

2014-01-01

Purpose The objective of this study was to test the efficacy of cognitive-behavioral therapy plus hypnosis (CBTH) to control fatigue in patients with breast cancer undergoing radiotherapy. We hypothesized that patients in the CBTH group receiving radiotherapy would have lower levels of fatigue than patients in an attention control group. Patients and Methods Patients (n = 200) were randomly assigned to either the CBTH (n = 100; mean age, 55.59 years) or attention control (n = 100; mean age, 55.97 years) group. Fatigue was measured at four time points (baseline, end of radiotherapy, 4 weeks, and 6 months after radiotherapy). Fatigue was measured using the Functional Assessment of Chronic Illness Therapy (FACIT) –Fatigue subscale and Visual Analog Scales (VASs; Fatigue and Muscle Weakness). Results The CBTH group had significantly lower levels of fatigue (FACIT) at the end of radiotherapy (z, 6.73; P < .001), 4-week follow-up (z, 6.98; P < .001), and 6-month follow-up (z, 7.99; P < .001) assessments. Fatigue VAS scores were significantly lower in the CBTH group at the end of treatment (z, 5.81; P < .001) and at the 6-month follow-up (z, 4.56; P < .001), but not at the 4-week follow-up (P < .07). Muscle Weakness VAS scores were significantly lower in the CBTH group at the end of treatment (z, 9.30; P < .001) and at the 6-month follow-up (z, 3.10; P < .02), but not at the 4-week follow-up (P < .13). Conclusion The results support CBTH as an evidence-based intervention to control fatigue in patients undergoing radiotherapy for breast cancer. CBTH is noninvasive, has no adverse effects, and its beneficial effects persist long after the last intervention session. CBTH seems to be a candidate for future dissemination and implementation. PMID:24419112

The dynamics of the oesophageal squamous epithelium 'normalisation' process in patients with gastro-oesophageal reflux disease treated with long-term acid suppression or anti-reflux surgery.

PubMed

Mastracci, L; Fiocca, R; Engström, C; Attwood, S; Ell, C; Galmiche, J P; Hatlebakk, J G; Långström, G; Eklund, S; Lind, T; Lundell, L

2017-05-01

Proton pump inhibitors and laparoscopic anti-reflux surgery (LARS) offer long-term symptom control to patients with gastro-oesophageal reflux disease (GERD). To evaluate the process of 'normalisation' of the squamous epithelium morphology of the distal oesophagus on these therapies. In the LOTUS trial, 554 patients with chronic GERD were randomised to receive either esomeprazole (20-40 mg daily) or LARS. After 5 years, 372 patients remained in the study (esomeprazole, 192; LARS, 180). Biopsies were taken at the Z-line and 2 cm above, at baseline, 1, 3 and 5 years. A severity score was calculated based on: papillae elongation, basal cell hyperplasia, intercellular space dilatations and eosinophilic infiltration. The epithelial proliferative activity was assessed by Ki-67 immunohistochemistry. A gradual improvement in all variables over 5 years was noted in both groups, at both the Z-line and 2 cm above. The severity score decreased from baseline at each subsequent time point in both groups (P < 0.001, all comparisons), attaining a normal level by 5 years. Corresponding decreases in Ki-67 expression were observed (P < 0.001, all comparisons). No significant differences were found between esomeprazole treatment and LARS. Neither baseline severity score nor Ki-67 expression predicted the risk of treatment failure. Five years of treatment is generally required before squamous epithelial cell morphology and proliferation are 'normalised' in patients with chronic GERD, despite endoscopic and symptomatic disease control. Control of the acid component of the refluxate seems to play the predominant role in restoring tissue morphology. © 2017 John Wiley & Sons Ltd.

Acute Kawasaki disease with emphasis on the echocardiographic profile: A single center experience

PubMed Central

Hamza, Hala S.; Zaher, Asmaa Z.; Agha, Hala M.

Background: Echocardiographic features of acute Kawasaki disease (KD) have not been well characterized in Egyptian children. This study aimed to provide insight into the pattern of cardiac involvement in Egyptian children with Kawasaki disease, focusing on echocardiographic coronary abnormalities and their associated risk predictors. Methods and Results: Medical records of 64 KD patients from 2012 to 2016 were retrospectively analyzed with recalculation of coronary artery z-scores during the first eight weeks after fever onset. All patients received intravenous immunoglobulin (IVIG) and 57.8% were treated within 10 days of illness onset. Coronary abnormalities were found in 53.1% of all patients, and in 43.2% of those who received IVIG within 10 days. Giant aneurysms (z-score>10) comprised 23.5% of all coronary abnormalities. Coronary thrombosis occurred in two patients (5%), both of whom developed myocardial infarction, and one succumbed to heart failure with eventual in-hospital death. Overall, 7% of patients had mitral regurgitation (n = 5), 1.5% had aortic regurgitation (n = 1), and 7.8% had pericardial effusion (n = 5). Among a number of laboratory and clinical predictors, platelet count had the strongest association with coronary abnormalities (Area under Receiver-operating characteristic (ROC) curve: 0.794; 95% confidence interval 0.678–0.910; P < 0.001). Conclusion: Coronary abnormalities occur in a substantial percentage of KD in Egypt, with associated evidence of severe inflammation. Further efforts are required to increase awareness of the disease and to emphasize the importance of early IVIG administration. Future studies should also be undertaken to characterize the long term progression profile of the disease as well as the possible genetic background of the disease in Egypt. PMID:29564348

Hands-Free Image Capture, Data Tagging and Transfer Using Google Glass: A Pilot Study for Improved Wound Care Management

PubMed Central

Aldaz, Gabriel; Shluzas, Lauren Aquino; Pickham, David; Eris, Ozgur; Sadler, Joel; Joshi, Shantanu; Leifer, Larry

2015-01-01

Chronic wounds, including pressure ulcers, compromise the health of 6.5 million Americans and pose an annual estimated burden of $25 billion to the U.S. health care system. When treating chronic wounds, clinicians must use meticulous documentation to determine wound severity and to monitor healing progress over time. Yet, current wound documentation practices using digital photography are often cumbersome and labor intensive. The process of transferring photos into Electronic Medical Records (EMRs) requires many steps and can take several days. Newer smartphone and tablet-based solutions, such as Epic Haiku, have reduced EMR upload time. However, issues still exist involving patient positioning, image-capture technique, and patient identification. In this paper, we present the development and assessment of the SnapCap System for chronic wound photography. Through leveraging the sensor capabilities of Google Glass, SnapCap enables hands-free digital image capture, and the tagging and transfer of images to a patient’s EMR. In a pilot study with wound care nurses at Stanford Hospital (n=16), we (i) examined feature preferences for hands-free digital image capture and documentation, and (ii) compared SnapCap to the state of the art in digital wound care photography, the Epic Haiku application. We used the Wilcoxon Signed-ranks test to evaluate differences in mean ranks between preference options. Preferred hands-free navigation features include barcode scanning for patient identification, Z(15) = -3.873, p < 0.001, r = 0.71, and double-blinking to take photographs, Z(13) = -3.606, p < 0.001, r = 0.71. In the comparison between SnapCap and Epic Haiku, the SnapCap System was preferred for sterile image-capture technique, Z(16) = -3.873, p < 0.001, r = 0.68. Responses were divided with respect to image quality and overall ease of use. The study’s results have contributed to the future implementation of new features aimed at enhancing mobile hands-free digital photography for chronic wound care. PMID:25902061

Biosynthetic Pathway for Sex Pheromone Components Produced in a Plusiinae Moth, Plusia festucae

PubMed Central

Watanabe, Hayaki; Matsui, Aya; Inomata, Sin-ichi; Yamamoto, Masanobu; Ando, Tetsu

2011-01-01

While many Plusiinae species commonly secrete (Z)-7-dodecenyl acetate (Z7-12:OAc) as a key pheromone component, female moths of the rice looper (Plusia festucae) exceptionally utilize (Z)-5-dodecenyl acetate (Z5-12:OAc) to communicate with their partners. GC–MS analysis of methyl esters derived from fatty acids included in the pheromone gland of P. festucae showed a series of esters monounsaturated at the ω7-position, i.e., (Z)-5-dodecenoate, (Z)-7-tetradecenoate, (Z)-9-hexadecenoate (Z9-16:Me), and (Z)-11-octadecenoate (Z11-18:Me). By topical application of D3-labled palmitic acid (16:Acid) and stearic acid (18:Acid) to the pheromone glands, similar amounts of D3-Z5-12:OAc were detected. The glands treated with D13-labeled monoenoic acids (Z9-16:Acid and Z11-18:Acid), which were custom-made by utilizing an acetylene coupling reaction with D13-1-bromohexane, also produced similar amounts of D13-Z5-12:OAc. These results suggested that Z5-12:OAc was biosynthesized by ω7-desaturase with low substrate specificity, which could introduce a double bond at the 9-position of a 16:Acid derivative and the 11-position of an 18:Acid derivative. Additional experiments with the glands pretreated with an inhibitor of chain elongation supported this speculation. Furthermore, a comparative study with another Plusiinae species (Chrysodeixis eriosoma) secreting Z7-12:OAc indicated that the β-oxidation systems of P. festucae and C. eriosoma were different. PMID:22649385

Comparison of high-resolution magnification narrow-band imaging and white-light endoscopy in the prediction of histology in Barrett's oesophagus.

PubMed

Singh, Rajvinder; Karageorgiou, Haris; Owen, Victoria; Garsed, Klara; Fortun, Paul J; Fogden, Edward; Subramaniam, Venkataraman; Shonde, Anthony; Kaye, Philip; Hawkey, Christopher J; Ragunath, Krish

2009-01-01

To evaluate whether there is any appreciable difference in imaging characteristics between high-resolution magnification white-light endoscopy (WLE-Z) and narrow-band imaging (NBI-Z) in Barrett's oesophagus (BE) and if this translates into superior prediction of histology. This was a prospective single-centre study involving 21 patients (75 areas, corresponding NBI-Z and WLE-Z images) with BE. Mucosal patterns (pit pattern and microvascular morphology) were evaluated for their image quality on a visual analogue scale (VAS) of 1-10 by five expert endoscopists. The endoscopists then predicted mucosal morphology based on four subtypes which can be visualized in BE. Type A: round pits, regular microvasculature; type B: villous/ridge pits, regular microvasculature; type C: absent pits, regular microvasculature; type D: distorted pits, irregular microvasculature. The sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (Acc) were then compared with the final histopathological analysis and the interobserver variability calculated. The overall pit and microvasculature quality was significantly higher for NBI-Z, pit: NBI-Z=6, WLE-Z=4.5, p < 0.001; microvasculature: NBI-Z=7.3, WLE-Z=4.9, p < 0.001. This translated into a superior prediction of histology (Sn: NBI-Z: 88.9, WLE-Z: 71.9, p < 0.001). For the prediction of dysplasia, NBI-Z was superior to WLE-Z (chi(2)=10.3, p < 0.05). The overall kappa agreement among the five endoscopists for NBI-Z and WLE-Z, respectively, was 0.59 and 0.31 (p < 0.001). NBI-Z is superior to WLE-Z in the prediction of histology in BE, with good reproducibility. This novel imaging modality could be an important tool for surveillance of patients with BE.

Nonalcoholic fatty liver disease in long-term survivors of childhood-onset craniopharyngioma.

PubMed

Jung, So Yoon; Lee, Yun Jeong; Lee, Hye Jin; Lee, Young Ah; Moon, Jin Soo; Ko, Jae Sung; Yang, Sei Won; Shin, Choong Ho

2017-09-01

Hypothalamic obesity in childhood-onset (CO-) craniopharyngioma patients may predispose to nonalcoholic fatty liver disease (NAFLD). This study reviewed the characteristics of NAFLD associated with CO-craniopharyngioma. This study retrospectively reviewed 75 patients who underwent surgery for craniopharyngioma while younger than 15 years of age between 2000 and 2016. Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above 40 IU/L was observed in 51 of the 75 (68%) CO-craniopharyngioma patients. Imaging studies were performed in 32 patients with elevated liver enzymes. The estimated prevalence of NAFLD in CO-craniopharyngioma was 47%. NAFLD was detected in 22 patients (male 59%, 4.3±4.0 years after first surgery). The mean age at the time of the initial operation was 9.1±2.9 years. Six patients (27.3%) were diagnosed within 1 year. Among the 19 patients with initial height and weight data, the body mass index (BMI) z-score (BMI_Z) at the time of diagnosis with NAFLD was 1.37±1.01 (range, -0.75 to 3.18), with 4 patients (18.2%) being overweight and 9 (40.9%) being obese. BMI_Z increased above BMI_Z at the time of the operation in 13 patients (68.4%). The increment in BMI_Z was 1.13 (range, 0.10-2.84). Seventeen patients did not receive growth hormone. An insulin-like growth factor-I level <3rd percentile was observed in 19 patients. NAFLD is common in survivors of CO-craniopharyngioma and may develop earlier. If the ALT or AST is above 40 IU/L, a diagnostic work-up should be started.

[A real-world study focused on the effectiveness and safety of adalimumab as first-line anti-TNF treatment for pediatric Crohn's disease].

PubMed

Navas-López, Víctor Manuel; Pujol Muncunill, Gemma; Llerena, Enrique; Navalón Rubio, María; Gil-Ortega, David; Varea-Calderón, Vicente; Sierra Salinas, Carlos; Martin-de-Carpi, Javier

2018-02-01

Adalimumab (ADA), a monoclonal humanised anti-TNF antibody, is usually prescribed as a second-line treatment in paediatric Crohn's disease (CD) patients who have become unresponsive or developed intolerance to infliximab (IFX). In the case series reported, more than 70% of patients had initially been treated with IFX. Data on short- and long-term effectiveness of ADA in anti-TNF naïve patients is limited. The aim of this study is to describe our experience with ADA as a first-line anti-TNF in paediatric CD patients. This is a multicentre retrospective study including anti-TNF naïve paediatric CD patients treated with ADA as first-line anti-TNF. Sixty-two patients (34males), with a mean age of 13.0±2.4years and a disease duration of 7.3 (IQR 2.7-21) months were included. Median wPCDAI was 35 (IQR 24.3-47.5). Fifty-eight out of 62 (93.5%) were on combo therapy at baseline. Clinical remission at week12 was achieved in 50 out of 62 (80.6%) and in 57 out of 60 (95.0%) at week52. Eight patients (13%) reported adverse events. Mean height, growth rate and BMI z-scores improved significantly between baseline and week 52, especially in patients with growth failure. ADA treatment leads to lasting clinical remission in anti-TNF naïve paediatric patients with CD. ADA significantly improved growth rate in children with CD who had growth delay at baseline. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Drug Treated Schizophrenia, Schizoaffective and Bipolar Disorder Patients Evaluated by qEEG Absolute Spectral Power and Mean Frequency Analysis.

PubMed

Wix-Ramos, Richard; Moreno, Xiomara; Capote, Eduardo; González, Gilbert; Uribe, Ezequiel; Eblen-Zajjur, Antonio

2014-04-01

Research of electroencephalograph (EEG) power spectrum and mean frequency has shown inconsistent results in patients with schizophrenic, schizoaffective and bipolar disorders during medication when compared to normal subjects thus; the characterization of these parameters is an important task. We applied quantitative EEG (qEEG) to investigate 38 control, 15 schizophrenic, 7 schizoaffective and 11 bipolar disorder subjects which remaine under the administration of psychotropic drugs (except control group). Absolute spectral power (ASP), mean frequency and hemispheric electrical asymmetry were measured by 19 derivation qEEG. Group mean values were compared with non parametrical Mann-Whitney test and spectral EEG maps with z-score method at p < 0.05. Most frequent drug treatments for schizophrenic patients were neuroleptic+antiepileptic (40% of cases) or 2 neuroleptics (33.3%). Schizoaffective patients received neuroleptic+benzodiazepine (71.4%) and for bipolar disorder patients neuroleptic+antiepileptic (81.8%). Schizophrenic (at all derivations except for Fp1, Fp2, F8 and T6) and schizoaffective (only at C3) show higher values of ASP (+57.7% and +86.1% respectively) compared to control group. ASP of bipolar disorder patients did not show differences against control group. The mean frequency was higher at Fp1 (+14.2%) and Fp2 (+17.4%) in bipolar disorder patients than control group, but no differences were found in frequencies between schizophrenic or schizoaffective patients against the control group. Majority of spectral differences were found at the left hemisphere in schizophrenic and schizoaffective but not in bipolar disorder subjects. The present report contributes to characterize quantitatively the qEEG in drug treated schizophrenic, schizoaffective or bipolar disorder patients.

An efficient biomarker panel for diagnosis of breast cancer using surface-enhanced laser desorption ionization time-of-flight mass spectrometry.

PubMed

Yigitbasi, Turkan; Calibasi-Kocal, Gizem; Buyukuslu, Nihal; Atahan, Murat Kemal; Kupeli, Hakan; Yigit, Seyran; Tarcan, Ercument; Baskin, Yasemin

2018-03-01

Breast cancer (BC) is the most frequently diagnosed cancer that affects women worldwide. Early detection of BC is important to improve survival rates and decrease mortality. The aim of the present study was to investigate serum biomarkers using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to distinguish patients with BC from the healthy population and patients with benign breast diseases (BBDs). A total of 62 patients with invasive ductal carcinoma, as confirmed by histopathology, and 47 non-cancerous individuals (NCIs) [16 healthy controls (HCs) and 31 patients with BBD] were enrolled in the present study. Serum protein profiles were determined by SELDI-TOF-MS using an immobilized metal affinity capture array. Serum from patients with BC were compared with that from the HC group using univariate and multivariate statistical analyses. A total of 118 clusters were generated from the individual serum. Univariate analysis revealed that 5 peaks were significantly downregulated (m/z 1,452, 2,670, 3,972, 5,354 and 5,523; P<0.001) and 4 were upregulated (m/z 6,850, 7,926, 8,115 and 8,143; P<0.001) in patients with BC compared with the HC group. A comparison of patients with BC and patients with BBD revealed an additional 9 protein peaks. Among these, 3 peaks (m/z 3,972, 5,336 and 11,185) were significantly downregulated and 6 peaks (m/z 4,062, 4,071, 4,609, 6,850, 8,115 and 8,133) were significantly upregulated. A total of 3 peaks [mass-to-change ratio (m/z) 3,972, 6,850 and 8,115 (BC2)] were common in both sets. The results of the present study suggest that a 4 protein peak set [m/z 3,972, 6,850 and 8,115 (BC2) and 8,949 (BC3)] could be used to distinguish patients with BC from NCI.

Prophylactic Z-plasty - correcting helical rim deformity from wedge excision.

PubMed

Kim, Peter

2010-09-01

Wedge excision is a popular and well documented surgical method for treating a wide range of skin lesions and cancers of the ear in the general practice setting. In the majority of cases, this is a simple and cosmetically pleasing treatment. However, it may create helical rim deformity. This article describes a simple method of preventing such deformity using prophylactic Z-plasty.

First-Order Model of Thermal Lensing in a Virtual Eye

DTIC Science & Technology

2009-03-01

beam would have an m 2 value of 1.0, but realistically, the value is greater than 1.0. To solve for the rJ2T/ i )r2, the eye can be treated as a cy...along the z axis in a medium as The complex beam parameter is described by the real and imaginary portions of a wavefront by 1 1 m 2X. q(z) =R(z) - i ...for solving this integral have been reported in Swofford and Morrell [27]. o Z.AD I -42 em ( I M3 1.2 Ll Ml/__I r- 7···_······0······K···~ J. r:..8 1

Zingiber officinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant status.

PubMed

Ajith, T A; Hema, U; Aswathy, M S

2007-11-01

A large number of xenobiotics are reported to be potentially hepatotoxic. Free radicals generated from the xenobiotic metabolism can induce lesions of the liver and react with the basic cellular constituents - proteins, lipids, RNA and DNA. Hepatoprotective activity of aqueous ethanol extract of Zingiber officinale was evaluated against single dose of acetaminophen-induced (3g/kg, p.o.) acute hepatotoxicity in rat. Aqueous extract of Z. officinale significantly protected the hepatotoxicity as evident from the activities of serum transaminase and alkaline phosphatase (ALP). Serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and ALP activities were significantly (p<0.01) elevated in the acetaminophen alone treated animals. Antioxidant status in liver such as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase and glutathione-S-transferase (GST), a phase II enzyme, and levels of reduced glutathione (GSH) were declined significantly (p<0.01) in the acetaminophen alone treated animals (control group). Hepatic lipid peroxidation was enhanced significantly (p<0.01) in the control group. Administration of single dose of aqueous extract of Z. officinale (200 and 400mg/kg, p.o.) prior to acetaminophen significantly declines the activities of serum transaminases and ALP. Further the hepatic antioxidant status was enhanced in the Z. officinale plus acetaminophen treated group than the control group. The results of the present study concluded that the hepatoprotective effect of aqueous ethanol extract of Z. officinale against acetaminophen-induced acute toxicity is mediated either by preventing the decline of hepatic antioxidant status or due to its direct radical scavenging capacity.

Negative correlation between bone mineral density and TSH receptor antibodies in long-term euthyroid postmenopausal women with treated Graves’ disease

PubMed Central

2013-01-01

Background Thyrotoxicosis is a cause of secondary osteoporosis. High concentrations of triiodotironine (T3) in Graves’ disease stimulate bone turnover, but it is unclear if euthyroidism will always normalize bone metabolism. Thyrotropin (TSH) is known to affect directly the bone metabolism through the TSH receptor and TSH receptor antibodies (TRAb) may have an important role in bone turn-over. The aim of our study was to determine, in pre and postmenopausal euthyroidism patients with previous overt hyperthyroidism due to Graves’ disease the bone mineral density (BMD) as well as factors that could affect BMD in each group, including TRAb. Methods Cross-sectional, non-interventional study. Fifty-seven patients with previous hyperthyroidism due to Graves’ disease (premenopausal: 30, postmenopausal: 27) that remained euthyroid for at least 6 months prior to study were included and compared with fifty- two matched respective controls. Thyrotoxine (T4), TSH, TRAb and BMD were measured. Results Only euthyroid postmenopausal patients with a history of hyperthyroidism due to Graves’ disease showed lower whole body BMD than matched controls. The BMD expressed as Z-score was less in whole body and lumbar spine in postmenopausal in relation to premenopausal women with previous overt hyperthyroidism due to Graves’ disease. In the postmenopausal patients, the Z-score of lumbar spine BMD correlated negatively with TRAb (r = −0,53, p < 0.008), positively with the time of evolution of the disease (r = +0.42, p < 0.032) and positively with the time of euthyroidism (r = + 0.50, p < 0.008), but neither with serum T4 nor TSH. In a multiple regression analysis TRAb was the only significant independent variable in relation to lumbar spine BMD (F = 3. 90, p < 0.01). Conclusions In euthyroid women with a history of Graves’ hyperthyroidism, BMD was only affected in the postmenopausal group. The negative correlation of Z-score of lumbar spine BMD with TRAb suggests that this antibody may affect the bone metabolism. PMID:24020400

Health-service Use in Women with Binge Eating Disorders

PubMed Central

Dickerson, John; DeBar, Lynn; Perrin, Nancy A.; Lynch, Frances; Wilson, G. Terence; Rosselli, Francine; Kraemer, Helena C.; Striegel-Moore, Ruth H.

2014-01-01

Objective To compare health-care utilization between participants who met DSM-IV criteria for Binge Eating Disorder (BED) and those engaged in Recurrent Binge Eating (RBE) and to evaluate whether objective binge eating (OBE) days, a key measurement for diagnosing BED, predicted health-care costs. Method We obtained utilization and cost data from electronic medical records to augment patient reported data for 100 adult female members of a large health maintenance organization (HMO) who were enrolled in a randomized clinical trial to treat binge eating. Results Total costs did not differ between the BED and RBE groups (β=−0.117, z=−0.48, p=0.629), nor did the number of OBE days predictor total costs (β= −0.017, z=−1.01, p=0.313). Conclusions Findings suggest that the medical impairment, as assessed through health care costs, caused by BED may not be greater than impairment caused by RBE. The current threshold number of two OBE days/week as a criterion for BED may need to be reconsidered PMID:21823138

[Regional cerebral blood flow measured by three-dimensional stereotactic surface projections (3D-SSP) of 123I-IMP SPECT in Parkinson disease patients with cognitive impairment].

PubMed

Sakai, Toshiyuki; Kuzuhara, Shigeki

2003-04-01

We investigated the regional cerebral blood flow (rCBF) in 8 patients with Parkinson disease (PD) with cognitive impairment (age; 64-82 years, Mini-Mental State Examination score = MMSE score; 22-6 points, Yahr stage; III-V), with the standard transaxial images and the Z-score images using the three-dimensional stereotactic surface projections (3D-SSP) of 123I-IMP SPECT. A contrast database was created by averaging extracted database sets of the contrast group (numbers; 14 cases, age; 64-82 years, MMSE score; > or = 29 points). The regions of the perfusion reduction shown on the standard transaxial images were similarly demonstrated on the Z-score images in 6 of the 8 patients, and only the Z-score images demonstrated definite regions of perfusion reduction in remaining 2 patients. Both the standard transaxial and Z-score images demonstrated the perfusion reduction in the temporo-parietal regions in all of the patients, and the Z-score images but not the standard transaxial ones detected the reduction in the posterior cingulate gyrus and precuneus in 3 patients. 3D-SSP images of 123I-IMP SPECT are thus more sensitive in detecting rCBF of the medial aspect of the parietal cortex than the standard transaxial images, and can be used as a diagnostic tool to objectively evaluate the cognitive function of PD patients.

Treating Zc(3900 ) and Z (4430 ) as the ground state and first radially excited tetraquarks

NASA Astrophysics Data System (ADS)

Agaev, S. S.; Azizi, K.; Sundu, H.

2017-08-01

Exploration of the resonances Zc(3900 ) and Z (4430 ) are performed by assuming that they are the ground state and first radial excitation of the same tetraquark with JP=1+. The mass and current coupling of the Zc(3900 ) and Z (4430 ) states are calculated using the QCD two-point sum rule method by taking into account vacuum condensates up to eight dimensions. We investigate the vertices ZcMhMl and Z MhMl, with Mh and Ml being the heavy and light mesons and evaluate the strong couplings gZcMhMl and gZ MhMl using the QCD sum rule on the light cone. The extracted couplings allow us to find the partial width of the decays Zc(3900 )→J /ψ π , ψ'π , ηcρ and Z (4430 )→ψ'π , J /ψ π , ηc'ρ , ηcρ , which may help in comprehensive investigation of these resonances. We compare the width of the decays of Zc(3900 ) and Z (4430 ) resonances with available experimental data as well as existing theoretical predictions.

Fluctuations, Electron Transport, and Flow Shear in 2D Axial, Azimuthal (z-θ) Hybrid Hall Thruster Simulations.

NASA Astrophysics Data System (ADS)

Fernandez, Eduardo; Gascon, Nicolas; Knoll, Aaron; Scharfe, Michelle; Cappelli, Mark

2007-11-01

Motivated by the inability of radial-axial (r-z) simulations to properly treat cross-field electron transport in Hall thrusters, a novel 2D z-θ model has been implemented. In common with many r-z descriptions, the simulation is hybrid in nature and assumes quasi-neutrality. Unlike r-z models, electron transport is not enhanced with an ad-hoc mobility coefficient; instead it is given by collisional or ``classical'' terms as well as ``anomalous'' contributions associated with azimuthal electric field fluctuations. Results indicate that anomalous transport dominates classical transport for most of the channel and near field, except in a strong electron flow shear region near the channel exit. The correlation between flow shear, fluctuation behavior, and electron transport will be examined, along with experimental data from the Stanford Hall Thruster. Our findings make a strong link to the turbulent transport suppression mechanism by flow shear seen in fusion devices. The scheme for combining the r-z and z-θ descriptions into an upcoming 3D hybrid model will be presented.

Randomized controlled trial of a cognitive-behavioral therapy plus hypnosis intervention to control fatigue in patients undergoing radiotherapy for breast cancer.

PubMed

Montgomery, Guy H; David, Daniel; Kangas, Maria; Green, Sheryl; Sucala, Madalina; Bovbjerg, Dana H; Hallquist, Michael N; Schnur, Julie B

2014-02-20

The objective of this study was to test the efficacy of cognitive-behavioral therapy plus hypnosis (CBTH) to control fatigue in patients with breast cancer undergoing radiotherapy. We hypothesized that patients in the CBTH group receiving radiotherapy would have lower levels of fatigue than patients in an attention control group. Patients (n = 200) were randomly assigned to either the CBTH (n = 100; mean age, 55.59 years) or attention control (n = 100; mean age, 55.97 years) group. Fatigue was measured at four time points (baseline, end of radiotherapy, 4 weeks, and 6 months after radiotherapy). Fatigue was measured using the Functional Assessment of Chronic Illness Therapy (FACIT) -Fatigue subscale and Visual Analog Scales (VASs; Fatigue and Muscle Weakness). The CBTH group had significantly lower levels of fatigue (FACIT) at the end of radiotherapy (z, 6.73; P < .001), 4-week follow-up (z, 6.98; P < .001), and 6-month follow-up (z, 7.99; P < .001) assessments. Fatigue VAS scores were significantly lower in the CBTH group at the end of treatment (z, 5.81; P < .001) and at the 6-month follow-up (z, 4.56; P < .001), but not at the 4-week follow-up (P < .07). Muscle Weakness VAS scores were significantly lower in the CBTH group at the end of treatment (z, 9.30; P < .001) and at the 6-month follow-up (z, 3.10; P < .02), but not at the 4-week follow-up (P < .13). The results support CBTH as an evidence-based intervention to control fatigue in patients undergoing radiotherapy for breast cancer. CBTH is noninvasive, has no adverse effects, and its beneficial effects persist long after the last intervention session. CBTH seems to be a candidate for future dissemination and implementation.

Tamoxifen metabolite isomer separation and quantification by liquid chromatography-tandem mass spectrometry.

PubMed

Jaremko, Malgorzata; Kasai, Yumi; Barginear, Myra F; Raptis, George; Desnick, Robert J; Yu, Chunli

2010-12-15

Tamoxifen (Tam), the antiestrogen used to treat estrogen receptor-positive breast cancer is a pro-drug that is converted to its major active metabolites, endoxifen and 4-hydroxy-tamoxifen (4-OH-Tam) by various biotransformation enzymes of which cytochrome P450-2D6 (CYP2D6) is key. The usual Tam dose is 20 mg daily; however, the plasma active metabolite concentrations vary due to common genetic variants encoding the biotransformation enzymes and environmental factors (e.g., concomitant drugs) that inhibit these enzymes. Effective treatment depends on adequate Tam conversion to its active isomers. To monitor metabolite plasma levels, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to separate and quantitate Tam, N-desmethyl-tamoxifen (ND-Tam), and tamoxifen-N-oxide (Tam-N-oxide), and the E, Z, and Z' isomers of endoxifen and 4-OH-Tam. Known standards were used to identify each metabolite/isomer. Quantitation of these metabolites in plasma was linear from 0.6 to 2000 nM. Intra- and inter-assay reproducibilities were 0.2-8.4% and 0.6-6.3%, respectively. Accuracy determined by spike experiments with known standards was 86-103%. Endoxifen, 4-OH-Tam, and their isomers were stable in fresh frozen plasma for ≥6 months. This method provides the first sensitive, specific, accurate, and reproducible quantitation of Tam and its metabolite isomers for monitoring Tam-treated breast cancer patients.

Synopsis of Nekemias Raf., a segregate genus from Ampelopsis Michx. (Vitaceae) disjunct between eastern/southeastern Asia and eastern North America, with ten new combinations

PubMed Central

Wen, Jun; Boggan, John; Nie, Ze-Long

2014-01-01

Abstract The genus Nekemias (Vitaceae) was first recognized by Rafinesque in 1838. It has been treated as a synonym of Ampelopsis Michx. Recent phylogenetic studies suggest that Ampelopsis as traditionally delimited is paraphyletic. To maintain the monophyly of each of the genera of Vitaceae, we herein segregate the Ampelopsis sect. Leeaceifoliae lineage from Ampelopsis and recognize these taxa in Nekemias Raf., which has a disjunct distribution in eastern to southeastern Asia and eastern North America. Nomenclatural changes are made for nine species and one variety: Nekemias arborea (L.) J. Wen & Boggan, Nekemias cantoniensis (Hook. & Arn.) J. Wen & Z.L. Nie, Nekemias celebica (Suess.) J. Wen & Boggan, Nekemias chaffanjonii (H. Lév. & Van.) J. Wen & Z.L. Nie, Nekemias gongshanensis (C.L. Li) J. Wen & Z.L. Nie, Nekemias grossedentata (Hand.-Mazz.) J. Wen & Z.L. Nie, Nekemias hypoglauca (Hance) J. Wen & Z.L. Nie, Nekemias megalophylla (Diels & Gilg) J. Wen & Z.L. Nie, Nekemias megalophylla var. jiangxiensis (W.T. Wang) J. Wen & Z.L. Nie, and Nekemias rubifolia (Wall.) J. Wen & Z.L. Nie. A taxonomic key is provided for the genus to facilitate identification. PMID:25383008

Effects of the Hydroalcoholic Extract of Zingiber officinale on Arginase I Activity and Expression in the Retina of Streptozotocin-Induced Diabetic Rats.

PubMed

Lamuchi-Deli, Nasrin; Aberomand, Mohammad; Babaahmadi-Rezaei, Hossein; Mohammadzadeh, Ghorban

2017-04-01

Emerging evidence suggests that an increased arginase activity is involved in vascular dysfunction in experimental animals. Zingiber officinale Roscoe, commonly known as ginger, has been widely used in the traditional medicine for treatment of diabetes. This study aimed at investigating the effects of the hydroalcoholic extract of Z. officinale on arginase I activity and expression in the retina of streptozotocin (STZ)-induced diabetic rats. In this experimental study, 16 male Wistar rats weighing 200 - 250 g were assessed. Diabetes was induced via a single intraperitoneal injection of STZ (60 mg/kg body weight). The rats were randomly allocated into four experimental groups. Untreated healthy and diabetic controls received 1.5 mL/kg distilled water. Treated diabetic rats received 200, and 400 mg/kg of the Z. officinale extract dissolved in distilled water (1.5 mL/kg). Body weight, blood glucose and insulin concentration were measured by standard methods. The arginase I activity and expression were determined by spectrophotometric and western blot analysis, respectively. Our results showed that blood glucose concentration was significantly decreased in diabetic rats treated with the extract compared to untreated diabetic controls (P < 0.01). Treatment with 400 mg/kg of the extract reduced arginase I activity and expression (P < 0.05). A significant elevation in body weight was observed in diabetic rats treated with the extract. Serum insulin was significantly increased in diabetic rats treated with 400 mg/kg of the extract compared to diabetic controls (P < 0.05). Our results suggest that the Z. officinale hydroalcoholic extract may potentially be a promising therapeutic option for treating diabetes-induced vascular disorders, possibly through reducing arginase I activity and expression in the retina.

Effects of the Hydroalcoholic Extract of Zingiber officinale on Arginase I Activity and Expression in the Retina of Streptozotocin-Induced Diabetic Rats

PubMed Central

Lamuchi-Deli, Nasrin; Aberomand, Mohammad; Babaahmadi-Rezaei, Hossein; Mohammadzadeh, Ghorban

2017-01-01

Background Emerging evidence suggests that an increased arginase activity is involved in vascular dysfunction in experimental animals. Zingiber officinale Roscoe, commonly known as ginger, has been widely used in the traditional medicine for treatment of diabetes. Objectives This study aimed at investigating the effects of the hydroalcoholic extract of Z. officinale on arginase I activity and expression in the retina of streptozotocin (STZ)-induced diabetic rats. Methods In this experimental study, 16 male Wistar rats weighing 200 – 250 g were assessed. Diabetes was induced via a single intraperitoneal injection of STZ (60 mg/kg body weight). The rats were randomly allocated into four experimental groups. Untreated healthy and diabetic controls received 1.5 mL/kg distilled water. Treated diabetic rats received 200, and 400 mg/kg of the Z. officinale extract dissolved in distilled water (1.5 mL/kg). Body weight, blood glucose and insulin concentration were measured by standard methods. The arginase I activity and expression were determined by spectrophotometric and western blot analysis, respectively. Results Our results showed that blood glucose concentration was significantly decreased in diabetic rats treated with the extract compared to untreated diabetic controls (P < 0.01). Treatment with 400 mg/kg of the extract reduced arginase I activity and expression (P < 0.05). A significant elevation in body weight was observed in diabetic rats treated with the extract. Serum insulin was significantly increased in diabetic rats treated with 400 mg/kg of the extract compared to diabetic controls (P < 0.05). Conclusions Our results suggest that the Z. officinale hydroalcoholic extract may potentially be a promising therapeutic option for treating diabetes-induced vascular disorders, possibly through reducing arginase I activity and expression in the retina. PMID:28835766

Z-100, a lipid-arabinomannan extracted from Mycobacterium tuberculosis, improves the resistance of thermally injured mice to herpes virus infections.

PubMed

Kobayashi, M; Herndon, D N; Pollard, R B; Suzuki, F

1994-06-01

The effect of Z-100, a lipid-arabinomannan extracted from Mycobacterium tuberculosis strain Aoyama B, was investigated on the resistance of thermally injured mice (TI-mice) to herpes simplex virus type 1 (HSV) infections. The susceptibility of TI mice to infection was about 100 times greater than it was in normal mice (N mice). However, the increased susceptibility of TI mice to infection was effectively counteracted to the levels observed in N mice when treated with Z-100 (10 mg/kg i.p.; 1, 3 and 5 days after thermal injury). Adoptive transfer of burn-associated CD8+ CD11b+ TCR gamma/delta + suppressor T (BAST) cells, prepared from TI mice, increased the susceptibility of N mice to infection by HSV, while the susceptibility of N mice, inoculated with the CD8+ T-cell fraction prepared from Z-100-treated TI mice (ZTC), to infection was not changed. In addition, the suppressor cell activity of BAST cells was not demonstrated when they were assayed in vitro in the presence of anti-IL-4 monoclonal antibody (mAb). BAST cells released IL-4 into their culture fluids without stimulation. The suppressor cell activity of ZTC and IL-4 production by ZTC were minimal. These results suggest that Z-100 may improve the resistance of TI mice to HSV infection through the regulation of BAST cells and/or the release of IL-4 from these cells.

A rare combination of amniotic constriction band with osteogenesis imperfecta.

PubMed

Shah, Krupa Hitesh; Shah, Hitesh

2015-11-11

Amniotic constriction bands and osteogenesis imperfecta are disorders arising from a collagen defect. We report a rare association of amniotic bands with osteogenesis imperfecta in a child. The child was born with multiple amniotic bands involving the right leg, both hands and both feet. Multiple fractures of long bones of lower limbs occurred in childhood due to trivial trauma. Deformities of the femur and tibia due to malunion with osteopenia and blue sclerae were present. The patient was treated with z plasty of constriction band of the right tibia and bisphosphonate for osteogenesis imperfecta. This rare association of both collagen diseases may provide further insight for the pathogenesis of these diseases. 2015 BMJ Publishing Group Ltd.

Clinical and pH-metric outcomes of transoral esophagogastric fundoplication for the treatment of gastroesophageal reflux disease.

PubMed

Bell, Reginald C W; Freeman, Katherine D

2011-06-01

Transoral treatment of gastroesophageal reflux disease (GERD) using the EsophyX device enables creation of an esophagogastric fundoplication with potential for better control of reflux than gastrogastric techniques. Efficacy and safety of a rotational/longitudinal esophagogastric transoral incisionless fundoplication (TIF) was evaluated retrospectively using subjective and objective outcomes. Thirty-seven consecutive patients on antisecretory medication and with proven gastroesophageal reflux and limited hiatal hernia underwent TIF for persistent GERD symptoms. Five patients were reoperations for failed laparoscopic fundoplication. Of the 37 treated patients, 57% were female. The median age was 58 (range=20-81) years and BMI was 25.5 (range=15.9-36.1) kg/m2. Sixty-eight percent indicated GERD-associated cough, asthma, or aspiration as a primary complaint and 32% complained of heartburn or regurgitation. The TIF procedures created tight wraps of 230°-330° extending 3-4 cm above the Z-line. Two complications occurred: one mediastinal abscess treated laparoscopically and one postoperative bleeding requiring transfusion. At 6 (range=3-14) months median follow-up TIF resulted in a significant improvement of both atypical and typical symptoms in 64% and 70-80% of patients, respectively, as indicated by the corresponding GERD health-related quality of life (HRQL) and reflux symptom index (RSI) score reduction by 50% or more compared to baseline on proton pump inhibitors (PPIs). No patient reported problems with dysphagia, bloating, or excess flatulence, and 82% were not taking any PPIs. Reflux characteristics were significantly improved and normalized in 61, 89, and 56% of patients in terms of acid exposure, number of refluxates, and DeMeester scores, respectively. TIF was effective in treating GERD in 75% of patients among whom 54% were in a complete "remission" and 21% were "improved." The remaining 25% were considered failures, and five (13.5%) patients underwent revision. Rotational/longitudinal esophagogastric fundoplication using the EsophyX device significantly improved symptomatic and objective outcomes in over 70% of patients at median 6-month follow-up. Post-fundoplication side effects were not reported after TIF.

A UPLC-MS/MS method for analysis of vancomycin in human cerebrospinal fluid and comparison with the chemiluminescence immunoassay.

PubMed

Mei, Shenghui; Wang, Jiaqing; Zhu, Leting; Chen, Ruiling; Li, Xingang; Chen, Kai; Chen, Guangqiang; Zhou, Jianxin; Wang, Qiang; Zhao, Zhigang

2017-08-01

Vancomycin (VCM) is clinically used in treating patients with postoperative intracranial infections. The cerebrospinal fluid (CSF) concentration of VCM varies greatly among patients. To guide the dosage regimens, monitoring of VCM in CSF is needed. However a method for analysis of VCM in human CSF is lacking. An ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed and validated for analysis of VCM in human CSF, and the agreement of UPLC-MS/MS and chemiluminescence immunoassay (CLIA) in the analysis of CSF VCM was evaluated. The ion transitions were m/z 725.5 > 144.1 for VCM and m/z 455.2 > 308.2 for methotrexate (internal standard). The agreement between UPLC-MS/MS and CLIA was evaluated by Bland-Altman plot in 179 samples. The calibration range of the UPLC-MS/MS method was 1-400 mg/L. The inaccuracy and imprecision were -0.69-10.80% and <4.95%. The internal standard normalized recovery and matrix factor were 86.14-99.31 and 85.84-92.07%, respectively. The measurements of CLIA and UPLC-MS/MS were strongly correlated (r > 0.98). The 95% limit of agreement of the ratio of CLIA to UPLC-MS/MS was 61.66-107.40%. Further studies are warranted to confirm the results. Copyright © 2017 John Wiley & Sons, Ltd.

An Antiestrogenic Activity Score for tamoxifen and its metabolites is associated with breast cancer outcome

PubMed Central

Alexi, X.; van Werkhoven, E.; Madlensky, L.; Natarajan, L.; Flatt, S. W.; Zwart, W.; Linn, S. C.; Parker, B. A.; Wu, A. H. B.; Pierce, J. P.; Huitema, A. D. R.; Beijnen, J. H.

2018-01-01

Purpose Endoxifen concentrations have been associated with breast cancer recurrence in tamoxifen-treated patients. However, tamoxifen itself and other metabolites also show antiestrogenic anti-tumor activity. Therefore, the aim of this study was to develop a comprehensive Antiestrogenic Activity Score (AAS), which accounts for concentration and antiestrogenic activity of tamoxifen and three metabolites. An association between the AAS and recurrence-free survival was investigated and compared to a previously published threshold for endoxifen concentrations of 5.97 ng/mL. Patients and methods The antiestrogenic activities of tamoxifen, (Z)-endoxifen, (Z)-4-hydroxytamoxifen, and N-desmethyltamoxifen were determined in a cell proliferation assay. The AAS was determined by calculating the sum of each metabolite concentration multiplied by an IC50 ratio, relative to tamoxifen. The AAS was calculated for 1370 patients with estrogen receptor alpha (ERα)-positive breast cancer. An association between AAS and recurrence was investigated using Cox regression and compared with the 5.97 ng/mL endoxifen threshold using concordance indices. Results An AAS threshold of 1798 was associated with recurrence-free survival, hazard ratio (HR) 0.67 (95% confidence interval (CI) 0.47–0.96), bias corrected after bootstrap HR 0.69 (95% CI 0.48–0.99). The concordance indices for AAS and endoxifen did not significantly differ; however, using the AAS threshold instead of endoxifen led to different dose recommendations for 5.2% of the patients. Conclusions Endoxifen concentrations can serve as a proxy for the antiestrogenic effect of tamoxifen and metabolites. However, for the aggregate effect of tamoxifen and three metabolites, defined by an integrative algorithm, a trend towards improving treatment is seen and moreover, is significantly associated with breast cancer recurrence. PMID:28005246

The cathepsin B inhibitor z-FA-CMK induces cell death in leukemic T cells via oxidative stress.

PubMed

Liow, K Y; Chow, Sek C

2018-01-01

The cathepsin B inhibitor benzyloxycarbonyl-phenylalanine-alanine-chloromethyl ketone (z-FA-CMK) was recently found to induce apoptosis at low concentrations in Jurkat T cells, while at higher concentrations, the cells die of necrosis. In the present study, we showed that z-FA-CMK readily depletes intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) generation. The toxicity of z-FA-CMK in Jurkat T cells was completely abrogated by N-acetylcysteine (NAC), suggesting that the toxicity mediated by z-FA-CMK is due to oxidative stress. We found that L-buthionine sulfoximine (BSO) which depletes intracellular GSH through the inhibition of GSH biosynthesis in Jurkat T cells did not promote ROS increase or induce cell death. However, NAC was still able to block z-FA-CMK toxicity in Jurkat T cells in the presence of BSO, indicating that the protective effect of NAC does not involve GSH biosynthesis. This is further corroborated by the protective effect of the non-metabolically active D-cysteine on z-FA-CMK toxicity. Furthermore, in BSO-treated cells, z-FA-CMK-induced ROS increased which remains unchanged, suggesting that the depletion of GSH and increase in ROS generation mediated by z-FA-CMK may be two separate events. Collectively, our results demonstrated that z-FA-CMK toxicity is mediated by oxidative stress through the increase in ROS generation.

[Therapeutic strategy for different types of epicanthus].

PubMed

Gaofeng, Li; Jun, Tan; Zihan, Wu; Wei, Ding; Huawei, Ouyang; Fan, Zhang; Mingcan, Luo

2015-11-01

To explore the reasonable therapeutic strategy for different types of epicanthus. Patients with epicanthus were classificated according to the shape, extent and inner canthal distance and treated with different methods appropriately. Modified asymmetric Z plasty with two curve method was used in lower eyelid type epicanthus, inner canthus type epicanthus and severe upper eyelid type epicanthus. Moderate upper epicanthus underwent '-' shape method. Mild Upper epicanthus in two conditions which underwent nasal augumentation and double eyelid formation with normal inner canthal distance need no correction surgery. The other mild epicanthus underwent '-' shape method. A total of 66 cases underwent the classification and the appropriate treatment. All wounds healed well. During 3 to 12 months follow-up period, all epicanthus were corrected completely with natural contour and unconspicuous scars. All patients were satisfied with the results. Classification of epicanthus hosed on the shape, extent and inner canthal distance and correction with appropriate methods is a reasonable therapeutic strategy.

Three-dimensional Reconstruction of Scar Contracture-bearing Axilla and Digital Webs Using the Square Flap Method.

PubMed

Huang, Chenyu; Ogawa, Rei

2014-05-01

Joint scar contractures are characterized by tight bands of soft tissue that bridge the 2 ends of the joint like a web. Classical treatment methods such as Z-plasties are mainly based on 2-dimensional designs. Our square flap method is an alternative surgical method that restores the span of the web in a stereometric fashion, thereby reconstructing joint function. In total, 20 Japanese patients with joint scar contractures on the axillary (n = 10) or first digital web (n = 10) underwent square flap surgery. The maximum range of motion and commissure length were measured before and after surgery. A theoretical stereometric geometrical model of the square flap was established to compare it to the classical single (60 degree), 4-flap (45 degree), and 5-flap (60 degree) Z-plasties in terms of theoretical web reconstruction efficacy. All cases achieved 100% contracture release. The maximum range of motion and web space improved after square flap surgery (P = 0.001). Stereometric geometrical modeling revealed that the standard square flap (α = 45 degree; β = 90 degree) yields a larger flap area, length/width ratio, and postsurgical commissure length than the Z-plasties. It can also be adapted by varying angles α and β, although certain angle thresholds must be met to obtain the stereometric advantages of this method. When used to treat joint scar contractures, the square flap method can fully span the web space in a stereometric manner, thus yielding a close-to-original shape and function. Compared with the classical Z-plasties, it also provides sufficient anatomical blood supply while imposing the least physiological tension on the adjacent skin.

Three-dimensional Reconstruction of Scar Contracture-bearing Axilla and Digital Webs Using the Square Flap Method

PubMed Central

Huang, Chenyu

2014-01-01

Background: Joint scar contractures are characterized by tight bands of soft tissue that bridge the 2 ends of the joint like a web. Classical treatment methods such as Z-plasties are mainly based on 2-dimensional designs. Our square flap method is an alternative surgical method that restores the span of the web in a stereometric fashion, thereby reconstructing joint function. Methods: In total, 20 Japanese patients with joint scar contractures on the axillary (n = 10) or first digital web (n = 10) underwent square flap surgery. The maximum range of motion and commissure length were measured before and after surgery. A theoretical stereometric geometrical model of the square flap was established to compare it to the classical single (60 degree), 4-flap (45 degree), and 5-flap (60 degree) Z-plasties in terms of theoretical web reconstruction efficacy. Results: All cases achieved 100% contracture release. The maximum range of motion and web space improved after square flap surgery (P = 0.001). Stereometric geometrical modeling revealed that the standard square flap (α = 45 degree; β = 90 degree) yields a larger flap area, length/width ratio, and postsurgical commissure length than the Z-plasties. It can also be adapted by varying angles α and β, although certain angle thresholds must be met to obtain the stereometric advantages of this method. Conclusions: When used to treat joint scar contractures, the square flap method can fully span the web space in a stereometric manner, thus yielding a close-to-original shape and function. Compared with the classical Z-plasties, it also provides sufficient anatomical blood supply while imposing the least physiological tension on the adjacent skin. PMID:25289342

Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.

2012-07-15

Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation ofmore » the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients should be enrolled in ongoing prospective trials of hippocampal sparing during cranial irradiation to confirm these preliminary results.« less

Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.

2013-02-01

Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation ofmore » the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients should be enrolled in ongoing prospective trials of hippocampal sparing during cranial irradiation to confirm these preliminary results.« less

Associations of various family characteristics and time use with children's body mass index.

PubMed

Forshee, Richard A; Anderson, Patricia A; Storey, Maureen L

2009-04-01

This study used multiple regression models to estimate associations of various family characteristics and time use with the body mass index (BMI) z-scores of 734 boys and 725 girls aged 5-18y from the Panel Study of Income Dynamics Child Development Supplement 2003. The strongest relationship in the data was between the BMI of the head of household and a child's BMI z-score (p < 0.001). Time spent sleeping, performing sedentary behaviors, and participating in physical activities was not associated with a child's BMI z-score. This suggests that a family-oriented approach to prevent and treat childhood and adolescent overweight is required.

Association between Allogeneic or Autologous Blood Transfusion and Survival in Patients after Radical Prostatectomy: A Systematic Review and Meta-Analysis

PubMed Central

Yuan, Xiao-Hua

2017-01-01

Background A number of studies have investigated the effect of perioperative blood transfusion (PBT) for patients after radical prostatectomy (RP), with some reporting conflicting results. A systematic review of the literature and a meta-analysis were conducted to explore the association between PBT (autologous or allogeneic) and biochemical recurrence-free survival (BRFS), overall survival (OS) and cancer-specific survival (CSS) in patients undergoing RP. Methods The PubMed, Medline, Cochrane Library, and Embase databases were searched for published controlled clinical studies on perioperative allogeneic or autologous blood transfusion (BT) and patient survival after RP. STATA software version 12.0 was used for data analysis. We used hazard ratios (HRs) and 95% confidence intervals (CIs) to test the correlation between BT and patient survival after RP. Results Data from a total of 26,698 patients in ten published studies were included in the meta-analysis. The meta-analysis results showed that autologous BT was not associated with BRFS (HR: 1.06; 95% CI: 0.96–1.18; Z = 1.17; P = 0.24), OS (HR: 0.86; 95% CI: 0.71–1.04; Z = 1.58; P = 0.11), or CSS (HR: 0.98; 95% CI: 0.49–1.96; Z = 0.05; P = 0.96). Allogeneic BT exhibited a significant association with worse BRFS (HR: 1.09; 95% CI: 1.01–1.16; Z = 2.37; P = 0.02), OS (HR: 1.43; 95% CI: 1.24–1.64; Z = 4.95; P<0.01) and CSS (HR: 1.74; 95% CI: 1.18–2.56; Z = 2.81; P = 0.005). Conclusion Our data showed an association between allogeneic BT and reduced BRFS, OS and CSS in patients after RP. These findings indicate that perioperative blood conservation strategies are important for decreasing the allogeneic BT rate. PMID:28135341

Exercise restriction is not associated with increasing body mass index over time in patients with anomalous aortic origin of the coronary arteries.

PubMed

Meza, James M; Elias, Matthew D; Wilder, Travis J; O'Brien, James E; Kim, Richard W; Mavroudis, Constantine; Williams, William G; Brothers, Julie; Cohen, Meryl S; McCrindle, Brian W

2017-10-01

Anomalous aortic origin of the coronary arteries is associated with exercise-induced ischaemia, leading some physicians to restrict exercise in patients with this condition. We sought to determine whether exercise restriction was associated with increasing body mass index over time. From 1998 to 2015, 440 patients ⩽30 years old were enrolled into an inception cohort. Exercise-restriction status was documented in 143 patients. Using linear mixed model repeated-measures regression, factors associated with increasing body mass index z-score over time, including exercise restriction and surgical intervention as time-varying covariates, were investigated. The 143 patients attended 558 clinic visits for which exercise-restriction status was recorded. The mean number of clinic visits per patient was 4, and the median duration of follow-up was 1.7 years (interquartile range (IQR) 0.5-4.4). The median age at first clinic visit was 10.3 years (IQR 7.1-13.9), and 71% (101/143) were males. All patients were alive at their most recent follow-up. At the first clinic visit, 54% (78/143) were exercise restricted, and restriction status changed in 34% (48/143) during follow-up. The median baseline body mass index z-score was 0.2 (IQR 0.3-0.9). In repeated-measures analysis, neither time-related exercise restriction nor its interaction with time was associated with increasing body mass index z-score. Surgical intervention and its interaction with time were associated with decreasing body mass index z-score. Although exercise restriction was not associated with increasing body mass index over time, surgical intervention was associated with decreasing body mass index z-score over time in patients with anomalous aortic origin of the coronary arteries.

Nutritional status and growth in Korean children with Crohn's disease: a single-center study.

PubMed

Song, Seung Min; Kim, Young; Oh, Seak Hee; Kim, Kyung Mo

2014-09-01

Malnutrition and growth retardation are important issues in treating pediatric Crohn's disease (CD). Thus, we aimed to investigate the prevalence of various nutritional and growth parameters at the time of diagnosis in Korean children with CD. Seventy-one children (<18 years) were enrolled. We analyzed the Z-scores of height-for-age (HAZ), weight-for-height (WHZ), body mass index for age (BMIZ), bone mineral density for age (BMDZ), and the biochemical markers measured at the time of diagnosis. At diagnosis, HAZ <-2 was observed in three patients (4%), WHZ <-2 in 20 patients (28%), BMIZ <-2 in 19 patients (27%), and BMDZ <-2 in 11 patients (18%). The HAZ was significantly lower in females and patients with extraintestinal manifestations, and the WHZ and BMIZ were significantly lower in patients with stricturing and penetrating disease. Subnormal serum levels were highly prevalent for hemoglobin, albumin, iron, ferritin, calcium, magnesium, folate, vitamin B12, and zinc. There was a significant correlation between nutritional status, growth retardation, and disease activity. Abnormal nutritional status was highly prevalent in Korean children with CD at the time of diagnosis and was associated with the extent, behavior, and activity of the disease.

Classification of Focal and Non Focal Epileptic Seizures Using Multi-Features and SVM Classifier.

PubMed

Sriraam, N; Raghu, S

2017-09-02

Identifying epileptogenic zones prior to surgery is an essential and crucial step in treating patients having pharmacoresistant focal epilepsy. Electroencephalogram (EEG) is a significant measurement benchmark to assess patients suffering from epilepsy. This paper investigates the application of multi-features derived from different domains to recognize the focal and non focal epileptic seizures obtained from pharmacoresistant focal epilepsy patients from Bern Barcelona database. From the dataset, five different classification tasks were formed. Total 26 features were extracted from focal and non focal EEG. Significant features were selected using Wilcoxon rank sum test by setting p-value (p < 0.05) and z-score (-1.96 > z > 1.96) at 95% significance interval. Hypothesis was made that the effect of removing outliers improves the classification accuracy. Turkey's range test was adopted for pruning outliers from feature set. Finally, 21 features were classified using optimized support vector machine (SVM) classifier with 10-fold cross validation. Bayesian optimization technique was adopted to minimize the cross-validation loss. From the simulation results, it was inferred that the highest sensitivity, specificity, and classification accuracy of 94.56%, 89.74%, and 92.15% achieved respectively and found to be better than the state-of-the-art approaches. Further, it was observed that the classification accuracy improved from 80.2% with outliers to 92.15% without outliers. The classifier performance metrics ensures the suitability of the proposed multi-features with optimized SVM classifier. It can be concluded that the proposed approach can be applied for recognition of focal EEG signals to localize epileptogenic zones.

Maternal Therapy with Ad.VEGF-A165 Increases Fetal Weight at Term in a Guinea-Pig Model of Fetal Growth Restriction.

PubMed

Swanson, Anna M; Rossi, Carlo A; Ofir, Keren; Mehta, Vedanta; Boyd, Michael; Barker, Hannah; Ledwozyw, Agata; Vaughan, Owen; Martin, John; Zachary, Ian; Sebire, Neil; Peebles, Donald M; David, Anna L

2016-12-01

In a model of growth-restricted sheep pregnancy, it was previously demonstrated that transient uterine artery VEGF overexpression can improve fetal growth. This approach was tested in guinea-pig pregnancies, where placental physiology is more similar to humans. Fetal growth restriction (FGR) was attained through peri-conceptual nutrient restriction in virgin guinea pigs. Ad.VEGF-A 165 or Ad.LacZ (1 × 10 10 vp) was applied at mid-gestation via laparotomy, delivered externally to the uterine circulation with thermosensitive gel. At short-term (3-8 days post surgery) or at term gestation, pups were weighed, and tissues were sampled for vector spread analysis, VEGF expression, and its downstream effects. Fetal weight at term was increased (88.01 ± 13.36 g; n = 26) in Ad.VEGF-A 165 -treated animals compared with Ad.LacZ-treated animals (85.52 ± 13.00 g; n = 19; p = 0.028). The brain, liver, and lung weight and crown rump length were significantly larger in short-term analyses, as well as VEGF expression in transduced tissues. At term, molecular analyses confirmed the presence of VEGF transgene in target tissues but not in fetal samples. Tissue histology analysis and blood biochemistry/hematological examination were comparable with controls. Uterine artery relaxation in Ad.VEGF-A 165 -treated dams was higher compared with Ad.LacZ-treated dams. Maternal uterine artery Ad.VEGF-A 165 increases fetal growth velocity and term fetal weight in growth-restricted guinea-pig pregnancy.

Propheromones that release pheromonal carbonyl compounds in light.

PubMed

Liu, X; Macaulay, E D; Pickett, J A

1984-05-01

Pheromonal carbonyl compounds; (Z)-11-hexadecanal, (E)-citral, and 2-heptanone were treated with six alcohols to give acetals or ketals, some of which acted as propheromones by releasing the pheromonal carbonyl compounds in ultraviolet or simulated sunlight. Highest yields of pheromone were obtained from adducts prepared witho-nitrobenzyl alcohol ando-nitrophenylethane-1,2-diol. Adducts from (Z)-11-hexadecenal and these two alcohols were employed in lures to catch diamondback moths,Plutella xylostella (L.).

Inverted Nipple Correction with Selective Dissection of Lactiferous Ducts Using an Operative Microscope and a Traction Technique.

PubMed

Sowa, Yoshihiro; Itsukage, Sizu; Morita, Daiki; Numajiri, Toshiaki

2017-10-01

An inverted nipple is a common congenital condition in young women that may cause breastfeeding difficulty, psychological distress, repeated inflammation, and loss of sensation. Various surgical techniques have been reported for correction of inverted nipples, and all have advantages and disadvantages. Here, we report a new technique for correction of an inverted nipple using an operative microscope and traction that results in low recurrence and preserves lactation function and sensation. Between January 2010 and January 2013, we treated eight inverted nipples in seven patients with selective lactiferous duct dissection using an operative microscope. An opposite Z-plasty was added at the junction of the nipple and areola. Postoperatively, traction was applied through an apparatus made from a rubber gasket attached to a sterile syringe. Patients were followed up for 15-48 months. Adequate projection was achieved in all patients, and there was no wound dehiscence or complications such as infection. Three patients had successful pregnancies and subsequent breastfeeding that was not adversely affected by the treatment. There was no loss of sensation in any patient during the postoperative period. Our technique for treating an inverted nipple is effective and preserves lactation function and nipple sensation. The method maintains traction for a longer period, which we believe increases the success rate of the surgery for correction of severely inverted nipples. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Initiation and long-term use of benzodiazepines and Z-drugs in bipolar disorder.

PubMed

Wingård, Louise; Taipale, Heidi; Reutfors, Johan; Westerlund, Anna; Bodén, Robert; Tiihonen, Jari; Tanskanen, Antti; Andersen, Morten

2018-02-16

Increasing evidence points to the harmful effects of long-term benzodiazepine treatment. Our objective was to study the incidence of, and predictors for, long-term use of benzodiazepines and Z-drugs in bipolar disorder. We conducted a population-based cohort study, using data from Swedish national registers. Swedish residents aged 18-75 years with a recorded diagnosis of bipolar disorder or mania between July 2006 and December 2012, and no history of benzodiazepine/Z-drug use in the past year, were included. Patients were followed for 1 year with regard to prescription fills of benzodiazepines/Z-drugs. Initiators were followed for another year during which continuous use for >6 months was defined as "long-term". Patient and prescription characteristics were investigated as potential predictors for long-term use in multivariate logistic regression models. Out of the 21 883 patients included, 29% started benzodiazepine/Z-drug treatment, of whom one in five became long-term users. Patients who were prescribed clonazepam or alprazolam had high odds for subsequent long-term use (adjusted odds ratios [aORs] 3.78 [95% confidence interval (CI) 2.24-6.38] and 2.03 [95% CI 1.30-3.18], respectively), compared to those prescribed diazepam. Polytherapy with benzodiazepines/Z-drugs also predicted long-term use (aOR 2.46, 95% CI 1.79-3.38), as did age ≥60 years (aOR 1.93, 95% CI 1.46-2.53, compared to age <30 years), and concomitant treatment with psychostimulants (aOR 1.78, 95% CI 1.33-2.39). The incidence of subsequent long-term use among bipolar benzodiazepine initiators is high. Patients on clonazepam, alprazolam or benzodiazepine/Z-drug polytherapy have the highest risk of becoming long-term users, suggesting that these treatments should be used restrictively. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Meta analysis of three-dimensional printing patient-specific instrumentation versus conventional instrumentation in total knee arthroplasty].

PubMed

Ren, J T; Xu, C; Wang, J S; Liu, X L

2017-10-01

Objective: To evaluate the effects of three-dimensional printing patient-specific instrumentation(PSI) versus conventional instrumentation(CI) in the total knee arthroplasty. Methods: According to "patient-specific" , "patient-matched" , "custom" , "Instrumentation" , "Guide Instrumentation" , "cutting blocks" , "total knee arthroplasty" , "total knee replacement" , "TKA" and "TKR" , the literature on PubMed, EMbase, Cochrane library, CBM and WanFang were searched. According to the inclusion and exclusion criteria, the high quality randomized control trial (RCT) studies about three-dimensional (3D) printing patient-specific instrumentation versus conventional instrumentation in the total knee arthroplasty were collected. The post-operative limb mechanical axis outlier, the position of the components outlier, post-operative knee function, operative time, post-operative blood transfusion and complications were analyzed by RevMan 5.3 software. Results: A total of 13 high quality RCT studies were included. The results of Meta-analysis show that there were no statistical differences in the post-operative limb mechanical axis outlier( Z =0.55, P =0.58, 95% CI: 0.78 to 1.56), femoral coronal component outlier( Z =0.38, P =0.71, 95% CI: 0.69 to 1.72), tibia coronal component outlier( Z =1.95, P =0.05, 95% CI: 1.00 to 3.38), femoral rotation angle outlier( Z =0.36, P =0.72, 95% CI: 0.49 to 1.64), post-operative knee function( Z =1.18, P =0.24, 95% CI : -0.66 to 2.63), post-operative blood transfusions( Z =0.74, P =0.46, 95% CI: -0.10 to 0.05) and complications( Z =0.18, P =0.86, 95% CI: -0.07 to 0.05) between the PSI group and the CI group. But there are statistical differences in the operation time( Z =2.66, P =0.01, 95% CI: -15.97 to -2.41)and tibia sagittal component outlier ( Z =3.69, P =0.00, 95% CI: 1.43 to 3.18)between the PSI group and the CI group. Conclusions: In the primary total knee arthroplasty the PSI is not superior over the CI for the knee without severe knee varus or valgus deformity or contracture deformity, without the deformity around the knee and without the knee bone loss and obesity. The use of PSI in the primary total knee arthroplasty are not recommend.

Focusers of obliquely incident laser radiation

NASA Astrophysics Data System (ADS)

Goncharskiy, A. V.; Danilov, V. A.; Popov, V. V.; Prokhorov, A. M.; Sisakyan, I. N.; Sayfer, V. A.; Stepanov, V. V.

1984-08-01

Focusing obliquely incident laser radiation along a given line in space with a given intensity distribution is treated as a problem of synthesizing a mirror surface. The intricate shape of such a surface, characterized by a function z= z (u,v) in the approximation of geometrical optics, is determined from the equation phi (u,v,z) - phi O(u,v,z)=O, which expresses that the incident field and the reflected field have identical eikonals. Further calculations are facilitated by replacing continuous mirror with a more easily manufactured piecewise continuous one. The problem is solved for the simple case of a plane incident wave with a typical iconal phi O(u,v,z)= -z cos0 at a large angle to a focus mirror in the z-plane region. Mirrors constructed on the basis of the theoretical solution were tested in an experiment with a CO2 laser. A light beam with Gaussian intensity distribution was, upon incidence at a 45 deg angle, focused into a circle or into an ellipse with uniform intensity distribution. Improvements in amplitudinal masking and selective tanning technology should reduce energy losses at the surface which results in efficient laser focusing mirrors.

The effect of GABA transporter 1 (GAT1) inhibitor, tiagabine, on scopolamine-induced memory impairments in mice.

PubMed

Sałat, Kinga; Podkowa, Adrian; Mogilski, Szczepan; Zaręba, Paula; Kulig, Katarzyna; Sałat, Robert; Malikowska, Natalia; Filipek, Barbara

2015-12-01

GABAergic neurotransmission is involved in long-term potentiation, a neurophysiological basis for learning and memory. On the other hand, GABA-enhancing drugs may impair memory and learning in humans and animals. The present study aims at investigating the effect of GAT1 inhibitor tiagabine on memory and learning. Albino Swiss (CD-1) and C57BL/6J mice were used in the passive avoidance (PA), Morris water maze (MWM) and radial arm water maze (RAWM) tasks. Scopolamine (1mg/kg ip) was applied to induce cognitive deficits. In the retention trial of PA scopolamine reduced step-through latency as compared to vehicle-treated mice, and pretreatment with tiagabine did not have any influence on this effect. In MWM the results obtained for vehicle-treated mice, scopolamine-treated group and combined scopolamine+tiagabine-treated mice revealed variable learning abilities in these groups. Tiagabine did not impair learning in the acquisition trial. In RAWM on day 1 scopolamine-treated group made nearly two-fold more errors than vehicle-treated mice and mice that received combined scopolamine and tiagabine. Learning abilities in the latter group were similar to those of vehicle-treated mice in the corresponding trial block on day 1, except for the last trial block, during which tiagabine+scopolamine-injected mice made more errors than control mice and the scopolamine-treated group. In all groups a complete reversal of memory deficits was observed in the last trial block of day 2. The lack of negative influence of tiagabine on cognitive functions in animals with scopolamine-induced memory impairments may be relevant for patients treated with this drug. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Monitoring codling moth (Lepidoptera: Tortricidae) in orchards treated with pear ester and sex pheromone combo dispensers

USDA-ARS?s Scientific Manuscript database

Lures for monitoring codling moth, Cydia pomonella (L.), were tested in apple and walnut blocks treated with Cidetrak CM-DA Combo dispensers loaded with pear ester, ethyl (E, Z)-2,4-decadienoate (PE), and sex pheromone (E,E)-8,10-dodecadien-1-ol (codlemone). Total and female moth catches with combin...

SAR Studies on Trisubstituted Benzimidazoles as Inhibitors of Mtb FtsZ for the Development of Novel Antitubercular Agents

PubMed Central

Awasthi, Divya; Kumar, Kunal; Knudson, Susan E.; Slayden, Richard A.; Ojima, Iwao

2014-01-01

FtsZ, an essential protein for bacterial cell division, is a highly promising therapeutic target, especially for the discovery and development of new-generation anti-TB agents. Following up the identification of two lead 2,5,6-trisubstituted benzimidazoles, 1 and 2, targeting Mtb-FtsZ in our previous study, an extensive SAR study for optimization of these lead compounds was performed through systematic modification of the 5 and 6 positions. This study has successfully led to the discovery of a highly potent advanced lead 5f (MIC 0.06 µg/mL) and several other compounds with comparable potencies. These advanced lead compounds possess a dimethylamino group at the 6 position. The functional groups at the 5 position exhibit substantial effects on the antibacterial activity as well. In vitro experiments such as the FtsZ polymerization inhibitory assay and TEM analysis of Mtb-FtsZ treated with 5f and others indicate that Mtb-FtsZ is the molecular target for their antibacterial activity. PMID:24266862

SAR studies on trisubstituted benzimidazoles as inhibitors of Mtb FtsZ for the development of novel antitubercular agents.

PubMed

Awasthi, Divya; Kumar, Kunal; Knudson, Susan E; Slayden, Richard A; Ojima, Iwao

2013-12-12

FtsZ, an essential protein for bacterial cell division, is a highly promising therapeutic target, especially for the discovery and development of new-generation anti-TB agents. Following up the identification of two lead 2,5,6-trisubstituted benzimidazoles, 1 and 2, targeting Mtb-FtsZ in our previous study, an extensive SAR study for optimization of these lead compounds was performed through systematic modification of the 5 and 6 positions. This study has successfully led to the discovery of a highly potent advanced lead 5f (MIC = 0.06 μg/mL) and several other compounds with comparable potencies. These advanced lead compounds possess a dimethylamino group at the 6 position. The functional groups at the 5 position exhibit substantial effects on the antibacterial activity as well. In vitro experiments such as the FtsZ polymerization inhibitory assay and TEM analysis of Mtb-FtsZ treated with 5f and others indicate that Mtb-FtsZ is the molecular target for their antibacterial activity.

On functions of quasi-Toeplitz matrices

NASA Astrophysics Data System (ADS)

Bini, D. A.; Massei, S.; Meini, B.

2017-11-01

Let a(z)=\\sumi\\in Za_iz^i be a complex-valued function, defined for |z|=1, such that \\sumi=-∞+∞|ia_i|<∞. Consider the semi-infinite Toeplitz matrix T(a)=(ti,j)i,j\\in Z^+ associated with the symbol a(z) such that {ti,j=aj-i}. A quasi-Toeplitz matrix associated with the symbol a(z) is a matrix of the form A=T(a)+E where E=(ei,j), \\sumi,j\\in Z^+|ei,j|<∞, and is called a {QT}-matrix. Given a function f(x) and a {QT}-matrix M, we provide conditions under which f(M) is well defined and is a {QT}-matrix. Moreover, we introduce a parametrization of {QT}-matrices and algorithms for the computation of f(M). We treat the case where f(x) is given in terms of power series and the case where f(x) is defined in terms of a Cauchy integral. This analysis is also applied to finite matrices which can be written as the sum of a Toeplitz matrix and a low rank correction. Bibliography: 27 titles.

Radiosensitization of high-Z compounds by medium-energy 160 kV vs. high-energy 6 MV X-rays for radiation therapy: Theoretical, in vitro and in vivo studies of platinum compounds activating glioma F98 cancer cells

NASA Astrophysics Data System (ADS)

Lim, S.; Pradhan, A.; Nahar, S.; Montenegro, M.; Barth, R.; Nakkula, R.; Turro, C.

2013-03-01

Energy dependence of X-ray irradiation of high-Z compounds for enhanced radiosensitization is explored thoeretically and via in vitro and in vivo experiments. The cell killing ability of medium-energy X-rays from 160 kV source are found to be more effective than 6 MV X-rays in activating high-Z contrast agents. Results are presented for a newly synthesized Pt compound, Pyridine Terpyridine Pt(II) Nitrate ([Pt(typ)(py)]) and carboplatin in treating F98 rat glioma. In-vitro results show considerable reduction in cell viability for radiosensitized cells irradiated with a 160 kV irradiator. Cells treated with 6 MV LINAC radiation find little variation with radiation dose. Maximum dose enhancement factors (DEFs) and minimum cancer cell survival fractions correspond to 50-200 keV range, and fall rapidly at higher energies. Theoretical calculations of photoelectric absorption vis-a-vis total scattering demonstrates this energy dependence. However, in vivo studies of rats treated with [Pt(tpy)(py)] had a severe negative neurotoxic response, confirmed by histopathological analysis. But subsequent in vivo studies using carboplatin showed very positive results in the treatment of F98 glioma bearing rats and potential clinical radiation therapy.

Oligo-carrageenan kappa-induced reducing redox status and activation of TRR/TRX system increase the level of indole-3-acetic acid, gibberellin A3 and trans-zeatin in Eucalyptus globulus trees.

PubMed

González, Alberto; Contreras, Rodrigo A; Zúiga, Gustavo; Moenne, Alejandra

2014-08-20

Eucalyptus globulus trees treated with oligo-carrageenan (OC) kappa showed an increase in NADPH, ascorbate and glutathione levels and activation of the thioredoxin reductase (TRR)/thioredoxin (TRX) system which enhance photosynthesis, basal metabolism and growth. In order to analyze whether the reducing redox status and the activation of thioredoxin reductase (TRR)/thioredoxin (TRX) increased the level of growth-promoting hormones, trees were treated with water (control), with OC kappa, or with inhibitors of ascorbate synthesis, lycorine, glutathione synthesis, buthionine sulfoximine (BSO), NADPH synthesis, CHS-828, and thioredoxin reductase activity, auranofine, and with OC kappa, and cultivated for four additional months. Eucalyptus trees treated with OC kappa showed an increase in the levels of the auxin indole 3-acetic acid (IAA), gibberellin A3 (GA3) and the cytokinin trans-zeatin (t-Z) as well as a decrease in the level of the brassinosteroid epi-brassinolide (EB). In addition, treatment with lycorine, BSO, CHS-828 and auranofine inhibited the increase in IAA, GA3 and t-Z as well as the decrease in EB levels. Thus, the reducing redox status and the activation of TRR/TRX system induced by OC kappa increased the levels of IAA, GA3 and t-Z levels determining, at least in part, the stimulation of growth in Eucalyptus trees.

Small Field-of-view single-shot EPI-DWI of the prostate: Evaluation of spatially-tailored two-dimensional radiofrequency excitation pulses.

PubMed

Attenberger, Ulrike I; Rathmann, Nils; Sertdemir, Metin; Riffel, Philipp; Weidner, Anja; Kannengiesser, Stefan; Morelli, John N; Schoenberg, Stefan O; Hausmann, Daniel

2016-06-01

Spatially-tailored (RF) excitation pulses in echo-planar imaging (EPI), combined with a decreased FOV in the phase-encoding direction, enable a reduction of k-space acquisition lines, which shortens the echo train length (ETL) and reduces susceptibility artifacts. The purpose of this study was to evaluate the image quality of a zoomed EPI (z-EPI) sequence in diffusion-weighted imaging (DWI) of the prostate in comparison to a conventional single-shot EPI using single-channel (c-EPI1) and multi-channel (c-EPI2) RF excitation, with and without use of an endorectal coil. 33 consecutive patients (mean age: 61 +/- 9 years; mean PSA: 8.67±6.23 ng/ml) with examinations between 10/2012 and 02/2014 were analyzed in this retrospective study. In 26 of 33 patients the initial multiparametric (mp)-MRI was performed on a whole-body 3T scanner (Magnetom Trio, Siemens, Erlangen, Germany) using an endorectal coil (c (conventional)-EPI1). Zoomed-EPI (Z-EPI) examinations of these patients and a complete mp-MRI protocol including c-EPI2 of 7 additional patients were carried out on another 3T wb MR scanner with two-channel dynamic parallel transmit capability (Magnetom Skyra with TimTX TrueShape, Siemens). For z-EPI, the one-dimensional spatially selective RF excitation pulse was replaced by a two-dimensional RF pulse. Degree of image blur and susceptibility artifacts (0=not present to 3= non-diagnostic), maximum image distortion (mm), apparent diffusion coefficient (ADC) values, as well as overall scan preference were evaluated. SNR maps were generated to compare c-EPI2 and z-EPI. Overall image quality of z-EPI was preferred by both readers in all examinations with a single exception. Susceptibility artifacts were rated significantly lower on z-EPI compared to both other methods (z-EPI vs c-EPI1: p<0.01; z-EPI vs c-EPI2: p<0.01) as well as image blur (z-EPI vs c-EPI1: p<0.01; z-EPI vs c-EPI2: p<0.01). Image distortion was not statistically significantly reduced with z-EPI (z-EPI vs c-EPI1: p=0.12; z-EPI vs c-EPI2: p=0.42). Interobserver agreement for ratings of susceptibility artifacts, image blur and overall scan preference was good. SNR was higher for z-EPI than for c-EPI1 (n=1). Z-EPI leads to significant improvements in image quality and artifacts as well as image blur reduction improving prostate DWI and enabling accurate fusion with conventional sequences. The improved fusion could lead to advantages in the field of MRI-guided biopsy suspicous lesions and performance of locally ablative procedures for prostate cancer. Copyright © 2015. Published by Elsevier GmbH.

Identification of novel serum peptides biomarkers for female breast cancer patients in Western China.

PubMed

Yang, Juan; Xiong, Xiaofan; Liu, Siyuan; Zhu, Jiang; Luo, Mai; Liu, Liying; Zhao, Lingyu; Qin, Yannan; Song, Tusheng; Huang, Chen

2016-03-01

This study aimed to identify novel serum peptides biomarkers for female breast cancer (BC) patients. We analyzed the serum proteomic profiling of 247 serum samples from 96 BC patients, 48 additional paired pre- and postoperative BC patients, 39 fibroadenoma patients as benign disease controls, and 64 healthy controls, using magnetic-bead-based separation followed by MALDI-TOF MS. ClinProTools software identified 78 m/z peaks that differed among all analyzed groups, ten peaks were significantly different (P < 0.0001), with Peaks 1-6 upregulated and Peaks 7-10 downregulated in BC. Moreover, three peaks of ten (Peak 1, m/z: 2660.11; Peak 2, m/z: 1061.09; Peak 10, m/z: 1041.25) showed a tendency to return to healthy control values after surgery. And these three peptide biomarkers were identified as FGA605-629, ITIH4 347-356, and APOA2 43-52. Methods used in this study could generate serum peptidome profiles of BC, and provide a new approach to identify potential biomarkers for diagnosis as well as prognosis of this malignancy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Elevated Z line: a new sign of Barrett's esophagus on double-contrast barium esophagograms.

PubMed

Levine, Marc S; Ahmad, Nuzhat A; Rubesin, Stephen E

2015-01-01

We describe an elevated Z line as a new radiographic sign of Barrett's esophagus characterized by a transversely oriented, zigzagging, barium-etched line extending completely across the circumference of the midesophagus. An elevated Z line is rarely seen in other patients, so this finding should be highly suggestive of Barrett's esophagus on double-contrast barium esophagograms. If the patient is a potential candidate for surveillance, endoscopy and biopsy should be performed to confirm the presence of Barrett's esophagus. Copyright © 2015 Elsevier Inc. All rights reserved.

Postnatal treatment factors affecting craniofacial morphology of unilateral cleft lip and palate (UCLP) patients in a Japanese population.

PubMed

Alam, M K; Iida, J; Sato, Y; Kajii, Takashi S

2013-12-01

We have evaluated the craniofacial morphology of Japanese patients with unilateral cleft lip and palate (UCLP) and assessed the various postnatal factors that affect it. Lateral cephalograms of 140 subjects (mean (SD) aged 7 (2) years) with UCLP were taken before orthodontic treatment. Surgeons from Hokkaido University Hospital had done the primary operations. The craniofacial morphology was assessed by angular and linear cephalometric measurements. Cheiloplasty, palatoplasty, and preoperative orthopaedic treatment were chosen as postnatal factors. To compare the assessments of the postnatal factors, we made angular and linear cephalometric measurements for each subject and converted them into Z scores in relation to the mean (SD) of the two variables. Subjects treated by the modified Millard cheiloplasty had larger sella-nasion-point A (SNA) and nasion-point A-pogonion (NA-POG) measurements than subjects treated by the modified Millard with a vomer flap cheiloplasty. Two-stage palatoplasty showed consistently better craniofacial morphology than the other palatoplasty. Subjects who had preoperative orthopaedic treatment with a Hotz plate had significantly larger upper incisor/sella-nasion (U1-SN) measurements than who had no preoperative orthopaedic treatment or an active plate. We conclude that in subjects treated by a modified Millard type of cheiloplasty, a two-stage palatoplasty, and a Hotz plate there were fewer adverse effects on craniofacial morphology. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Using Modeling to Predict Medical Requirements for Special Operations Missions

DTIC Science & Technology

2008-07-30

Ventilator 280 Patient Discharge Instructions 044 Setup Drainage Bottles/Pleurevac 359 Induce Local Anesthesia 046 Maintain Chest Tube Suction 453 Closed...Incision) Z094 Extremity Traction, Application/Adjust 110 Test Vision Z103 Re-Establish IV Access ( Intraosseous ) 121 Eye Irrigation Z277 Prepare For Evac

When is category specific in Alzheimer's disease?

PubMed

Laws, Keith R; Gale, Tim M; Leeson, Verity C; Crawford, John R

2005-08-01

Mixed findings have emerged concerning whether category-specific disorders occur in Alzheimer's disease. Factors that may contribute to these inconsistencies include: ceiling effects/skewed distributions for control data in some studies; differences in the severity of cognitive deficit in patients; and differences in the type of analysis (in particular, if and how controls are used to analyse single case data). We examined picture naming in Alzheimer's patients and matched elderly healthy normal controls in three experiments. These experiments used stimuli that did and did not produce ceiling effects/skewed data in controls. In Experiment 1, we examined for category effects in individual DAT patients using commonly used analyses for single cases (chi2 and z-scores). The different techniques produced quite different outcomes. In Experiment 2a, we used the same techniques on a different group of patients with similar outcomes. Finally, in Experiment 2b, we examined the same patients but (a) used stimuli that did not produce ceiling effects/skewed distributions in healthy controls, and (b) used statistical methods that did not treat the control sample as a population. We found that ceiling effects in controls may markedly inflate the incidence of dissociations in which living things are differentially impaired and seriously underestimate dissociations in the opposite direction. In addition, methods that treat the control sample as a population led to inflation in the overall number of dissociations detected. These findings have implications for the reliability of category effects previously reported both in Alzheimer patients and in other pathologies. In particular, they suggest that the greater proportion of living than nonliving deficits reported in the literature may be an artifact of the methods used.

Caries inhibition with a CO2 9.3 μm laser: An in vitro study.

PubMed

Rechmann, Peter; Rechmann, Beate M T; Groves, William H; Le, Charles Q; Rapozo-Hilo, Marcia L; Kinsel, Richard; Featherstone, John D B

2016-07-01

The caries preventive effects of different laser wavelengths have been studied in the laboratory as well as in pilot clinical trials. The objective of this in vitro study was to evaluate whether irradiation with a new 9.3 μm microsecond short-pulsed CO2 -laser could enhance enamel caries resistance with and without additional fluoride applications. One hundred and one human tooth enamel samples were divided into seven groups. Each group was treated with different laser parameters (CO2 -laser, wavelength 9.3 μm, 43 Hz pulse-repetition rate, pulse duration between 3 µs at 1.5 mJ/pulse to 7 µs at 2.9 mJ/pulse). A laboratory pH-cycling model followed by cross-sectional microhardness testing determined the mean relative mineral loss delta Z (ΔZ) for each group to assess caries inhibition in tooth enamel by the CO2 9.3 µm short-pulsed laser irradiation. The pH-cycling was performed with or without additional fluoride. The non-laser control groups with additional fluoride had a relative mineral loss (ΔZ, vol% × µm) that ranged between 646 ± 215 and 773 ± 223 (mean ± SD). The laser irradiated and fluoride treated samples had a mean ΔZ ranging between 209 ± 133 and 403 ± 245 for an average 55% ± 9% reduction in mineral loss (ANOVA test, P < 0.0001). Increased mean mineral loss (ΔZ between 1166 ± 571 and 1339 ± 347) was found for the non-laser treated controls without additional fluoride. In contrast, the laser treated groups without additional fluoride showed a ΔZ between 470 ± 240 and 669 ± 209 (ANOVA test, P < 0.0001) representing an average 53% ± 11% reduction in mineral loss. Scanning electron microscopical assessment revealed that 3 µs pulses did not markedly change the enamel surface, while 7 µs pulses caused some enamel ablation. The CO2 9.3 µm short-pulsed laser energy renders enamel caries resistant with and without additional fluoride use. The observed enhanced acid resistance occurred with the laser irradiation parameters used without obvious melting of the enamel surface as well as after irradiation with energies causing cutting of the enamel. Lasers Surg. Med. 48:546-554, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Quasi-parton distribution functions, momentum distributions, and pseudo-parton distribution functions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radyushkin, Anatoly V.

Here, we show that quasi-PDFs may be treated as hybrids of PDFs and primordial rest-frame momentum distributions of partons. This results in a complicated convolution nature of quasi-PDFs that necessitates using large p 3≳ 3 GeV momenta to get reasonably close to the PDF limit. Furthemore, as an alternative approach, we propose to use pseudo-PDFs P(x, zmore » $$2\\atop{3}$$) that generalize the light-front PDFs onto spacelike intervals and are related to Ioffe-time distributions M (v, z$$2\\atop{3}$$), the functions of the Ioffe time v = p 3 z 3 and the distance parameter z$$2\\atop{3}$$ with respect to which it displays perturbative evolution for small z 3. In this form, one may divide out the z$$2\\atop{3}$$ dependence coming from the primordial rest-frame distribution and from the problematic factor due to lattice renormalization of the gauge link. The v-dependence remains intact and determines the shape of PDFs.« less

Quasi-parton distribution functions, momentum distributions, and pseudo-parton distribution functions

DOE PAGES

Radyushkin, Anatoly V.

2017-08-28

Here, we show that quasi-PDFs may be treated as hybrids of PDFs and primordial rest-frame momentum distributions of partons. This results in a complicated convolution nature of quasi-PDFs that necessitates using large p 3≳ 3 GeV momenta to get reasonably close to the PDF limit. Furthemore, as an alternative approach, we propose to use pseudo-PDFs P(x, zmore » $$2\\atop{3}$$) that generalize the light-front PDFs onto spacelike intervals and are related to Ioffe-time distributions M (v, z$$2\\atop{3}$$), the functions of the Ioffe time v = p 3 z 3 and the distance parameter z$$2\\atop{3}$$ with respect to which it displays perturbative evolution for small z 3. In this form, one may divide out the z$$2\\atop{3}$$ dependence coming from the primordial rest-frame distribution and from the problematic factor due to lattice renormalization of the gauge link. The v-dependence remains intact and determines the shape of PDFs.« less

Terbinafine in the treatment of dermatophyte toenail onychomycosis: a meta-analysis of efficacy for continuous and intermittent regimens.

PubMed

Gupta, A K; Paquet, M; Simpson, F; Tavakkol, A

2013-03-01

To compare mycological and complete cures of terbinafine continuous and intermittent regimens in the treatment of toenail onychomycosis. The PubMed database was searched using the terms "terbinafine", "onychomycosis", "continuous" and "pulse(d)" or "intermittent". The inclusion criteria were head-to-head comparison of terbinafine pulse and continuous regimens for dermatophyte toenail infections. Risk ratios were calculated for intention-to-treat and evaluable patient analyses, when possible. Pooled estimates for total and subgroup analyses were calculated using a random effect model, Mantel-Haenszel method and their probabilities were calculated with z-statistics. Nine studies from eight publications were included. Two continuous regimens and four intermittent regimens were investigated. A pooled risk ratio of 0.87 was obtained for intention-to-treat (95% CI: 0.79-0.96, P = 0.004, n = 6) and evaluable patient (95% CI: 0.80-0.96, P = 0.003, n = 8) analyses of mycological cure, favouring continuous terbinafine. For complete cure, pooled risk ratios of 0.97 (95% CI: 0.77-1.23, P = 0.82, n = 7) for intention-to-treat and 0.93 (95% CI: 0.76-1.13, P = 0.44, n = 9) for evaluable patient analyses showed equality of the two regimens. The pulse regimen that demonstrated consistently comparable results to the continuous terbinafine regimen was two pulses of terbinafine 250 mg/day for 4 weeks on/4 weeks off. Meta-analysis of published studies of toenail onychomycosis showed that a continuous terbinafine regimen is generally significantly superior to a pulsed terbinafine regimen for mycological cure. In contrast, some pulse terbinafine regimens were as effective as continuous terbinafine regimens for complete cure. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Lie integrable cases of the simplified multistrain/two-stream model for tuberculosis and dengue fever

NASA Astrophysics Data System (ADS)

Nucci, M. C.; Leach, P. G. L.

2007-09-01

We apply the techniques of Lie's symmetry analysis to a caricature of the simplified multistrain model of Castillo-Chavez and Feng [C. Castillo-Chavez, Z. Feng, To treat or not to treat: The case of tuberculosis, J. Math. Biol. 35 (1997) 629-656] for the transmission of tuberculosis and the coupled two-stream vector-based model of Feng and Velasco-Hernandez [Z. Feng, J.X. Velasco-Hernandez, Competitive exclusion in a vector-host model for the dengue fever, J. Math. Biol. 35 (1997) 523-544] to identify the combinations of parameters which lead to the existence of nontrivial symmetries. In particular we identify those combinations which lead to the possibility of the linearization of the system and provide the corresponding solutions. Many instances of additional symmetry are analyzed.

The Relationship Between the Changes in Local Stiffness of Chicken Myofibril and the Tenderness of Muscle During Postmortem Aging

NASA Astrophysics Data System (ADS)

Iwasaki, T.; Hasegawa, Y.; Yamamoto, K.; Nakamura, K.

We have investigated that the relationship between the stiffness of myofibrils and the tenderness of muscle during postmortem aging. The stiffness (elasticity) of A and I bands as well as Z-line of chicken myofibrils during postmortem aging were measured by atomic force microscope. The stiffness of all regions increased till 12 hr of postmortem, then it decreased to 96 hr. This tendency was the same as the changes of shear force value of whole muscle during postmortem aging. The elasticity of the Z-line of chicken myofibrils treated with calcium ions in the presence of protease inhibitor decreased with treating time. This indicates that the nonenzymatic structural changes of myofibrils is one of the causes of meat tenderization.

Computer Models of Underwater Acoustic Propagation.

DTIC Science & Technology

1980-01-02

deterministic propagation loss result. Development of a model for the more general problem is required, as evidenced by the trends in future sonar designs ...air. The water column itself is treated as an ideal fluid incapable of supporting showr stresses and having a uniform or, at most, piecewise constant...evaluated at any depth (zs 4 z -zN). The layer in which the source is located will be designated by LS and the receiver layer by LR. The depth dependent

Caspase inhibitors promote vestibular hair cell survival and function after aminoglycoside treatment in vivo

NASA Technical Reports Server (NTRS)

Matsui, Jonathan I.; Haque, Asim; Huss, David; Messana, Elizabeth P.; Alosi, Julie A.; Roberson, David W.; Cotanche, Douglas A.; Dickman, J. David; Warchol, Mark E.

2003-01-01

The sensory hair cells of the inner ear undergo apoptosis after acoustic trauma or aminoglycoside antibiotic treatment, causing permanent auditory and vestibular deficits in humans. Previous studies have demonstrated a role for caspase activation in hair cell death and ototoxic injury that can be reduced by concurrent treatment with caspase inhibitors in vitro. In this study, we examined the protective effects of caspase inhibition on hair cell death in vivo after systemic injections of aminoglycosides. In one series of experiments, chickens were implanted with osmotic pumps that administrated the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (zVAD) into inner ear fluids. One day after the surgery, the animals received a 5 d course of treatment with streptomycin, a vestibulotoxic aminoglycoside. Direct infusion of zVAD into the vestibule significantly increased hair cell survival after streptomycin treatment. A second series of experiments determined whether rescued hair cells could function as sensory receptors. Animals treated with streptomycin displayed vestibular system impairment as measured by a greatly reduced vestibulo-ocular response (VOR). In contrast, animals that received concurrent systemic administration of zVAD with streptomycin had both significantly greater hair cell survival and significantly increased VOR responses, as compared with animals treated with streptomycin alone. These findings suggest that inhibiting the activation of caspases promotes the survival of hair cells and protects against vestibular function deficits after aminoglycoside treatment.

The cathepsin B inhibitor, z-FA-CMK is toxic and readily induced cell death in human T lymphocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liow, K.Y.; Chow, S.C., E-mail: chow.sek.chuen@monash.edu

The cathepsin B inhibitor, benzyloxycarbonyl-phenylalanine-alanine-chloromethylketone (z-FA-CMK) was found to be toxic and readily induced cell death in the human T cell line, Jurkat, whereas two other analogs benzyloxycarbonyl-phenylalanine-alanine-fluoromethylketone (z-FA-FMK) and benzyloxycarbonyl-phenylalanine-alanine-diazomethylketone (z-FA-DMK) were not toxic. The toxicity of z-FA-CMK requires not only the CMK group, but also the presence of alanine in the P1 position and the benzyloxycarbonyl group at the N-terminal. Dose–response studies showed that lower concentrations of z-FA-CMK induced apoptosis in Jurkat T cells whereas higher concentrations induced necrosis. In z-FA-CMK-induced apoptosis, both initiator caspases (-8 and -9) and effector caspases (-3, -6 and -7) were processed tomore » their respective subunits in Jurkat T cells. However, only the pro-form of the initiator caspases were reduced in z-FA-CMK-induced necrosis and no respective subunits were apparent. The caspase inihibitor benzyloxycarbonyl-valine-alanine-aspartic acid-(O-methyl)-fluoromehylketone (z-VAD-FMK) inhibits apoptosis and caspase processing in Jurkat T cells treated with low concentration of z-FA-CMK but has no effect on z-FA-CMK-induced necrosis and the loss of initiator caspases. This suggests that the loss of initiator caspases in Jurkat T cells during z-FA-CMK-induced necrosis is not a caspase-dependent process. Taken together, we have demonstrated that z-FA-CMK is toxic to Jurkat T cells and induces apoptosis at low concentrations, while at higher concentrations the cells die of necrosis. - Highlights: • z-FA-CMK is toxic and induce cell death in the human T cells. • z-FA-CMK toxicity requires the CMK group, alanine and the benzyloxycarbonyl group. • z-FA-CMK induced apoptosis at low concentration and necrosis at high concentration.« less

Complex network structure of musical compositions: Algorithmic generation of appealing music

NASA Astrophysics Data System (ADS)

Liu, Xiao Fan; Tse, Chi K.; Small, Michael

2010-01-01

In this paper we construct networks for music and attempt to compose music artificially. Networks are constructed with nodes and edges corresponding to musical notes and their co-occurring connections. We analyze classical music from Bach, Mozart, Chopin, as well as other types of music such as Chinese pop music. We observe remarkably similar properties in all networks constructed from the selected compositions. We conjecture that preserving the universal network properties is a necessary step in artificial composition of music. Power-law exponents of node degree, node strength and/or edge weight distributions, mean degrees, clustering coefficients, mean geodesic distances, etc. are reported. With the network constructed, music can be composed artificially using a controlled random walk algorithm, which begins with a randomly chosen note and selects the subsequent notes according to a simple set of rules that compares the weights of the edges, weights of the nodes, and/or the degrees of nodes. By generating a large number of compositions, we find that this algorithm generates music which has the necessary qualities to be subjectively judged as appealing.

Association of Severity of Coronary Artery Aneurysms in Patients With Kawasaki Disease and Risk of Later Coronary Events.

PubMed

Miura, Masaru; Kobayashi, Tohru; Kaneko, Tetsuji; Ayusawa, Mamoru; Fukazawa, Ryuji; Fukushima, Naoya; Fuse, Shigeto; Hamaoka, Kenji; Hirono, Keiichi; Kato, Taichi; Mitani, Yoshihide; Sato, Seiichi; Shimoyama, Shinya; Shiono, Junko; Suda, Kenji; Suzuki, Hiroshi; Maeda, Jun; Waki, Kenji; Kato, Hitoshi; Saji, Tsutomu; Yamagishi, Hiroyuki; Ozeki, Aya; Tomotsune, Masako; Yoshida, Makiko; Akazawa, Yohei; Aso, Kentaro; Doi, Shouzaburoh; Fukasawa, Yoshi; Furuno, Kenji; Hayabuchi, Yasunobu; Hayashi, Miyuki; Honda, Takafumi; Horita, Norihisa; Ikeda, Kazuyuki; Ishii, Masahiro; Iwashima, Satoru; Kamada, Masahiro; Kaneko, Masahide; Katyama, Hiroshi; Kawamura, Yoichi; Kitagawa, Atushi; Komori, Akiko; Kuraishi, Kenji; Masuda, Hiroshi; Matsuda, Shinichi; Matsuzaki, Satoshi; Mii, Sayaka; Miyamoto, Tomoyuki; Moritou, Yuji; Motoki, Noriko; Nagumo, Kiyoshi; Nakamura, Tsuneyuki; Nishihara, Eiki; Nomura, Yuichi; Ogata, Shohei; Ohashi, Hiroyuki; Okumura, Kenichi; Omori, Daisuke; Sano, Tetsuya; Suganuma, Eisuke; Takahashi, Tsutomu; Takatsuki, Shinichi; Takeda, Atsuhito; Terai, Masaru; Toyono, Manatomo; Watanabe, Kenichi; Watanabe, Makoto; Yamamoto, Masaki; Yamamura, Kenichiro

2018-05-07

Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA). To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA. This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011. The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ≥5 to <10; actual internal diameter, <8 mm), and large (z score, ≥10 or ≥8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications. Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P < .001) and 100%, 100%, and 75% in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1-15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7-4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4-3.6) were significantly associated with CE. Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.

Kidney (Renal) Failure

MedlinePlus

... News Physician Resources Professions Site Index A-Z Kidney Failure Kidney failure, also known as renal failure, ... evaluated? How is kidney failure treated? What is kidney (renal) failure? The kidneys are designed to maintain ...

New estimate of valvuloarterial impedance in aortic valve stenosis: A cardiac magnetic resonance study.

PubMed

Soulat, Gilles; Kachenoura, Nadjia; Bollache, Emilie; Perdrix, Ludivine; Diebold, Benoit; Zhygalina, Valentina; Latremouille, Christian; Laurent, Stephane; Fabiani, Jean-Noel; Mousseaux, Elie

2017-03-01

Valvuloarterial impedance (Z VA ), estimating left ventricle (LV) afterload, has been proposed in transthoracic echocardiography (TTE) as a predictor of mortality in aortic valve stenosis (AVS). However, its calculation differs from arterial characteristic impedance (Z C ). Our aim was to apply the concept of Z C calculation to estimate Z VA from MR with carotid tonometry and to evaluate these indices through their associations with symptoms, LV diastolic function and aortic stiffness. In 40 patients with AVS (76 ± 13 years), Z VA-TI derived from velocity time integral and E/Ea were estimated by TTE. Z VA-INS , based on Z C formula, calculated as the instantaneous pressure gradient to peak flow ratio and aortic compliance were estimated by using MRI at 1.5 Tesla. Both Z VA estimates were higher in symptomatic than asymptomatic patients (707 ± 22 versus 579 ± 53 dyne.s/cm 5 , P = 0.031 for Z VA-INS and 4.35 ± 0.16 versus 3.33 ± 0.38 mmHg.m 2 /mL, P = 0.018 for Z VA-TI ). Although they were both associated with aortic compliance (r = -0.45; P = 0.006 for Z VA-INS and r = -0.43; P = 0.008 for Z VA-TI ) only Z VA-INS was associated with E/Ea (r = 0.50; P < 0.001). In multivariate analysis to identify determinants of E/Ea, a model including age, mean blood pressure, LV ejection fraction, LV mass, and aortic valve area was performed (R 2  = 0.41; P < 0.01). When Z VA-INS was added to the model, its overall significance was higher R 2  = 0.56 (P < 0.01) and Z VA-INS and LV mass were the only significant determinants. Z VA-INS was more strongly associated with diastolic dysfunction than usual parameters quantifying AVS severity. This new Z VA estimate could improve LV afterload evaluation. 1 J. Magn. Reson. Imaging 2017;45:795-803. © 2016 International Society for Magnetic Resonance in Medicine.

Benzodiazepine dependence in subjects with alcohol use disorders: what prevalence?

PubMed

Morel, A; Grall-Bronnec, M; Bulteau, S; Chauvin-Grelier, P; Gailledrat, L; Pinot, M L; Jolliet, P; Victorri-Vigneau, C

2016-10-01

To our knowledge, no studies have been conducted in France on benzodiazepine (BZD) dependence among outpatients with alcohol use disorders (AUD). Some international studies have been conducted on the consumption of BZD in this specific population, but the comparisons among them are difficult. We aimed to assess the current prevalence of probable benzodiazepine and BZD-like hypnotics (Z-drugs) dependence among outpatients seeking treatment for AUD. Participants were patients seeking treatment for AUD for the first time or repeating treatment after more than twelve months. Recruitment took place in seven addiction centres between January and December 2013 in the Nantes region (France). BZD/Z-drug dependence was assessed according to the DSM-IV diagnostic criteria for dependence. This information was gathered through a self-report questionnaire. Among the 1005 patients included in this study, 413 were BZD/Z-drug users (41.1%). Among the 413 patients, 217 were probably dependent on at least one substance, which represents 21.6% of the total population and 52.5% of BZD/Z-drug users. BZD/Z-drug dependence represents a public health concern. Prescribers should take the risks into account and keep treatment courses to a minimum.

A neutral effect of testosterone therapy on macroprolactin content in men with macroprolactinemia and late-onset hypogonadism.

PubMed

Krysiak, Robert; Kowalska, Beata; Szkróbka, Witold; Okopień, Bogusław

2016-02-01

In the light of recent studies, macroprolactinemia seems to occur much more frequently than previously thought. In women, oral contraceptive pills exhibit a stimulatory effect on macroprolactin production. No previous study has investigated macroprolactin levels in androgen-treated hypogonadal men. We studied 10 men with isolated macroprolactinemia and 14 men with normal prolactin levels who because of late-onset hypogonadism were treated with intramuscular testosterone enanthate. Serum prolactin, macroprolactin content, serum testosterone and gonadotropin levels were assessed at baseline and after 4 months of therapy. Although baseline levels of testosterone and gonadotropins were similar in men with and without macroprolactinemia, clinical symptoms were more severe in patients with elevated big-big prolactin levels. As expected, testosterone treatment increased serum testosterone, slightly reduced serum gonadotropins, as well as improved clinical condition in both patients with and without macroprolactinemia, with no difference between the groups. However, testosterone therapy did not affect serum prolactin and macroprolactin content, even after replacing intramuscular testosterone enanthate with oral testosterone undecanoate. Our results suggest a negligible effect of testosterone replacement on macroprolactin levels in macroprolactinemic men with late-onset hypogonadism. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Using Zero Balance Ultrafiltration with Dialysate as a Replacement Fluid for Hyperkalemia during Cardiopulmonary Bypass

PubMed Central

Heath, Michele; Raghunathan, Karthik; Welsby, Ian; Maxwell, Cory

2014-01-01

Abstract: Avoiding or managing hyperkalemia during cardiac surgery, especially in a patient with chronic renal insufficiency, can be challenging. Hyperkalemic cardioplegia solution is usually administered to achieve and maintain an electrical arrest of the heart. This solution eventually mixes in with the systemic circulation, contributing to elevated systemic potassium levels. Administration of packed red blood cells, hemolysis, tissue damage, and acidosis are also common causes of hyperkalemia. Current strategies to avoid or manage hyperkalemia include minimizing the volume of cardioplegia administered, shifting potassium from the extracellular into the intracellular space (by the administration of sodium bicarbonate when the pH is low and/or dextrose–insulin when effects relatively independent of serum pH are desired), using zero-balanced ultrafiltration (Z-BUF) with normal saline as the replacement fluid (to remove potassium from the body rather than simply shift the electrolyte across cellular membranes), and, occasionally, hemodialysis (1). We report the application of Z-BUF using an electrolyte-balanced, low potassium dialysate solution rather than isotonic saline to avoid a high chloride load and the potential for hyperchloremic acidosis to successfully treat hyperkalemia while on cardiopulmonary bypass. PMID:26357794

Z-Guggulsterone Produces Antidepressant-Like Effects in Mice through Activation of the BDNF Signaling Pathway

PubMed Central

Liu, Feng-Guo; Hu, Wen-Feng; Wang, Ji-Li; Wang, Peng; Gong, Yu; Tong, Li-Juan; Jiang, Bo; Zhang, Wei; Qin, Yi-Bin; Chen, Zhuo

2017-01-01

Abstract Background: Z-guggulsterone, an active compound extracted from the gum resin of the tree Commiphora mukul, has been shown to improve animal memory deficits via activating the brain-derived neurotrophic factor signaling pathway. Here, we investigated the antidepressant-like effect of Z-guggulsterone in a chronic unpredictable stress mouse model of depression. Methods: The effects of Z-guggulsterone were assessed in mice with the tail suspension test and forced swimming test. Z-guggulsterone was also investigated in the chronic unpredictable stress model of depression with fluoxetine as the positive control. Changes in hippocampal neurogenesis as well as the brain-derived neurotrophic factor signaling pathway after chronic unpredictable stress/Z-guggulsterone treatment were investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressant-like mechanisms of Z-guggulsterone. Results: Z-guggulsterone (10, 30 mg/kg) administration protected the mice against the chronic unpredictable stress-induced increases in the immobile time in the tail suspension test and forced swimming test and also reversed the reduction in sucrose intake in sucrose preference experiment. Z-guggulsterone (10, 30 mg/kg) administration prevented the reductions in brain-derived neurotrophic factor protein expression levels as well as the phosphorylation levels of cAMP response element binding protein, extracellular signal-regulated kinase 1/2, and protein kinase B in the hippocampus and cortex induced by chronic unpredictable stress. Z-guggulsterone (10, 30 mg/kg) treatment also improved hippocampal neurogenesis in chronic unpredictable stress-treated mice. Blockade of the brain-derived neurotrophic factor signal, but not the monoaminergic system, attenuated the antidepressant-like effects of Z-guggulsterone. Conclusions: Z-guggulsterone exhibits antidepressant activity via activation of the brain-derived neurotrophic factor signaling pathway and upregulation of hippocampal neurogenesis. PMID:28339691

Low bone mineral density in achondroplasia and hypochondroplasia.

PubMed

Matsushita, Masaki; Kitoh, Hiroshi; Mishima, Kenichi; Kadono, Izumi; Sugiura, Hiroshi; Hasegawa, Sachi; Nishida, Yoshihiro; Ishiguro, Naoki

2016-08-01

Achondroplasia (ACH) and hypochondroplasia (HCH) are the most common form of short-limb skeletal dysplasias caused by activated fibroblast growth factor receptor 3 (FGFR3) signaling. Although decreased bone mass was reported in gain-of-function mutation in Fgfr3 mice, both disorders have never been described as osteoporotic. In the present study, we evaluated bone mineral density (BMD) in ACH and HCH patients. We measured spinal BMD (L1-L4) in 18 ACH and four HCH patients with an average age of 19.8 ± 7.5 years (range, 10-33 years). BMD Z-score in each individual was calculated for normalizing age and gender. Correlation between body mass index (BMI) and BMD was analyzed. Moreover, BMD and Z-score were compared between ACH patients and HCH patients. The average BMD of ACH/HCH patients was 0.805 ± 0.141 g/cm(2) (range, 0.554-1.056 g/cm(2) ), resulting in an average Z-score of -1.1 ± 0.8 (range, -2.4 to 0.6) of the standard value. A slightly positive correlation was observed between BMI and BMD (r = 0.45; P = 0.13). There was no significant difference in BMD and Z-score between ACH and HCH patients. Spinal BMD was reduced in ACH/HCH patients, and was mildly correlated with individual BMI. We should carefully monitor BMD and examine osteoporosis-related symptoms in adolescent and adult ACH/HCH patients. © 2016 Japan Pediatric Society. © 2015 Japan Pediatric Society.

The effect of CPAP treatment on EEG of OSAS patients.

PubMed

Zhang, Cheng; Lv, Jun; Zhou, Junhong; Su, Li; Feng, Liping; Ma, Jing; Wang, Guangfa; Zhang, Jue

2015-12-01

Continuous positive airway pressure (CPAP) is currently the most effective treatment method for obstructive sleep apnea syndrome (OSAS). The purpose of this study was to compare the sleep electroencephalogram (EEG) changes before and after the application of CPAP to OSAS patients. A retrospective study was conducted and 45 sequential patients who received both polysomnography (PSG) and CPAP titration were included. The raw data of sleep EEG were extracted and analyzed by engineers using two main factors: fractal dimension (FD) and the zero-crossing rate of detrended FD (zDFD). FD was an effective indicator reflecting the EEG complexity and zDFD was useful to reflect the variability of the EEG complexity. The FD and zDFD indexes of sleep EEG of 45 OSAS patients before and after CPAP titration were analyzed. The age of 45 OSAS patients was 52.7 ± 5.6 years old and the patients include 12 females and 33 males. After CPAP treatment, FD of EEG in non-rapid eye movement (NREM) sleep decreased significantly (P < 0.05), while FD of EEG increased in rapid eye movement (REM) sleep (P < 0.05). Meanwhile, zDFD were decreased remarkably in both NREM and REM sleep after CPAP therapy (P < 0.05, respectively). CPAP therapy had a significant influence on sleep EEG in patients with OSAHS, which lead to a more stable EEG pattern. This may be one of the mechanisms that CPAP could improve sleep quality and brain function of OSAS patients.

Correlation between trans and intra-thoracic impedance and conductance in patients with chronic heart failure.

PubMed

Malfatto, Gabriella; Villani, Alessandra; Rosa, Francesco Della; Rella, Valeria; Oldani, Matteo; Giglio, Alessia; Facchini, Mario; Parati, Gianfranco

2016-04-01

In chronic heart failure, changes of intra-thoracic impedance (Z0IT) may suggest impending pulmonary congestion; a similar result has been found by measuring trans-thoracic conductance (TFCTT = 1/Z0 = 1/kΩ). We assumed that a relationship could exist between Z0IT and TFCTT. We collected 140 measurements from 70 patients carrying an implantable cardioverter-defibrillator/cardiac resynchronization device with the CareLink function (71 ± 9 years, New York Heart Association (NYHA) 2.4 ± 0.9, ejection fraction 31 ± 8%, optimal treatment); they were studied during system alarms and after appropriate treatment (diuretics and/or vasodilators, n = 42) or during clinical stability and at the time of a system alarm (n = 28); correspondent BNP values were obtained. We related Z0IT obtained by the device, with TFCTT obtained with a commercial system. A strong relationship was found between Z0IT and TFCTT. Changes in the variables after treatment or during worsening conditions were of the same direction and order of magnitude, and were related to BNP levels obtained simultaneously. Trans-thoracic conductance, similarly to intra-thoracic impedance, may noninvasively point to pulmonary congestion and be useful in patients not carrying an implanted device. The possibility of remotely obtaining this variable should be evaluated for the telemonitoring of heart failure patients.

Blood Clots

MedlinePlus

... News Physician Resources Professions Site Index A-Z Blood Clots Blood clots are semi-solid masses of blood ... evaluated? How are blood clots treated? What are blood clots? Blood clots are semi-solid masses of blood. ...

Preparation and characterisation of poly p-phenylene-2,6-benzobisoxazole fibre-reinforced resin matrix composite for endodontic post material: a preliminary study.

PubMed

Hu, Chen; Wang, Feng; Yang, Huiyong; Ai, Jun; Wang, Linlin; Jing, Dongdong; Shao, Longquan; Zhou, Xingui

2014-12-01

Currently used fibre-reinforced composite (FRC) intracanal posts possess low flexural strength which usually causes post fracture when restoring teeth with extensive loss. To improve the flexural strength of FRC, we aimed to apply a high-performance fibre, poly p-phenylene-2, 6-benzobisoxazole (PBO), to FRCs to develop a new intracanal post material. To improve the interfacial adhesion strength, the PBO fibre was treated with coupling agent (Z-6040), argon plasma, or a combination of above two methods. The effects of the surface modifications on PBO fibre were characterised by determining the single fibre tensile strength and interfacial shear strength (IFSS). The mechanical properties of PBO FRCs were characterised by flexural strength and flexural modulus. The cytotoxicity of PBO FRC was evaluated by the MTT assay. Fibres treated with a combination of Z-6040 and argon plasma possessed a significantly higher IFSS than untreated fibres. Fibre treated with the combination of Z-6040-argon-plasma FRC had the best flexural strength (531.51 ± 26.43MPa) among all treated fibre FRCs and had sufficient flexural strength and appropriate flexural moduli to be used as intracanal post material. Furthermore, an in vitro cytotoxicity assay confirmed that PBO FRCs possessed an acceptable level of cytotoxicity. In summary, our study verified the feasibility of using PBO FRC composites as new intracanal post material. Although the mechanical property of PBO FRC still has room for improvement, our study provides a new avenue for intracanal post material development in the future. To our knowledge, this is the first study to verify the feasibility of using PBO FRC composites as new intracanal post material. Our study provided a new option for intracanal post material development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Osteoporosis in patients on long-term home parenteral nutrition: a longitudinal study.

PubMed

Cohen-Solal, M; Baudoin, C; Joly, F; Vahedi, K; D'Aoust, L; De Vernejoul, M C; Messing, B

2003-11-01

The prevalence of osteoporosis was investigated in 88 patients with intestinal failure (IF). Osteoporosis was found in 67%, dependent of body mass index and age when IF occurred. In 56 patients on HPN, followed prospectively, changes in bone density were dependent on the duration of HPN; older patients had a higher increase. It has been suggested that low bone mass and negative bone balance may occur in adult patients receiving home parenteral nutrition (HPN). The aim of this study was to assess prospectively the prevalence of osteoporosis in intestinal failure (IF) patients and the changes in bone mineral density in those on long-term HPN and to analyze the factors that may influence the occurrence and evolution of osteoporosis. Bone mineral density was measured at the lumbar spine and femoral neck in 88 IF patients. At the first bone mineral density determination (baseline), the prevalence of osteoporosis was 67% in this population (median age, 52 years). Ten percent of the patients with osteoporosis experienced fragility fractures. Osteoporosis was independent of age and gender but occurred earlier in patients who had received corticosteroids. At baseline, the lumbar Z-score was positively correlated mainly to body mass index and age when IF occurred; these two parameters explained 34% of the Z-score. Repeated measurements were performed in 56 patients during long-term HPN (mean duration, 5.5 +/- 1.2 years). The changes in Z-score at the lumbar spine were dependent on the age when IF occurred and on the duration of HPN, with a synergistic effect between them. The older the patients, the higher the increase in Z-score during HPN. HPN had no deleterious effect on cortical bone and actually improved trabecular bone in patients whose intestinal disease started after the age of 21 years.

Best Medications to Treat Fibromyalgia

MedlinePlus

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The collisional drift mode in a partially ionized plasma. [in the F region

NASA Technical Reports Server (NTRS)

Hudson, M. K.; Kennel, C. F.

1974-01-01

The structure of the drift instability was examined in several density regimes. Let sub e be the total electron mean free path, k sub z the wave-vector component along the magnetic field, and the ratio of perpendicular ion diffusion to parallel electron streaming rates. At low densities (k sub z lambda 1) the drift mode is isothermal and should be treated kineticly. In the finite heat conduction regime square root of m/M k sub z Lambda sub 1) the drift instability threshold is reduced at low densities and increased at high densities as compared to the isothermal threshold. Finally, in the energy transfer limit (k sub z kambda sub e square root of m/M) the drift instability behaves adiabatically in a fully ionized plasma and isothermally in a partially ionized plasma for an ion-neutral to Coulomb collision frequency ratio.

z -Weyl gravity in higher dimensions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moon, Taeyoon; Oh, Phillial, E-mail: dpproject@skku.edu, E-mail: ploh@skku.edu

We consider higher dimensional gravity in which the four dimensional spacetime and extra dimensions are not treated on an equal footing. The anisotropy is implemented in the ADM decomposition of higher dimensional metric by requiring the foliation preserving diffeomorphism invariance adapted to the extra dimensions, thus keeping the general covariance only for the four dimensional spacetime. The conformally invariant gravity can be constructed with an extra (Weyl) scalar field and a real parameter z which describes the degree of anisotropy of conformal transformation between the spacetime and extra dimensional metrics. In the zero mode effective 4D action, it reduces tomore » four-dimensional scalar-tensor theory coupled with nonlinear sigma model described by extra dimensional metrics. There are no restrictions on the value of z at the classical level and possible applications to the cosmological constant problem with a specific choice of z are discussed.« less

Separating Visuospatial from Visuomotor Coordination in Skill Estimation in Learning Disabled Children: The Eta-Mu Model.

PubMed

Aleci, Carlo; Piccoli, Marzia; Melotti, Valentina; Melis, Elena; Canavese, Lorenzo

2017-12-01

Purpose A model aimed at detecting the proportion of visuoperceptive and visuomotor coordination impairment in children with ascertained or suspected learning disability is described. The final purpose is to provide customized rehabilitation programs. Methods In this pilot study, four children (8-9 years) were administered a set of standardized tests to evaluate their ability to perform visuoperceptive and visuomotor tasks. Depending on the individual outcomes, two indexes have been computed from the resulting z-scores: η (Eta) that quantifies the visuoperceptive impairment, and μ (Mu) that expresses the alteration in visuomotor coordination. Results A condition of abnormality was evident in each patient: Subjects 1 and 3 suffered mainly from a visuoperceptive alteration (η higher than expected), while Subject 4 had reduced visuomotor coordination (μ higher than expected). Subject 2 showed balanced visuoperceptive and visuomotor impairment. Based on the obtained η and μ values, each child underwent a customized rehabilitation treatment, then they were examined again. At re-test, η or μ turned balanced and z-scores improved in the four patients. Conclusions The Eta/Mu model is effective in detecting the type of damage by quantifying the share of visuoperceptive and visuomotor coordination involvement in dyslexic children, allowing a customized rehabilitative approach. Such an approach, focused on treating the function found to be defective, appears to be effective in rebalancing individual visuomotor and visuoperceptive skills; it should, therefore, be taken into consideration when updating the rehabilitation plans of learning disabled children.

What determines nutritional recovery in malnourished children after correction of congenital heart defects?

PubMed

Vaidyanathan, Balu; Radhakrishnan, Reshma; Sarala, Deepa Aravindakshan; Sundaram, Karimassery Ramaiyar; Kumar, Raman Krishna

2009-08-01

Malnutrition is common in children with congenital heart disease (CHD), especially in developing countries. To examine the impact of corrective intervention on the nutritional status of children with CHD and identify factors associated with suboptimal recovery. Consecutive patients with CHD in a tertiary center in South India were evaluated for nutritional status before and 2 years after corrective intervention. Anthropometry was performed at presentation and every 6 months for 2 years, and z scores were compared. Malnutrition was defined as a weight-for-age, height-for-age, and weight/height z score <-2. Determinants of malnutrition were entered into a multivariate logistic regression analysis model. Of 476 patients undergoing corrective intervention (surgical: 344; catheter-based: 132) z scores of less than -2 for weight for age, height for age, and weight/height were recorded in 59%, 26.3%, and 55.9% of patients, respectively, at presentation. On follow-up (425 patients [92.5% of survivors; 20.63 +/- 13.1 months of age]), z scores for weight for age and weight/height improved significantly from the baseline (weight: -1.42 +/- 1.03 vs -2.19 +/- 1.16; P < .001; weight/height: -1.15 +/- 1.25 vs -2.09 +/- 1.3; P < .001). Height-for-age z scores were not significantly different. Malnutrition persisted in 116 (27.3%) patients on follow-up and was associated with a birth weight of

[The role of the multidisciplinary team in the diagnosis and treatment of patients with laryngeal and hypopharynx cancer].

PubMed

Golusiński, Wojciech; Sówka, Marcin; Uczułka, Renata; Golusińska, Ewelina; Kardach, Hubert; Wegner, Anna; Pazdrowski, Jakub

2013-01-01

In Poland the annual incidence of cancer of the larynx is about 3,000 cases which accounts 2% of all malignant tumors. Results of treatment of head and neck cancers are still unsatisfactory (five-year survival - 50%). In order to improve the outcome in Greater Poland Cancer Centre in 2010 a multidisciplinary team was created which is involved in the individual qualification of each patient to the best form of therapy. The aim of the publication is to evaluate the work of the multidisciplinary team in the diagnostic, therapeutic, and post-operative follow-up of patients with larynx and hypopharynx cancer treated in Greater Poland Cancer Centre in 2007-2012. The analysis included 558 patients (84% men, 16% women) aged 38-82 years who were treated in the Department of Head and Neck Surgery Greater Poland Cancer Centre in the years 2007 to 2012 because of cancer of larynx and hypopharynx. Patients were divided into two groups - the first consisted of patients qualified without the cooperation of the multidisciplinary team - 312 patients (56%), the second - patients qualified with help of the multidisciplinary team - 246 patients (44%). In the two groups of patients evaluated were: mean time required for the implementation of additional tests and specialist consultations before treatment, the average time from the appearance of the patient to the start of treatment, the distribution of qualifications to specific forms of therapy. Evaluating type of treatment administered after the establishment of the team noticed were an increase by 11% the number of patients treated with surgery. There has been a reduction in the time between the appearance of the patient at the clinic and the start of treatment and reduce the waiting time for diagnostic imaging and specialist consultations. It was also an increase in the number of regular check-ups and a decrease in the number of patients who stopped visits. The work of the multidisciplinary team improves the effectiveness of treatment by optimizing the process of preparation and organization, and finally by contributing knowledge and experience in decision-making. His creation results in benefits for the patient, his family and the medical staff. Qualification for the most optimal treatment within the multidisciplinary team should be used in all patients with cancer of the head and neck. Copyright © 2013 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

Nuclear translocation of doublecortin-like protein kinase and phosphorylation of a transcription factor JDP2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagamine, Tadashi; Nomada, Shohgo; Onouchi, Takashi

2014-03-28

Highlights: • Doublecortin-like protein kinase (DCLK) is a microtubule-associated protein kinase. • In living cells, DCLK was cleaved into two functional fragments. • zDCLK(kinase) was translocated into the nucleus by osmotic stresses. • Jun dimerization protein 2 (JDP2) was identified as zDCLK(kinase)-binding protein. • JDP2 was efficiently phosphorylated by zDCLK(kinase) only when histone was present. - Abstract: Doublecortin-like protein kinase (DCLK) is a microtubule-associated protein kinase predominantly expressed in brain. In a previous paper, we reported that zebrafish DCLK2 (zDCLK) was cleaved into two functional fragments; the N-terminal zDCLK(DC + SP) with microtubule-binding activity and the C-terminal zDCLK(kinase) with amore » Ser/Thr protein kinase activity. In this study, we demonstrated that zDCLK(kinase) was widely distributed in the cytoplasm and translocated into the nucleus when the cells were treated under hyperosmotic conditions with NaCl or mannitol. By two-hybrid screening using the C-terminal domain of DCLK, Jun dimerization protein 2 (JDP2), a nuclear transcription factor, was identified as zDCLK(kinase)-binding protein. Furthermore, JDP2 served as an efficient substrate for zDCLK(kinase) only when histone was present. These results suggest that the kinase fragment of DCLK is translocated into the nucleus upon hyperosmotic stresses and that the kinase efficiently phosphorylates JDP2, a possible target in the nucleus, with the aid of histones.« less

Bipolar diagnosis in China: Evaluating diagnostic confidence using the Bipolarity Index.

PubMed

Ma, Yantao; Gao, Huimin; Yu, Xin; Si, Tianmei; Wang, Gang; Fang, Yiru; Liu, Zhening; Sun, Jing; Yang, Haichen; Wang, Xueyi; Li, Jing; Zhang, Yonghua; Sachs, Gary

2016-09-15

Diagnosis of bipolar disorder is inherently difficult. The goal of this study was to examine the utility and psychometric properties of the Bipolarity Index (BPx) in a population of patients treated in China. At nine Chinese health facilities participating in CAFÉ-BD, clinicians completed a standardized affective disorder evaluation for consecutive patients (N=615) with a clinical diagnosis of MDD and BPD and scored the Bipolarity Index. The investigators constructed ROC curves to determine the optimal cut off points to discriminate subjects in three clinical diagnostic groups: bipolar disorder (BPD), major depressive disorder (MDD) and healthy (no psychiatric diagnosis) controls (HC). This study is registered with ClinicalTrials.gov, number NCT02015143. 1) The cut-off score between the MDD and BPD groups was 42.0, with a sensitivity of 0.957 and specificity of 0.881 (Z=63.064, P<0.001); the cut-off score between the MDD and BPD II groups was 34.0, with a sensitivity of 0.810 and specificity of 0.855 (Z=20.174, P<0.001); and the cut-off score between the BPD II and BPD I groups was 57.0, with a sensitivity of 0.680 and specificity of 0.772 (Z=9.636, P<0.001). 2) Five domains contributed to the discrimination results. State-related domains (episode characteristics and course of illness) made greater contributions than trait-related domains (age of onset, family history, and treatment response). The data are purely descriptive. The BPD II sample and the family history dataset were small. Our finding indicates good reliability and validity for the Chinese version of the BPx, which encourages its use as a measure of diagnostic confidence for bipolar spectrum disorders. Further prospective study is necessary to determine if the BPx is useful in identifying subgroups among MDD subjects at high risk for conversion to BPD. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical experience in coronary stenting with the Vivant Z Stent.

PubMed

Chee, K H; Siaw, F S; Chan, C G; Chong, W P; Imran, Z A; Haizal, H K; Azman, W; Tan, K H

2005-06-01

This single centre study was designed to demonstrate feasibility, safety and efficacy of the Vivant Z stent (PFM AG, Cologne, Germany). Patients with de novo lesion were recruited. Coronary angioplasty was performed with either direct stenting or after balloon predilatation. Repeated angiogram was performed 6 months later or earlier if clinically indicated. Between January to June 2003, a total of 50 patients were recruited (mean age 55.8 +/- 9 years). A total of 52 lesions were stented successfully. Mean reference diameter was 2.77 mm (+/-0.59 SD, range 2.05-4.39 mm) with mean target lesion stenosis of 65.5% (+/-11.6 SD, range 50.1-93.3%). Forty-six lesions (88.5%) were American College of Cardiologist/American Heart Association class B/C types. Direct stenting was performed in 18 (34.6%) lesions. Mean stent diameter was 3.18 mm (+/-0.41 SD, range 2.5-4 mm), and mean stent length was 14.86 mm (+/-2.72 SD, range 9-18 mm). The procedure was complicated in only one case which involved the loss of side branch with no clinical sequelae. All treated lesions achieved Thrombolysis In Myocardial Infarction 3 flow. Mean residual diameter stenosis was 12.2% (+/-7.55 SD, range 0-22.6%) with acute gain of 1.72 mm (+/-0.50 SD, range 0.5-2.8). At 6 months, there was no major adverse cardiovascular event. Repeated angiography after 6 months showed a restenosis rate of 17% (defined as >50% diameter restenosis). Mean late loss was 0.96 mm (+/-0.48 SD) with loss index of 0.61 (+/-0.38 SD). The restenosis rate of those lesions less than 3.0 mm in diameter was 22.2% compared with 6.25% in those lesions more than 3.0 mm in diameter. The Vivant Z stent was shown to be safe and efficacious with low restenosis rate in de novo coronary artery lesion.

Handgrip strength and nutrition status in hospitalized pediatric patients.

PubMed

Silva, Catarina; Amaral, Teresa F; Silva, Diana; Oliveira, Bruno M P M; Guerra, António

2014-06-01

Handgrip strength (HGS) is a useful indicator of nutrition status in adults, but evidence is lacking in pediatric patients. The aim of this study was to describe the association between undernutrition and HGS in pediatric patients at hospital admission, quantifying the modifying effect of disease severity, anthropometrics, and other patient characteristics on HGS. Eighty-nine inpatients aged ≥6 years consecutively admitted were recruited in a longitudinal study. Nutrition status was evaluated using body mass index (BMI) z scores, and HGS was evaluated at admission and discharge. In the total sample, 30.3% of patients were undernourished at admission, and 64% lost HGS during the hospital stay. This study showed that HGS at admission was independently associated with undernutrition defined by BMI z scores (β = 0.256, P = .037). In this multivariate analysis, sex, age, height, and BMI z scores explained 67.1% of HGS at hospital admission. Lower HGS may be a potential marker of undernutrition in hospitalized pediatric patients, although HGS data should be interpreted according to sex, age, and height of the patient.

Toxicity of a dental adhesive compared with ionizing radiation and zoledronic acid.

PubMed

Alcaraz, Miguel; Olivares, Amparo; Achel, Daniel-Giyngiri; García-Cruz, Emilio; Fondevilla-Soler, Adriana; Canteras-Jordana, Manuel

2015-07-01

To determine the toxicity of aqueous dilutions of a universal self-priming dental adhesive (DA) and comparing these with those elicited by exposure to ionizing radiation (IR), Zoledronic acid (Z) treatment and the synergic effects of the combined treatment with IR+Z. The genotoxic effect of DA was determined by the increase in the frequency of micronuclei in cytokinesis-blocked in cultured human lymphocytes before and after exposure to 2Gy of X-rays. The cytotoxic effect was studied by using the MTT cell viability test in normal prostate cell lines (PNT2) after exposure to different X-ray doses (0Gy-20Gy). The cell lines divided into different groups and treated with different test substances: DA in presence of O2, DA in absence of O2, Z-treated and control. An in vitro dose-dependent and time-dependent cytotoxic effect of DA, Z and IR on PNT2 cells (p>0.001) was demonstrated. DA without-O2, following the recommendations of manufacturers, had a more pronounced effect of increasing cell death than DA with-O2 (p<0.001). In the genotoxicity assay, DA at 25% of its original concentration significantly increased chromosome damage (p<0.001). The samples studied were found to be toxic, and the samples photo-polymerized in absence of O2 showed a bigger cytotoxic effect comparable to the additive toxic effect showed by the combined treatment of IR+Z. Additional effort should be carried out to develop adhesives, which would reduce the release of hazardous substances; since toxic effects are similar to that reported by other agents whose clinical use is controlled by the health authorities.

Numerical simulation of fiber and wire array Z-pinches with Trac-II

NASA Astrophysics Data System (ADS)

Reisman, David Barton

Trac-II is a two dimensional axisymmetric resistive MHD code. It simulates all three spatial components (r, z, φ) of the magnetic field and fluid velocity vectors, and the plasma is treated as a single fluid with two temperatures (Te,Ti). In addition, it can optionally include a self-consistent external circuit. Recent modifications to the code include the addition of the 3-T radiation model, a 4-phase (solid- liquid-vapor-plasma) equation of state model (QEOS), a 4- phase electrical/thermal conductivity model, and an implicit solution of poloidal (Bz,Br) magnetic field diffusion. These changes permit a detailed study of fiber and wire array Z-pinches. Specifically, Trac-II is used to study the wire array Z-pinch at the PBFA-Z pulse power generator at Sandia National Laboratory. First, in 1-D we examine the behavior of a single wire in the Z-pinch. Then, using these results as initial radial conditions in 2-D, we investigate the dynamics of wire array configurations in the r-z and r-θ plane. In the r- z plane we examine the growth of the m = 0 or ``sausage'' instability in single wires within the array. In the r-θ plane we examine the merging behavior between neighboring wires. Special emphasis is placed on trying to explain how instability growth affects the performance of the Z-pinch. Lastly, we introduce Trac-III, a 3-D MHD code, and illustrate the m = 1 or ``kink'' instability. We also discuss how Trac-III can be modified to simulate the wire array Z-pinch.

Anorectal Function and Quality of Life in Patients With Early Stage Rectal Cancer Treated With Chemoradiation and Local Excision.

PubMed

Lynn, Patricio B; Renfro, Lindsay A; Carrero, Xiomara W; Shi, Qian; Strombom, Paul L; Chow, Oliver; Garcia-Aguilar, Julio

2017-05-01

Little is known about anorectal function and quality of life after chemoradiation followed by local excision, which is an alternative to total mesorectal excision for selected patients with early rectal cancer. The purpose of this study was to prospectively assess anorectal function and health-related quality of life of patients with T2N0 rectal cancer who were treated with an alternative approach. This was a prospective, phase II trial. The study was multicentric (American College of Surgeons Oncology Group trial Z6041). Patients with stage cT2N0 rectal adenocarcinomas were treated with an oxaliplatin/capecitabine-based chemoradiation regimen followed by local excision. Anorectal function and quality of life were assessed at enrollment and 1 year postoperatively with the Fecal Incontinence Severity Index, Fecal Incontinence Quality of Life scale, and Functional Assessment of Cancer Therapy-Colorectal Questionnaire. Results were compared, and multivariable analysis was performed to identify predictors of outcome. Seventy-one patients (98%) were evaluated at enrollment and 66 (92%) at 1 year. Compared with baseline, no significant differences were found on Fecal Incontinence Severity Index scores at 1 year. Fecal Incontinence Quality of Life results were significantly worse in the lifestyle (p < 0.001), coping/behavior (p < 0.001), and embarrassment (p = 0.002) domains. There were no differences in the Functional Assessment of Cancer Therapy overall score, but the physical well-being subscale was significantly worse and emotional well-being was improved after surgery. Treatment with the original chemoradiation regimen predicted worse depression/self-perception and embarrassment scores in the Fecal Incontinence Quality of Life, and male sex was predictive of worse scores in the Functional Assessment of Cancer Therapy overall score and trial outcome index. Small sample size, relatively short follow-up, and absence of information before cancer diagnosis were study limitations. Chemoradiation followed by local excision had minimal impact on anorectal function 1 year after surgery. Overall quality of life remained stable, with mixed effects on different subscales. This information should be used to counsel patients about expected outcomes.

Best Drugs to Treat Inflammatory Bowel Disease

MedlinePlus

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Characterization of new metabolites from in vivo biotransformation of 2-amino-3-methylimidazo[4,5-f]quinoline in mouse by mass spectrometry

PubMed Central

Hsu, Fong-Fu; Lakshmi, Vijaya M.; Zenser, Terry V.

2010-01-01

In studying the metabolic pathways underlying the mechanism of carcinogenesis of the heterocyclic amine of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), we recently found a new metabolite, which gave a [M + H]+ ion of m/z 217 when subjected to ESI in positive-ion mode. Following ip injection of this metabolite of m/z 217 (designated as m/z 217) to beta-naphthoflavone-treated mice, 57% of the total radioactivity was recovered in a 24-hr mouse urine sample. HPLC separation followed by MS analysis indicates that the urine sample contained m/z 217 (36 ± 3% of total recovered radioactivity) and two other peaks that gave rise to the [M + H]+ ions of m/z 393 (31 ± 4%, designated as m/z 393) and m/z 233 (14 ± 1%, designated as m/z 233). Beta-glucuronidase treatment of m/z 393 resulted in a radioactive peak corresponding to m/z 217. Electrospray ionization in combination with various mass spectrometry techniques, including multiple-stage mass spectrometry, exact mass measurements, and H-D exchange followed by tandem mass spectrometry was used for structural characterization. The urinary metabolites of m/z 217, 393, and 233 were identified as 1,2-dihydro-2-amino-5-hydroxy-3-methylimidazo[4,5-f]quinoline, 1,2-dihydro-2-amino-5-O-glucuronide-3-methylimidazo[4,5-f]quinoline, and 1,2-dihydro-2-amino-5,7-dihydroxy-3-methylimidazo[4,5-f]quinoline, respectively. Our results demonstrated that m/z 217 is biotransformed in vivo to m/z 393 by O-glucuronidation and to m/z 233 by oxidation. The observation of these more polar metabolites relative to IQ suggests that they may arise from a previously undescribed detoxicification pathway. PMID:19629964

THE CHANDRA COSMOS-LEGACY SURVEY: THE z > 3 SAMPLE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marchesi, S.; Civano, F.; Urry, C. M.

2016-08-20

We present the largest high-redshift (3 < z < 6.85) sample of X-ray-selected active galactic nuclei (AGNs) on a contiguous field, using sources detected in the Chandra COSMOS-Legacy survey. The sample contains 174 sources, 87 with spectroscopic redshift and the other 87 with photometric redshift (z {sub phot}). In this work, we treat z {sub phot} as a probability-weighted sum of contributions, adding to our sample the contribution of sources with z {sub phot} < 3 but z {sub phot} probability distribution >0 at z > 3. We compute the number counts in the observed 0.5–2 keV band, finding amore » decline in the number of sources at z > 3 and constraining phenomenological models of the X-ray background. We compute the AGN space density at z > 3 in two different luminosity bins. At higher luminosities (log L (2–10 keV) > 44.1 erg s{sup −1}), the space density declines exponentially, dropping by a factor of ∼20 from z ∼ 3 to z ∼ 6. The observed decline is ∼80% steeper at lower luminosities (43.55 erg s{sup −1} < logL(2–10 keV) < 44.1 erg s{sup −1}) from z ∼ 3 to z ∼ 4.5. We study the space density evolution dividing our sample into optically classified Type 1 and Type 2 AGNs. At log L (2–10 keV) > 44.1 erg s{sup −1}, unobscured and obscured objects may have different evolution with redshift, with the obscured component being three times higher at z ∼ 5. Finally, we compare our space density with predictions of quasar activation merger models, whose calibration is based on optically luminous AGNs. These models significantly overpredict the number of expected AGNs at log L (2–10 keV) > 44.1 erg s{sup −1} with respect to our data.« less

WHAT ARE THE Omh {sup 2} ( z {sub 1}, z {sub 2}) AND Om ( z {sub 1}, z {sub 2}) DIAGNOSTICS TELLING US IN LIGHT OF H ( z ) DATA?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Xiaogang; Ding, Xuheng; Biesiada, Marek

2016-07-01

The two-point diagnostics Om ( z {sub i} , z {sub j} ) and Omh {sup 2}( z {sub i} , z {sub j} ) have been introduced as an interesting tool for testing the validity of the Λ cold dark matter (ΛCDM) model. Recently, Sahni et al. combined two independent measurements of H ( z ) from baryon acoustic oscillation (BAO) data with the value of the Hubble constant H {sub 0}, and used the second of these diagnostics to test the ΛCDM (a constant equation-of-state parameter for dark energy) model. Their result indicated a considerable tension between observationsmore » and predictions of the ΛCDM model. Since reliable data concerning the expansion rates of the universe at different redshifts H ( z ) are crucial for the successful application of this method, we investigate both two-point diagnostics on the most comprehensive set of N = 36 measurements of H ( z ) from BAOs and the differential ages (DAs) of passively evolving galaxies. We discuss the uncertainties of the two-point diagnostics and find that they are strongly non-Gaussian and follow the patterns deeply rooted in their very construction. Therefore we propose that non-parametric median statistics is the most appropriate way of treating this problem. Our results support the claims that ΛCDM is in tension with H ( z ) data according to the two-point diagnostics developed by Shafieloo, Sahni, and Starobinsky. However, other alternatives to the ΛCDM model, such as the wCDM or Chevalier–Polarski–Linder models, perform even worse. We also note that there are serious systematic differences between the BAO and DA methods that ought to be better understood before H ( z ) measurements can compete with other probes methods.« less

Protective Effect of Zingiber officinale Against Dalton's Lymphoma Ascites Tumour by Regulating Inflammatory Mediator and Cytokines.

PubMed

Rubila, Sundararaj; Ranganathan, Thottiam Vasudevan; Sakthivel, Kunnathur Murugesan

2016-12-01

The aim of the present investigation was to evaluate Zingiber officinale paste against Dalton's lymphoma ascites (DLA)-induced tumours in Swiss albino mice. Experimental animals received Z. officinale paste (low dose 100 mg/kg bw and high dose 500 mg/kg bw) orally for eight alternative days. Treatment with Z. officinale paste showed significant increase in haemoglobin level and decrease in aspartate amino transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transferase (γ-GT) level. Z. officinale paste reduced the inflammatory mediators and cytokine levels, such as inducible nitric oxide (iNOS), tumour necrosis factor level (TNF-α) and interleukin-1β (IL-1β). Treatment with Z. officinale paste also significantly increased the antioxidant enzyme level, such as superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione transferase (GST), and decreased the lipid peroxidation. Treatment also increased the vitamin C and E levels in treated animals compared with the DLA-bearing host. Histopathological studies also confirmed the protective influence of Z. officinale paste against DLA. The present study suggested that Z. officinale paste could be used as natural spice and a potent antitumour agent.

Elimination characteristics of post-operative isoflurane levels in alveolar exhaled breath via PTR-MS analysis.

PubMed

Fernández Del Río, R; O'Hara, M E; Pemberton, P; Whitehouse, T; Mayhew, C A

2016-10-12

Isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether), C 3 H 2 ClF 5 O, is a commonly used inhalation anaesthetic. Using a proton transfer reaction mass spectrometer (PTR-MS) we have detected isoflurane in the breath of patients several weeks following major surgery. That isoflurane is detected in the breath of patients so long after being anaesthetised raises questions about when cognitive function has fully returned to a patient. Temporal profiles of isoflurane concentrations in breath are presented for five patients (F/M 3/2, mean age 50 years, min-max 36-58 years) who had undergone liver transplant surgery. In addition, results from a headspace analysis of isoflurane are presented so that the product ions resulting from the reactions of H 3 O + with isoflurane in PTR-MS could be easily identified in the absence of the complex chemical environment of breath. Six product ions were identified. In order of increasing m/z (using the 35 Cl isotope where appropriate) these are [Formula: see text] (m/z 51), CHFCl + (m/z 67), CF 3 CHCl + (m/z 117), C 3 F 4 OCl + (m/z 163), C 3 H 2 F 4 OCl + (m/z 165), and C 3 F 4 OCl + H 2 O (m/z 183). No protonated parent was detected. For the headspace study both clean air and CO 2 enriched clean air (4% CO 2 ) were used as buffer gases in the drift tube of the PTR-MS. The CO 2 enriched air was used to determine if exhaled breath would affect the product ion branching ratios. Importantly no significant differences were observed, and therefore for isoflurane the product ion distributions determined in a normal air mixture can be used for breath analysis. Given that PTR-MS can be operated under different reduced electric fields (E/N), the dependence of the product ion branching percentages for isoflurane on E/N (96-138 Td) are reported.

Two Pilot Randomized Trials To Examine Feasibility and Impact of Treated Parents as Peer Interventionists in Family-Based Pediatric Weight Management.

PubMed

Saelens, Brian E; Scholz, Kelley; Walters, Kelly; Simoni, Jane M; Wright, Davene R

2017-08-01

To examine feasibility and initial efficacy of having previously treated parents serve as peer interventionists in family-based behavioral weight management treatment (FBT). Children aged 7-11 years with overweight/obesity and parents (n = 59 families) were enrolled in one of two pilot trials, the EPICH (Engaging Parents in Child Health) randomized trial comparing professional versus peer FBT delivery or the Parent Partnership trial, which provided professionally delivered FBT to families (first generation) and then randomly assigned first generation parents to either be or not be peer interventionists for subsequent families (second generation). Efficacy (child zBMI change), feasibility, and costs for delivering FBT, and impacts of being a peer interventionist were examined. In EPICH, families receiving professional versus peer intervention had similar decreases in child zBMI and parent BMI, with markedly lower costs for peer versus professional delivery. In Parent Partnership, families receiving peer intervention significantly decreased weight status, with very preliminary evidence suggesting better maintenance of child zBMI changes if parents served as peer interventionists. Previously treated parents were willing, highly confident, and able to serve as peer interventionists in FBT. Two pilot randomized clinical trials suggest parents-as-peer interventionists in FBT may be feasible, efficacious, and delivered at lower costs, with perhaps some additional benefits to serving as a peer interventionist. More robust investigation is warranted of peer treatment delivery models for pediatric weight management.

Prognostic Metabolite Biomarkers for Soft Tissue Sarcomas Discovered by Mass Spectrometry Imaging

NASA Astrophysics Data System (ADS)

Lou, Sha; Balluff, Benjamin; Cleven, Arjen H. G.; Bovée, Judith V. M. G.; McDonnell, Liam A.

2017-02-01

Metabolites can be an important read-out of disease. The identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients is one of the main current research aspects. Mass spectrometry has become the technique of choice for metabolomics studies, and mass spectrometry imaging (MSI) enables their visualization in patient tissues. In this study, we used MSI to identify prognostic metabolite biomarkers in high grade sarcomas; 33 high grade sarcoma patients, comprising osteosarcoma, leiomyosarcoma, myxofibrosarcoma, and undifferentiated pleomorphic sarcoma were analyzed. Metabolite MSI data were obtained from sections of fresh frozen tissue specimens with matrix-assisted laser/desorption ionization (MALDI) MSI in negative polarity using 9-aminoarcridine as matrix. Subsequent annotation of tumor regions by expert pathologists resulted in tumor-specific metabolite signatures, which were then tested for association with patient survival. Metabolite signals with significant clinical value were further validated and identified by high mass resolution Fourier transform ion cyclotron resonance (FTICR) MSI. Three metabolite signals were found to correlate with overall survival ( m/z 180.9436 and 241.0118) and metastasis-free survival ( m/z 160.8417). FTICR-MSI identified m/z 241.0118 as inositol cyclic phosphate and m/z 160.8417 as carnitine.

[CBO guideline 'Osteoporosis' (second revision].

PubMed

Pols, H A P; Wittenberg, J

2002-07-20

Risk factors for osteoporotic fractures that can be used for case-finding according to the recent guidelines from the Dutch Institute for Health Care Improvement (CBO) include: a vertebral fracture, a fracture past the age of 50, a positive family history, low body weight, severe immobility and the use of corticosteroids. Measurement of bone mineral density (BMD) is only recommended for case-finding and not for population screening. Measurement of the BMD is advised in women > or = 50 years of age with a fracture, women with a vertebral fracture regardless of age, women > or = 60 years of age with three of the following risk factors, and women > or = 70 years of age with two of the following risk factors: positive family history, low body weight and severe immobility. Persons with less than 1000-1200 mg calcium in their daily food who are using corticosteroids, persons with osteoporotic fractures and persons who are being treated with drugs for osteoporosis are eligible for calcium supplementation. Vitamin D supplementation is recommended for persons who do not come outdoors. For the drug treatment of osteoporosis in the first years after menopause, oestrogens, tibolone and raloxifene may be used. It is recommended that postmenopausal women with one or more osteoporotic vertebral fractures or an increased risk and a T-score below -2.5 be treated with a bisphosphonate. Patients who are expected to be treated with > or = 15 mg prednisolone equivalent per day for more than 3 months and postmenopausal women and older men (> or = 70) who will be treated with > or = 7.5 mg prednisolone equivalent per day should be started on a bisphosphonate as soon as possible. Other patients who will be treated with > or = 7.5 mg prednisolone equivalent per day should take a bisphosphonate if their Z-score is below -1 or their T-score is below -2.5.

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis.

PubMed

Hauser, Stephen L; Bar-Or, Amit; Comi, Giancarlo; Giovannoni, Gavin; Hartung, Hans-Peter; Hemmer, Bernhard; Lublin, Fred; Montalban, Xavier; Rammohan, Kottil W; Selmaj, Krzysztof; Traboulsee, Anthony; Wolinsky, Jerry S; Arnold, Douglas L; Klingelschmitt, Gaelle; Masterman, Donna; Fontoura, Paulo; Belachew, Shibeshih; Chin, Peter; Mairon, Nicole; Garren, Hideki; Kappos, Ludwig

2017-01-19

B cells influence the pathogenesis of multiple sclerosis. Ocrelizumab is a humanized monoclonal antibody that selectively depletes CD20+ B cells. In two identical phase 3 trials, we randomly assigned 821 and 835 patients with relapsing multiple sclerosis to receive intravenous ocrelizumab at a dose of 600 mg every 24 weeks or subcutaneous interferon beta-1a at a dose of 44 μg three times weekly for 96 weeks. The primary end point was the annualized relapse rate. The annualized relapse rate was lower with ocrelizumab than with interferon beta-1a in trial 1 (0.16 vs. 0.29; 46% lower rate with ocrelizumab; P<0.001) and in trial 2 (0.16 vs. 0.29; 47% lower rate; P<0.001). In prespecified pooled analyses, the percentage of patients with disability progression confirmed at 12 weeks was significantly lower with ocrelizumab than with interferon beta-1a (9.1% vs. 13.6%; hazard ratio, 0.60; 95% confidence interval [CI], 0.45 to 0.81; P<0.001), as was the percentage of patients with disability progression confirmed at 24 weeks (6.9% vs. 10.5%; hazard ratio, 0.60; 95% CI, 0.43 to 0.84; P=0.003). The mean number of gadolinium-enhancing lesions per T 1 -weighted magnetic resonance scan was 0.02 with ocrelizumab versus 0.29 with interferon beta-1a in trial 1 (94% lower number of lesions with ocrelizumab, P<0.001) and 0.02 versus 0.42 in trial 2 (95% lower number of lesions, P<0.001). The change in the Multiple Sclerosis Functional Composite score (a composite measure of walking speed, upper-limb movements, and cognition; for this z score, negative values indicate worsening and positive values indicate improvement) significantly favored ocrelizumab over interferon beta-1a in trial 2 (0.28 vs. 0.17, P=0.004) but not in trial 1 (0.21 vs. 0.17, P=0.33). Infusion-related reactions occurred in 34.3% of the patients treated with ocrelizumab. Serious infection occurred in 1.3% of the patients treated with ocrelizumab and in 2.9% of those treated with interferon beta-1a. Neoplasms occurred in 0.5% of the patients treated with ocrelizumab and in 0.2% of those treated with interferon beta-1a. Among patients with relapsing multiple sclerosis, ocrelizumab was associated with lower rates of disease activity and progression than interferon beta-1a over a period of 96 weeks. Larger and longer studies of the safety of ocrelizumab are required. (Funded by F. Hoffmann-La Roche; OPERA I and II ClinicalTrials.gov numbers, NCT01247324 and NCT01412333 , respectively.).

Growth in children with pulmonary arterial hypertension: a longitudinal retrospective multiregistry study.

PubMed

Ploegstra, Mark-Jan; Ivy, D Dunbar; Wheeler, Jeremy G; Brand, Monika; Beghetti, Maurice; Rosenzweig, Erika B; Humpl, Tilman; Iriart, Xavier; Rouzic, Erwan Muros-Le; Bonnet, Damien; Berger, Rolf M F

2016-04-01

To enable adequate interpretation of growth measurements in the management of children with pulmonary arterial hypertension (PAH), we assessed growth and its associated determinants in children with PAH. We did a retrospective longitudinal study of height and body-mass index in reference to WHO growth standards by pooling data from four contemporary prospective registries of paediatric PAH representing 53 centres in 19 countries. The main outcome measures were median height for age and body-mass index for age percentiles and longitudinal deviation of height for age and body-mass index for age Z scores from WHO standards. 601 children were followed up for a median of 2·9 years (IQR 1·5-4·4). Baseline median height for age percentile was 26 (IQR 4-54) and baseline median body-mass index for age percentile was 41 (IQR 12-79). Mean height for age Z score was significantly lower than the reference (-0·81, 95% CI -0·93 to -0·69; p<0·0001), as was body-mass index for age Z score (-0·12, -0·25 to -0·01; p=0·047). Height for age Z score was particularly decreased in young patients (aged ≤5 years) with idiopathic or hereditary PAH and in all patients with PAH associated with congenital heart disease. Although Z scores increased in some patients and decreased in others, we detected no significant trend in height for age Z score (p=0·57) or body-mass index for age Z score (p=0·48) before taking account of covariates. Multivariable linear mixed effects modelling showed that age, cause of PAH, ex-prematurity, WHO functional class, trisomy 21, and time since diagnosis were associated with height for age Z score, whereas age, ethnicity, and trisomy 21 were associated with body-mass index for age Z score. A favourable WHO functional class course was independently associated with increases in height for age Z score. PAH is associated with impaired growth, especially in younger children and those with pulmonary arterial hypertension associated with congenital heart disease. The degree of impairment is independently associated with cause of PAH and comorbidities, but also with disease severity and duration. Because a favourable clinical course was associated with catch-up growth, height for age could serve as an additional and globally available clinical parameter to monitor patients' clinical condition. Actelion Pharmaceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

GENETIC MODIFIERS OF LIVER DISEASE IN CYSTIC FIBROSIS

PubMed Central

Bartlett, Jaclyn R.; Friedman, Kenneth J.; Ling, Simon C.; Pace, Rhonda G.; Bell, Scott C.; Bourke, Billy; Castaldo, Giuseppe; Castellani, Carlo; Cipolli, Marco; Colombo, Carla; Colombo, John L.; Debray, Dominique; Fernandez, Adriana; Lacaille, Florence; Macek, Milan; Rowland, Marion; Salvatore, Francesco; Taylor, Christopher J.; Wainwright, Claire; Wilschanski, Michael; Zemková, Dana; Hannah, William B.; Phillips, M. James; Corey, Mary; Zielenski, Julian; Dorfman, Ruslan; Wang, Yunfei; Zou, Fei; Silverman, Lawrence M.; Drumm, Mitchell L.; Wright, Fred A.; Lange, Ethan M.; Durie, Peter R.; Knowles, Michael R.

2013-01-01

Context A subset (~3–5%) of patients with cystic fibrosis (CF) develops severe liver disease (CFLD) with portal hypertension. Objective To assess whether any of 9 polymorphisms in 5 candidate genes (SERPINA1, ACE, GSTP1, MBL2, and TGFB1) are associated with severe liver disease in CF patients. Design, Setting, and Participants A 2-stage design was used in this case–control study. CFLD subjects were enrolled from 63 U.S., 32 Canadian, and 18 CF centers outside of North America, with the University of North Carolina at Chapel Hill (UNC) as the coordinating site. In the initial study, we studied 124 CFLD patients (enrolled 1/1999–12/2004) and 843 CF controls (patients without CFLD) by genotyping 9 polymorphisms in 5 genes previously implicated as modifiers of liver disease in CF. In the second stage, the SERPINA1 Z allele and TGFB1 codon 10 genotype were tested in an additional 136 CFLD patients (enrolled 1/2005–2/2007) and 1088 CF controls. Main Outcome Measures We compared differences in distribution of genotypes in CF patients with severe liver disease versus CF patients without CFLD. Results The initial study showed CFLD to be associated with the SERPINA1 (also known as α1-antiprotease and α1-antitrypsin) Z allele (P value=3.3×10−6; odds ratio (OR) 4.72, 95% confidence interval (CI) 2.31–9.61), and with transforming growth factor β-1 (TGFB1) codon 10 CC genotype (P=2.8×10−3; OR 1.53, CI 1.16–2.03). In the replication study, CFLD was associated with the SERPINA1 Z allele (P=1.4×10−3; OR 3.42, CI 1.54–7.59), but not with TGFB1 codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with SERPINA1 Z allele (P=1.5×10−8; OR 5.04, CI 2.88–8.83). Conclusion The SERPINA1 Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater odds (OR ~5) to develop severe liver disease with portal hypertension. PMID:19738092

Source-reconstruction of event-related fields reveals hyperfunction and hypofunction of cortical circuits in antipsychotic-naive, first-episode schizophrenia patients during Mooney face processing.

PubMed

Rivolta, Davide; Castellanos, Nazareth P; Stawowsky, Cerisa; Helbling, Saskia; Wibral, Michael; Grützner, Christine; Koethe, Dagmar; Birkner, Katharina; Kranaster, Laura; Enning, Frank; Singer, Wolf; Leweke, F Markus; Uhlhaas, Peter J

2014-04-23

Schizophrenia is characterized by dysfunctions in neural circuits that can be investigated with electrophysiological methods, such as EEG and MEG. In the present human study, we examined event-related fields (ERFs), in a sample of medication-naive, first-episode schizophrenia (FE-ScZ) patients (n = 14) and healthy control participants (n = 17) during perception of Mooney faces to investigate the integrity of neuromagnetic responses and their experience-dependent modification. ERF responses were analyzed for M100, M170, and M250 components at the sensor and source levels. In addition, we analyzed peak latency and adaptation effects due to stimulus repetition. FE-ScZ patients were characterized by significantly impaired sensory processing, as indicated by a reduced discrimination index (A'). At the sensor level, M100 and M170 responses in FE-ScZ were within the normal range, whereas the M250 response was impaired. However, source localization revealed widespread elevated activity for M100 and M170 in FE-ScZ and delayed peak latencies for the M100 and M250 responses. In addition, M170 source activity in FE-ScZ was not modulated by stimulus repetitions. The present findings suggest that neural circuits in FE-ScZ may be characterized by a disturbed balance between excitation and inhibition that could lead to a failure to gate information flow and abnormal spreading of activity, which is compatible with dysfunctional glutamatergic neurotransmission.

Adherence to dietary recommendations in diabetes mellitus: disease acceptance as a potential mediator.

PubMed

Jaworski, Mariusz; Panczyk, Mariusz; Cedro, Małgorzata; Kucharska, Alicja

2018-01-01

Adherence by diabetic patients to dietary recommendations is important for effective therapy. Considering patients' expectations in case of diet is significant in this regard. The aim of this paper was to analyze the relationship between selected independent variables (eg, regular blood glucose testing) and patients' adherence to dietary recommendations, bearing in mind that the degree of disease acceptance might play a mediation role. A cross-sectional study was conducted in 91 patients treated for type 2 diabetes mellitus in a public medical facility. Paper-and-pencil interviewing was administered ahead of the planned visit with a diabetes specialist. Two measures were applied in the study: the Acceptance and Action Diabetes Questionnaire and the Patient Diet Adherence in Diabetes Scale. Additionally, data related to sociodemographic characteristics, lifestyle-related factors, and the course of the disease (management, incidence of complications, and dietician's supervision) were also collected. The regression method was used in the analysis, and Cohen's methodology was used to estimate partial mediation. Significance of the mediation effect was assessed by the Goodman test. P -values of <0.05 were considered statistically significant. Patients' non-adherence to dietary recommendations was related to a low level of disease acceptance (standardized regression coefficient =-0.266; P =0.010). Moreover, failure to perform regular blood glucose testing was associated with a lack of disease acceptance (standardized regression coefficient =-0.455; P =0.000). However, the lack of regular blood glucose testing and low level of acceptance had only partially negative impacts on adherence to dietary recommendations (Goodman mediation test, Z =1.939; P =0.054). This dependence was not seen in patients treated with diet and concomitant oral medicines and/or insulin therapy. Effective dietary education should include activities promoting a more positive attitude toward the disease. This may be obtained by individual counseling, respecting the patient's needs, and focus on regular blood glucose testing.

Role of (3Z,6Z,8E)-dodecatrien-1-ol in trail following, feeding, and mating behavior of Reticulitermes hesperus.

PubMed

Saran, Raj K; Millar, Jocelyn G; Rust, Michael K

2007-02-01

Trail pheromones mediate communication among western subterranean termites, Reticulitermes hesperus Banks. Repetitive passages of >or=28 termites were required to establish a pheromone trail and trails needed to be reinforced because they lasted <48 hr. The minimal threshold concentration for inducing responses from termite workers and secondary reproductives was between 0.01 and 0.1 fg/cm of (3Z,6Z,8E)-dodecatrien-1-ol (henceforth, dodecatrienol). Workers showed optimal trail-following behavior to dodecatrienol at a concentration of 10 fg/cm. Trails with concentrations >10 pg/cm were repellent to workers. Workers did not detect pheromone gradients, responding equally to increasing or decreasing gradients of dodecatrienol, and termite workers were not able to differentiate between different concentrations of dodecatrienol. Termites preferred dodecatrienol trails to 2-phenoxyethanol trails. Antennae played a key role in trail pheromone perception. Dodecatrienol acted as an arrestant for worker termites (10 fg/cm2) and male alates (5 ng/cm2), whereas sternal gland extracts from females attracted male alates. Workers and alates, upon contact with filter paper disks treated with higher doses (10 fg/cm2 and 5 ng/cm2, respectively) of dodecatrienol, were highly excited (increased antennation and palpation) and repeatedly returned to the treated disks. Dodecatrienol did not act as a phagostimulant when offered on a paper towel disk. Reticulitermes hesperus is highly responsive to dodecatrienol, and it may play an important role in orientation of workers and alates.

Ziziphora clinopodioides Essential Oil and Nisin as Potential Antimicrobial Agents against Escherichia coli O157:H7 in Doogh (Iranian Yoghurt Drink)

PubMed Central

Shahbazi, Yasser

2015-01-01

The aim of the present study was to evaluate the effects of Ziziphora clinopodioides essential oil (0.1 and 0.2%) and nisin (250 and 500 IU/mL) separately and in combination on survival of Escherichia coli O157:H7 inoculated in Doogh (Iranian yoghurt drink) during storage under refrigerated temperature (4 ± 1°C) for 9 days. Viability of Lactobacillus casei at different concentrations of Z. clinopodioides essential oil (0.1 and 0.2%) in Doogh was also examined. The major components were carvacrol (64.22%), thymol (19.22%), γ-terpinene (4.63%), and p-cymene (4.86%). There was no significant difference (p > 0.05) between samples treated with nisin and those of untreated samples. Samples treated with both concentrations of the essential oil (0.1 and 0.2%) showed populations of E. coli O157:H7 significantly (p < 0.05) lower than those of untreated samples. The essential oil of Z. clinopodioides in combination with nisin had a potential synergistic effect against E. coli O157:H7 in Doogh samples after 5 days. The count of L. casei was not inhibited by different concentrations of the Z. clinopodioides essential oil. It is concluded that the leaf essential oil of Z. clinopodioides in combination with nisin can be applied as alternative antimicrobial agents in Doogh to inhibit the growth of E. coli O157:H7. PMID:26783466

Virtuality Distributions and γγ * -> π 0 Transition at Handbag Level

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radyushkin, Anatoly V.

2015-09-01

We outline a new approach to transverse momentum dependence in hard processes using as an example the exclusive transitionmore » $${\\gamma^{*}\\gamma \\to \\pi^{0}}$$ at the handbag level. We start with the coordinate representation for a matrix element $${\\langle p |{\\cal O}(0,z) |0 \\rangle}$$ of a bilocal operator $${{\\cal O} (0,z)}$$ describing a hadron with momentum p. Treated as a function of (pz) and z$$^{2}$$, it is parametrized through virtuality distribution amplitude (VDA) Φ (x, σ), with x being Fourier-conjugate to (pz) and σ Laplace-conjugate to z$$^{2}$$. For intervals with z$$^{+}$$ = 0, we introduce the transverse momentum distribution amplitude (TMDA) $${\\Ψ (x,k_{\\perp})}$$ , and write it in terms of VDA Φ (x, σ). The results of covariant calculations, written in terms of Φ (x, σ) are converted into expressions involving $${\\Ψ (x,k_{\\perp})}$$ . We propose simple models for soft VDAs/TMDAs, and use them for comparison of handbag results with experimental (BaBar and BELLE) data on the pion transition form factor.« less

Interference effects for Higgs boson mediated Z -pair plus jet production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campbell, John M.; Ellis, R. Keith; Furlan, Elisabetta

2014-11-25

Here, we study interference effects in the production channel ZZ + jet, in particular focusing on the role of the Higgs boson. This production channel receives contributions both from Higgs boson mediated diagrams via the decay H → ZZ (signal diagrams), as well as from diagrams where the Z bosons couple directly to a quark loop (background diagrams). We consider the partonic processes gggZZ and gqmore » $$\\bar{q}$$ZZ in which interference between signal and background diagrams first occurs. Since interference is primarily an off-resonant effect for the Higgs boson, we treat the Z bosons as on shell. Thus our analysis is limited to the region above threshold, where the invariant mass of the Z-pair mZZ satisfies the condition m ZZ>2m Z. In the region m ZZ > 300 GeV we find that the interference in the ZZ + jet channel is qualitatively similar to interference in the inclusive ZZ channel. Moreover, the rates are sufficient to study these effects at the LHC once jet-binned data become available.« less

How Is Vaginitis Treated?

MedlinePlus

... Browse AZTopics Browse A-Z Adrenal Gland Disorders Autism Spectrum Disorder (ASD) Down Syndrome Endometriosis Learning Disabilities Menstruation and ... NICHD Research Information Find a Study More Information Autism Spectrum Disorder (ASD) About NICHD Research Information Find a Study ...

Increasing topical anesthetic efficacy with microneedle application.

PubMed

Buhsem, Ömer; Aksoy, Alper; Kececi, Yavuz; Sir, Emin; Güngör, Melike

2016-10-01

Since topical anesthetics alone seldom provide adequate analgesia for laser resurfacing procedures, injectable forms of anesthesia are often required. However, their application is uncomfortable for the patient. In this study, it is investigated whether microneedle application would enhance the efficacy of topical anesthetics. Forty-seven patients participated in the study. Topical anesthetic agent EMLA was applied to the whole face of the patients. Microneedle treatment was applied to one side of the face with a roller-type device. Whole-face carbon dioxide laser resurfacing therapy was carried out then. The pain that patients experienced was assessed by using visual analog scale (VAS) method. VAS scores of two sides of the face were compared by using Wilcoxon signed-rank test. The mean of VAS score of the microneedle treated side was 2.1 ± 1.1 while that of the untreated side was 5.9 ± 0.9 and this difference was statistically significant (Wilcoxon signed-rank test, the Z-value is - 5.9683 and the p-value is < 0.001). This study revealed that microneedle application, with a roller-type device, is a safe and easy procedure in providing sufficient anesthesia for facial laser resurfacing without the need for supplementary nerve blocks or injections.

The Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification independently predicts wound healing in diabetic foot ulcers.

PubMed

Hicks, Caitlin W; Canner, Joseph K; Mathioudakis, Nestoras; Sherman, Ronald; Malas, Mahmoud B; Black, James H; Abularrage, Christopher J

2018-04-02

Previous studies have reported correlation between the Wound, Ischemia, and foot Infection (WIfI) classification system and wound healing time on unadjusted analyses. However, in the only multivariable analysis to date, WIfI stage was not predictive of wound healing. Our aim was to examine the association between WIfI classification and wound healing after risk adjustment in patients with diabetic foot ulcers (DFUs) treated in a multidisciplinary setting. All patients presenting to our multidisciplinary DFU clinic from June 2012 to July 2017 were enrolled in a prospective database. A Cox proportional hazards model accounting for patients' sociodemographics, comorbidities, medication profiles, and wound characteristics was used to assess the association between WIfI classification and likelihood of wound healing at 1 year. There were 310 DFU patients enrolled (mean age, 59.0 ± 0.7 years; 60.3% male; 60.0% black) with 709 wounds, including 32.4% WIfI stage 1, 19.9% stage 2, 25.2% stage 3, and 22.4% stage 4. Mean wound healing time increased with increasing WIfI stage (stage 1, 96.9 ± 8.3 days; stage 4, 195.1 ± 10.6 days; P < .001). Likelihood of wound healing at 1 year was 94.1% ± 2.0% for stage 1 wounds vs 67.4% ± 4.4% for stage 4 (P < .001). After risk adjustment, increasing WIfI stage was independently associated with poor wound healing (stage 4 vs stage 1: hazard ratio, [HR] 0.44; 95% confidence interval, 0.33-0.59). Peripheral artery disease (HR, 0.73), increasing wound area (HR, 0.99 per square centimeter), and longer time from wound onset to first assessment (HR, 0.97 per month) also decreased the likelihood of wound healing, whereas use of clopidogrel was protective (HR, 1.39; all, P ≤ .04). The top three predictors of poor wound healing were WIfI stage 4 (z score, -5.40), increasing wound area (z score, -3.14), and WIfI stage 3 (z score, -3.11), respectively. Among patients with DFU, the WIfI classification system predicts wound healing at 1 year in both crude and risk-adjusted analyses. This is the first study to validate the WIfI score as an independent predictor of wound healing using multivariable analysis. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Use of dried blood spots for the determination of serum concentrations of tamoxifen and endoxifen.

PubMed

Jager, N G L; Rosing, H; Schellens, J H M; Beijnen, J H; Linn, S C

2014-07-01

The anti-estrogenic effect of tamoxifen is suggested to be mainly attributable to its metabolite (Z)-endoxifen, and a minimum therapeutic threshold for (Z)-endoxifen in serum has been proposed. The objective of this research was to establish the relationship between dried blood spot (DBS) and serum concentrations of tamoxifen and (Z)-endoxifen to allow the use of DBS sampling, a simple and patient-friendly alternative to venous sampling, in clinical practice. Paired DBS and serum samples were obtained from 50 patients using tamoxifen and analyzed using HPLC-MS/MS. Serum concentrations were calculated from DBS concentrations using the formula calculated serum concentration = DBS concentration/([1-haematocrit (Hct)] + blood cell-to-serum ratio × Hct). The blood cell-to-serum ratio was determined ex vivo by incubating a batch of whole blood spiked with both analytes. The average Hct for female adults was imputed as a fixed value. Calculated and analyzed serum concentrations were compared using weighted Deming regression. Weighted Deming regression analysis comparing 44 matching pairs of DBS and serum samples showed a proportional bias for both analytes. Serum concentrations were calculated using [Tamoxifen] serum, calculated  = [Tamoxifen] DBS /0.779 and [(Z)-Endoxifen] serum, calculated = [(Z)-Endoxifen] DBS /0.663. Calculated serum concentrations were within 20 % of analyzed serum concentrations in 84 and 100 % of patient samples for tamoxifen and (Z)-endoxifen, respectively. In conclusion, DBS concentrations of tamoxifen and (Z)-endoxifen were equal to serum concentrations after correction for Hct and blood cell-to-serum ratio. DBS sampling can be used in clinical practice.

Evaluation of Glutathione-S-Transferase P1 Polymorphism and its Relation to Bone Mineral Density in Egyptian Children and Adolescents with Beta-Thalassemia Major

PubMed Central

Ragab, Seham M.; Badr, Eman A.; Ibrahim, Ahmed S.

2016-01-01

Background Osteoporosis is a major complication of beta thalassemia major (TM). Increased oxidative stress and its controlling genes were linked to osteoporosis. Ile105 Val variant is a functional polymorphism of Glutathione S-transferase P1 (GSTP1), with reduced anti-oxidative property. No data are available about this variant or its association with osteoporosis among thalassemia patients yet. Objectives To investigate Ile105Val polymorphism and its possible association with bone mineral density (BMD) values in a group of TM children. Methods Thirty five TM children and 30 age and sex matched healthy controls were included. Liver and renal functions, serum ferritin, calcium, phosphorous, alkaline phosphatase and osteocalcin were assayed. BMD was determined by DXA with calculation of Z-scores at lumbar spine (LS) and femoral neck (FN). Height for age Z- score (HAZ) adjusted BMD Z-scores were calculated. GSTP1 Ile105Val polymorphism was studied by polymerase chain reaction-restriction fragment length polymorphism. Results The relative frequency of 105 Val allele was significantly higher in TM patients than the controls (p<0.0001). Significant association between genotype subgroups and BMD parameters was detected. Compared to wild homozygotes, polymorphic homozygotes had lower LS-BMD (p =0.029), LS-BMD Z –score (p=0.008 ), LS- BMD haz - Z-score (p=0.011), FN- BMD (p= 0.001), FN- BMD Z –score (p=0.02) and FN-BMD haz - Z-score (p=0.001). They exhibited higher osteocalcin levels compared to heterozygotes and wild homozygotes (p=0.012, p=0.013, respectively). Conclusion Ile105Val polymorphism was frequent among TM patients and could increase their susceptibility to reduced BMD. Large sample studies are required to confirm these findings. PMID:26740865

The impact of disease-related impairments on disability and health-related quality of life: a systematic review

PubMed Central

Weisscher, Nadine; de Haan, Rob J; Vermeulen, Marinus

2007-01-01

Background To investigate the interchangeability of measures of disability and health-related quality of life (HRQL) by comparing their associations patterns with disease-related impairment measures in patients with a variety of conditions. Methods A systematic literature search of MEDLINE, EMBASE, Web of Science and a hand search of reference lists through January 2006. Studies were included if they reported associations patterns between impairment and disability and between impairment and HRQL. Correlation coefficients were transformed to Fisher's z effect size (ES(z)). Weighted averages were reported as pooled ES(z) with 95% confidence intervals (CI). Results The relationship between impairment and disability was stronger (pooled ES(z) = 0.69; 95% CI, 0.66 – 0.72) than between impairment and HRQL (pooled ES(z) = 0.38; 95% CI, 0.36 – 0.41). The physical component score (pooled ES(z) = 0.43; 95% CI, 0.39 – 0.47) and disease-specific HRQL (pooled ES(z) = 0.46; 95% CI, 0.40 – 0.51) were stronger associated with impairments than the mental component score (pooled ES(z) = 0.28; 95% CI, 0.20 – 0.36) and generic HRQL (pooled ES(z) = 0.36; 95% CI, 0.33 – 0.39). Conclusion This study shows measures of disability and different HRQL domains were not equally related to impairment. Patient's impairments are better reflected in disability measures, than in HRQL instruments. There are many outcomes of interest and precisely defining them and measuring them will improve assessing the impact of new interventions. PMID:17578571

[Study on proteomics of familial systemic lupus erythematosus patients in one family from Sichuan, China].

PubMed

Wu, Yong-kang; Huang, Zhuo-chun; Shi, Yun-ying; Cai, Bei; Wang, Lan-lan; Ying, Bin-wu; Hu, Chao-jun; Li, Yong-zhe

2009-05-01

To investigate the proteomic characteristics of systemic lupus erythematosus (SLE) in a SLE family from Sichuan, China which consisting of 7 members with 3 SLE cases, and to find the proteins correlated with the heredity of SLE. A total of 153 serum samples were collected from 7 members including 3 SLE sisters in this SLE family, 63 individual SLE patients, as well as 83 healthy controls. The diagnosis of SLE is based on the American College of Rheumatology criteria (1997). All serum samples were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) combined with magnetic beads technology. Serum protein profiles were obtained by MALDI-TOF-MS combined with magnetic beads in order to identify predictive biomarkers of risk of suffering SLE. The resulting spectra were analyzed with Biomarker Wizard software 3.1.0. Four discriminative mass/charge (m/z) proteins serving as pathogenic biomarkers were identified on arrays for family SLE cases versus individual SLE and healthy controls. The protein level of peak intensities at m/z of 9342.23 was significantly greater in SLE family group compared with that in individual SLE patients and healthy controls (P<0.05), those of individual SLE patients were significantly greater compared with healthy controls (P<0.05); the proteins level of peak intensities at m/z of 4094.03, 5905.35 and 7973.53 in SLE family group were significantly lower compared with that in individual SLE patients and healthy controls (P<0.05), those of individual SLE patients were significantly lower compared with healthy controls (P<0.05). The proteins of m/z of 9342.23, 4094.03, 5905.35 and 7973.53 maybe play a great role in assemble pathogenesis of SLE and predict the risk of suffering SLE. The higher protein level of m/z of 9342.23 and the lower protein level of m/z of 4094.03, 5905.35 and 7973.53, the higher risk of sufferring with SLE.

A preliminary investigation to explore the cognitive resources of physicians experiencing difficulty in training.

PubMed

Patterson, Fiona; Cousans, Fran; Coyne, Iain; Jones, Jo; Macleod, Sheona; Zibarras, Lara

2017-05-15

Treating patients is complex, and research shows that there are differences in cognitive resources between physicians who experience difficulties, and those who do not. It is possible that differences in some cognitive resources could explain the difficulties faced by some physicians. In this study, we explore differences in cognitive resources between different groups of physicians (that is, between native (UK) physicians and International Medical Graduates (IMG); those who continue with training versus those who were subsequently removed from the training programme); and also between physicians experiencing difficulties compared with the general population. A secondary evaluation was conducted on an anonymised dataset provided by the East Midlands Professional Support Unit (PSU). One hundred and twenty one postgraduate trainee physicians took part in an Educational Psychology assessment through PSU. Referrals to the PSU were mainly on the basis of problems with exam progression and difficulties in communication skills, organisation and confidence. Cognitive resources were assessed using the Wechsler Adult Intelligence Scale (WAIS-IV). Physicians were categorised into three PSU outcomes: 'Continued in training', 'Removed from training' and 'Active' (currently accessing the PSU). Using a one-sample Z test, we compared the referred physician sample to a UK general population sample on the WAIS-IV and found the referred sample significantly higher in Verbal Comprehension (VCI; z = 8.78) and significantly lower in Working Memory (WMI; z = -4.59). In addition, the native sample were significantly higher in Verbal Comprehension than the UK general population sample (VCI; native physicians: z = 9.95, p < .001, d = 1.25), whilst there was a lesser effect for the difference between the IMG sample and the UK general population (z = 2.13, p = .03, d = 0.29). Findings also showed a significant difference in VCI scores between those physicians who were 'Removed from training' and those who 'Continued in training'. Our results suggest it is important to understand the cognitive resources of physicians to provide a more focussed explanation of those who experience difficulties in training. This will help to implement more targeted interventions to help physicians develop compensatory strategies.

Association between BIM deletion polymorphism and clinical outcome of EGFR-mutated NSCLC patient with EGFR-TKI therapy: A meta-analysis.

PubMed

Ma, Ji-Yong; Yan, Hai-Jun; Gu, Wei

2015-01-01

BIM deletion polymorphism was deemed to be associated with downregulation of BIM, resulting in a decreased apoptosis induced by epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutation-positive non-small cell lung cancer (NSCLC). However, accumulating evidences concerning the association between BIM deletion polymorphism and efficacy of EGFR-TKI and survival in EGFR-mutation-driven NSCLC patient reported contradictory results. A meta-analysis was conducted by combing six original eligible studies including 871 NSCLC patients. Our study showed that BIM deletion polymorphism was significantly associated with poor response to EGFR-TKI therapy in mutant EGFRNSCLC patients (P(h) = 0.309, P(z) = 0.001, OR = 0.39, 95% confidence interval (CI) = 0.23-0.67). Disease control rate (DCR) in mutant EGFRNSCLC patient with treatment of EGFR-TKI was significantly decreased in patients with BIM deletion polymorphism comparing to patients harbored BIM wild variant (P(h) = 0.583, P(Z) = 0.007, OR = 0.46, 95%CI = 0.25-0.85). EGFR mutation-derived NSCLC patient carrying BIM deletion polymorphism had a shorter progression-free survival (PFS; P(h) < 0.001, P(z) < 0.001, hazard ratio (HR) = 1.37, 95%CI = 1.09-1.71) and overall survival (OS; P(h) = 0.90, P(z) = 0.003, HR = 1.25, 95%CI = 1.08-1.45), than those harbored BIM wild variant. These results suggested that BIM deletion polymorphism might be a cause that contributes to primary EGFR-TKI resistance, and it could be used as a genetic predictor for EGFR-TKI outcome and an independent prognostic factor of EGFR mutation-driven NSCLC patient.

Decreased bone mineral density in young adults treated with SCT in childhood: the role of 25-hydroxyvitamin D.

PubMed

Frisk, P; Arvidson, J; Ljunggren, O; Gustafsson, J

2012-05-01

We measured bone mineral density (BMD) with dual-energy X-ray absorptiometry in the total body, at the lumbar spine, at the femoral neck and in the total hip, in 18 young adults with a median of 18.2 years after SCT. Fifteen patients had undergone auto-SCT and all patients had received TBI. The patients had significantly lower BMD in the total body, at the femoral neck, and in the total hip compared with age- and sex-matched controls. Six of 18 patients (33%) had low bone mass (z-score <-1) at one or more measurement sites, as opposed to two of the controls (11%, P=0.29). We found no significant influence of growth hormone levels or of untreated hypogonadism on BMD variables. Levels of 25-hydroxy (25(OH)) vitamin D were lower among the patients (35.2 vs 48.8 nmol/L, P=0.044) and were significantly correlated with total body BMD in the patient group (r=0.55, P=0.021). All six patients with low bone mass had hypovitaminosis D (≤37 nmol/L as opposed to 4 of the 11 (36%) patients without low bone mass (P=0.035). In conclusion, we found decreased BMD in SCT survivors, which may in part be caused by 25(OH) vitamin D deficiency.

Changes in body mass index in children with juvenile idiopathic arthritis treated with tumor necrosis factor inhibitors.

PubMed

Shafferman, Ashley; Fontaine, Kevin R; Cron, Randy Q; Beukelman, Timothy

2014-01-01

To evaluate changes in body mass index (BMI) among cohorts of children with juvenile idiopathic arthritis (JIA) with and without tumor necrosis factor (TNF) inhibitor therapy. We performed a retrospective chart review of children with JIA who newly initiated TNF inhibitor therapy and had at least 1 year of subsequent followup (TNF cohort). We also included children with JIA and at least 1 year of followup without any TNF inhibitor therapy (comparator cohort). Children with systemic arthritis were excluded. Age and sex specific BMI z-scores and their corresponding categories (normal, overweight, obese) were determined. We compared changes from a baseline visit to the last followup visit using t-test for BMI z-scores and chi square and Kruskal-Wallis tests for BMI categories. The TNF cohort had 167 patients; the comparator cohort had 37. The median study followup was 2.8 and 2.2 years, respectively. The cohorts had similar age, sex, race, weight, and height distributions. The TNF cohort had a statistically significant increase in BMI z-score from baseline (+0.15; p = 0.02) that was not significantly different from the increase (+0.09) observed in the comparator cohort (p = 0.5). There was no significant change in the proportions of overweight and obese children in the TNF cohort compared to baseline (p = 0.6) or compared to the change in the comparator cohort (p = 0.2). Over more than 2 years of followup, we did not observe a significant increase in BMI among children with JIA receiving TNF inhibitor compared to those not receiving it.

Higher Caspase-like activity in symptomatic isolates of Blastocystis spp

PubMed Central

2014-01-01

Background Biochemical evidence of a caspase-like execution pathway has been demonstrated in a variety of protozoan parasites, including Blastocystis spp. The distinct differences in the phenotypic characterization reported previously have prompted us to compare the rate of apoptosis in Blastocystis spp. isolated from individuals who were symptomatic and asymptomatic. In the current study, we analysed the caspase activation involved in PCD mediated by a cytotoxic drug, (metronidazole) in both symptomatic & asymptomatic isolates. Methods Apoptosis was induced in Blastocystis spp. by treating cultures of symptomatic and asymptomatic isolates of 3 sub-types namely 1, 3 and 5 with two different concentrations, 0.1 and 0.0001 mg/ml of metronidazole (with and without pre-treatment with a pan-caspase inhibitor, zVAD.fmk). The experiment was repeated to assess the number of apoptotic cells in all the isolates of both conditions. Results Symptomatic isolates of subtype 3 (without pre-treatment with a pan-caspase inhibitor, zVAD.fmk) showed high fluorescence intensity for active caspase-like proteases [0.0001 mg/ml, 88% (p < 0.001) at 0.1 mg/ml, 70% (p < 0.001)] at the 72nd hour in vitro culture in comparison with asymptomatic isolates [0.0001 mg/ml, 65%, at 0.1 mg/ml, 55%]. The number of apoptotic cells was higher [0.0001 mg/ml, 89% (p < 0.001) and at 0.1 mg/ml, 70% (p < 0.001)] at the 72nd hour of in vitro culture in comparison with asymptomatic isolates [0.0001 mg/ml, 66% (p < 0.001) and at 0.1 mg/ml, 45% (p < 0.01)]. Cells treated with metronidazole in the presence of zVAD.fmk showed less than 10% caspase activation. Conclusion The high number of symptomatic cells expressing active caspase-like proteases and becoming apoptotic compared to asymptomatic cells clearly demonstrates that the response to metronidazole treatment is isolate dependent. Hence this justifies the conflicting reports on the curative success rates when treated with this drug. The study has also created a need to identify apoptosis effectors in Blastocystis spp of different isolates especially as it was shown that apoptosis was sub-typed related. These findings can be exploited for the development of diagnostic markers and novel therapeutic drugs to enhance the effectiveness of the diagnosis and treatment of the patients infected with Blastocystis spp. PMID:24886677

High Thermal Conductivity NARloy-Z-Diamond Composite Liner for Advanced Rocket Engines

NASA Technical Reports Server (NTRS)

Bhat, Biliyar; Greene, Sandra

2015-01-01

NARloy-Z (Cu-3Ag-0.5Zr) alloy is state-of-the-art combustion chamber liner material used in liquid propulsion engines such as the RS-68 and RS-25. The performance of future liquid propulsion systems can be improved significantly by increasing the heat transfer through the combustion chamber liner. Prior work1 done at NASA Marshall Space Flight Center (MSFC) has shown that the thermal conductivity of NARloy-Z alloy can be improved significantly by embedding high thermal conductivity diamond particles in the alloy matrix to form NARloy-Z-diamond composite (fig. 1). NARloy-Z-diamond composite containing 40vol% diamond showed 69% higher thermal conductivity than NARloy-Z. It is 24% lighter than NARloy-Z and hence the density normalized thermal conductivity is 120% better. These attributes will improve the performance and life of the advanced rocket engines significantly. The research work consists of (a) developing design properties (thermal and mechanical) of NARloy-Z-D composite, (b) fabrication of net shape subscale combustion chamber liner, and (c) hot-fire testing of the liner to test performance. Initially, NARloy-Z-D composite slabs were made using the Field Assisted Sintering Technology (FAST) for the purpose of determining design properties. In the next step, a cylindrical shape was fabricated to demonstrate feasibility (fig. 3). The liner consists of six cylinders which are sintered separately and then stacked and diffusion bonded to make the liner (fig. 4). The liner will be heat treated, finish-machined, and assembled into a combustion chamber and hot-fire tested in the MSFC test facility (TF 115) to determine perform.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnston, David C.

Here, the influence of uniaxial single-ion anisotropy –DS 2 z on the magnetic and thermal properties of Heisenberg antiferromagnets (AFMs) is investigated. The uniaxial anisotropy is treated exactly and the Heisenberg interactions are treated within unified molecular field theory (MFT), where thermodynamic variables are expressed in terms of directly measurable parameters. The properties of collinear AFMs with ordering along the z axis (D>0) in applied field H z = 0 are calculated versus D and temperature T, including the ordered moment μ, the Néel temperature T N, the magnetic entropy, internal energy, heat capacity, and the anisotropic magnetic susceptibilities χmore » ∥ and χ ⊥ in the paramagnetic (PM) and AFM states. The high-field average magnetization per spin μ z(H z,D,T) is found, and the critical field H c(D,T) is derived at which the second-order AFM to PM phase transition occurs. The magnetic properties of the spin-flop (SF) phase are calculated, including the zero-field properties T N(D) and μ(D,T). The high-field μ z(H z,D,T) is determined, together with the associated spin-flop field H SF(D,T) at which a second-order SF to PM phase transition occurs. The free energies of the AFM, SF, and PM phases are derived from which H z–T phase diagrams are constructed. For f J =–1 and –0.75, where f J = θ pJ/T NJ and θ pJ and T NJ are the Weiss temperature in the Curie-Weiss law and the Néel temperature due to exchange interactions alone, respectively, phase diagrams in the H z–T plane similar to previous results are obtained. However, for f J = 0 we find a topologically different phase diagram where a spin-flop bubble with PM and AFM boundaries occurs at finite H z and T. Also calculated are properties arising from a perpendicular magnetic field, including the perpendicular susceptibility χ ⊥(D,T), the associated effective torque at low fields arising from the –DS 2 z term in the Hamiltonian, the high-field perpendicular magnetization μ ⊥, and the perpendicular critical field H c⊥ at which the second-order AFM to PM phase transition occurs. In addition to the above results for D > 0, the T N(D) and ordered moment μ(T,D) for collinear AFM ordering along the x axis with D < 0 are determined. In order to compare the properties of the above spin systems with those of noninteracting systems with –DS 2 z uniaxial anisotropy with either sign of D, Supplemental Material is provided in which results for the thermal and magnetic properties of such noninteracting spin systems are given.« less

UK Renal Registry 17th Annual Report: Chapter 9 Clinical, Haematological and Biochemical Parameters in Patients Receiving Renal Replacement Therapy in Paediatric Centres in the UK in 2013: National and Centre-specific Analyses.

PubMed

Hamilton, Alexander J; Pruthi, Rishi; Maxwell, Heather; Casula, Anna; Braddon, Fiona; Inward, Carol; Lewis, Malcolm; O'Brien, Catherine; Stojanovic, Jelena; Tse, Yincent; Sinha, Manish D

2015-01-01

The Paediatric Registry analyses renal replacement therapy (RRT) data in children. All 13 UK paediatric nephrology centres submit electronic data. To provide centre specific data and to determine adherence to relevant audit standards. Data analysis to calculate summary statistics and achievement of an audit standard. The median height z-score for children on dialysis was -2.0 and for children with a functioning transplant -1.3. Children transplanted before age 11 years improved their height z score subsequently, whereas those >11 maintained their height z-score, with all transplanted patients having a similar height z-score after 3 years of starting RRT.The median weight z-score for children on dialysis was -1.2, and for children with a functioning transplant -0.2.Of those with data, 75% of the prevalent paediatric RRT population had .1 risk factors for cardiovascular disease, with 1 in 10 having all three risk factors evaluated. For transplant patients, 76% achieved the systolic blood pressure (SBP)standard and 91% achieved the haemoglobin standard. For haemodialysis patients, 53% achieved the SBP standard,66% the haemoglobin standard, 84% the calcium standard,43% the phosphate standard and 43% achieved the parathyroid hormone (PTH) standard. For peritoneal dialysis patients, 61% achieved the SBP standard, 83% the haemoglobin standard, 71% the calcium standard, 56% the phosphate standard and 36% achieved the PTH standard. Quarterly data collection will improve quality and reporting. Continued focus on improving height and avoiding obesity is needed. Awareness and management of cardiovascular risk is an important long term strategy.

Cercosporoid fungi (Mycosphaerellaceae) 2. Species on monocots (Acoraceae to Xyridaceae, excluding Poaceae).

PubMed

Braun, Uwe; Crous, Pedro W; Nakashima, Chiharu

2014-12-01

Cercosporoid fungi (formerly Cercospora s. lat.) represent one of the largest groups of hyphomycetes belonging to the Mycosphaerellaceae (Ascomycota). They include asexual morphs, asexual holomorphs, or species with mycosphaerella-like sexual morphs. Most of them are leaf-spotting plant pathogens with special phytopathological relevance. In the first part of a new monographic work, cercosporoid hyphomycetes occurring on other fungi (fungicolous species), on ferns (pteridophytes) and gymnosperms were treated. This second part deals with cercosporoid fungi on monocots (Liliopsida; Equisetopsida, Magnoliidae, Lilianae), which covers species occurring on host plants belonging to families arranged in alphabetical order from Acoraceae to Xyridaceae, excluding Poaceae (cereals and grasses) which requires a separate treatment. The species are described and illustrated in alphabetical order under the particular cercosporoid genera, supplemented by keys to the species concerned. A detailed introduction, a survey of currently recognised cercosporoid genera, a key to the genera concerned, and a discussion of taxonomically relevant characters were published in the first part of this series. Neopseudocercospora, an additional recently introduced cercosporoid genus, is briefly discussed. The following taxonomic novelties are introduced: Cercospora alpiniigena sp. nov., C. neomaricae sp. nov., Corynespora palmicola comb. nov., Exosporium miyakei comb. nov., E. petersii comb. nov., Neopseudocercospora zambiensis comb. nov., Passalora caladiicola comb. nov., P. streptopi comb. nov., P. togashiana comb. nov., P. tranzschelii var. chinensis var. nov., Pseudocercospora beaucarneae comb. nov., P. constrictoflexuosa comb. et stat. nov., P. curcumicola sp. nov., P. dispori comb. nov., P. smilacicola sp. nov., P. urariigena nom. nov., Zasmidium agavicola comb. nov., Z. cercestidis-afzelii comb. nov., Z. citri-griseum comb. nov., Z. cyrtopodii comb. nov., Z. gahnae comb. nov., Z. indicum comb. nov., Z. liriopes comb. nov., Z. mycovellosielloides sp. nov., Z. scleriae comb. nov., Z. smilacicola comb. nov., and Z. thaliae comb. nov.

Simultaneous quantification of 5 main components of Psoralea corylifolia L. in rats' plasma by utilizing ultra high pressure liquid chromatography tandem mass spectrometry.

PubMed

Gao, Qianqian; Xu, Zisheng; Zhao, Genhua; Wang, Heng; Weng, Zebin; Pei, Ke; Wu, Li; Cai, Baochang; Chen, Zhipeng; Li, Weidong

2016-02-01

Psoralea corylifolia L. has long been used in traditional Chinese medicine for treating and preventing many diseases. A group of flavonoid components are regarded as the active principals within the seeds. In this research, a rapid, accurate and sensitive ultra high pressure liquid chromatography tandem mass spectrometry (UHPLC/MS/MS) method has been established for simultaneous quantification of its 5 main components, namely, neobavaisoflavone, bavachin, isobavachalcone, bavachinin and corylifol A in rats' plasma after the rats were orally administrated with Buguzhi extract. Negative ion electrospray mode was applied in the detection process. Multiple reactions monitoring (MRM) mode was utilized for simultaneous quantitative analyzing of neobavaisoflavone (m/z 321.1→m/z 265.1), bavachin (m/z 323.1→m/z 119.0), isobavachalcone (m/z 323.2→m/z 119.0), bavachinin (m/z 337.2→m/z 119.0), corylifol A (m/z 389.2→m/z 277.0) and liquiritigenin (Internal Standard, m/z 255.1→m/z 119.0). Chromatographic separation of the above mentioned components was conducted on a Waters BEH-C18 column (100 mm×2.1mm, 1.7μm) with gradient elution system at flow rate of 0.3mL/min. The mobile phase was composed of acetonitrile and 0.1% formic acid solution. The lower limit of quantification (LLOQ) for each of the above analytes was 0.5ng/mL. Each of the analytes exhibited good linearity within the concentration range of 0.5-100ng/mL. The method was fully validated for its selectivity, accuracy, precision, stability, matrix effect and extraction recovery. The validated method has been successfully applied for simultaneous determination of the 5 flavonoids in rat plasma for the first time. Copyright © 2016 Elsevier B.V. All rights reserved.

Kaiser Permanente Georgia's Experience with Operation Zero: A Group Medical Appointment to Address Pediatric Overweight

PubMed Central

Hinchman, Josephine; Beno, Luke; Mims, Adrienne

2006-01-01

Context: The rate of overweight (OW) in children in the United States has more than tripled since 1980. The health consequences of pediatric OW include type 2 diabetes and significant illness later in life. Treating pediatric OW is a necessity; however, health care clinicians have minimal access to successful and comprehensive treatment modalities for addressing it. Objective: Kaiser Permanente of Georgia (KPGA) offers a group medical appointment clinic, Operation Zero (O.Z.), as a referral program for preadolescent and adolescent patients who are in the 85th or higher percentile for body mass index (BMI) for their age. The eight-session clinic uses a family-oriented approach and provides a supportive group environment with interactive learning, games, physical activity, and creative problem solving. The goal of the program is to improve lifestyle behaviors for nutrition and physical activity. Clinically, meeting these goals can manifest as reductions in body fat (BF), waist size, and BMI-for-age percentile. Two implementation models help improve dissemination of the program within KPGA. Design: Baseline and eight-week postclinical outcomes for O.Z. participants were analyzed to determine program effectiveness. A retrospective analysis with a control group looked at long-term clinical outcomes to determine weight maintenance. Main outcome measures were weight, BMI-for-age percentile, waist size, and percentage of body fat (%BF). Results: At eight weeks after program completion compared with baseline, there were significant reductions in %BF and waist size for the total sample and specifically for adolescents, preteens, and participants who attended six or more sessions. Among O.Z. participants, there were insignificant increases in weight at six months after program participation and BMI-for-age percentile at one year after participation. At six months, the mean change in weight and BMI in the O.Z. group was statistically less than the mean change in the control group. Conclusions: A structured, family-oriented weight management program is effective in changing measures consistent with improved weight management. PMID:21519478

Outcomes of bone density measurements in coeliac disease.

PubMed

Bolland, Mark J; Grey, Andrew; Rowbotham, David S

2016-01-29

Some guidelines recommend that patients with newly diagnosed coeliac disease undergo bone density scanning. We assessed the bone density results in a cohort of patients with coeliac disease. We searched bone density reports over two 5-year periods in all patients from Auckland District Health Board (2008-12) and in patients under 65 years from Counties Manukau District Health Board (2009-13) for the term 'coeliac.' Reports for 137 adults listed coeliac disease as an indication for bone densitometry. The average age was 47 years, body mass index (BMI) 25 kg/m(2), and 77% were female. The median time between coeliac disease diagnosis and bone densitometry was 261 days. The average bone density Z-score was slightly lower than expected (Z-score -0.3 to 0.4) at the lumbar spine, total hip and femoral neck, but 88-93% of Z-scores at each site lay within the normal range. Low bone density was strongly related to BMI: the proportions with Z-score <-2 for BMI <20, 20-25, 25-30, and >30 kg/m(2) were 28%, 15%, 6% and 0% respectively. Average bone density was normal, suggesting that bone density measurement is not indicated routinely in coeliac disease, but could be considered on a case-by-case basis for individuals with strong risk factors for fracture.

Sun-screening bioactive compounds mycosporine-like amino acids in naturally occurring cyanobacterial biofilms: role in photoprotection.

PubMed

Rastogi, R P; Madamwar, D; Incharoensakdi, A

2015-09-01

To investigate the occurrence of UV sunscreening biomolecules and their role in photoprotection in cyanobacterial biofilms growing in brightly lit habitats with high UV fluxes. High performance liquid chromatography with photodiode-array and mass spectrometry revealed the presence of mycosporine-like amino acids (MAAs) shinorine (λ(max) 334 nm, m/z 333), porphyra-334 (λ(max) 334 nm, m/z 347), mycosporine-glycine (λ(max) 310 nm, m/z 246) and palythinol (λ(max) 332 nm, m/z 303). Two unknown MAAs with λ(max) at 320 (m/z 289) and 329 nm (m/z 318) were also found. Biosynthesis of MAAs was found to increase with increase in exposure time under UV radiation. The MAAs from biofilms showed efficient radical scavenging activity as well as photoprotective potential on the survival of UV-treated Escherichia coli cells. Biosynthesis of photoprotectants is an important mechanism to prevent photodamage in Cyanobacteria. UV-induction and photoprotective function of MAAs may facilitate them to perform important ecological functions under harsh environmental conditions. There are very few reports on qualitative and quantitative characterization of different MAAs in cyanobacterial biofilms. Due to strong UV absorption and photoprotective function, MAAs may be used as an active ingredient in cosmetic and other pharmaceutical industries. © 2015 The Society for Applied Microbiology.

Improvements in Sensible Heat-Flux Parametrization in the High-Resolution Regional Model (HRM) Through the Modified Treatment of the Roughness Length for Heat

NASA Astrophysics Data System (ADS)

Anurose, T. J.; Subrahamanyam, D. Bala

2013-06-01

We discuss the impact of the differential treatment of the roughness lengths for momentum and heat (z_{0m} and z_{0h}) in the flux parametrization scheme of the high-resolution regional model (HRM) for a heterogeneous terrain centred around Thiruvananthapuram, India (8.5°N, 76.9°E). The magnitudes of sensible heat flux ( H) obtained from HRM simulations using the original parametrization scheme differed drastically from the concurrent in situ observations. With a view to improving the performance of this parametrization scheme, two distinct modifications are incorporated: (1) In the first method, a constant value of 100 is assigned to the z_{0m}/z_{0h} ratio; (2) and in the second approach, this ratio is treated as a function of time. Both these modifications in the HRM model showed significant improvements in the H simulations for Thiruvananthapuram and its adjoining regions. Results obtained from the present study provide a first-ever comparison of H simulations using the modified parametrization scheme in the HRM model with in situ observations for the Indian coastal region, and suggest a differential treatment of z_{0m} and z_{0h} in the flux parametrization scheme.

Growth in Prepubertal Children With Cystic Fibrosis Treated With Ivacaftor

PubMed Central

Pace, Jesse; Niknian, Minoo; Higgins, Mark N.; Tarn, Valerie; Davis, Joy; Heltshe, Sonya L.; Rowe, Steven M.

2017-01-01

BACKGROUND AND OBJECTIVES: Cystic fibrosis (CF) is known for its impact on the lung and pancreas of individuals; however, impaired growth is also a common complication. We hypothesized that targeting the biological defect in the CF transmembrane conductance regulator (CFTR) protein may affect growth outcomes. METHODS: In this post hoc analysis, we assessed linear growth and weight in 83 children (aged 6–11 years) enrolled in 2 clinical trials, the longitudinal-observation GOAL study and the placebo-controlled ENVISION study, to evaluate the effects of ivacaftor, a CFTR potentiator. We calculated height and weight z scores and height and weight growth velocities (GVs). RESULTS: In ivacaftor-treated children in GOAL, height and weight z scores increased significantly from baseline to 6 months (increases of 0.1 [P < .05] and 0.26 [P < .0001], respectively); height GV increased significantly from 3 to 6 months (2.10-cm/year increase; P < .01). In ivacaftor-treated children in ENVISION, height and weight z scores increased significantly from baseline to 48 weeks (increases of 0.17 [P < .001] and 0.35 [P < .001], respectively). Height and weight GVs from baseline to 48 weeks were also significantly higher with ivacaftor than with placebo (differences of 1.08 cm/year [P < .05] and 3.11 kg/year [P < .001], respectively). CONCLUSIONS: Ivacaftor treatment in prepubescent children may help to address short stature and altered GV in children with CF; results from these analyses support the existence of an intrinsic defect in the growth of children with CF that may be ameliorated by CFTR modulation. PMID:28143919

Growth in Prepubertal Children With Cystic Fibrosis Treated With Ivacaftor.

PubMed

Stalvey, Michael S; Pace, Jesse; Niknian, Minoo; Higgins, Mark N; Tarn, Valerie; Davis, Joy; Heltshe, Sonya L; Rowe, Steven M

2017-02-01

Cystic fibrosis (CF) is known for its impact on the lung and pancreas of individuals; however, impaired growth is also a common complication. We hypothesized that targeting the biological defect in the CF transmembrane conductance regulator (CFTR) protein may affect growth outcomes. In this post hoc analysis, we assessed linear growth and weight in 83 children (aged 6-11 years) enrolled in 2 clinical trials, the longitudinal-observation GOAL study and the placebo-controlled ENVISION study, to evaluate the effects of ivacaftor, a CFTR potentiator. We calculated height and weight z scores and height and weight growth velocities (GVs). In ivacaftor-treated children in GOAL, height and weight z scores increased significantly from baseline to 6 months (increases of 0.1 [P < .05] and 0.26 [P < .0001], respectively); height GV increased significantly from 3 to 6 months (2.10-cm/year increase; P < .01). In ivacaftor-treated children in ENVISION, height and weight z scores increased significantly from baseline to 48 weeks (increases of 0.17 [P < .001] and 0.35 [P < .001], respectively). Height and weight GVs from baseline to 48 weeks were also significantly higher with ivacaftor than with placebo (differences of 1.08 cm/year [P < .05] and 3.11 kg/year [P < .001], respectively). Ivacaftor treatment in prepubescent children may help to address short stature and altered GV in children with CF; results from these analyses support the existence of an intrinsic defect in the growth of children with CF that may be ameliorated by CFTR modulation. Copyright © 2017 by the American Academy of Pediatrics.

Dynamic FtsA and FtsZ localization and outer membrane alterations during polar growth and cell division in Agrobacterium tumefaciens

PubMed Central

Zupan, John R.; Cameron, Todd A.; Anderson-Furgeson, James; Zambryski, Patricia C.

2013-01-01

Growth and cell division in rod-shaped bacteria have been primarily studied in species that grow predominantly by peptidoglycan (PG) synthesis along the length of the cell. Rhizobiales species, however, predominantly grow by PG synthesis at a single pole. Here we characterize the dynamic localization of several Agrobacterium tumefaciens components during the cell cycle. First, the lipophilic dye FM 4-64 predominantly stains the outer membranes of old poles versus growing poles. In cells about to divide, however, both poles are equally labeled with FM 4-64, but the constriction site is not. Second, the cell-division protein FtsA alternates from unipolar foci in the shortest cells to unipolar and midcell localization in cells of intermediate length, to strictly midcell localization in the longest cells undergoing septation. Third, the cell division protein FtsZ localizes in a cell-cycle pattern similar to, but more complex than, FtsA. Finally, because PG synthesis is spatially and temporally regulated during the cell cycle, we treated cells with sublethal concentrations of carbenicillin (Cb) to assess the role of penicillin-binding proteins in growth and cell division. Cb-treated cells formed midcell circumferential bulges, suggesting that interrupted PG synthesis destabilizes the septum. Midcell bulges contained bands or foci of FtsA-GFP and FtsZ-GFP and no FM 4-64 label, as in untreated cells. There were no abnormal morphologies at the growth poles in Cb-treated cells, suggesting unipolar growth uses Cb-insensitive PG synthesis enzymes. PMID:23674672

Dosimetric considerations for patients with HIP prostheses undergoing pelvic irradiation. Report of the AAPM Radiation Therapy Committee Task Group 63.

PubMed

Reft, Chester; Alecu, Rodica; Das, Indra J; Gerbi, Bruce J; Keall, Paul; Lief, Eugene; Mijnheer, Ben J; Papanikolaou, Nikos; Sibata, Claudio; Van Dyk, Jake

2003-06-01

This document is the report of a task group of the Radiation Therapy Committee of the AAPM and has been prepared primarily to advise hospital physicists involved in external beam treatment of patients with pelvic malignancies who have high atomic number (Z) hip prostheses. The purpose of the report is to make the radiation oncology community aware of the problems arising from the presence of these devices in the radiation beam, to quantify the dose perturbations they cause, and, finally, to provide recommendations for treatment planning and delivery. Some of the data and recommendations are also applicable to patients having implanted high-Z prosthetic devices such as pins, humeral head replacements. The scientific understanding and methodology of clinical dosimetry for these situations is still incomplete. This report is intended to reflect the current state of scientific understanding and technical methodology in clinical dosimetry for radiation oncology patients with high-Z hip prostheses.

Formal verification of medical monitoring software using Z language: a representative sample.

PubMed

Babamir, Seyed Morteza; Borhani, Mehdi

2012-08-01

Medical monitoring systems are useful aids assisting physicians in keeping patients under constant surveillance; however, taking sound decision by the systems is a physician concern. As a result, verification of the systems behavior in monitoring patients is a matter of significant. The patient monitoring is undertaken by software in modern medical systems; so, software verification of modern medial systems have been noticed. Such verification can be achieved by the Formal Languages having mathematical foundations. Among others, the Z language is a suitable formal language has been used to formal verification of systems. This study aims to present a constructive method to verify a representative sample of a medical system by which the system is visually specified and formally verified against patient constraints stated in Z Language. Exploiting our past experience in formal modeling Continuous Infusion Insulin Pump (CIIP), we think of the CIIP system as a representative sample of medical systems in proposing our present study. The system is responsible for monitoring diabetic's blood sugar.

Functions of the uvula and Z-pharyngoplasty.

PubMed

Mukai, S; Mukai, C; Nitta, M

2000-06-01

UPPP includes uvulotomy. The uvula works as the pilot for eating and swallowing. We performed an operation which left the uvula intact and opened the pharynx by Z-opening the palate, Z-pharyngoplasty (ZPP). Twenty-four patients were studied before and after ZPP. The results of the operations were satisfactory. No patients complained of symptoms after uvulectomy. As for the changes indicated by sleep monitoring, minimum SaO2 increased significantly (P = 0.0026), pulse rate decreased significantly (P = 0.0144), apnea index decreased significantly (P = 0.0392), snoring decreased (P = 0.064), and the amount of hours of sleep when SaO2 was over 95% increased (P = 0.0690) after ZPP.

Relation of Biochemical Parameters with Flow-mediated Dilatation in Patients with Metabolic Syndrome

PubMed Central

Sipahioglu, Nurver Turfaner; Ilerigelen, Barıs; Gungor, Zeynep B.; Ayaz, Gulsel; Ekmekci, Hakan; Gurel, Cigdem Bayram; Can, Gunay; Sonmez, Huseyin; Ulutin, Turgut; Sipahioglu, Fikret

2017-01-01

Background: Metabolic syndrome (MetS) is one of the high cardiovascular (CV) situations. Endothelial dysfunction, which is a common finding in patients with MetS, is related with increased CV risk. In patients with MetS, the effect of the major CV risk factors, not included in the MetS definition, on endothelial dysfunction is not well known. The aim of this study was to determine the effect of major CV risk factors such as gender, smoking, family history, and biochemical parameters on endothelial dysfunction in patients with MetS. Methods: The study was performed between December 2010 and August 2014. A total of 55 patients (15 females and 40 males) with MetS and 81 healthy controls (37 females and 44 males) with a body mass index <25 kg/m2 were enrolled in the study. Endothelial dysfunction was measured by flow-mediated dilatation (FMD), oxidative stress parameters; high-sensitivity C-reactive protein (hs-CRP), oxidized low-density lipoprotein (ox-LDL), endothelial nitric oxide synthase (e-NOS), nitric oxide, and cell adhesion markers; von Willebrand factor, and e-selectin. Platelet aggregation (endothelial adenosine diphosphate), total platelet count, and mean platelet volume were additionally analyzed and demographic parameters were explored. Student's t-test, Mann-Whitney U-test, and Chi-square test were used to analyze the results. Results: The fasting blood glucose (z = 3.52, P = 0.001), hs-CRP (z = 3.23, P = 0.004), ox-LDL (z = 2.62, P = 0.013), and e-NOS (z = 2.22, P = 0.026) levels and cardiac risk score (z = 5.23, P < 0.001) were significantly higher in patients with MetS compared with the control group. Smoking was correlated with decreased FMD (χ2 = 9.26, P = 0.002) in MetS patients but not in the control group. Conclusions: Increased ox-LDL, hs-CRP, and e-NOS are likely to be a result of oxidative stress, a condition in which an imbalance occurs between the production and inactivation of reactive nitrogen and oxygen species. In addition, in patients with MetS, smoking is independently related to endothelial dysfunction. PMID:28639572

Metabolic profiling of hepatitis B virus-related hepatocellular carcinoma with diverse differentiation grades.

PubMed

Zhang, Lei; Huang, Ya; Lian, Mingjian; Fan, Zhijuan; Tian, Yaqiong; Wang, Yufan; Kang, Hua; Liu, Shuang; Liu, Shuye; Li, Tong; Shan, Zhongqiang

2017-03-01

The most effective diagnostic tool for the majority of hepatocellular carcinoma (HCC) patients is determining the differentiation grade of their tumors. However liver biopsies, which are currently the most effective way of determining tumor differentiation grade, have several limitations. The present study was designed to select serum characteristic metabolites that correlate with the differentiation grades of hepatitis B virus (HBV)-related HCC, and so could be used in the clinic as a non-invasive method of differentiating patients with different grades of HCC. A total of 58 patients with HBV-related HCC were included in the present study, and divided into three groups according to their tumor differentiation grade. A further 20 patients with HBV-related liver cirrhosis and 19 healthy volunteers were enrolled. Ultra-performance liquid chromatography-mass spectrometry was used to analyze endogenous metabolites. Multivariate statistical analysis was used to examine the data using MZmine 2.0 software. The 14 metabolites that were highly correlated with specific differentiation grades of HCC were then selected for additional study. Receiver operator characteristic curve analysis was used to evaluate their clinical value. In total, 5 metabolites were finally identified, including lysophosphatidylcholine (16:0), oleamide, monoglyceride (0:0/15:0/0:0), lysophosphatidylcholine (18:0) and lysophosphatidylcholine [22:5(7Z,10Z,13Z,16Z,19Z)]. All these metabolites exhibited an excellent ability to distinguish different types of HCC with various differentiation grades and the area under the curve of these metabolites was up to 0.942, showing promising clinical value.

Prevalence and predictors of overweight and obesity among a multiethnic population of pediatric acute lymphoblastic leukemia survivors: a cross-sectional assessment

PubMed Central

Brown, Austin L.; Lupo, Philip J.; Danysh, Heather E.; Okcu, M. Fatih; Scheurer, Michael E.; Kamdar, Kala Y.

2016-01-01

As previous studies of obesity in survivors of pediatric acute lymphoblastic leukemia (ALL) have primarily been conducted among non-Hispanic white survivors or children treated on older protocols, our objective was to describe the prevalence and correlates of overweight status among an ethnically diverse population of pediatric ALL survivors, largely treated with more contemporary therapies. We evaluated the overweight/obesity status of pediatric ALL survivors (n=406) followed in the Texas Children's Cancer Center between 2004 and 2014. Survivors were classified as underweight, normal weight, overweight, or obese on the basis of their Body Mass Index (BMI) at their most current follow-up visit. Our results showed that Hispanic ethnicity (39% of subjects) was associated with being overweight (adjusted odds ratio [aOR]=1.88; 95% confidence interval [CI]: 1.13-3.14) or obese (aOR=2.84; 95% CI: 1.59-5.06) at follow-up, even after adjusting for cranial radiotherapy (CRT) exposure. BMI z-score at diagnosis was also associated with overweight/obesity at follow-up. Additionally, there was a statistically significant interaction between younger age at diagnosis and CRT, indicating that younger age at diagnosis was associated with obesity among patients who received CRT. These findings may help identify pediatric ALL patients that are at increased risk of being overweight or obese following treatment. PMID:26989911

Acetyl-L-carnitine for alcohol craving and relapse prevention in anhedonic alcoholics: a randomized, double-blind, placebo-controlled pilot trial.

PubMed

Martinotti, Giovanni; Reina, Daniela; Di Nicola, Marco; Andreoli, Sara; Tedeschi, Daniela; Ortolani, Ilaria; Pozzi, Gino; Iannoni, Emerenziana; D'Iddio, Stefania; Janiri, Luigi

2010-01-01

The study aimed to evaluate the efficacy of acetyl-l-carnitine (ALC), at different doses, in relapse prevention and craving in anhedonic detoxified alcohol-dependent subjects. Randomized, double-blind, placebo-controlled, pilot study in 64 alcohol-dependent anhedonic patients: 23 received ALC at a dose of 3 g/day, 21 received ALC at a dosage of 1 g/day and 20 were given placebo. Intensity of alcohol craving was evaluated by Visual Analogue Scale. Subjects were evaluated at the beginning of treatment and after 10, 30, 60 and 90 days. Survival analysis showed that patients treated with ALC remained completely abstinent for longer than those treated with placebo (Z = -2.27; P < 0.05). From the 10th day onwards, a greater reduction of craving was observed in the ALC 1 g group than with placebo (P = 0.035). The two groups did not differ in the percentage of subjects remaining abstinent for the entire study period or the number of subjects who relapsed (defined as five or more standard drinks (four for women) on a single occasion or drinking on five or more days in 1 week). The results of this study suggest that ALC can reduce craving and the time to first drink. ALC use was safe. Further studies are needed to clarify to confirm, over longer periods, these short-term outcome benefits.

Prevalence and Predictors of Overweight and Obesity Among a Multiethnic Population of Pediatric Acute Lymphoblastic Leukemia Survivors: A Cross-Sectional Assessment.

PubMed

Brown, Austin L; Lupo, Philip J; Danysh, Heather E; Okcu, Mehmet F; Scheurer, Michael E; Kamdar, Kala Y

2016-08-01

As previous studies of obesity in survivors of pediatric acute lymphoblastic leukemia (ALL) have primarily been conducted among non-Hispanic white survivors or children treated on older protocols, our objective was to describe the prevalence and correlates of overweight status among an ethnically diverse population of pediatric ALL survivors, largely treated with more contemporary therapies. We evaluated the overweight/obesity status of pediatric ALL survivors (n=406) followed in the Texas Children's Cancer Center between 2004 and 2014. Survivors were classified as underweight, normal weight, overweight, or obese on the basis of their body mass index at their most current follow-up visit. Our results showed that Hispanic ethnicity (39% of the subjects) was associated with being overweight (adjusted odds ratio=1.88; 95% confidence interval, 1.13-3.14) or obese (adjusted odds ratio=2.84; 95% confidence interval, 1.59-5.06) at follow-up, even after adjusting for cranial radiotherapy (CRT) exposure. Body mass index z-score at diagnosis was also associated with overweight/obesity at follow-up. In addition, there was a statistically significant interaction between younger age at diagnosis and CRT, indicating that younger age at diagnosis was associated with obesity among patients who received CRT. These findings may help identify pediatric ALL patients that are at increased risk of being overweight or obese after treatment.

Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial.

PubMed

Faria, Vanda; Gingnell, Malin; Hoppe, Johanna M; Hjorth, Olof; Alaie, Iman; Frick, Andreas; Hultberg, Sara; Wahlstedt, Kurt; Engman, Jonas; Månsson, Kristoffer N T; Carlbring, Per; Andersson, Gerhard; Reis, Margareta; Larsson, Elna-Marie; Fredrikson, Mats; Furmark, Tomas

2017-10-01

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety, but their efficacy relative to placebo has been questioned. We aimed to test how manipulation of verbally induced expectancies, central for placebo, influences SSRI treatment outcome and brain activity in patients with social anxiety disorder (SAD). We did a randomized clinical trial, within an academic medical center (Uppsala, Sweden), of individuals fulfilling the DSM-IV criteria for SAD, recruited through media advertising. Participants were 18years or older and randomized in blocks, through a computer-generated sequence by an independent party, to nine weeks of overt or covert treatment with escitalopram (20mg daily). The overt group received correct treatment information whereas the covert group was treated deceptively with the SSRI described, by the psychiatrist, as active placebo. The treating psychiatrist was necessarily unmasked while the research staff was masked from intervention assignment. Treatment efficacy was assessed primarily with the self-rated Liebowitz Social Anxiety Scale (LSAS-SR), administered at week 0, 1, 3, 6 and 9, also yielding a dichotomous estimate of responder status (clinically significant improvement). Before and at the last week of treatment, brain activity during an emotional face-matching task was assessed with functional magnetic resonance imaging (fMRI) and during fMRI sessions, anticipatory speech anxiety was also assessed with the Spielberger State-Trait Anxiety Inventory - State version (STAI-S). Analyses included all randomized patients with outcome data at posttreatment. This study is registered at ISRCTN, number 98890605. Between March 17th 2014 and May 22nd 2015, 47 patients were recruited. One patient in the covert group dropped out after a few days of treatment and did not provide fMRI data, leaving 46 patients with complete outcome data. After nine weeks of treatment, overt (n=24) as compared to covert (n=22) SSRI administration yielded significantly better outcome on the LSAS-SR (adjusted difference 21.17, 95% CI 10.69-31.65, p<0.0001) with more than three times higher response rate (50% vs. 14%; χ 2 (1)=6.91, p=0.009) and twice the effect size (d=2.24 vs. d=1.13) from pre-to posttreatment. There was no significant between-group difference on anticipatory speech anxiety (STAI-S), both groups improving with treatment. No serious adverse reactions were recorded. On fMRI outcomes, there was suggestive evidence for a differential neural response to treatment between groups in the posterior cingulate, superior temporal and inferior frontal gyri (all z thresholds exceeding 3.68, p≤0.001). Reduced social anxiety with treatment correlated significantly with enhanced posterior cingulate (z threshold 3.24, p=0.0006) and attenuated amygdala (z threshold 2.70, p=0.003) activity. The clinical and neural effects of escitalopram were markedly influenced by verbal suggestions. This points to a pronounced placebo component in SSRI-treatment of SAD and favors a biopsychosocial over a biomedical explanatory model for SSRI efficacy. The Swedish Research Council for Working Life and Social Research (grant 2011-1368), the Swedish Research Council (grant 421-2013-1366), Riksbankens Jubileumsfond - the Swedish Foundation for Humanities and Social Sciences (grant P13-1270:1). Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Importance of anatomical dominance in the evaluation of coronary dilatation in Kawasaki disease.

PubMed

Dionne, Audrey; Hanna, Baher; Trinh Tan, Frédérick; Desjardins, Laurent; Lapierre, Chantale; Déry, Julie; Fournier, Anne; Dahdah, Nagib

2017-07-01

Introduction In Kawasaki disease, although coronary dilatation is attributed to vasculitis, the effect of myocardial inflammation is underestimated. Coronary dilatations are determined by Z-scores, which do not take into account dominance. The aim of the present study was to describe the impact of coronary dominance on dilatation in Kawasaki disease. We performed a retrospective analysis of coronary dilatations according to angiography categorisation of dominance. Of 28 patients (2.6 [0.2-10.1] years), right dominance was present in 15 patients and left in 13. Early dilatation was present in all patients, of whom 11 were ipsilateral to the dominant segment and 17 contralateral. Ipsilateral dilatations were present at diagnosis (9/11 versus 6/17, p=0.02) compared with contralateral dilatations, which developed 2 weeks after diagnosis (9/11 versus 16/17, p=0.29). Coronary artery Z-scores of patients with contralateral dilatation increased at 2 weeks, before returning to baseline values (2.0±2.2 at diagnosis, 4.1±1.8 at 2 weeks, 1.8±1.2 at 3-6 months, p=0.001), compared with patients with ipsilateral dilatation in whom Z-scores were maximal at diagnosis and remained stable (3.0±0.9, 2.7±1.1 and 2.6±1.5, respectively, p=0.13). Dominant coronary artery Z-scores were higher compared with non-dominant segments at diagnosis (3.0±0.9 versus 1.0±0.8, p<0.001) and at late follow-up (2.6±1.5 versus 0.4±1.4, p=0.002) in patients with ipsilateral dilatation. Progression of coronary dilatation after diagnosis may be a sign of dilatation secondary to vasculitis, as opposed to regression of Z-scores in ipsilateral dilatations, probably related to physiological vasodilatation in response to carditis. This needs to be validated in larger studies against vasculitic and myocardial inflammatory markers.

Change in body mass index and insulin resistance after 1-year treatment with gonadotropin-releasing hormone agonists in girls with central precocious puberty.

PubMed

Park, Jina; Kim, Jae Hyun

2017-03-01

Gonadotropin-releasing hormone agonist (GnRHa) is used as a therapeutic agent for central precocious puberty (CPP); however, increased obesity may subsequently occur. This study compared body mass index (BMI) and insulin resistance during the first year of GnRHa treatment for CPP. Patient group included 83 girls (aged 7.0-8.9 years) with developed breasts and a peak luteinizing hormone level of ≥5 IU/L after GnRH stimulation. Control group included 48 prepubertal girls. BMI and insulin resistance-related indices (homeostasis model assessment of insulin resistance [HOMA-IR] and quantitative insulin sensitivity check index [QUICKI]) were used to compare the groups before treatment, and among the patient group before and after GnRHa treatment. No statistical difference in BMI z -score was detected between the 2 groups before treatment. Fasting insulin and HOMA-IR were increased in the patient group; fasting glucose-to-insulin ratio and QUICKI were increased in the control group (all P <0.001). In normal-weight subjects in the patient group, BMI z -score was significantly increased during GnRHa treatment (-0.1±0.7 vs. 0.1±0.8, P <0.001), whereas HOMA-IR and QUICKI exhibited no differences. In overweight subjects in the patient group; BMI z -score and HOMA-IR were not significantly different, whereas QUICKI was significantly decreased during GnRHa treatment (0.35±0.03 vs. 0.33±0.02, P =0.044). Girls with CPP exhibited increased insulin resistance compared to the control group. During GnRHa treatment, normal-weight individuals showed increased BMI z -scores without increased insulin resistance; the overweight group demonstrated increased insulin resistance without significantly altered BMI z -scores. Long-term follow-up of BMI and insulin resistance changes in patients with CPP is required.

Does vaginal irrigation with saline solution in women with infectious vaginitis contribute to the clinical and microbiological results of antibiotic therapy?

PubMed

Derbent, Aysel Uysal; Ulukanlıgil, Mustafa; Keskin, Esra Aktepe; Soylu, Gül; Kafalı, Hasan

2012-01-01

To compare the clinical and microbiological results between patients with infectious vaginitis receiving vaginal irrigation with saline or no irrigation before standard antibiotic therapy. Women with vaginitis (n = 109) were randomized to receive vaginal irrigation with saline or no irrigation before standard antibiotic therapy. The vaginal symptoms perceived by subjects and clinical findings were assessed with a standardized scale during four follow-up visits, and Gram stain Nugent scores and vaginal fluid cultures were analyzed at each visit. Vaginal discharge (z = 7.159; p < 0.001), pruritus (z = 5.169; p < 0.001), itching (z = 2.969; p < 0.003) and odor scores (z = 2.303; p < 0.021) were significantly reduced in the study group compared to the control group between the first visit and 3-5 days after irrigation, before the start of antibiotic therapy. The second and third visits (15 and 30-45 days after antibiotic therapy) showed that the patients' symptoms and amounts of visible vaginal discharge did not differ between the two groups. Moreover, the microbiological cures of patients in each group did not differ at these visits (z = 0.447; p = 0.655). Vaginal irrigation with saline significantly reduces self-reported symptoms in the short term but has no effect on long-term clinical and laboratory results in women with infectious vaginitis. Copyright © 2012 S. Karger AG, Basel.

Histone variant H2A.Z.2 mediates proliferation and drug sensitivity of malignant melanoma

PubMed Central

Vardabasso, Chiara; Gaspar-Maia, Alexandre; Hasson, Dan; Pünzeler, Sebastian; Valle-Garcia, David; Straub, Tobias; Keilhauer, Eva C.; Strub, Thomas; Dong, Joanna; Panda, Taniya; Chung, Chi-Yeh; Yao, Jonathan L.; Singh, Rajendra; Segura, Miguel F.; Fontanals-Cirera, Barbara; Verma, Amit; Mann, Matthias; Hernando, Eva; Hake, Sandra B.; Bernstein, Emily

2015-01-01

SUMMARY Histone variants are emerging as key regulatory molecules in cancer. Here we report a novel role for the H2A.Z isoform H2A.Z.2 as a driver of malignant melanoma. H2A.Z.2 is highly expressed in metastatic melanoma, correlates with decreased patient survival, and is required for cellular proliferation. Our integrated genomic analyses reveal that H2A.Z.2 controls the transcriptional output of E2F target genes in melanoma cells. These genes are highly expressed and display a distinct signature of H2A.Z occupancy. We identify BRD2 as an H2A.Z interacting protein, whose levels are also elevated in melanoma. We further demonstrate that H2A.Z.2 regulated genes are bound by BRD2 and E2F1 in a H2A.Z.2-dependent manner. Importantly, H2A.Z.2 deficiency sensitizes melanoma cells to chemotherapy and targeted therapies. Collectively, our findings implicate H2A.Z.2 as a mediator of cell proliferation and drug sensitivity in malignant melanoma, holding translational potential for novel therapeutic strategies. PMID:26051178

Evaluation of nurses' workload in intensive care unit of a tertiary care university hospital in relation to the patients' severity of illness: A prospective study.

PubMed

Kraljic, Snjezana; Zuvic, Marta; Desa, Kristian; Blagaic, Ana; Sotosek, Vlatka; Antoncic, Dragana; Likic, Robert

2017-11-01

Costs of intensive care reach up to 30% of the hospital budget with workforce expenses being substantial. Determining proper nurse-patient ratio is necessary for optimizing patients' health related outcomes and hospitals' cost effective functioning. To evaluate nurses' workload using Nine Equivalents of Nursing Manpower Use Score and Nursing Activities Score scoring systems while assessing correlation between both scores and the severity of illness measured by Simplified Acute Physiology Score II. A Prospective study SETTINGS: Cardiac Surgery Intensive Care Unit of the Clinical Hospital Centre Rijeka, Croatia, from October 2014 to February 2015. This Intensive Care Unit has 3 beds that can be expanded upon need. The study included 99 patients treated at this Unit during the study's period. The scores were obtained by 6 nurses, working in 12h shifts. Measurements were obtained for each patient 24h after admission and subsequently twice a day, at the end of the day shift (7pm) and at the end of the night shift (7 am). The necessary data were obtained from the patient's medical records. Nursing Activities Score showed significantly higher number of nurses are required for one 12h shift (Z=3.76, p<0.001). Higher scores were obtained on day shifts vs. night shifts. (Nursing Manpower Use Score, z=3.25, p<0.001; Nursing Activities Score, z=4.16, p<0.001). When comparing Nursing Activities Score and Nursing Manpower Use Score during the week, we calculated higher required number of nurses on weekdays than on weekends and holidays, (Nursing Manpower Use Score, p<0.001; Nursing Activities Score, p<0.001). Correlation analysis of Nursing Activities Score and Nursing Manpower Use Score with Simplified Acute Physiology Score II has shown that Nursing Manpower Use Score positively associated with severity of disease, while Nursing Activities Score shows no association. Both scores can be used to estimate required number of nurses in 12-h shifts, although Nursing Activities Score seems more suitable for units with prolonged length of stay, while Nursing Manpower Use Score appears better for units with shorter duration of stay (up to four days). Higher workload measured by Nursing Manpower Use Score scale can be predicted with higher Simplified Acute Physiology Score II. However, with low Simplified Acute Physiology Score II scores it cannot be assumed that the nursing workload will also be low. Further research is needed to determine the best tool to asses nursing workload in intensive care units. Copyright © 2017 Elsevier Ltd. All rights reserved.

Osteoporotic vertebral fractures during pregnancy: be aware of a potential underlying genetic cause.

PubMed

Campos-Obando, Natalia; Oei, Ling; Hoefsloot, Lies H; Kiewiet, Rosalie M; Klaver, Caroline C W; Simon, Marleen E H; Zillikens, M Carola

2014-04-01

Although the baby growing in its mother's womb needs calcium for skeletal development, osteoporosis and fractures very rarely occur during pregnancy. A 27-year-old woman in the seventh month of her first pregnancy contracted midthoracic back pain after lifting an object. The pain was attributed to her pregnancy, but it remained postpartum. Her past medical history was uneventful, except for severely reduced vision of her left eye since birth. Family history revealed that her maternal grandmother had postmenopausal osteoporosis and her half-brother had three fractures during childhood after minor trauma. Her height was 1.58 m; she had no blue sclerae or joint hyperlaxity. Laboratory examination including serum calcium, phosphate, alkaline phosphatase, creatinine, β-carboxyterminal cross-linking telopeptide of type I collagen, 25-hydroxyvitamin D, and TSH was normal. Multiple thoracic vertebral fractures were diagnosed on x-ray examination, and dual-energy x-ray absorptiometry scanning showed severe osteoporosis (Z-scores: L2-L4, -5.6 SD; femur neck, -3.9 SD). DNA analyses revealed two compound heterozygous missense mutations in LRP5. The patient's mother carried one of the LRP5 mutations and was diagnosed with osteoporosis. Her half-brother, treated with cabergoline for a microprolactinoma, also had osteoporosis of the lumbar spine on dual-energy x-ray absorptiometry and carried the same LRP5 mutation. The patient was treated with risedronate for 2.5 years. Bone mineral density and back pain improved. She stopped bisphosphonate use 6 months before planning a second pregnancy. Our patient was diagnosed with osteoporosis pseudoglioma syndrome/familial exudative vitreoretinopathy. Potential underlying genetic causes should be considered in pregnancy-associated osteoporosis with implications for patients and relatives. More studies regarding osteoporosis treatment preceding conception are desirable.

Alpha Klotho and Fibroblast Growth Factor-23 Among Alcoholics.

PubMed

Quintero-Platt, Geraldine; González-Reimers, Emilio; Rodríguez-Gaspar, Melchor; Martín-González, Candelaria; Pérez-Hernández, Onán; Romero-Acevedo, Lucía; Espelosín-Ortega, Elisa; Vega-Prieto, María José de la; Santolaria-Fernández, Francisco

2017-09-01

Alcoholism may be a cardiovascular risk factor. Osteocyte derived molecules such as fibroblast growth factor 23 (FGF-23) and soluble α Klotho have recently been associated with cardiovascular disease, but their role in alcoholics is unknown. We here analyze the behavior of FGF23 and α Klotho in alcoholics. Ninety-seven alcoholic patients were assessed for liver function, presence of hypertension, diabetes, atrial fibrillation, left ventricular hypertrophy (LVH), vascular calcifications (assessed by chest X-ray) and nutritional status (lean and fat mass measured by densitometry). We measured plasma levels of FGF-23 and serum soluble α Klotho, using ELISA in 97 patients and 20 age- and sex-matched controls. FGF-23 levels were higher in patients than in controls (Z = 3.50; P < 0.001). FGF-23 (Z = 5.03; P < 0.001) and soluble α Klotho (Z = 5.61; P < 0.001) were higher in cirrhotics, and both were related to liver function, independently of serum creatinine FGF-23 levels were higher among alcoholics with diabetes (Z = 2.55; P = 0.011) or hypertension (Z = 2.56; P = 0.01), and increased body fat (ρ = 0.28; P = 0.022 for trunk fat), whereas α Klotho levels were higher in patients with LVH (Z = 2.17; P = 0.03) or atrial fibrillation (Z = 2.34; P = 0.019). FGF-23 was higher in alcoholics than in controls, especially among cirrhotics, and soluble α Klotho levels were also higher among cirrhotics. Both were related to liver function impairment, independently of serum creatinine levels, and also showed significant associations with vascular risk factors, such as hypertension, diabetes or trunk fat amount in the case of FGF-23, or LVH or atrial fibrillation in the case of α Klotho. We report increased values of fibroblast growth factor 23 (FGF-23) and soluble α Klotho in cirrhotic alcoholics. Both molecules are associated with liver function impairment, and with some cardiovascular risk factors such as diabetes, hypertension, increased body fat, left ventricular hypertrophy and atrial fibrillation independently of serum creatinine. © The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Antitumor activity of (2E,5Z)-5-(2-hydroxybenzylidene)-2-((4-phenoxyphenyl)imino) thiazolidin-4-one, a novel microtubule-depolymerizing agent, in U87MG human glioblastoma cells and corresponding mouse xenograft model.

PubMed

Zhang, Qiu; Liu, Xiaojun; Li, Xiue; Li, Changlong; Zhou, Hongyu; Yan, Bing

2013-01-01

Glioblastoma is the most lethal brain cancer. In spite of intensive therapy, the prognosis of patients with glioblastoma is very poor. To discover novel therapeutic agents, we screened a combinatorial compound library containing 372 thiazolidinone compounds using U87MG human glioblastoma cells. (2E,5Z)-5-(2-hydroxybenzylidene)-2-((4-phenoxyphenyl)imino) thiazolidin-4-one (HBPT) was identified as the most potent anti-glioblastoma compound. HBPT inhibits U87MG human glioblastoma cell proliferation with an IC50 of 20 μM, which is almost 5-fold more potent than temozolomide (a widely used drug for treating malignant glioma in the clinic). Mechanistic investigation demonstrated that HBPT is a novel microtubule-depolymerizing agent, which arrests cancer cells at the G2/M phase of the cell cycle and induces cell apoptosis. In the mouse U87MG xenograft model, HBPT elicits a robust tumor inhibitory effect. More importantly, no obvious toxicity was observed for HBPT therapy in animal experiments. These findings indicate that HBPT has the potential to be developed as a novel agent for the treatment of glioblastoma. [Supplementary Tables: available only at http://dx.doi.org/10.1254/jphs.13064FP].

An UPLC-MS/MS method for separation and accurate quantification of tamoxifen and its metabolites isomers.

PubMed

Arellano, Cécile; Allal, Ben; Goubaa, Anwar; Roché, Henri; Chatelut, Etienne

2014-11-01

A selective and accurate analytical method is needed to quantify tamoxifen and its phase I metabolites in a prospective clinical protocol, for evaluation of pharmacokinetic parameters of tamoxifen and its metabolites in adjuvant treatment of breast cancer. The selectivity of the analytical method is a fundamental criteria to allow the quantification of the main active metabolites (Z)-isomers from (Z)'-isomers. An UPLC-MS/MS method was developed and validated for the quantification of (Z)-tamoxifen, (Z)-endoxifen, (E)-endoxifen, Z'-endoxifen, (Z)'-endoxifen, (Z)-4-hydroxytamoxifen, (Z)-4'-hydroxytamoxifen, N-desmethyl tamoxifen, and tamoxifen-N-oxide. The validation range was set between 0.5ng/mL and 125ng/mL for 4-hydroxytamoxifen and endoxifen isomers, and between 12.5ng/mL and 300ng/mL for tamoxifen, tamoxifen N-desmethyl and tamoxifen-N-oxide. The application to patient plasma samples was performed. Copyright © 2014 Elsevier B.V. All rights reserved.

Zoledronic acid and alendronate sodium and the implications in orthodontic movement.

PubMed

Franzoni, J S; Soares, F M P; Zaniboni, E; Vedovello Filho, M; Santamaria, M P; Dos Santos, G M T; Esquisatto, M A M; Felonato, M; Mendonca, F A S; Franzini, C M; Santamaria, M

2017-08-01

To evaluate orthodontic tooth movement (OTM) in rats treated with two types of bisphosphonates (BPs), alendronate sodium (A) and zoledronic acid (Z). In all, 15 male Wistar rats were randomly divided into three groups. Group OTM+A: orthodontic tooth movement and subcutaneous administration of alendronate sodium (2.5 mg/kg); Group OTM+Z: orthodontic tooth movement and subcutaneous administration of zoledronic acid (0.02 mg/kg), and Group OTM: orthodontic tooth movement and subcutaneous injection of saline. The BPs were administered once a day during 25 days before OTM started and during 10 days of OTM. The left upper first molar was moved with a stainless-steel closed coil spring which delivered an initial force of 0.4N. OTM was measured with a digital caliper comparing the moved and the contralateral side. The histomorphometric analysis counted the number of osteoclasts, inflammatory cells, blood vessels and fibroblasts (n/10 4  m 2 ) in periodontal ligament (PDL) of the distobuccal root. A reduction of 58.3% of OTM was found in Group OTM+A and 99.6% in Group OTM+Z, when compared with Group OTM. There was a significant decrease of osteoclasts and inflammatory cells in BP-treated groups. Blood vessels and fibroblastic cells decreased mainly in Group OTM+Z. Alendronate sodium and zoledronic acid have similar effects on the periodontal tissue during orthodontic treatment in rats. Especially, zoledronic acid can affect orthodontic tooth movement. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

RxHope: Patient Assistance Information

MedlinePlus

... FAQ Pharma Companies Below is a list current Patient Assistance Programs. Click on the first letter of ... V W X Y Z AbbVie Norvir Kaletra Patient Assistance Program AbbVie Patient Assistance Foundation AbbVie Patient ...

Case of immediate hypersensitivity to beer.

PubMed

Inoue, Tomoko; Yagami, Akiko; Shimojo, Naoshi; Hara, Kazuhiro; Nakamura, Masashi; Matsunaga, Kayoko

2016-06-01

We report here a case of immediate hypersensitivity to beer, in which a female patient developed angioedema of the eyelids shortly after consuming beer. In skin prick tests, the patient showed positive reactions to the base ingredients of beer, particularly malt and barley. The specific serum immunoglobulin E antibodies against barley and malt displayed weakly positive reactivity. To identify the immunoreactive antigens, malt and barley proteins were separated by 2-D polyacrylamide gel electrophoresis and immunoreacted with the patient's serum. The results of mass spectrometric analysis revealed that the main antigen was a protein with similarity to protein z-type serpin. Notably, the identified antigen had a molecular weight of 20-25 kDa, which is markedly smaller than that previously reported for protein Z4 (44 kDa). Taken together, these analyses indicate that a possible new antigen which belongs to the protein Z family elicits immediate hypersensitivity to beer. © 2015 Japanese Dermatological Association.

Quantitative evaluation of knee cartilage and meniscus destruction in patients with rheumatoid arthritis using T1ρ and T2 mapping.

PubMed

Meng, Xiang Hong; Wang, Zhi; Guo, Li; Liu, Xiu Chan; Zhang, Yu Wei; Zhang, Ze Wei; Ma, Xin Long

2017-11-01

To calculate T1ρ and T2 values of articular cartilage and menisci in knee joints of patients with RA, and compare the values between RA patients and healthy volunteers, to gain insight into the pathogenesis of cartilage and meniscus degradation in patients with RA. Nine patients with RA and knee joints symptoms were enrolled in the study, twenty healthy volunteers without knee joint diseases were included as controls. Sagittal fat-saturated T1ρ and T2 mapping images were obtained on a 3T MR scanner (GE750, GE Healthcare, Waukesha, WI), using a dedicated 8-channel knee coil. In the T1rho mapping sequence, the amplitude of the spin-lock pulse was 500Hz, spin lock durations=10/20/30/50ms. In the T2 mapping sequence,TR/TE were 1794/6.5, 13.4, 27, 40.7ms. Both sequences were performed with the following parameters: flip angle (FA)=90°, matrix: 320×256, FOV: 16×16cm 2 , slice thickness: 3mm, bandwidth: 62.5kHZ, and a total scan time of 5:11min. T1ρ- and T2-mapping images were used for the segmentation of the articular cartilage of the patella, femoral trochlea, medial and lateral femoral condyle, medial and lateral tibial plateau. These images were also used for the segmentation of the anterior and posterior horns of the medial and lateral menisci with livewire semi-automatic segmentation algorithm of MATLAB. A Mann-Whitney U test was performed to compare the T1ρ and T2 values of the above mentioned regions between the two groups. T1ρ (Z=-3.913 to -2.121, P=0.000-0.034) and T2 (Z=-3.866 to -2.216, P=0.000-0.026) values of knee cartilage in patients with RA were higher than that in healthy volunteers, except the cartilage of the patella (T1ρ: Z=-1.273, P=0.203,T2: Z=-0.236, P=0.814) and lateral tibial plateau (T1ρ:Z=-1.037, P=0.317). The T1ρ (Z=-1.462 to 0.572, P=0.095-0.908) and T2 (Z=-1.461 to 0.278, P=0.153-0.764) values of medial and lateral menisci showed no difference between the two groups. Patients with RA exhibit diffuse knee cartilage destruction in the medial and lateral tibiofemoral joints and in the femoral trochlea. However, we found no increase in T1ρ and T2 values in menisci, this finding warrants further investigation. Copyright © 2017 Elsevier B.V. All rights reserved.

[Proton nuclear magnetic resonance spectroscopy recognition of metabolic patterns in fecal extracts for early diagnosis of colorectal cancer].

PubMed

Lin, Y; Wang, Z N; Ma, C C; Liu, C K; Yang, J R; Shen, Z W; Wu, R H

2016-09-06

Objective: To characterize the metabolic " fingerprint" of fecal extracts for diagnosis of early-stage colorectal cancer(CRC)using proton nuclear magnetic resonance spectroscopy( 1 H-NMR)-based metabolomics coupled with pattern recognition. Methods: From January 2014 to December 2014, we collected fecal samples at the Second Affiliated Hospital of Shantou University Medical College, from 25 patients with colorectal adenomas(CR-Ad), 20 with stage Ⅰ/Ⅱ CRC, and 32 healthy controls(HCs). The patients were diagnosed by histopathology. No subjects had any complicating diseases. HCs showed no abnormalities from blood tests, endoscopic examination, diagnostic imaging, and/or medical interviews. We excluded participants who used antibiotics, NSAIDS, statins, or probiotics within two months of study participation, and any patients who underwent chemotherapy or radiation treatments prior to surgery. We used orthogonal partial least-squares-discriminant analysis(OPLS-DA)for pattern recognition(dimension reduction)on 1 H-NMR processed data( 1 H frequency of 400.13 MHz), to find metabolic differences among CR-Ad, carcinoma and HC fecal samples; and receiver operating characteristic(ROC)analysis to determine the diagnostic value of the fecal metabolic biomarkers. Results: Fecal samples were collected from 20 patients with Stage Ⅰ/Ⅱ CRC(11 M, 9 F, median age(52±13)years), 25 with CR-Ad(14 M, 11 F, median age(53 ± 11)years)and 32 HCs(15 M, 17 F, median age(53 ± 14)years). OPLS-DA clearly distinguished CR-Ad and stage Ⅰ/Ⅱ CRC from HC samples, based on their metabolomic profiles. Relative signal intensities in HCs were significantly lower than in the cancer patients for butyrate(HC: 23.0±6.0; CR-Ad: 18.0±5.0; CRC: 14.0±6.0; Z =-2.07, P =0.008), acetate(HC: 45.0±11.0; CR-Ad: 31.0±11.0; CRC: 24.0±8.0; Z =- 2.32, P =0.011), propionate(HC: 26.0 ± 7.0; CR-Ad: 22.0 ± 6.0; CRC: 19.0 ± 5.0; Z =- 2.43, P =0.032), glucose(HC: 37.0±7.0; CR-Ad: 31.0±7.0; CRC: 26.0±8.0; Z =-2.07, P =0.044)and glutamine(HC: 4.5±2.0; CR-Ad: 4.9 ± 1.0; CRC: 5.4 ± 1.0; Z =2.21, P =0.044). However, relative signal intensities in HCs were significantly higher than in patients for lactate(HC: 4.8±1.0; CR-Ad: 6.9±2.0; CRC: 4.8± 1.0; Z =2.02, P = 0.038), glutamate(HC: 3.2 ± 2.0; CR-Ad: 4.9 ± 1.0; CRC: 3.2 ± 2.0; Z =2.21, P =0.044)and succinate(HC: 12.0±2.0; CR-Ad: 15.0±3.0; CRC: 12.0± 2.0; Z =2.25, P =0.011). Among the potential biomarkers, acetate at 1.92 ppm, and succinate at 2.41 ppm displayed relatively high area under ROC, with sensitivity and specificity both >90%, to distinguish early-stage CRC patients from HCs. Conclusion: Fecal metabolic profiles distinguish of HCs from patients with CRC patients, even in the early stages(stage Ⅰ/Ⅱ), highlighting the potential of NMR-based fecal metabolomic fingerprinting as tools for early CRC diagnosis.

Serum uric acid levels in patients with Parkinson's disease: A meta-analysis.

PubMed

Wen, Min; Zhou, Bo; Chen, Yun-Hua; Ma, Zhao-Lei; Gou, Yun; Zhang, Chun-Lin; Yu, Wen-Feng; Jiao, Ling

2017-01-01

Lower serum uric acid (UA) levels have been reported as a risk factor in Parkinson's disease (PD). However, the results have been inconsistent so far. The aim of the present study was to clarify the potential relationship of uric acid with PD. Comprehensive electronic search in pubmed, web of science, and the Cochrane Library database to find original articles about the association between PD and serum uric acid levels published before Dec 2015. Literature quality assessment was performed with the Newcastle-Ottawa Scale. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity across studies was assessed using I2 and H2 statistics. Sensitivity analyses to assess the influence of individual studies on the pooled estimate. Publication bias was investigated using funnel plots and Egger's regression test. Analyses were performed by using Review Manager 5.3 and Stata 11.0. Thirteen studies with a total of 4646 participants (2379 PD patients and 2267 controls) were included in this meta-analysis. The current results showed that the serum UA levels in PD patients were significantly lower compared to sex and age-matched healthy controls (SMD: -0.49, 95% CI: [-0.67, -0.30], Z = 5.20, P < 0.001) and these results showed no geographic regional (Asia: SMD = -0.65, 95% CI [-0.84, -0.46], Z = 6.75, p <0.001; Non-Asia: SMD = -0.25, 95% CI [-0.43, -0.07], Z = 2.70, p = 0.007) and sex differences (women: SMD = -0.53, 95% CI [-0.70, -0.35], z = 5.98, p <0.001; men: SMD = -0.66, 95% CI [-0.87, -0.44], z = 6.03, p <0.001). Serum UA levels in middle-late stage PD patients with higher H&Y scales were significantly lower than early stage PD patients with lower H&Y scales (SMD = 0.63, 95% CI [0.36,0.89], z = 4.64, p <0.001). Our study showed that the serum UA levels are significantly lower in PD and the level is further decreased as the disease progresses. Thus it might be a potential biomarker to indicate the risk and progression of PD.

Celiac disease in normal-weight and overweight children: clinical features and growth outcomes following a gluten-free diet.

PubMed

Reilly, Norelle Rizkalla; Aguilar, Kathleen; Hassid, Benjamin G; Cheng, Jianfeng; Defelice, Amy R; Kazlow, Philip; Bhagat, Govind; Green, Peter H

2011-11-01

There are few data on pediatric celiac disease in the United States. The aim of our study was to describe the presentation of celiac disease among children with a normal and an elevated body mass index (BMI) for age, and to study their BMI changes following a gluten-free diet (GFD). One hundred forty-two children (age 13 months-19 years) with biopsy-proven celiac disease, contained in a registry of patients studied at our center from 2000 to 2008, had follow-up growth data available. Patients' height, weight, and BMI were converted to z scores for age and grouped by BMI as underweight, normal, and overweight. Compliance was confirmed using results of serological assays, and data of noncompliant patients were analyzed separately. Data were analyzed during the observation period and were expressed as change in height, weight, and BMI z score per month of dietary treatment. Nearly 19% of patients had an elevated BMI at diagnosis (12.6% overweight, 6% obese) and 74.5% presented with a normal BMI. The mean duration of follow-up was 35.6 months. Seventy-five percent of patients with an elevated BMI at diagnosis decreased their BMI z scores significantly after adherence to a GFD, normalizing it in 44% of cases. Of patients with a normal BMI at diagnosis, weight z scores increased significantly after treatment, and 13% became overweight. Both normal weight and overweight frequently occur in North American children presenting with celiac disease. A GFD may have a beneficial effect upon the BMI of overweight and obese children with celiac disease.

Effects of a self-management education program on self-efficacy in patients with COPD: a mixed-methods sequential explanatory designed study.

PubMed

Ng, Wai I; Smith, Graeme Drummond

2017-01-01

Self-management education programs (SMEPs) are potentially effective in the symptomatic management of COPD. Little is presently known about the effectiveness of these programs in Chinese COPD patients. The objective of this study was to evaluate the effectiveness of a specifically designed SMEP on levels of self-efficacy in Chinese patients with COPD. Based on the Medical Research Council framework for evaluating complex interventions, an exploratory phase randomized controlled trial was employed to examine the effects of an SMEP. Self-efficacy was the primary outcome using the COPD Self-efficacy Scale, measured at baseline and 6 months after the program. Qualitative data were sequentially collected from these patients via three focus groups to supplement the quantitative findings. The experimental group displayed significant improvement in their general self-efficacy ( Z =-2.44, P =0.015) and specifically in confronting 1) physical exertion ( Z =-2.57, P =0.01), 2) weather/environment effects ( Z =-2.63, P <0.001) and 3) intense emotions ( Z =-2.54, P =0.01). Three themes emerged from the focus groups: greater disease control, improved psychosocial well-being and perceived incapability and individuality. The connection of the quantitative and qualitative data demonstrated that individual perceptual constancy of patients could be a determining factor modulating the effectiveness of this type of intervention. These findings highlight the potential putative benefits of an SMEP in Chinese patients with COPD. Further attention should be given to cultural considerations when developing this type of intervention in Chinese populations with COPD and other chronic diseases.

Serum Metabonomics of Articular Cartilage Destruction Induced by T-2 Toxin in Wistar Rats.

PubMed

Zhu, Lei; Zhao, Zhi Jun; Ren, Xiao Bin; Li, Qiang; Ding, Hua; Sun, Zhou; Kao, Qing Jun; Wang, Li Hua

2018-01-01

The molecular pathogenesis of T-2 toxin-induced cartilage destruction has not been fully unraveled yet. The aim of this study was to detect changes in serum metabolites in a rat anomaly model with articular cartilage destruction. Thirty healthy male Wistar rats were fed a diet containing T-2 toxin (300 ng/kg chow) for 3 months. Histopathological changes in femorotibial cartilage were characterized in terms of chondrocyte degeneration/necrosis and superficial cartilage defect, and the endogenous metabolite profile of serum was determined by UPLC/Q-TOF MS. Treated rats showed extensive areas of chondrocyte necrosis and superficial cartilage defect in the articular cartilage. In addition, 8 metabolites were found to change significantly in these rats compared to the control group, including lysoPE (18:0/0:0), lysoPC(14:0), lysoPC[18:4 (6Z,9Z,12Z,15Z)], lysoPC[(16:1(9Z)], lysoPC(16:0), L-valine, hippuric acid, and asparaginyl-glycine. These 8 metabolites associated with cartilage injury are mainly involved in phospholipid and amino acid metabolic pathways. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Growth and nutritional status, and their association with lung function: a study from the international Primary Ciliary Dyskinesia Cohort.

PubMed

Goutaki, Myrofora; Halbeisen, Florian S; Spycher, Ben D; Maurer, Elisabeth; Belle, Fabiën; Amirav, Israel; Behan, Laura; Boon, Mieke; Carr, Siobhan; Casaulta, Carmen; Clement, Annick; Crowley, Suzanne; Dell, Sharon; Ferkol, Thomas; Haarman, Eric G; Karadag, Bulent; Knowles, Michael; Koerner-Rettberg, Cordula; Leigh, Margaret W; Loebinger, Michael R; Mazurek, Henryk; Morgan, Lucy; Nielsen, Kim G; Phillipsen, Maria; Sagel, Scott D; Santamaria, Francesca; Schwerk, Nicolaus; Yiallouros, Panayiotis; Lucas, Jane S; Kuehni, Claudia E

2017-12-01

Chronic respiratory disease can affect growth and nutrition, which can influence lung function. We investigated height, body mass index (BMI), and lung function in patients with primary ciliary dyskinesia (PCD).In this study, based on the international PCD (iPCD) Cohort, we calculated z-scores for height and BMI using World Health Organization (WHO) and national growth references, and assessed associations with age, sex, country, diagnostic certainty, age at diagnosis, organ laterality and lung function in multilevel regression models that accounted for repeated measurements.We analysed 6402 measurements from 1609 iPCD Cohort patients. Height was reduced compared to WHO (z-score -0.12, 95% CI -0.17 to -0.06) and national references (z-score -0.27, 95% CI -0.33 to -0.21) in male and female patients in all age groups, with variation between countries. Height and BMI were higher in patients diagnosed earlier in life (p=0.026 and p<0.001, respectively) and closely associated with forced expiratory volume in 1 s and forced vital capacity z-scores (p<0.001).Our study indicates that both growth and nutrition are affected adversely in PCD patients from early life and are both strongly associated with lung function. If supported by longitudinal studies, these findings suggest that early diagnosis with multidisciplinary management and nutritional advice could improve growth and delay disease progression and lung function impairment in PCD. Copyright ©ERS 2017.

Lattice QCD exploration of parton pseudo-distribution functions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Orginos, Kostas; Radyushkin, Anatoly; Karpie, Joseph

Here, we demonstrate a new method of extracting parton distributions from lattice calculations. The starting idea is to treat the generic equal-time matrix elementmore » $${\\cal M} (Pz_3, z_3^2)$$ as a function of the Ioffe time $$\

Lattice QCD exploration of parton pseudo-distribution functions

DOE PAGES

Orginos, Kostas; Radyushkin, Anatoly; Karpie, Joseph; ...

2017-11-08

Here, we demonstrate a new method of extracting parton distributions from lattice calculations. The starting idea is to treat the generic equal-time matrix elementmore » $${\\cal M} (Pz_3, z_3^2)$$ as a function of the Ioffe time $$\

Drug-induced sedation endoscopy in pediatric obstructive sleep apnea syndrome.

PubMed

Boudewyns, A; Verhulst, S; Maris, M; Saldien, V; Van de Heyning, P

2014-12-01

To describe the pattern of upper airway (UA) obstruction during drug-induced sedation endoscopy (DISE) and to evaluate the outcome of DISE-directed treatment. Prospective study of DISE in surgically naive obstructive sleep apnea syndrome (OSAS) children without syndromic comorbidity or craniofacial abnormalities. Treatment was individually tailored according to UA findings during DISE and polysomnographic data. Reported values are median (lower-upper quartile). Thirty-seven children aged 4.1 years (2.1-6.0), with body mass index z-score 0.3 (-0.9 to 0.9), and obstructive apnea-hypopnea index (oAHI) 9.0/h (6.1-19.3) were included. Adenotonsillar obstruction was found in 33 cases (89%) as an isolated entity or as part of a multi-level obstruction. These children were treated with adenotonsillectomy (n = 28), adenoidectomy (n = 3), or tonsillectomy (n = 2). The remaining four patients received non-surgical treatment. Pre-postoperative polysomnographic data in 22 patients showed a significant improvement in oAHI from 8.6/h (6.7-20.7) to 1.0/h (0.6-2.0) (P = 0.001). Only two of these 22 children had residual OSAS (oAHI ≥ 5/h), indicating a success rate of 91%. Based on UA findings during DISE, a non-surgical treatment was proposed for 11% of children. A 91% success rate was obtained in those treated with (adeno)tonsillectomy. These data suggest that DISE may be helpful to identify patients most likely to benefit from UA surgery. Copyright © 2014 Elsevier B.V. All rights reserved.

[Case-control study on cable-pin system in the treatment of olecranon fractures].

PubMed

Ma, Hu-Jing; Shan, Lei; Zhou, Jun-Lin; Liu, Qing-He; Lu, Tie; Sun, Song

2012-05-01

To prospectively evaluate the clinical result of Cable-Pin system in the treatment of olecranon fractures and compare with tension band wiring (TBW) method. From March 2008 to June 2010,65 patients with olecranon fractures were divided into two groups: 32 patients in Cable-Pin group were treated with Cable-Pin system, including 18 males and 14 females, ranging in age from 21 to 69 years, with an average of (53.69 +/- 13.42) years; 33 patients in TBW group were treated with Kirschner tension bend, including 20 males and 13 females, ranging in age from 20 to 70 years, with an average of (53.18 +/- 13.36) years. The incision length, operation time, the amounts of hemoglobin after operation, fracture healing time, complications and HSS elbow scores were recorded and analyzed statistically. The follow-up period ranged from 12 to 24 months, with an average period of 18.4 months. There were statistical differences (P<0.05) in fracture healing time (t= 2.588, P=0.012), complication rate (chi2=4.534, P=0.033) and HSS elbow joint scores (Z=-2.039, P=0.041) between two groups, which all were superior to TBW in Cable-Pin group. There was no statistical differences (P>0.05) in the length of incision (t= 0.416, P=0.679), operation time (t=0.816, P=0.417) and the postoperative amounts of hemoglobin (t=-0.553, P=0.294) between two groups. Cable-Pin system is an easy and reliable method for the treatment of olecranon fractures with less complications and better functions than TBW.

A decrease in D-dimer concentration and an occurrence of skin rash as iatrogenic events and complementary predictors of survival in lung cancer patients treated with EGFR tyrosine kinase inhibitors.

PubMed

Zaborowska-Szmit, Magdalena; Kowalski, Dariusz M; Piórek, Aleksandra; Krzakowski, Maciej; Szmit, Sebastian

2016-12-01

Progression of lung cancer is associated with some abnormalities in coagulation. The aim of the study was to determine the predictive and prognostic value of changes in D-dimer concentration in non-small cell lung cancer (NSCLC) patients on anti-EGFR targeted therapy. The analysis included fifty two NSCLC patients treated with EGFR tyrosine kinase inhibitors (TKIs): erlotinib or gefitinib. All clinical data were collected before treatment and after 2 cycles (60days) of therapy and correlated with progression free and overall survival (PFS, OS). Two iatrogenic events were noted within the first 60days of anti-EGFR treatment: typical skin rash in 38 (73.1%) and a decrease in D-dimer concentration in 26 (50%) patients. Multivariate analysis revealed a decrease of D-dimer concentration as the strongest factor associated with longer PFS (HR=0.39; 95%CI: 0.16-0.91; p=0.029) and OS (HR=0.33; 95%CI: 0.13-0.82, p=0.017) independently of skin rash, baseline level of D-dimer and other clinical characteristics. Coexisting a decrease in D-dimer concentration with an occurrence of skin rash correlated significantly with the positive objective response after 60days of anti-EGFR therapy (p=0.0175) and indicated the longest PFS (HR=0.31; 95%CI: 0.16-0.60, p=0.0005) as well as OS (HR=0.30; 95%CI: 0.15-0.59, p=0.0005). Adverse events may predict the outcomes of cancer patients. Apart from skin rash, change in D-dimer concentration may be valuable parameter in creation of predictive and prognostic models in NSCLC patients receiving anti-EGFR targeted therapy. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

[Effect of preventive treatment on cognitive performance in patients with multiple sclerosis].

PubMed

Shorobura, Maria S

2018-01-01

Introduction: cognitive, emotional and psychopathological changes play a significant role in the clinical picture of multiple sclerosis and influence the effectiveness of drug therapy, working capacity, quality of life, and the process of rehabilitation of patients with multiple sclerosis. The aim: investigate the changes in cognitive function in patients with multiple sclerosis, such as information processing speed and working memory of patients before and after treatment with immunomodulating drug. Materials and methods:33 patients examined reliably diagnosed with multiple sclerosis who were treated with preventive examinations and treatment from 2012 to 2016. For all patients with multiple sclerosis had clinical-neurological examination (neurological status using the EDSS scale) and the cognitive status was evaluated using the PASAT auditory test. Patient screening was performed before, during and after the therapy. Statistical analysis of the results was performed in the system Statistica 8.0. We used Student's t-test (t), Mann-Whitney test (Z). Person evaluated the correlation coefficients and Spearman (r, R), Wilcoxon criterion (T), Chi-square (X²). Results: The age of patients with multiple sclerosis affects the growth and EDSS scale score decrease PASAT to treatment. Duration of illness affects the EDSS scale score and performance PASAT. Indicators PASAT not significantly decreased throughout the treatment. Conclusions: glatiramer acetate has a positive effect on cognitive function, information processing speed and working memory patients with multiple sclerosis, which is one of the important components of the therapeutic effect of this drug.

Preemptive heme oxygenase-1 gene delivery reveals reduced mortality and preservation of left ventricular function 1 yr after acute myocardial infarction.

PubMed

Liu, Xiaoli; Simpson, Jeremy A; Brunt, Keith R; Ward, Christopher A; Hall, Sean R R; Kinobe, Robert T; Barrette, Valerie; Tse, M Yat; Pang, Stephen C; Pachori, Alok S; Dzau, Victor J; Ogunyankin, Kofo O; Melo, Luis G

2007-07-01

We reported previously that predelivery of heme oxygenase-1 (HO-1) gene to the heart by adeno-associated virus-2 (AAV-2) markedly reduces ischemia and reperfusion (I/R)-induced myocardial injury. However, the effect of preemptive HO-1 gene delivery on long-term survival and prevention of postinfarction heart failure has not been determined. We assessed the effect of HO-1 gene delivery on long-term survival, myocardial function, and left ventricular (LV) remodeling 1 yr after myocardial infarction (MI) using echocardiographic imaging, pressure-volume (PV) analysis, and histomorphometric approaches. Two groups of Lewis rats were injected with 2 x 10(11) particles of AAV-LacZ (control) or AAV-human HO-1 (hHO-1) in the anterior-posterior apical region of the LV wall. Six weeks after gene transfer, animals were subjected to 30 min of ischemia by ligation of the left anterior descending artery followed by reperfusion. Echocardiographic measurements and PV analysis of LV function were obtained at 2 wk and 12 mo after I/R. One year after acute MI, mortality was markedly reduced in the HO-1-treated animals compared with the LacZ-treated animals. PV analysis demonstrated significantly enhanced LV developed pressure, elevated maximal dP/dt, and lower end-diastolic volume in the HO-1 animals compared with the LacZ animals. Echocardiography showed a larger apical anterior-to-posterior wall ratio in HO-1 animals compared with LacZ animals. Morphometric analysis revealed extensive myocardial scarring and fibrosis in the infarcted LV area of LacZ animals, which was reduced by 62% in HO-1 animals. These results suggest that preemptive HO-1 gene delivery may be useful as a therapeutic strategy to reduce post-MI LV remodeling and heart failure.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Midulla, Marco, E-mail: marco.midulla@chru-lille.fr; Moreno, Ramiro, E-mail: ramoroa@gmail.com; Negre-Salvayre, Anne, E-mail: anne.negre-salvayre@inserm.fr

PurposeAlthough the widespread acceptance of thoracic endovascular aortic repair (TEVAR) as a first-line treatment option for a multitude of thoracic aortic diseases, little is known about the consequences of the device implantation on the native aortic anatomy. We propose a comparative analysis of the pre- and postoperative geometry on a clinical series of patients and discuss the potential clinical implicationsMethodsCT pre- and postoperative acquisitions of 30 consecutive patients treated by TEVAR for different pathologies (20 thoracic aortic aneurysms, 6 false aneurysms, 3 penetrating ulcers, 1 traumatic rupture) were used to model the vascular geometry. Pre- and postoperative geometries were comparedmore » for each patient by pairing and matching the 3D models. An implantation site was identified, and focal differences were detected and described.ResultsSegmentation of the data sets was successfully performed for all 30 subjects. Geometry differences between the pre- and postoperative meshes were depicted in 23 patients (76 %). Modifications at the upper implantation site were detected in 14 patients (47 %), and among them, the implantation site involved the arch (Z0–3) in 11 (78 %).ConclusionModeling the vascular geometry on the basis of imaging data offers an effective tool to perform patient-specific analysis of the vascular geometry before and after the treatment. Future studies will evaluate the consequences of these changes on the aortic function.« less

ATZ11 recognizes not only Z-α1-antitrypsin-polymers and complexed forms of non-Z-α1-antitrypsin but also the von Willebrand factor.

PubMed

Goltz, Diane; Hittetiya, Kanishka; Yadegari, Hamideh; Driesen, Julia; Kirfel, Jutta; Neuhaus, Thomas; Steiner, Susanne; Esch, Christiane; Bedorf, Jörg; Hertfelder, Hans-Jörg; Fischer, Hans-Peter

2014-01-01

The ATZ11 antibody has been well established for the identification of α1-anti-trypsin (AAT) molecule type PiZ (Z-AAT) in blood samples and liver tissue. In this study, we systematically analyzed the antibody for additional binding sites in human tissue. Ultrastructural ATZ11 binding was investigated immunoelectron microscopically in human umbilical vein endothelial cells (HUVECs) and in platelets of a healthy individual. Human embryonic kidney (HEK293) cells were transiently transfected with Von Willebrand factor (VWF) and analyzed immunocytochemically using confocal microscopy and SDS-PAGE electrophoresis followed by western blotting (WB). Platelets and serum samples of VWF-competent and VWF-deficient patients were investigated using native PAGE and SDS-PAGE electrophoresis followed by WB. The specificity of the ATZ11 reaction was tested immunohistochemically by extensive antibody-mediated blocking of AAT- and VWF-antigens. ATZ11-positive epitopes could be detected in Weibel-Palade bodies (WPBs) of HUVECs and α-granules of platelets. ATZ11 stains pseudo-WBP containing recombinant wild-type VWF (rVWF-WT) in HEK293 cells. In SDS-PAGE electrophoresis followed by WB, anti-VWF and ATZ11 both identified rVWF-WT. However, neither rVWF-WT-multimers, human VWF-multimers, nor serum proteins of VWF-deficient patients were detected using ATZ11 by WB, whereas anti-VWF antibody (anti-VWF) detected rVWF-WT-multimers as well as human VWF-multimers. In human tissue specimens, AAT-antigen blockade using anti-AAT antibody abolished ATZ11 staining of Z-AAT in a heterozygous AAT-deficient patient, whereas VWF-antigen blockade using anti-VWF abolished ATZ11 staining of endothelial cells and megakaryocytes. ATZ11 reacts with cellular bound and denatured rVWF-WT and human VWF as shown using immunocytochemistry and subsequent confocal imaging, immunoelectron microscopy, SDS-PAGE and WB, and immunohistology. These immunoreactions are independent of the binding of Z-AAT-molecules and non-Z-AAT complexes.

Alpha1-Antitrypsin Deficiency–Related Alleles Z and S and the Risk of Wegener’s Granulomatosis

PubMed Central

Mahr, Alfred D.; Edberg, Jeffrey C.; Stone, John H.; Hoffman, Gary S.; St. Clair, E. William; Specks, Ulrich; Dellaripa, Paul F.; Seo, Philip; Spiera, Robert F.; Rouhani, Farshid N.; Brantly, Mark L.; Merkel, Peter A.

2011-01-01

Objective Deficiency of α1-antitrypsin (α1AT) may be a determinant of susceptibility to Wegener’s granulomatosis (WG). Several previous, mainly small, case–control studies have shown that 5–27% of patients with WG carried the α1AT deficiency Z allele. It is not clear whether the S allele, the other major α1AT deficiency variant, is associated with WG. This study investigated the relationship of the α1AT deficiency Z and S alleles with the risk of developing WG in a large cohort. Methods We studied the distribution of the α1AT deficiency alleles Z and S in 433 unrelated Caucasian patients with WG and 421 ethnically matched controls. Genotyping was performed using an allele discrimination assay. Results were compared between cases and controls using exact statistical methods. Results Among the patients with WG, the allele carriage frequencies of Z and S were 7.4% and 11.5%, respectively. The frequencies of the 6 possible genotypes differed in a statistically significant manner between cases and controls (P = 0.01). The general genetic 2-parameter codominant model provided the best fit to the data. Compared with the normal MM genotype, the odds ratio (OR) for MZ or MS genotypes was 1.47 (95% confidence interval [95% CI] 0.98–2.22), and the OR for ZZ, SS, or SZ genotypes was 14.58 (95% CI 2.33–∞). ORs of similar direction and magnitude were observed within the restricted cohorts that excluded cases and controls carrying ≥1 Z or ≥1 S allele. Conclusion Both Z and S alleles display associations with risk of WG in a codominant genetic pattern. These findings strengthen the evidence of a causal link between α1AT deficiency and susceptibility to WG. PMID:20827781

Utility of Intermediate-Delay Washout CT Images for Differentiation of Malignant and Benign Adrenal Lesions: A Multivariate Analysis.

PubMed

Ng, Chaan S; Altinmakas, Emre; Wei, Wei; Ghosh, Payel; Li, Xiao; Grubbs, Elizabeth G; Perrier, Nancy D; Lee, Jeffrey E; Prieto, Victor G; Hobbs, Brian P

2018-06-27

The objective of this study was to identify features that impact the diagnostic performance of intermediate-delay washout CT for distinguishing malignant from benign adrenal lesions. This retrospective study evaluated 127 pathologically proven adrenal lesions (82 malignant, 45 benign) in 126 patients who had undergone portal venous phase and intermediate-delay washout CT (1-3 minutes after portal venous phase) with or without unenhanced images. Unenhanced images were available for 103 lesions. Quantitatively, lesion CT attenuation on unenhanced (UA) and delayed (DL) images, absolute and relative percentage of enhancement washout (APEW and RPEW, respectively), descriptive CT features (lesion size, margin characteristics, heterogeneity or homogeneity, fat, calcification), patient demographics, and medical history were evaluated for association with lesion status using multiple logistic regression with stepwise model selection. Area under the ROC curve (A z ) was calculated from both univariate and multivariate analyses. The predictive diagnostic performance of multivariate evaluations was ascertained through cross-validation. A z for DL, APEW, RPEW, and UA was 0.751, 0.795, 0.829, and 0.839, respectively. Multivariate analyses yielded the following significant CT quantitative features and associated A z when combined: RPEW and DL (A z = 0.861) when unenhanced images were not available and APEW and UA (A z = 0.889) when unenhanced images were available. Patient demographics and presence of a prior malignancy were additional significant factors, increasing A z to 0.903 and 0.927, respectively. The combined predictive classifier, without and with UA available, yielded 85.7% and 87.3% accuracies with cross-validation, respectively. When appropriately combined with other CT features, washout derived from intermediate-delay CT with or without additional clinical data has potential utility in differentiating malignant from benign adrenal lesions.

The Relationship of the Post-reflux Swallow-induced Peristaltic Wave Index and Esophageal Baseline Impedance with Gastroesophageal Reflux Disease Symptoms

PubMed Central

Cho, Young Kyu; Lee, Joon Seong; Lee, Tae Hee; Hong, Su Jin; Park, Sang Joon; Jeon, Seong Ran; Kim, Hyun Gun; Kim, Jin-Oh

2017-01-01

Background/Aims The post-reflux swallow-induced peristaltic wave (PSPW) index and esophageal baseline impedance (BI) are novel impedance parameters used to evaluate esophageal chemical clearance and mucosal integrity. However, their relationship with reflux symptoms is not known. We aim to evaluate the correlations of PSPW index and esophageal BI with gastroesophageal reflux disease (GERD) symptoms. Methods We performed a retrospective review of multichannel intraluminal impedance and pH (MII-pH) tracings in patients with suspected GERD. Reflux symptoms were also analyzed from checklists using ordinal scales. The PSPW index and esophageal BIs in 6 spots (z1–z6) were measured. Bivariate (Spearman) correlation was used to analyze the relationship between the PSPW index or esophageal BI, and the degree of GERD symptoms measured. Results The MII-pH records of 143 patients were analyzed. The PSPW index was significantly lower in patients who had heartburn and negatively correlated with the degree of heartburn (r = −0.186, P < 0.05). On the contrary, the PSPW index was not significantly correlated with the degree of dysphagia (r = −0.013, P = 0.874). Distal esophageal BI was not significantly correlated with heartburn, but negatively correlated with the degree of dysphagia (z3: r = −0.328, z4: r = −0.361, z5: r = −0.316, z6: r = −0.273; P < 0.05). Conclusions These findings suggest that delayed chemical clearance of the esophagus may induce heartburn, but that it is not related to dysphagia. However, a lack of esophageal mucosal integrity may be related to dysphagia. PMID:28044052

Influence of uniaxial single-ion anisotropy on the magnetic and thermal properties of Heisenberg antiferromagnets within unified molecular field theory

DOE PAGES

Johnston, David C.

2017-03-17

Here, the influence of uniaxial single-ion anisotropy –DS 2 z on the magnetic and thermal properties of Heisenberg antiferromagnets (AFMs) is investigated. The uniaxial anisotropy is treated exactly and the Heisenberg interactions are treated within unified molecular field theory (MFT), where thermodynamic variables are expressed in terms of directly measurable parameters. The properties of collinear AFMs with ordering along the z axis (D>0) in applied field H z = 0 are calculated versus D and temperature T, including the ordered moment μ, the Néel temperature T N, the magnetic entropy, internal energy, heat capacity, and the anisotropic magnetic susceptibilities χmore » ∥ and χ ⊥ in the paramagnetic (PM) and AFM states. The high-field average magnetization per spin μ z(H z,D,T) is found, and the critical field H c(D,T) is derived at which the second-order AFM to PM phase transition occurs. The magnetic properties of the spin-flop (SF) phase are calculated, including the zero-field properties T N(D) and μ(D,T). The high-field μ z(H z,D,T) is determined, together with the associated spin-flop field H SF(D,T) at which a second-order SF to PM phase transition occurs. The free energies of the AFM, SF, and PM phases are derived from which H z–T phase diagrams are constructed. For f J =–1 and –0.75, where f J = θ pJ/T NJ and θ pJ and T NJ are the Weiss temperature in the Curie-Weiss law and the Néel temperature due to exchange interactions alone, respectively, phase diagrams in the H z–T plane similar to previous results are obtained. However, for f J = 0 we find a topologically different phase diagram where a spin-flop bubble with PM and AFM boundaries occurs at finite H z and T. Also calculated are properties arising from a perpendicular magnetic field, including the perpendicular susceptibility χ ⊥(D,T), the associated effective torque at low fields arising from the –DS 2 z term in the Hamiltonian, the high-field perpendicular magnetization μ ⊥, and the perpendicular critical field H c⊥ at which the second-order AFM to PM phase transition occurs. In addition to the above results for D > 0, the T N(D) and ordered moment μ(T,D) for collinear AFM ordering along the x axis with D < 0 are determined. In order to compare the properties of the above spin systems with those of noninteracting systems with –DS 2 z uniaxial anisotropy with either sign of D, Supplemental Material is provided in which results for the thermal and magnetic properties of such noninteracting spin systems are given.« less

Construction of a patient observation system using KINECTTM

NASA Astrophysics Data System (ADS)

Miyaura, Kazunori; Kumazaki, Yu; Fukushima, Chika; Kato, Shingo; Saitoh, Hidetoshi

2014-03-01

Improvement in the positional accuracy of irradiation is expected by capturing patient motion (intra-fractional error) during irradiation. The present study reports the construction of a patient observation system using Microsoft® KINECTTM. By tracking movement, we made it possible to add a depth component to the acquired position coordinates and to display three-axis (X, Y, and Z) movement. Moreover, the developed system can be displayed in a graph which is constructed from the coordinate position at each time interval. Using the developed system, an observer can easily visualize patient movement. When the body phantom was moved a known distance in the X, Y, and Z directions, good coincidence was shown with each axis. We built a patient observation system which captures a patient's motion using KINECTTM.

Impedance cardiography: a comparison of cardiac output vs waveform analysis for assessing left ventricular systolic dysfunction.

PubMed

DeMarzo, Arthur P; Kelly, Russell F; Calvin, James E

2007-01-01

Early detection of asymptomatic left ventricular systolic dysfunction (LVSD) is beneficial in managing heart failure. Recent studies have cast doubt on the usefulness of cardiac output as an indicator of LVSD. In impedance cardiography (ICG), the dZ/dt waveform has a systolic wave called the E wave. This study looked at measurements of the amplitude and area of the E wave compared with ICG-derived cardiac output, stroke volume, cardiac index, and stroke index as methods of assessing LVSD. ICG data were obtained from patients (n=26) admitted to a coronary care unit. Clinical LVSD severity was stratified into 4 groups (none, mild, moderate, and severe) based on echocardiography data and standard clinical assessment by a cardiologist blinded to ICG data. Statistical analysis showed that the E wave amplitude and area were better indicators of the level of LVSD than cardiac output, stroke volume, cardiac index, or stroke index. ICG waveform analysis has potential as a simple point-of-care test for detecting LVSD in asymptomatic patients at high risk for developing heart failure and for monitoring LVSD in patients being treated for heart failure.

40 CFR 437.1 - General applicability.

Code of Federal Regulations, 2010 CFR

2010-07-01

... centralized silver recovery from used photographic or x-ray materials activities. The discharge resulting from centralized silver recovery from used photographic or x-ray materials that is treated at a CWT facility along... Nickel Subcategory), Subpart X (Secondary Precious Metals Subcategory), Subpart Z (Secondary Tantalum...

40 CFR 437.1 - General applicability.

Code of Federal Regulations, 2011 CFR

2011-07-01

... centralized silver recovery from used photographic or x-ray materials activities. The discharge resulting from centralized silver recovery from used photographic or x-ray materials that is treated at a CWT facility along... Nickel Subcategory), subpart X (Secondary Precious Metals Subcategory), subpart Z (Secondary Tantalum...

Apolipoprotein C-II Is a Potential Serum Biomarker as a Prognostic Factor of Locally Advanced Cervical Cancer After Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harima, Yoko, E-mail: harima@takii.kmu.ac.jp; Ikeda, Koshi; Utsunomiya, Keita

Purpose: To determine pretreatment serum protein levels for generally applicable measurement to predict chemoradiation treatment outcomes in patients with locally advanced squamous cell cervical carcinoma (CC). Methods and Materials: In a screening study, measurements were conducted twice. At first, 6 serum samples from CC patients (3 with no evidence of disease [NED] and 3 with cancer-caused death [CD]) and 2 from healthy controls were tested. Next, 12 serum samples from different CC patients (8 NED, 4 CD) and 4 from healthy controls were examined. Subsequently, 28 different CC patients (18 NED, 10 CD) and 9 controls were analyzed in themore » validation study. Protein chips were treated with the sample sera, and the serum protein pattern was detected by surface-enhanced laser desorption and ionization–time-of-flight mass spectrometry (SELDI-TOF MS). Then, single MS-based peptide mass fingerprinting (PMF) and tandem MS (MS/MS)-based peptide/protein identification methods, were used to identify protein corresponding to the detected peak. And then, turbidimetric assay was used to measure the levels of a protein that indicated the best match with this peptide peak. Results: The same peak 8918 m/z was identified in both screening studies. Neither the screening study nor the validation study had significant differences in the appearance of this peak in the controls and NED. However, the intensity of the peak in CD was significantly lower than that of controls and NED in both pilot studies (P=.02, P=.04) and validation study (P=.01, P=.001). The protein indicated the best match with this peptide peak at 8918 m/z was identified as apolipoprotein C-II (ApoC-II) using PMF and MS/MS methods. Turbidimetric assay showed that the mean serum levels of ApoC-II tended to decrease in CD group when compared with NED group (P=.078). Conclusion: ApoC-II could be used as a biomarker for detection in predicting and estimating the radiation treatment outcome of patients with CC.« less

Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal Dysfunction: A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study.

PubMed

Zheng, Ying; Cai, Guang-Yan; He, Li-Qun; Lin, Hong-Li; Cheng, Xiao-Hong; Wang, Nian-Song; Jian, Gui-Hua; Liu, Xu-Sheng; Liu, Yu-Ning; Ni, Zhao-Hui; Fang, Jing-Ai; Ding, Han-Lu; Guo, Wang; He, Ya-Ni; Wang, Li-Hua; Wang, Ya-Ping; Yang, Hong-Tao; Ye, Zhi-Ming; Yu, Ren-Huan; Zhao, Li-Juan; Zhou, Wen-Hua; Li, Wen-Ge; Mao, Hui-Juan; Zhan, Yong-Li; Hu, Zhao; Yao, Chen; Wei, Ri-Bao; Chen, Xiang-Mei

2017-10-20

Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD. The present study was a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml·min-1·1.73 m-2, aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1:1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment. The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test. The present study reported results based on an intention-to-treat (ITT) analysis. A total of 292 participants underwent the ITT analysis. At 24 weeks, the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the test and control groups, respectively (Z = 2.642, P = 0.008), and the median change in eGFR was -0.2 (-4.3-2.7) and -2.2 (-5.7-0.8) ml·min-1·1.73 m-2, respectively (Z = -2.408, P = 0.016). There were no significant differences in adverse events between the groups. Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction. Chinese Clinical Trial Register, ChiCTR-TRC-12002448; http://www.chictr.org.cn/showproj.aspx?proj=7102.

Bone Mineral Density, 25-OH Vitamin D and Inflammation in Patients with Psoriasis.

PubMed

Solak, Berna; Dikicier, Bahar Sevimli; Celik, Hanife Duzgun; Erdem, Teoman

2016-05-01

Low levels of vitamin D may play a role in the pathogenesis of psoriasis and is related to increased risk of osteoporosis. There are a few studies showing increased rate of osteoporosis in patients with psoriasis; however, none of them investigated impact of vitamin D levels and gender status together. We aimed to evaluate relationship between vitamin D and osteoporosis in psoriasis patients with an emphasis on gender difference. Forty-three psoriasis patients without arthritis and 41 healthy controls were enrolled. All patients were <50 years, and women were premenopausal. Participants were questioned about demographic features, sun exposure, regular physical exercise, and smoking status. The serum levels of 25-OH vitamin D, calcium, phosphorus, C-reactive protein, parathyroid hormone, total alkaline phosphatase, and sedimentation rate were measured. Body mass index was calculated. We determined the bone mineral density of the lumbar spine and femur using dual-energy X-ray absorptiometry. Femur neck Z score and lumbar spine total Z score were lower in psoriasis group than those of the control group. Additionally, total femoral Z score, lumbar spine total T, and Z scores were lower in female patients with psoriasis than female controls, whereas for male subjects there was not a remarkable difference between the groups. There was no significant difference between the two groups regarding vitamin D levels. The latter was significantly lower in psoriasis group than in controls for females; however, there was no significant difference between the two groups of males. Patients with psoriasis had higher CRP level and sedimentation rate, than control subjects. Female patients had also higher CRP level and sedimentation rate, than female controls, but there were no significant differences between male patients and controls. As osteoporosis has multifactorial etiology, psoriasis may be among the triggering or facilitating factors for osteoporosis particularly in psoriatic women via several mechanisms such as low blood level of vitamin D and increased inflammation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A crimean - congo haemorrhagic Fever outbreak in northern balochistan.

PubMed

Ali, Nadir; Chotani, Rashid A; Anwar, Masood; Nadeem, Mansoor; Karamat, Karamat Ahmed; Tariq, Waheed Uz Zaman

2007-08-01

To describe the clinical characteristics, epidemiology, predictors of fatal outcome (PFO), and management effects of Crimean-Congo haemorrhagic fever (CCHF) patients during an outbreak in Northern Balochistan. Descriptive study. Fatima Jinnah Hospital and Combined Military Hospital, Quetta, from June to October, 2001. Patients presenting with a fever of less than 2 weeks duration and bleeding manifestations were included. Clinical history was recorded and patients were placed on oral ribavirin, and hematological support. Diagnosis was established by PCR for CCHF or detection of CCHF specific IgM and IgG. Eighty-four patients were received, 34 (40.5%) were suspected of suffering from classical CCHF. All 34 (100%) patients presented with a history of fever and bleeding (epistaxis, gum bleeding, melena or haematuria). Mean platelet count was 30 x 109/L and mean ALT (alanine transferase) was 288 U/L. Among fatal cases, the mean platelet count was 18.4 x 109/L and ALT was 781 units/L. PCR for CCHF viral RNA performed on 10 patients was positive in 3 (30%) patients. CCHF specific IgM and IgG was positive in 17.6% (6/34). Four patients were brought in moribund condition and expired before treatment could be started, 4 patients expired during treatment and 76.5% (26/34) were cured. The overall mortality was 23.5% (8/34). Main predictors of fatal outcome were ALT Z 150 units/L, activated partial thromboplastin time(aPT) Z 60 seconds, prothrombin time (PT) Z 34 seconds, aspartate transferase (AST) Z 200 units/L, platelets 20 x 109/L, and fibrinogen 110 mg/dL. In this series of CCHF occurring in Northern parts of Balochistan, gastrointestinal tract bleeding was the worst prognostic factor associated with fatal outcome. Providing education to healthcare workers and at risk populations, hematological support, anti-viral drugs, and barrier nursing may help reduce mortality.

Simultaneous quantitation of hydrazine and acetylhydrazine in human plasma by high performance liquid chromatography-tandem mass spectrometry after derivatization with p-tolualdehyde.

PubMed

Song, Lu; Gao, Dan; Li, Shangfu; Wang, Yanwei; Liu, Hongxia; Jiang, Yuyang

2017-09-15

A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for simultaneous quantitative analysis of hydrazine and acetylhydrazine in human plasma based on the strategy of p-tolualdehyde derivatization. The derivatization reactions were easily realized by ultrasonic manipulation for 40min. Good separation of the derivatization products was achieved using a C 18 column by gradient elution. The optimized mass transition ion-pairs (m/z) monitored for the two hydrazine derivatives were m/z 237.1≫>119.9 and m/z 176.9≫>117.8, respectively. The limit of detection (LOD) and limit of quantification (LOQ) for hydrazine were 0.002 and 0.005ngmL -1 separately. And they were 0.03 and 0.05ngmL -1 for acetylhydrazine, respectively. The linear range was 0.005-50ngmL -1 for hydrazine and 0.05-500ngmL -1 for acetylhydrazine with R 2 greater than 0.999. The recovery range was determined to be 95.38-108.12% with the relative standard deviation (RSD) in the range of 1.24-14.89%. The method was successfully applied to detect 30 clinical plasma samples of pulmonary tuberculosis patients treated with isoniazid. The concentrations were from 0.04-1.99ngmL -1 for hydrazine and 0.06-142.43ngmL -1 for acetylhydrazine. The results indicated that our developed method had the potential for the detection of hydrazine toxicology in complex biological samples. Furthermore, the method has an important significance to clinical treatment with drugs. Copyright © 2017. Published by Elsevier B.V.

Surgical Treatment of Dupuytren's Contracture; Results and Complications of Surgery: Our Experience.

PubMed

Khan, Parwez Sajad; Iqbal, Shabir; Zaroo, Inam; Hayat, Humera

2010-12-01

Dupuytren's disease is one of the fibro-proliferative conditions affecting the palmar and digital fascia. This disease has been known to surgeons and treated by them for at least 200 years. Dupuytren's disease is very common in Northern Europe and also in countries inhabited by immigrants from Northern Europe. Dupuytren's contracture is stated to be uncommon in Indian subcontinent and very little has been written about this disease in India. The authors have however come across 30 patients with Dupuytren's contracture and they are the subject of this paper, with special emphasis on its surgical correction and complications of surgical treatment. Patients were categorized into stages I, II and III as per the severity of disease. Regional fasciectomy was performed in 90% of the patients and extensive fasciectomy in 10% of patients. Most of wounds were closed by primary closure with z-plasty. In rest of the patients free skin grafts were used to close the wound, when primary closure was not possible. The patients were followed up regularly for 5 years and the results of surgical treatment were categorized into excellent, good, fair and poor. The results were excellent in 23 patients (76.66%), good in six patients (20%) and fair in one patient (3.33%). Post operative edema and some stiffness was seen in two patients. Wound infection was seen in one patient and haematoma in one patient. The correct surgical technique and meticulous post operative care is needed to achieve higher rates of correction and to limit the complications and recurrence.

MIDI face-lift and tricuspidal SMAS-flap.

PubMed

Panfilov, Dimitrije E

2003-01-01

Looking tired is enough for many 40-50-years-olds to ask a plastic surgeon for prophylactic rejuvenation. They want to achieve good and long lasting effects with harmonious features, small scars, and--as they are still very active in their professional and private lives--a quick recovery is very important to them. We have developed a modification of the short-scar face-lift with solid deep support. We call it the MIDI face-lift. MIDI stands for Minimal, Invasive, Deep, Intensive. Technical details are as follows. Two half Z-plasties were performed at each end of modest skin excision, supra-auriculary and retro-auriculary, to avoid even suture edges. By doing so we achieve very unobtrusive scarring. For solid SMAS tension we perform SMAS-plication, simple SMAS-flap, or tricuspidal SMAS-flap. This is an overview of 200 patients we treated over three years. By applying tumescent local anesthesia with adrenaline and ornipressin, and fibrin glue at the end of the procedure, we can the draining so that 96% of our patients were outpatients. Technical details will be discussed as well as complications, adjuvant and alternative procedures. The satisfaction of our patients was high (88%) and no major complications have occurred. Only three out of 200 patients had to undergo revisionary surgery.

The streptomycin-treated mouse intestine selects Escherichia coli envZ missense mutants that interact with dense and diverse intestinal microbiota.

PubMed

Leatham-Jensen, Mary P; Frimodt-Møller, Jakob; Adediran, Jimmy; Mokszycki, Matthew E; Banner, Megan E; Caughron, Joyce E; Krogfelt, Karen A; Conway, Tyrrell; Cohen, Paul S

2012-05-01

Previously, we reported that the streptomycin-treated mouse intestine selected nonmotile Escherichia coli MG1655 flhDC deletion mutants of E. coli MG1655 with improved colonizing ability that grow 15% faster in vitro in mouse cecal mucus and 15 to 30% faster on sugars present in mucus (M. P. Leatham et al., Infect. Immun. 73:8039-8049, 2005). Here, we report that the 10 to 20% remaining motile E. coli MG1655 are envZ missense mutants that are also better colonizers of the mouse intestine than E. coli MG1655. One of the flhDC mutants, E. coli MG1655 ΔflhD, and one of the envZ missense mutants, E. coli MG1655 mot-1, were studied further. E. coli MG1655 mot-1 is more resistant to bile salts and colicin V than E. coli MG1655 ΔflhD and grows ca. 15% slower in vitro in mouse cecal mucus and on several sugars present in mucus compared to E. coli MG1655 ΔflhD but grows 30% faster on galactose. Moreover, E. coli MG1655 mot-1 and E. coli MG1655 ΔflhD appear to colonize equally well in one intestinal niche, but E. coli MG1655 mot-1 appears to use galactose to colonize a second, smaller intestinal niche either not colonized or colonized poorly by E. coli MG1655 ΔflhD. Evidence is also presented that E. coli MG1655 is a minority member of mixed bacterial biofilms in the mucus layer of the streptomycin-treated mouse intestine. We offer a hypothesis, which we call the "Restaurant" hypothesis, that explains how nutrient acquisition in different biofilms comprised of different anaerobes can account for our results.

Cow excrements enhance the occurrence of tetracycline resistance genes in soil regardless of their oxytetracycline content.

PubMed

Kyselková, Martina; Jirout, Jiří; Chroňáková, Alica; Vrchotová, Naděžda; Bradley, Robert; Schmitt, Heike; Elhottová, Dana

2013-11-01

Fertilizing soils with animal excrements from farms with common antibiotic use represents a risk of disseminating antibiotic resistance genes into the environment. In the case of tetracycline antibiotics, it is not clear, however, whether the presence of antibiotic residues further enhances the gene occurrence in manured soils. We established a microcosm experiment in which 3 farm soils that had no recent history of fertilization with animal excrements were amended on a weekly basis (9 times) with excrements from either an oxytetracycline-treated or an untreated cow. Throughout the study, the concentration of oxytetracycline in excrements from the treated cow was above 500 μg g(-1)dw, whereas no oxytetracycline was detected in excrements from the healthy cow. Both excrements contained tetracycline resistance (TC-r) genes tet(L), tet(M), tet(V), tet(Z), tet(Q) and tet(W). The excrements from the treated cow also contained the tet(B) gene, and a higher abundance of tet(Z), tet(Q) and tet(W). Three weeks after the last excrement addition, the individual TC-r genes differed in their persistence in soil: tet(Q) and tet(B) were not detectable while tet(L), tet(M), tet(Z) and tet(W) were found in all 3 soils. There were, however, no significant differences in the total number, nor in the abundance, of TC-r genes between soil samples amended with each excrement type. The oxytetracycline-rich and the oxytetracycline-free excrement therefore contributed equally to the increase of tetracycline resistome in soil. Our results indicate that other mechanisms than OTC-selection pressure may be involved in the maintenance of TC-r genes in manured soils. Copyright © 2013. Published by Elsevier Ltd.

A comparison of GP, pharmacist and nurse prescriber responses to patients' emotional cues and concerns in primary care consultations.

PubMed

Riley, Ruth; Weiss, Marjorie C; Platt, Jo; Taylor, Gordon; Horrocks, Susan; Taylor, Andrea

2013-04-01

Recognising patients' cues and concerns is an important part of patient centred care. With nurses and pharmacists now able to prescribe in the UK, this study compared the frequency, nature, and professionals' responses to patient cues and concerns in consultations with GPs, nurse prescribers and pharmacist prescribers. Audio-recording and analysis of primary care consultations in England between patients and nurse prescribers, pharmacist prescribers and GPs. Recordings were coded for the number of cues and concerns raised, cue or concern type and whether responded to positively or missed. A total of 528 consultations were audio-recorded with 51 professionals: 20 GPs, 19 nurse prescribers and 12 pharmacist prescribers. Overall there were 3.5 cues or concerns per consultation, with no difference between prescriber groups. Pharmacist prescribers responded positively to 81% of patient's cues and concerns with nurse prescribers responding positively to 72% and GPs 53% (PhP v NP: U = 7453, z = -2.1, p = 0.04; PhP v GP: U = 5463, z = -5.9, p < 0.0001; NP v GP: U = 12,070, z = -4.9, p < 0.0001). This evidence suggests that pharmacists and nurses are responding supportively to patients' cues and concerns. The findings support the importance of patient-centredness in training new prescribers and their potential in providing public health roles. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Probing the Metal Enrichment of the Intergalactic Medium at z = 5-6 Using the Hubble Space Telescope

NASA Astrophysics Data System (ADS)

Cai, Zheng; Fan, Xiaohui; Dave, Romeel; Finlator, Kristian; Oppenheimer, Ben

2017-11-01

We test the galactic outflow model by probing associated galaxies of four strong intergalactic C IV absorbers at z = 5-6 using the Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS) ramp narrowband filters. The four strong C IV absorbers reside at z = 5.74, 5.52, 4.95, and 4.87, with column densities ranging from N C IV = 1013.8 to 1014.8 cm-2. At z = 5.74, we detect an I-dropout Lyα emitter (LAE) candidate with a projected impact parameter of 42 physical kpc from the C IV absorber. This LAE candidate has a Lyα-based star formation rate (SFRLyα ) of 2 M ⊙ yr-1 and a UV-based SFR of 4 M ⊙ yr-1. Although we cannot completely rule out that this I-dropout emitter may be an [O II] interloper, its measured properties are consistent with the C IV powered galaxy at z = 5.74. For C IV absorbers at z = 4.95 and z = 4.87, although we detect two LAE candidates with impact parameters of 160 and 200 kpc, such distances are larger than that predicted from the simulations. Therefore, we treat them as nondetections. For the system at z = 5.52, we do not detect LAE candidates, placing a 3σ upper limit of SFRLyα ≈ 1.5 M ⊙ yr-1. In summary, in these four cases, we only detect one plausible C IV source at z = 5.74. Combining the modest SFR of the one detection and the three nondetections, our HST observations strongly support that smaller galaxies (SFRLyα ≲ 2 M ⊙ yr-1) are main sources of intergalactic C IV absorbers, and such small galaxies play a major role in the metal enrichment of the intergalactic medium at z ≳ 5.

Z-LASIK and Trans-PRK for correction of high-grade myopia: safety, efficacy, predictability and clinical outcomes.

PubMed

Gershoni, Assaf; Mimouni, Michael; Livny, Eitan; Bahar, Irit

2018-03-12

The aim of the study was to examine the outcomes of transepithelial photorefractive keratectomy (Trans-PRK) and Femtosecond Laser-assisted in situ keratomileusis (Z-LASIK) for the correction of high myopia. A retrospective cohort study design was used. The study group included 792 eyes with high-grade myopia (- 6.0 diopters or higher) or high-grade myopia with astigmatism that were treated with Z-LASIK or Trans-PRK in 2013 through 2014 in an optical outpatient clinic of a large private medical service. The Trans-PRK group comprised of 674 eyes with a spherical equivalent (SE) of - 7.87 ± 1.46 and the Z-LASIK group comprised of 118 eyes with a SE of - 7.19 ± 0.81 (P < 0.001). The mean postoperative SE in the Trans-PRK group was - 0.06 and - 0.02 in the Z-LASIK group (P = 0.545). Efficacy index values were 0.92 in the Trans-PRK group and 0.95 in the Z-LASIK group (P = 0.083), and corresponding safety index values were 0.95 and 0.97 (P = 0.056). An UCVA of 20/40 or better was achieved in 94.20% of eyes in the Trans-PRK group, and 98.31% in the Z-LASIK group (P = 0.063). The majority of eyes in both the Trans-PRK and Z-LASIK groups were within ± 0.5D of attempted correction: 59.35 and 64.71%, respectively (P = 0.271). Both Trans-PRK and Z-LASIK demonstrated excellent efficacy, safety and predictability profiles, with results comparable and in some cases superior to the current literature. Results of Z-LASIK were slightly better than those of Trans-PRK, though the preoperative SE of the latter was higher.

PubMed Central

BOLZONI, A.; MAPELLI, A.; BAJ, A.; SIDEQUERSKY, F.V; GIANNÌ, A.B.

2015-01-01

SUMMARY Seven patients who underwent mandibular reconstruction with a fibula free flap (one on the midline, six on either right or left side) and were rehabilitated with implant supported prostheses, performed free mandibular border movements (maximal mouth opening and closing, right and left lateral excursions, protrusion) that were recorded by a non-invasive motion analyser. Temporomandibular joint (TMJ) kinematic parameters were compared to those calculated in healthy control subjects using z-scores. Maximum mouth opening was reduced in all patients, with z-scores ranging from -2.742 to -0.106, and performed with a reduced sagittal plane mandibular rotation. Interincisal point forward movement during protrusion was reduced in all but one patient. Lateral mandibular movements (displacement of the interincisal point) and bilateral condylar movements during mouth opening were very variable and sometimes asymmetrical. Mandibular rotation was also variable, with z-scores ranging from -1.265 to 1.388. Together with mandibular range of motion, we investigated biomechanical characteristics of TMJ motion that can provide further information about the joint without submitting the patient to harmful procedures, and that can be followed-up during healing. The investigation indicates those areas that need to be given special attention in preoperative planning, patient information and rehabilitation. PMID:26900241

Abnormal spontaneous brain activity is associated with impaired emotion and cognition in hyperthyroidism: A rs-fMRI study.

PubMed

Zhi, Mengmeng; Hou, Zhenghua; We, Qiong; Zhang, Yuqun; Li, Ling; Yuan, Yonggui

2018-06-07

Hyperthyroid patients undergo emotional and cognitive dysfunction. However, the neurological basis for it remains ambiguous. Amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo) were used to investigate abnormal spontaneous activity in hyperthyroidism for the first time. 29 hyperthyroid patients and 29 healthy controls (HC) received 3.0T magnetic resonance imaging (MRI) scans and neuropsychological assessments. Compared with HC, hyperthyroid patients showed decreased ALFF in left medial frontal gyrus (MeFG) and left posterior cingulate cortex (PCC). Hyperthyroidism group exhibited decreased ReHo in left MeFG. Within hyperthyroidism group, ALFF values in left MeFG were positively correlated with Hamilton Anxiety Rating Scale (HARS) Z-scores, but negatively correlated with processing speed Z-scores. Besides, ALFF values in left precuneus had a positive correlation with HARS Z-scores. As a result, abnormal brain spontaneous activity mainly in default mode network (DMN) implicated the neuro-pathological substrate of relevant emotional and cognitive dysfunction in hyperthyroid patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Promising new technology for managing diamondback moth (Lepidoptera: Plutellidae) in cabbage with pheromone.

PubMed

Mitchell, Everett R

2002-05-01

Experiments were conducted in plantings of cabbage in spring 1999 and 2000 to evaluate a novel, new matrix system for delivering sex pheromone to suppress sexual communication by diamondback moth, Plutella xylostella (L.). The liquid, viscous, slow-release formulation contained a combination of diamondback moth pheromone, a blend of Z-11-hexadecenyl acetate, 27%:Z-11-hexadecen-1-ol, 1%:Z-11-tetradecen-1-ol, 9%:Z-11-hexadecenal, 63%, and the insecticide permethrin (0.16% and 6% w/w of total formulated material, respectively). Field trapping experiments showed that the lure-toxicant combination was highly attractive to male moths for at least four weeks using as little as a 0.05 g droplet of formulated material per trap; and the permethrin insecticide had no apparent influence on response of moths to lure baited traps. Small field plots of cabbage were treated with the lure-toxicant-matrix combination using droplets of 0.44 and 0.05 g each applied to cabbage in a grid pattern at densities ranging from 990 to 4396 droplets/ha to evaluate the potential for disrupting sexual communication of diamondback moth. There was no significant difference in the level of suppression of sexual communication of diamondback moth, as measured by captures of males in pheromone-baited traps located in the treated plots, versus moths captured in untreated control plots, among the treatments regardless of droplet size (0.05 or 0.44 g) or number of droplets applied per ha. Plots treated with the smallest droplet size (0.05 g) and with the fewest number of droplets per ha (990) suppressed captures of male diamondback moths > 90% for up to 3 weeks post treatment. Although laboratory assays showed that the lure-toxicant combination was 100% effective at killing the diamondback moth, the mode of action in the field trials was not determined. The results indicate that the liquid, viscous, slow release formulation containing diamondback moth pheromone could be used to effectively suppress sexual communication of this pest in cabbage and other crucifers, although as many as three applications probably would be required for suppression over an entire growing season.

The effect of the ketogenic diet on the developing skeleton.

PubMed

Simm, Peter J; Bicknell-Royle, Jillian; Lawrie, Jock; Nation, Judy; Draffin, Kellie; Stewart, Karen G; Cameron, Fergus J; Scheffer, Ingrid E; Mackay, Mark T

2017-10-01

The ketogenic diet (KD) is a medically supervised, high fat, low carbohydrate and restricted protein diet which has been used successfully in patients with refractory epilepsy. Only one published report has explored its effect on the skeleton. We postulated that the KD impairs skeletal health parameters in patients on the KD. Patients commenced on the KD were enrolled in a prospective, longitudinal study, with monitoring of Dual-energy X-ray absorptiometry (DXA) derived bone parameters including bone mineral content and density (BMD). Areal BMD was converted to bone mineral apparent density (BMAD) where possible. Biochemical parameters, including Vitamin D, and bone turnover markers, including osteocalcin, were assessed. Patients were stratified for level of mobility using the gross motor functional classification system (GMFCS). 29 patients were on the KD for a minimum of 6 months (range 0.5-6.5 years, mean 2.1 years). There was a trend towards a reduction in lumbar spine (LS) BMD Z score of 0.1562 (p=0.071) per year and 20 patients (68%) had a lower BMD Z score at the end of treatment. While less mobile patients had lower baseline Z scores, the rate of bone loss on the diet was greater in the more mobile patients (0.28 SD loss per year, p=0.026). Height adjustment of DXA data was possible for 13 patients, with a mean reduction in BMAD Z score of 0.19 SD. Only two patients sustained fractures. Mean urinary calcium-creatinine ratios were elevated (0.77), but only 1 patient developed renal calculi. Children on the KD exhibited differences in skeletal development that may be related to the diet. The changes were independent of height but appear to be exaggerated in patients who are ambulant. Clinicians should be aware of potential skeletal side effects and monitor bone health during KD treatment. Longer term follow up is required to determine adult/peak bone mass and fracture risk throughout life. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Effects of a self-management education program on self-efficacy in patients with COPD: a mixed-methods sequential explanatory designed study

PubMed Central

Ng, Wai I; Smith, Graeme Drummond

2017-01-01

Background Self-management education programs (SMEPs) are potentially effective in the symptomatic management of COPD. Little is presently known about the effectiveness of these programs in Chinese COPD patients. The objective of this study was to evaluate the effectiveness of a specifically designed SMEP on levels of self-efficacy in Chinese patients with COPD. Materials and methods Based on the Medical Research Council framework for evaluating complex interventions, an exploratory phase randomized controlled trial was employed to examine the effects of an SMEP. Self-efficacy was the primary outcome using the COPD Self-efficacy Scale, measured at baseline and 6 months after the program. Qualitative data were sequentially collected from these patients via three focus groups to supplement the quantitative findings. Results The experimental group displayed significant improvement in their general self-efficacy (Z =−2.44, P=0.015) and specifically in confronting 1) physical exertion (Z =−2.57, P=0.01), 2) weather/environment effects (Z =−2.63, P<0.001) and 3) intense emotions (Z =−2.54, P=0.01). Three themes emerged from the focus groups: greater disease control, improved psychosocial well-being and perceived incapability and individuality. The connection of the quantitative and qualitative data demonstrated that individual perceptual constancy of patients could be a determining factor modulating the effectiveness of this type of intervention. Conclusion These findings highlight the potential putative benefits of an SMEP in Chinese patients with COPD. Further attention should be given to cultural considerations when developing this type of intervention in Chinese populations with COPD and other chronic diseases. PMID:28790816

Satisfaction with cancer care, self-efficacy, and health-related quality of life in Latino cancer survivors.

PubMed

Moreno, Patricia I; Ramirez, Amelie G; San Miguel-Majors, Sandra L; Fox, Rina S; Castillo, Leopoldo; Gallion, Kipling J; Munoz, Edgar; Estabrook, Ryne; Perez, Arely; Lad, Thomas; Hollowell, Courtney; Penedo, Frank J

2018-04-15

The objective of the current study was to examine how modifiable factors such as satisfaction with cancer care and self-efficacy impact health-related quality of life (HRQOL) among Latino cancer survivors. Latinos previously diagnosed with breast, prostate, or colorectal cancer (N = 288) completed questionnaires (Patient Satisfaction with Cancer Care Scale, Stanford Chronic Disease Self-Management Measures, Functional Assessment of Cancer Therapy-General, and Short Acculturation Scale for Hispanics) within 2 years after receiving primary cancer treatment. Path model analyses demonstrated that satisfaction with cancer care was associated with greater HRQOL and that this relationship was explained by several facets of self-efficacy (ie, confidence in managing psychological distress [z = 3.81; P<.001], social support from close others [z = 2.46; P = .014], social/recreational activities [z = 3.30; P = .001], and patient-provider communication [z = -3.72; P<.001]). Importantly, foreign-born, less acculturated, and monolingual Spanish-speaking survivors reported lower self-efficacy in patient-provider communication; however, adjusting for acculturation, language, nativity, and other covariates did not alter these results. Factors that contribute to disparities in HRQOL among Latino cancer survivors compared with non-Latino whites, such as low income, less education, and a lack of health insurance, can be difficult to address. The findings of the current study emphasize the importance of self-efficacy within the context of patient-centered cancer care practices (eg, patient inclusion in care decisions, sufficient time with provider, ready access to medical advice) and suggest that improving satisfaction with care may increase patients' confidence in managing important aspects of their cancer experience and, in turn, improve HRQOL among Latino cancer survivors. Cancer 2018. © 2018 American Cancer Society. Cancer 2018;124:1770-9. © 2018 American Cancer Society. © 2018 American Cancer Society.

Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy

PubMed Central

Hollyman, Daniel; Stefanski, Jolanta; Przybylowski, Mark; Bartido, Shirley; Borquez-Ojeda, Oriana; Taylor, Clare; Yeh, Raymond; Capacio, Vanessa; Olszewska, Malgorzata; Hosey, James; Sadelain, Michel; Brentjens, Renier J.; Rivière, Isabelle

2009-01-01

Summary Based on promising pre-clinical data demonstrating the eradication of systemic B cell malignancies by CD19-targeted T lymphocytes in vivo in SCID beige mouse models, we are launching Phase 1 clinical trials in patients with chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL). We present here the validation of the bioprocess we developed for the production and expansion of clinical grade autologous T cells derived from patients with CLL. We demonstrate that T cells genetically modified with a replication-defective gammaretroviral vector derived from the Moloney murine leukemia virus encoding a chimeric antigen receptor (CAR) targeted to CD19 (1928z) can be expanded with Dynabeads® CD3/CD28. This bioprocess allows us to generate clinical doses of 1928z+ T cells in approximately 2 to 3 weeks in a large-scale semi-closed culture system using the Wave bioreactor. These 1928z+ T cells remain biologically functional not only in vitro but also in SCID beige mice bearing disseminated tumors. The validation requirements in terms of T cell expansion, T cell transduction with the 1928z CAR, biological activity, quality control testing and release criteria were met for all four validation runs using apheresis products from patients with CLL. Additionally, following expansion of the T cells, the diversity of the skewed Vβ T cell receptor repertoire was significantly restored. This validated process will be used in phase I clinical trials in patients with chemo-refractory CLL and in patients with relapsed ALL. It can also be adapted for other clinical trials involving the expansion and transduction of patient or donor T cells using any chimeric antigen receptor or T cell receptor. PMID:19238016

Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients: role of enhanced brain reward functional connectivity and homeostasis redeeming joy.

PubMed

McLaughlin, Thomas; Blum, Kenneth; Oscar-Berman, Marlene; Febo, Marcelo; Agan, Gozde; Fratantonio, James L; Simpatico, Thomas; Gold, Mark S

2015-06-01

Lucid dreams are frequently pleasant and training techniques have been developed to teach dreamers to induce them. In addition, the induction of lucid dreams has also been used as a way to ameliorate nightmares. On the other hand, lucid dreams may be associated with psychiatric conditions, including Post-Traumatic Stress Disorder (PTSD) and Reward Deficiency Syndrome-associated diagnoses. In the latter conditions, lucid dreams can assume an unpleasant and frequently terrifying character. We present two cases of dramatic alleviation of terrifying lucid dreams in patients with PTSD. In the first case study, a 51-year-old, obese woman, diagnosed with PTSD and depression, had attempted suicide and experienced terrifying lucid nightmares linked to sexual/physical abuse from early childhood by family members including her alcoholic father. Her vivid "bad dreams" remained refractory in spite of 6 months of treatment with Dialectical Behavioral Therapy (DBT) and standard pharmaceutical agents which included prazosin, clonidie and Adderall. The second 39-year-old PTSD woman patient had also suffered from lucid nightmares. The medication visit notes reveal changes in the frequency, intensity and nature of these dreams after the complex putative dopamine agonist KB220Z was added to the first patient's regimen. The patient reported her first experience of an extended period of happy dreams. The second PTSD patient, who had suffered from lucid nightmares, was administered KB220Z to attenuate methadone withdrawal symptoms and incidentally reported dreams full of happiness and laughter. These cases are discussed with reference to the known effects of KB220Z including enhanced dopamine homeostasis and functional connectivity of brain reward circuitry in rodents and humans. Their understanding awaits intensive investigation involving large-population, double-blinded studies.

Manufacturing validation of biologically functional T cells targeted to CD19 antigen for autologous adoptive cell therapy.

PubMed

Hollyman, Daniel; Stefanski, Jolanta; Przybylowski, Mark; Bartido, Shirley; Borquez-Ojeda, Oriana; Taylor, Clare; Yeh, Raymond; Capacio, Vanessa; Olszewska, Malgorzata; Hosey, James; Sadelain, Michel; Brentjens, Renier J; Rivière, Isabelle

2009-01-01

On the basis of promising preclinical data demonstrating the eradication of systemic B-cell malignancies by CD19-targeted T lymphocytes in vivo in severe combined immunodeficient-beige mouse models, we are launching phase I clinical trials in patients with chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia. We present here the validation of the bioprocess which we developed for the production and expansion of clinical grade autologous T cells derived from patients with CLL. We demonstrate that T cells genetically modified with a replication-defective gammaretroviral vector derived from the Moloney murine leukemia virus encoding a chimeric antigen receptor (CAR) targeted to CD19 (1928z) can be expanded with Dynabeads CD3/CD28. This bioprocess allows us to generate clinical doses of 1928z+ T cells in approximately 2 to 3 weeks in a large-scale semiclosed culture system using the Wave Bioreactor. These 1928z+ T cells remain biologically functional not only in vitro but also in severe combined immunodeficient-beige mice bearing disseminated tumors. The validation requirements in terms of T-cell expansion, T-cell transduction with the 1928z CAR, biologic activity, quality control testing, and release criteria were met for all 4 validation runs using apheresis products from patients with CLL. Additionally, after expansion of the T cells, the diversity of the skewed Vbeta T-cell receptor repertoire was significantly restored. This validated process will be used in phase I clinical trials in patients with chemorefractory CLL and in patients with relapsed acute lymphoblastic leukemia. It can also be adapted for other clinical trials involving the expansion and transduction of patient or donor T cells using any CAR or T-cell receptor.

Α₁-antitrypsin PiMZ heterozygosity has an independent aggravating effect on liver fibrosis in alcoholic liver disease.

PubMed

Goltz, Diane; Hittetiya, Kanishka; Vössing, Lena Marie; Kirfel, Jutta; Spengler, Ulrich; Fischer, Hans-Peter

2014-11-01

Heterozygous α1-antitrypsin deficiency type PiZ (PiMZ) results in chronic liver injury and predisposes to hepatocellular carcinoma. Gene frequency of the PiZ allele ranges from 0.005 to 0.027 in Western and Central Europe; therefore, there is a substantial risk of coincidence with chronic alcohol abuse. This retrospective case-control study evaluates the impact of PiMZ genotype on the development of chronic liver disease in alcohol consuming patients. Six thousand eight hundred eighty-six consecutive liver specimens were immunohistochemically tested for PiZ-deposits. From 254 PiZ-positive patients, the liver biopsies of 30 PiMZ adults without concomitant liver disease other than alcoholic liver disease (ALD) were selected and matched to PiMM (wild type) patients with respect to age, gender and lifetime daily alcohol ingestion (LDAI). Histomorphological changes were assessed using the SAF score and by digital image analysis. Liver cirrhosis was significantly more frequent in PIMZ patients than in matched PiMM patients (PiMM 9/30 vs. PiMZ 14/30, p = 0.04). Comparison of the extent of fibrosis in PiMZ and PiMM livers by two-way ANOVA indicated that the amount of LDAI has a major effect in PiMZ and PiMM patients (30.04 % of total variation, p < 0.0001), whereas PIMZ genotype has a minor but independent effect on liver fibrosis as assessed by digital planimetric evaluation (9.27 % of total variation, p = 0.005). Semiquantitative assessment was in agreement with this finding. Histomorphological findings support that PiMZ heterozygosity has an independent aggravating effect on liver fibrosis, even though the pathogenic effect of alcohol consumption is much stronger.

Improved survival among older acute myeloid leukemia patients - a population-based study.

PubMed

Shah, Binay Kumar; Ghimire, Krishna Bilas

2014-07-01

Survival in acute myeloid leukemia (AML) has improved in younger patients over the last decade. This study was conducted to evaluate the relative survival rates in older AML patients over two decades in the US. We analyzed Surveillance, Epidemiology, and End Results (SEER) registry database to evaluate relative survival rate in older (≥ 75 years) AML population diagnosed during 1992-2009. We selected AML patients from 13 registries of SEER 18 database to compare RS during 1992-2000 and 2001-2009. The relative survival rates improved significantly during 2001-2009 compared to 1992-2000 for all age groups and sex. For young elderly patients (75-84 years) RS increased from 13.1 ± 0.8% to 17.4 ± 0.9% at one year Z-value = 3.98, p < 0.0001 and from 2.0 ± 0.4 to 2.6 ± 0.5%, Z-value = 3.61, p < 0.0005 at five years. Similarly, for very elderly (≥ 85 years) patients RS increased from 5.3 ± 1.0% to 8.0 ± 1.0%, Z-value = 3.03, p < 0.005 at one year, but no improvement seen at five years. The relative survival in elderly AML has increased significantly during 2001-2009 compared to 1992-2000.

Cerebral metabonomics study on Parkinson's disease mice treated with extract of Acanthopanax senticosus harms.

PubMed

Li, Xu-zhao; Zhang, Shuai-nan; Lu, Fang; Liu, Chang-feng; Wang, Yu; Bai, Yu; Wang, Na; Liu, Shu-min

2013-10-15

Extract of Acanthopanax senticosus harms (EAS) has neuroprotective effect on Parkinson's disease (PD) mice against dopaminergic neuronal damage. However, studies of its anti-PD mechanism are challenging, owing to the complex pathophysiology of PD, and complexity of EAS with multiple constituents acting on different metabolic pathways. Here, we have investigated the metabolic profiles and potential biomarkers in a mice model of MPTP-induced PD after treatment of EAS. Metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to profile the metabolic fingerprints of mesencephalon obtained from 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine Hydrochloride (MPTP-HCl)-induced PD mice model with and without EAS treatment. Through partial least squares-discriminate analysis (PLS-DA), it was observed that metabolic perturbations induced by MPTP were restored after treatment with EAS. Metabolites with significant changes induced by MPTP, including L-dopa, 5'-methylthioadenosine, tetradecanoylcarnitine, phytosphingosine-1-P, Cer(d18:0/18:0), LysoPC(20:4(5Z,8Z,11Z,14Z)), L-palmitoyl -carnitine, tetracosanoylglycine, morphiceptin and stearoylcarnitine, were characterized as potential biomarkers involved in the pathogenesis of PD. The derivations of all those biomarkers can be regulated by EAS treatment except Cer(d18:0/18:0), LysoPC(20:4(5Z,8Z,11Z,14Z)), morphiceptin. The therapeutic effect of EAS on PD may involve in regulating the tyrosine metabolism, mitochondrial beta-oxidation of long chain saturated fatty acids, fatty acid metabolism, methionine metabolism, and sphingolipid metabolism. This study indicated that changed metabolites can be certainly recovered by EAS, and the treatment of EAS can be connected with the regulation of related metabolic pathways. Copyright © 2013 Elsevier GmbH. All rights reserved.

Erratum to: Constraining couplings of top quarks to the Z boson in $$ t\\overline{t} $$ + Z production at the LHC

DOE PAGES

Röntsch, Raoul; Schulze, Markus

2015-09-21

We study top quark pair production in association with a Z boson at the Large Hadron Collider (LHC) and investigate the prospects of measuring the couplings of top quarks to the Z boson. To date these couplings have not been constrained in direct measurements. Such a determination will be possible for the first time at the LHC. Our calculation improves previous coupling studies through the inclusion of next-to-leading order (NLO) QCD corrections in production and decays of all unstable particles. We treat top quarks in the narrow-width approximation and retain all NLO spin correlations. To determine the sensitivity of amore » coupling measurement we perform a binned log-likelihood ratio test based on normalization and shape information of the angle between the leptons from the Z boson decay. The obtained limits account for statistical uncertainties as well as leading theoretical systematics from residual scale dependence and parton distribution functions. We use current CMS data to place the first direct constraints on the ttbZ couplings. We also consider the upcoming high-energy LHC run and find that with 300 inverse fb of data at an energy of 13 TeV the vector and axial ttbZ couplings can be constrained at the 95% confidence level to C_V=0.24^{+0.39}_{-0.85} and C_A=-0.60^{+0.14}_{-0.18}, where the central values are the Standard Model predictions. This is a reduction of uncertainties by 25% and 42%, respectively, compared to an analysis based on leading-order predictions. We also translate these results into limits on dimension-six operators contributing to the ttbZ interactions beyond the Standard Model.« less

Discovery of Novel Small-molecule Inhibitors of Nuclear Factor-κB Signaling with Anti-inflammatory and Anti-cancer Properties.

PubMed

Zhang, Lei; Shi, Lei; Soars, Shafer; Kamps, Joshua; Yin, Hang Hubert

2018-06-05

Excessive NF-κB activation contributes to the pathogenesis of numerous diseases. Small-molecule inhibitors of NF-κB signaling have significant therapeutic potential especially in treating inflammatory diseases and cancers. In this study, we performed a cell-based high-throughput screening to discover novel agents capable of inhibiting NF-κB signaling. Based on two hit scaffolds from the screening, we synthesized 69 derivatives to optimize the potency for inhibition of NF-κB activation, leading to successful discovery of the most potent compound Z9j with over 170-fold enhancement of inhibitory activity. Preliminary mechanistic studies revealed that Z9j inhibited NF-κB signaling via suppression of Src/Syk, PI3K/Akt and IKK/IκB pathways. This novel compound also demonstrated anti-inflammatory and anti-cancer activities, warranting its further development as a potential multifunctional agent to treat inflammatory diseases and cancers.

Beyond Dizziness: Virtual Navigation, Spatial Anxiety and Hippocampal Volume in Bilateral Vestibulopathy

PubMed Central

Kremmyda, Olympia; Hüfner, Katharina; Flanagin, Virginia L.; Hamilton, Derek A.; Linn, Jennifer; Strupp, Michael; Jahn, Klaus; Brandt, Thomas

2016-01-01

Bilateral vestibulopathy (BVP) is defined as the impairment or loss of function of either the labyrinths or the eighth nerves. Patients with total BVP due to bilateral vestibular nerve section exhibit difficulties in spatial memory and navigation and show a loss of hippocampal volume. In clinical practice, most patients do not have a complete loss of function but rather an asymmetrical residual functioning of the vestibular system. The purpose of the current study was to investigate navigational ability and hippocampal atrophy in BVP patients with residual vestibular function. Fifteen patients with BVP and a group of age- and gender- matched healthy controls were examined. Self-reported questionnaires on spatial anxiety and wayfinding were used to assess the applied strategy of wayfinding and quality of life. Spatial memory and navigation were tested directly using a virtual Morris Water Maze Task. The hippocampal volume of these two groups was evaluated by voxel-based morphometry. In the patients, the questionnaire showed a higher spatial anxiety and the Morris Water Maze Task a delayed spatial learning performance. MRI revealed a significant decrease in the gray matter mid-hippocampal volume (Left: p = 0.006, Z = 4.58, Right: p < 0.001, Z = 3.63) and posterior parahippocampal volume (Right: p = 0.005, Z = 4.65, Left: p < 0.001, Z = 3.87) compared to those of healthy controls. In addition, a decrease in hippocampal formation volume correlated with a more dominant route-finding strategy. Our current findings demonstrate that even partial bilateral vestibular loss leads to anatomical and functional changes in the hippocampal formation and objective and subjective behavioral deficits. PMID:27065838

Should Tricuspid Annuloplasty be Performed With Pulmonary Valve Replacement for Pulmonary Regurgitation in Repaired Tetralogy of Fallot?

PubMed

Kurkluoglu, Mustafa; John, Anitha S; Cross, Russell; Chung, David; Yerebakan, Can; Zurakowski, David; Jonas, Richard A; Sinha, Pranava

2015-01-01

Indications for prophylactic tricuspid annuloplasty in patients with pulmonary regurgitation (PR) after tetralogy of Fallot (TOF) repair are unclear and often extrapolated from acquired functional tricuspid regurgitation (TR) data in adults, where despite correction of primary left heart pathology, progressive tricuspid annular dilation is noted beyond a threshold diameter >4 cm (21 mm/m(2)). We hypothesized that unlike in adult functional TR, in pure volume-overload conditions such as patients with PR after TOF, the tricuspid valve size is likely to regress after pulmonary valve replacement (PVR). A total of 43 consecutive patients who underwent PVR from 2005 until 2012 at a single institution were retrospectively reviewed. Absolute and indexed tricuspid annulus diameters (TADs), tricuspid annulus Z-scores, grade of TR along with right ventricular size, and function indices were recorded before and after PVR. Preoperative and postoperative echocardiographic data were available in all patients. A higher tricuspid valve Z-score correlated with greater TR both preoperatively (P = 0.005) and postoperatively (P = 0.02). Overall reductions in the absolute and indexed TAD and tricuspid valve Z-scores were seen postoperatively, with greater absolute as well as percentage reduction seen with larger preoperative TAD index (P = 0.007) and higher tricuspid annulus Z-scores (P = 0.06). In pure volume-overload conditions such as patients with PR after TOF, reduction in the tricuspid valve size is seen after PVR. Concomitant tricuspid annuloplasty should not be considered based on tricuspid annular dilation alone. Copyright © 2015 Elsevier Inc. All rights reserved.

MLN4924 sensitizes monocytes and maturing dendritic cells for TNF-dependent and -independent necroptosis.

PubMed

El-Mesery, Mohamed; Seher, Axel; Stühmer, Thorsten; Siegmund, Daniela; Wajant, Harald

2015-03-01

MLN4924 prevents the formation of active cullin-RING ubiquitin ligase complexes and thus inhibits NF-κB signalling. Here, we evaluated the effects of this compound on monocytes and dendritic cells (DCs). Monocytes and DCs were challenged with TNF or LPS in the presence and absence of MLN4924. The effects of MLN4924 on cellular viability, pro-inflammatory gene induction and DC maturation were investigated using the MTT assay, elisa and FACS analysis. Mechanisms of cell death induction were evaluated by using inhibitors of caspases, RIPK1 and MLKL. MLN4924 inhibited NF-κB activation and sensitized monocytes and immature DCs (iDCs) for TNFR1-induced cell death. Neither the caspase inhibitor zVAD-fmk, the RIPK1 inhibitor necrostatin-1 (nec-1) nor the MLKL inhibitor necrosulfonamide (NSA) alone prevented TNF-induced cell death. A combination of zVAD-fmk and nec-1 or NSA, however, rescued monocytes and iDCs from MLN4924/TNF-induced cell death indicating that MLN4924 affects anti-apoptotic and anti-necrotic activities in TNFR1 signalling. MLN4924 also converted the response of iDCs to LPS from maturation to cell death. LPS-induced cell death in MLN4924-treated iDCs was again only effectively blocked by cotreatment with zVAD-fmk and nec-1 or NSA. Noteworthy, MLN4924/LPS-induced cell death was almost completely independent of endogenous TNF. MLN4924 also strongly inhibited maturation and activation of iDCs that were rescued from cell death by zVAD-fmk and nec-1. Our data reveal a strong dual suppressive effect of MLN4924 on DC activity. The targeting of NAE by MLN4924 could be a new way to treat inflammatory diseases. © 2014 The British Pharmacological Society.

Stepwise radical endoscopic resection for Barrett's esophagus with early neoplasia: report on a Brussels' cohort.

PubMed

Pouw, R E; Peters, F P; Sempoux, C; Piessevaux, H; Deprez, P H

2008-11-01

The aim of this retrospective study was to assess safety and efficacy of stepwise radical endoscopic resection (SRER) in patients with Barrett's esophagus with high-grade intraepithelial neoplasia (HGIN) or early cancer. Patients undergoing SRER between 2000 and 2006 were retrospectively evaluated. Patients with Barrett's esophagus who also had HGIN or early cancer were included if they had no signs of submucosal infiltration or metastases. SRER was performed using the cap-technique, at 8-week intervals until all Barrett's esophagus was removed. Follow-up endoscopy was scheduled every 6 months. A total of 34 patients were included (31 male, mean 67 years, median Barrett's dimensions C1M4). HGIN / early cancer was eradicated in all patients in a median of two endoscopic resection sessions (IQR 1-2 sessions). Twelve patients underwent additional argon plasma coagulation for small islets or an irregular Z-line. Barrett's esophagus was eradicated in 28 patients (82 %). Complications occurred in 3/34 patients (9 %): two perforations, one delayed bleeding. In all, 19 patients (56 %) developed dysphagia, which was resolved with dilatation or stent placement. During a median follow-up period of 23 months (IQR 15 - 41 months), HGIN / early cancer recurred in three patients (9 %): two were retreated with endoscopic resection and one patient was referred for curative surgery. Five patients (15 %) had recurrence of nondysplastic Barrett's esophagus. At the end of the follow-up period all patients were free of HGIN / early cancer (one patient after surgery), and 23 patients (68 %) had complete endoscopic and histological eradication of Barrett's esophagus. SRER resulted in complete eradication of HGIN/early cancer in all patients, and eradication of Barrett's esophagus in a majority of cases. A significant number of patients develop dysphagia, which can be successfully treated endoscopically.

Benzodiazepine and Z-drug prescribing in Ireland: analysis of national prescribing trends from 2005 to 2015.

PubMed

Cadogan, Cathal A; Ryan, Cristín; Cahir, Caitriona; Bradley, Colin P; Bennett, Kathleen

2018-06-01

The aim of this study was to examine prescribing trends for benzodiazepines and Z-drugs to General Medical Services (GMS) patients in Ireland. A repeated cross-sectional analysis of the national pharmacy claims database was conducted for GMS patients aged ≥16 years from 2005 to 2015. Prescribing rates per 1000 eligible GMS population were calculated with 95% confidence intervals (CIs). Negative binomial regression was used to determine longitudinal trends and compare prescribing rates across years, gender and age groups. Duration of supply and rates of concomitant benzodiazepine and Z-drug prescribing were determined. Age (16-44, 45-64, ≥65 years) and gender trends were investigated. Benzodiazepine prescribing rates decreased significantly from 225.92/1000 population (95% CI 224.94-226.89) in 2005 to 166.07/1000 population (95% CI 165.38-166.75) in 2015 (P < 0.0001). Z-drug prescribing rates increased significantly from 95.36/1000 population (95% CI 94.73-96.00) in 2005 to 109.11/1000 population (95% CI 108.56-109.67) in 2015 (P = 0.048). Approximately one-third of individuals dispensed either benzodiazepines or Z-drugs were receiving long-term prescriptions (>90 days). The proportion of those receiving >1 benzodiazepine and/or Z-drug concomitantly increased from 11.9% in 2005 to 15.3% in 2015. Benzodiazepine and Z-drug prescribing rates were highest for older women (≥65 years) throughout the study period. Benzodiazepine prescribing to the GMS population in Ireland decreased significantly from 2005 to 2015, and was coupled with significant increases in Z-drug prescribing. The study shows that benzodiazepine and Z-drug prescribing is common in this population, with high proportions of individuals receiving long-term prescriptions. Targeted interventions are needed to reduce potentially inappropriate long-term prescribing and use of these medications in Ireland. © 2018 The British Pharmacological Society.

Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial.

PubMed

Lai, Zhi-Wei; Kelly, Ryan; Winans, Thomas; Marchena, Ivan; Shadakshari, Ashwini; Yu, Julie; Dawood, Maha; Garcia, Ricardo; Tily, Hajra; Francis, Lisa; Faraone, Stephen V; Phillips, Paul E; Perl, Andras

2018-03-24

Patients with systemic lupus erythematosus have T-cell dysfunction that has been attributed to the activation of the mammalian target of rapamycin (mTOR). Rapamycin inhibits antigen-induced T-cell proliferation and has been developed as a medication under the generic designation of sirolimus. We assessed safety, tolerance, and efficacy of sirolimus in a prospective, biomarker-driven, open-label clinical trial. We did a single-arm, open-label, phase 1/2 trial of sirolimus in patients with active systemic lupus erythematosus disease unresponsive to, or intolerant of, conventional medications at the State University of New York Upstate Medical University (Syracuse, NY, USA). Eligible participants (aged ≥18 years) had active systemic lupus erythematosus fulfilling four or more of 11 diagnostic criteria defined by the American College of Rheumatology. We excluded patients with allergy or intolerance to sirolimus, patients with life-threatening manifestations of systemic lupus erythematosus, proteinuria, a urine protein to creatinine ratio higher than 0·5, anaemia, leucopenia, or thrombocytopenia. Patients received oral sirolimus at a starting dose of 2 mg per day, with dose adjusted according to tolerance and to maintain a therapeutic range of 6-15 ng/mL. Patients were treated with sirolimus for 12 months. Safety outcomes included tolerance as assessed by the occurrence of common side-effects. The primary efficacy endpoint was decrease in disease activity, assessed using the British Isles Lupus Assessment Group (BILAG) index and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Blood samples of 56 matched healthy individuals were obtained as controls for immunobiological outcomes monitored at each visit. The primary efficacy endpoint was assessed in all patients who completed 12 months of treatment, and all patients who received at least one dose of treatment were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT00779194. Between March 9, 2009, and Dec 8, 2014, 43 patients were enrolled, three of whom did not meet eligibility criteria. 11 of the 40 eligible patients discontinued study treatment because of intolerance (n=2) or non-compliance (n=9). SLEDAI and BILAG disease activity scores were reduced during 12 months of treatment in 16 (55%) of 29 patients who completed treatment. Mean SLEDAI score decreased from 10·2 (SD 5·6) at enrolment to 4·8 (4·5) after 12 months of treatment (p<0·001) and the mean total BILAG index score decreased from 28·4 (12·4) at enrolment to 17·4 (10·7) after 12 months of treatment (p<0·001). The mean daily dose of prednisone required to control disease activity decreased from 23·7 mg (SD 9·6) to 7·2 mg (2·3; p<0·001) after 12 months of treatment. Sirolimus expanded CD4 + CD25 + FoxP3 + regulatory T cells and CD8 + memory T-cell populations and inhibited interleukin-4 and interleukin-17 production by CD4 + and CD4 - CD8 - double-negative T cells after 12 months. CD8 + memory T cells were selectively expanded in SRI-responders. Patient liver function and lymphocyte counts were unchanged. Although HDL-cholesterol (Z=-2·50, p=0·012), neutrophil counts (Z=-1·92, p=0·054), and haemoglobin (Z=-2·83, p=0·005) were moderately reduced during treatment, all changes occurred within a range that was considered safe. Platelet counts were slightly elevated during treatment (Z=2·06, p=0·0400). These data show that a progressive improvement in disease activity is associated with correction of pro-inflammatory T-cell lineage specification in patients with active systemic lupus erythematosus during 12 months of sirolimus treatment. Follow-up placebo-controlled clinical trials in diverse patient populations are warranted to further define the role of mTOR blockade in treatment of systemic lupus erythematosus. Pfizer, the National Institutes of Health, and the Central New York Community Foundation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Large Eddy Simulation of Bubbly Ship Wakes

DTIC Science & Technology

2005-08-01

as, [Cm +BI(p)+ DE (u)+D,(u,)] (2.28) aRm, =-[E,+FE )(p) (229O•., L pe•,z+_tpjj.( F.(]-](2.29) where Ci and EP represent the convective terms, Bi is the...discrete operator for the pressure gradient term, DE and D, (FE and FI) are discrete operators for the explicitly treated off diagonal terms and the...Bashforth scheme is employed for all the other terms. The off diagonal viscous terms ( DE ) are treated explicitly in order to simplify the LHS matrix of the

Voxel-based statistical analysis of cerebral blood flow using Tc-99m ECD brain SPECT in patients with traumatic brain injury: group and individual analyses.

PubMed

Shin, Yong Beom; Kim, Seong-Jang; Kim, In-Ju; Kim, Yong-Ki; Kim, Dong-Soo; Park, Jae Heung; Yeom, Seok-Ran

2006-06-01

Statistical parametric mapping (SPM) was applied to brain perfusion single photon emission computed tomography (SPECT) images in patients with traumatic brain injury (TBI) to investigate regional cerebral abnormalities compared to age-matched normal controls. Thirteen patients with TBI underwent brain perfusion SPECT were included in this study (10 males, three females, mean age 39.8 +/- 18.2, range 21 - 74). SPM2 software implemented in MATLAB 5.3 was used for spatial pre-processing and analysis and to determine the quantitative differences between TBI patients and age-matched normal controls. Three large voxel clusters of significantly decreased cerebral blood perfusion were found in patients with TBI. The largest clusters were area including medial frontal gyrus (voxel number 3642, peak Z-value = 4.31, 4.27, p = 0.000) in both hemispheres. The second largest clusters were areas including cingulated gyrus and anterior cingulate gyrus of left hemisphere (voxel number 381, peak Z-value = 3.67, 3.62, p = 0.000). Other clusters were parahippocampal gyrus (voxel number 173, peak Z-value = 3.40, p = 0.000) and hippocampus (voxel number 173, peak Z-value = 3.23, p = 0.001) in the left hemisphere. The false discovery rate (FDR) was less than 0.04. From this study, group and individual analyses of SPM2 could clearly identify the perfusion abnormalities of brain SPECT in patients with TBI. Group analysis of SPM2 showed hypoperfusion pattern in the areas including medial frontal gyrus of both hemispheres, cingulate gyrus, anterior cingulate gyrus, parahippocampal gyrus and hippocampus in the left hemisphere compared to age-matched normal controls. Also, left parahippocampal gyrus and left hippocampus were additional hypoperfusion areas. However, these findings deserve further investigation on a larger number of patients to be performed to allow a better validation of objective SPM analysis in patients with TBI.

A pilot study identifying a potential plasma biomarker for determining EGFR mutations in exons 19 or 21 in lung cancer patients

PubMed Central

Pamungkas, Aryo D.; Medriano, Carl A.; Sim, Eunjung; Lee, Sungyong; Park, Youngja H.

2017-01-01

The most common type of lung cancer is non-small cell lung cancer (NSCLC), which is frequently characterized by a mutation in the epidermal growth factor receptor (EGFR). Determining the presence of an EGFR mutation in lung cancer is important, as it determines the type of treatment that a patients will receive. Therefore, the aim of the present study was to apply high-resolution metabolomics (HRM) using liquid chromatography-mass spectrometry to identify significant compounds in human plasma samples obtained from South Korean NSCLC patients, as potential biomarkers for providing early detection and diagnosis of minimally-invasive NSCLC. The metabolic differences between lung cancer patients without EGFR mutations were compared with patients harboring EGFR mutations. Univariate analysis was performed, with a false discovery rate of q=0.05, in order to identify significant metabolites between the two groups. In addition, hierarchical clustering analysis was performed to discriminate between the metabolic profiles of the two groups. Furthermore, the significant metabolites were identified and mapped using Mummichog software, in order to generate a potential metabolic network model. Using metabolome-wide association studies, metabolic alterations were identified. Linoleic acid [303.23 m/z, (M+Na)+], 5-methyl tetrahydrofolate [231.10 m/z, (M+2H)+] and N-succinyl-L-glutamate-5 semialdehyde [254.06 m/z, (M+Na)+], were observed to be elevated in patients harboring EGFR mutations, whereas tetradecanoyl carnitine [394.29 m/z, (M+Na)+] was observed to be reduced. This suggests that these compounds may be affected by the EGFR mutation. In conclusion, the present study identified four potential biomarkers in patients with EGFR mutations, using HRM combined with pathway analysis. These results may facilitate the development of novel diagnostic tools for EGFR mutation detection in patients with lung cancer. PMID:28487968

An Approach for Treating the Hepatobiliary Disease of Cystic Fibrosis by Somatic Gene Transfer

NASA Astrophysics Data System (ADS)

Yang, Yiping; Raper, Steven E.; Cohn, Jonathan A.; Engelhardt, John F.; Wilson, James M.

1993-05-01

Cystic fibrosis (CF) is an inherited disease of epithelial cell ion transport that is associated with pathology in multiple organ systems, including lung, pancreas, and liver. As treatment of the pulmonary manifestations of CF has improved, management of CF liver disease has become increasingly important in adult patients. This report describes an approach for treating CF liver disease by somatic gene transfer. In situ hybridization and immunocytochemistry analysis of rat liver sections indicated that the endogenous CFTR (cystic fibrosis transmembrane conductance regulator) gene is primarily expressed in the intrahepatic biliary epithelial cells. To specifically target recombinant genes to the biliary epithelium in vivo, recombinant adenoviruses expressing lacZ or human CFTR were infused retrograde into the biliary tract through the common bile duct. Conditions were established for achieving recombinant gene expression in virtually all cells of the intrahepatic bile ducts in vivo. Expression persisted in the smaller bile ducts for the duration of the experiment, which was 21 days. These studies suggest that it may be feasible to prevent CF liver disease by genetically reconstituting CFTR expression in the biliary tract, using an approach that is clinically feasible.

Longitudinal evaluation of the prevalence of overweight/obesity in children with congenital heart disease.

PubMed

Tamayo, Catalina; Manlhiot, Cedric; Patterson, Katie; Lalani, Sheliza; McCrindle, Brian W

2015-02-01

Regarding long-term cardiovascular health, obesity may have greater implications for children with congenital heart disease (CHD). We sought to determine trends in anthropometry over time and its association with exercise capacity. Medical records of pediatric patients with CHD were randomly sampled. Serial measurements of weight and height were abstracted, body mass index (BMI) was calculated, and measurements were converted to percentiles and z scores. Analyses of trends were performed using regression models adjusted for repeated measures. Median follow-up after diagnosis for 725 patients was 7.1 years (interquartile range, 1.9-12.8 years). The median initial weight z score was -1.1 (fifth/95th percentile, -3.6/+1.1) and increased over time (+0.103 [0.007] standard deviations [SD]/y; P < 0.001). BMI and height z scores could only be calculated for patients > 2 years old; at that age, the median BMI z score was -0.2 (fifth/95th percentile, -2.6/+1.9) and increased over time (+0.042 [0.007] SD/y; P < 0.001), whereas the median height z score was -0.3 (fifth/95th percentile, -2.7/+1.4) with no change over time (-0.007 [0.006] SD/y; P = 0.18). Using standard BMI percentile cut points to define overweight and obesity, 28% of patients had at least 1 BMI measurement indicating overweight and 17% indicating obesity. Available exercise test results (n = 153) showed that overweight/obese patients had lower percent predicted maximum oxygen consumption (-16 [2]%; P < 0.001), higher peak systolic blood pressure (+11 [4] mm Hg; P = 0.002), and higher systolic blood pressure response (+7 [3] mm Hg; P = 0.01) than normal weight patients. In conclusion, children with repaired CHD have an important risk of overweight/obesity over time that may increase their cardiovascular risk and impair their exercise capacity. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Construction and comparative evaluation of different activity detection methods in brain FDG-PET.

PubMed

Buchholz, Hans-Georg; Wenzel, Fabian; Gartenschläger, Martin; Thiele, Frank; Young, Stewart; Reuss, Stefan; Schreckenberger, Mathias

2015-08-18

We constructed and evaluated reference brain FDG-PET databases for usage by three software programs (Computer-aided diagnosis for dementia (CAD4D), Statistical Parametric Mapping (SPM) and NEUROSTAT), which allow a user-independent detection of dementia-related hypometabolism in patients' brain FDG-PET. Thirty-seven healthy volunteers were scanned in order to construct brain FDG reference databases, which reflect the normal, age-dependent glucose consumption in human brain, using either software. Databases were compared to each other to assess the impact of different stereotactic normalization algorithms used by either software package. In addition, performance of the new reference databases in the detection of altered glucose consumption in the brains of patients was evaluated by calculating statistical maps of regional hypometabolism in FDG-PET of 20 patients with confirmed Alzheimer's dementia (AD) and of 10 non-AD patients. Extent (hypometabolic volume referred to as cluster size) and magnitude (peak z-score) of detected hypometabolism was statistically analyzed. Differences between the reference databases built by CAD4D, SPM or NEUROSTAT were observed. Due to the different normalization methods, altered spatial FDG patterns were found. When analyzing patient data with the reference databases created using CAD4D, SPM or NEUROSTAT, similar characteristic clusters of hypometabolism in the same brain regions were found in the AD group with either software. However, larger z-scores were observed with CAD4D and NEUROSTAT than those reported by SPM. Better concordance with CAD4D and NEUROSTAT was achieved using the spatially normalized images of SPM and an independent z-score calculation. The three software packages identified the peak z-scores in the same brain region in 11 of 20 AD cases, and there was concordance between CAD4D and SPM in 16 AD subjects. The clinical evaluation of brain FDG-PET of 20 AD patients with either CAD4D-, SPM- or NEUROSTAT-generated databases from an identical reference dataset showed similar patterns of hypometabolism in the brain regions known to be involved in AD. The extent of hypometabolism and peak z-score appeared to be influenced by the calculation method used in each software package rather than by different spatial normalization parameters.

Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial.

PubMed

Corbacioglu, Selim; Cesaro, Simone; Faraci, Maura; Valteau-Couanet, Dominique; Gruhn, Bernd; Rovelli, Attilio; Boelens, Jaap J; Hewitt, Annette; Schrum, Johanna; Schulz, Ansgar S; Müller, Ingo; Stein, Jerry; Wynn, Robert; Greil, Johann; Sykora, Karl-Walter; Matthes-Martin, Susanne; Führer, Monika; O'Meara, Anne; Toporski, Jacek; Sedlacek, Petr; Schlegel, Paul G; Ehlert, Karoline; Fasth, Anders; Winiarski, Jacek; Arvidson, Johan; Mauz-Körholz, Christine; Ozsahin, Hulya; Schrauder, Andre; Bader, Peter; Massaro, Joseph; D'Agostino, Ralph; Hoyle, Margaret; Iacobelli, Massimo; Debatin, Klaus-Michael; Peters, Christina; Dini, Giorgio

2012-04-07

Hepatic veno-occlusive disease is a leading cause of morbidity and mortality after haemopoietic stem-cell transplantation (HSCT). We aimed to assess whether defibrotide can reduce the incidence of veno-occlusive disease in this setting. In our phase 3 open-label, randomised controlled trial, we enrolled patients at 28 European university hospitals or academic medical centres. Eligible patients were younger than 18 years, had undergone myeloablative conditioning before allogeneic or autologous HSCT, and had one or more risk factor for veno-occlusive disease based on modified Seattle criteria. We centrally assigned eligible participants on the basis of a computer-generated randomisation sequence (1:1), stratified by centre and presence of osteopetrosis, to receive intravenous defibrotide prophylaxis (treatment group) or not (control group). The primary endpoint was incidence of veno-occlusive disease by 30 days after HSCT, adjudicated by a masked, independent review committee, in eligible patients who consented to randomisation (intention-to-treat population), and was assessed with a competing risk approach. Patients in either group who developed veno-occlusive disease received defibrotide for treatment. We assessed adverse events to 180 days after HSCT in all patients who received allocated prophylaxis. This trial is registered with ClinicalTrials.gov, number NCT00272948. Between Jan 25, 2006, and Jan 29, 2009, we enrolled 356 eligible patients to the intention-to-treat population. 22 (12%) of 180 patients randomly allocated to the defibrotide group had veno-occlusive disease by 30 days after HSCT compared with 35 (20%) of 176 controls (risk difference -7·7%, 95% CI -15·3 to -0·1; Z test for competing risk analysis p=0·0488; log-rank test p=0·0507). 154 (87%) of 177 patients in the defibrotide group had adverse events by day 180 compared with 155 (88%) of 176 controls. Defibrotide prophylaxis seems to reduce incidence of veno-occlusive disease and is well tolerated. Thus, such prophylaxis could present a useful clinical option for this serious complication of HSCT. Gentium SpA, European Group for Blood and Marrow Transplantation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Anthropometric adjustments are helpful in the interpretation of BMD and BMC Z-scores of pediatric patients with Prader-Willi syndrome.

PubMed

Hangartner, T N; Short, D F; Eldar-Geva, T; Hirsch, H J; Tiomkin, M; Zimran, A; Gross-Tsur, V

2016-12-01

Anthropometric adjustments of bone measurements are necessary in Prader-Willi syndrome patients to correctly assess the bone status of these patients. This enables physicians to get a more accurate diagnosis of normal versus abnormal bone, allow for early and effective intervention, and achieve better therapeutic results. Bone mineral density (BMD) is decreased in patients with Prader-Willi syndrome (PWS). Because of largely abnormal body height and weight, traditional BMD Z-scores may not provide accurate information in this patient group. The goal of the study was to assess a cohort of individuals with PWS and characterize the development of low bone density based on two adjustment models applied to a dataset of BMD and bone mineral content (BMC) from dual-energy X-ray absorptiometry (DXA) measurements. Fifty-four individuals, aged 5-20 years with genetically confirmed PWS, underwent DXA scans of spine and hip. Thirty-one of them also underwent total body scans. Standard Z-scores were calculated for BMD and BMC of spine and total hip based on race, sex, and age for all patients, as well as of whole body and whole-body less head for those patients with total-body scans. Additional Z-scores were generated based on anthropometric adjustments using weight, height, and percentage body fat and a second model using only weight and height in addition to race, sex, and age. As many PWS patients have abnormal anthropometrics, addition of explanatory variables weight, height, and fat resulted in different bone classifications for many patients. Thus, 25-70 % of overweight patients, previously diagnosed as normal, were subsequently diagnosed as below normal, and 40-60 % of patients with below-normal body height changed from below normal to normal depending on bone parameter. This is the first study to include anthropometric adjustments into the interpretation of BMD and BMC in children and adolescents with PWS. This enables physicians to get a more accurate diagnosis of normal versus abnormal BMD and BMC and allows for early and effective intervention.

Relationship between patient-reported and objective measurements of hand function in patients with rheumatoid arthritis.

PubMed

Günay, S M; Tuna, Z; Oskay, D

2016-12-31

Rheumatoid arthritis (RA) often results in impairments in upper extremities, especially in the small joints of hand. Involvement of hand brings limitations in activities of daily living. However, it is commonly observed that patient-reported functional status of hand does not always corresponds to their actual physical performance in the clinical setting. The aim of this pilot study is to investigate the relationship between patient self-reported and objectively measured hand functions in patients with RA. Twenty-six patients (51±13 years) with RA diagnosis participated in the study. Hand grip and pinch (lateral, bipod, tripod) strengths were measured and Jebsen Hand Function Test (JHFT) was performed for objective functional performance. Duruöz Hand Index and Beck Depression Inventory - Turkish version were completed by patients. Grip and all three-pinch strength results significantly correlated with Duruöz Hand Index scores (p<0.05). JHFT results except the sentence writing also correlated with the Duruöz scores (p<0.05). Our results showed that self-reported outcome scales might be used for determining functional level of hand in patients with RA in rheumatology practice. Objective quantitative functional tests are the best methods in evaluating functional level of hand, but require valid and reliable equipment with accurate calibration. Therefore, in case of unavailability of objective assessment tools, patient-reported scales may also reflect the real status of hand functions.

Acute rupture of the descending thoracic aorta: repair with use of endovascular stent-grafts.

PubMed

Semba, C P; Kato, N; Kee, S T; Lee, G K; Mitchell, R S; Miller, D C; Dake, M D

1997-01-01

To describe the use of endovascular stent-grafts to treat acute ruptures of the descending thoracic aorta as an alternative to surgery in high-risk patients. From July 1992 to August 1996, 95 patients underwent stent-grafting of the descending thoracic aorta for a variety of lesions. Of these, 11 patients with acute (< or = 7 days) rupture from aneurysms (n = 8) or trauma (n = 3) underwent repair with use of endovascular stent-grafts. Rupture was confirmed with preoperative imaging studies and occurred in the mediastinum (n = 9), the pleural space (n = 1), or the lung (n = 1). All patients were considered high surgical risk due to generalized cardiopulmonary disease and/or previous thoracotomies. Stent-grafts were constructed from Z stents covered with polyester fabric and delivered through a catheter under fluoroscopic control from a remote access site. Stent-graft deployment was successful in all patients. There were no complications of perigraft leak, stent migration, paraplegia, or intraoperative death. Two patients died in the follow-up period: one of ventricular perforation during unrelated thoracic surgery for tumor resection (day 1) and one of cardiac arrest (day 28). All others are alive (mean follow-up, 15.1 months). For acute rupture of the thoracic aorta, endovascular stent-graft repair is technically feasible and may be a therapeutic alternative to a surgical interposition graft in patients considered high risk for conventional thoracotomy. Long-term studies are necessary to determine the role of stent-grafts in preventing future aortic rupture.

Disease duration and age influence CARD15 expression in Crohn's disease.

PubMed

Poniewierka, Elżbieta; Neubauer, Katarzyna; Kempiński, Radosław; Sadakierska-Chudy, Anna

2016-01-05

One of the susceptibility genes in Crohn's disease (CD) is CARD15. Our study examined the relationship between peripheral CARD15 expression and phenotype and duration of CD, treatment methods and inflammatory indices. Sixty patients with CD and 30 healthy volunteers as controls were enrolled in the study. Total RNA was isolated from peripheral blood mononuclear cells (PBMCs) with E.Z.N.A. Total RNA Kit (Omega Bio-tek) then quantitative real-time PCR was performed on the ABI Prism 7900 HT Real-Time PCR System. CARD15 gene expression in PBMCs in CD was significantly higher than in the control group. The highest level of gene expression was found in CD patients in the fourth decade of life. The mRNA level of the CARD15 gene was higher in patients with disease duration between 12 and 60 months. A positive correlation was found between erythrocyte sedimentation rate (ESR) and gene expression level. Gene expression increased with increasing level of C-reactive protein and ESR, but it was not statistically significant. CARD15 expression significantly decreased in CD patients treated with anti-TNFα agents compared to azathioprine or steroid treatment groups. Expression of the CARD15 gene in Crohn›s disease is higher than in healthy individuals. Disease duration and age of patients seem to be the most important factors influencing CARD15 expression.

[Is therapy with local infiltrations feasible in primary care consultations?].

PubMed

Magaña Loarte, J E; Pérez Franco, J; Sánchez Sánchez, G

1999-01-01

To study the feasibility of local infiltration in primary care consultations. Before-and-after intervention study. Two clinics at an urban health centre. Patients diagnosed with pathology of tender areas and treated with corticosteroid infiltration between May 1997 and May 1998. Corticoid infiltration plus local anaesthetic. Weekly check-up. Analysis of the variables: sex, age, diagnosis, time elapsed between indication and start of treatment, subjective assessment of pain before and after treatment (VRS scale), number of infiltrations per patient, side-effects. Evaluation of overall and individual effectiveness. 41 patients were infiltrated. Average age was 58. Most common pathologies were: rotary joint tendinitis (48.7%), anserine bursitis (24.4%), plantar fasciitis (7.3%). Average number of infiltrations per pathology: 1.3. Mean waiting time: 3.5 days. Comparison of pain by means of VRS (range 0-5) before and after treatment used the Wilcoxon test, with a statistically significant difference and p < 0.001 (z = -5.5109). For 35 patients (85.4%), pain was solved very well (values 0 and 1 on the VRS). For 3 patients (7.3%), improvement was moderate; and for 3 (7.3%) there was no improvement. 1. Treatment with local infiltration of corticosteroids is effective in dealing with pain, and is an alternative to treatment with NSAIDs. 2. It is feasible in primary care, and there are many advantages if the general practitioner employs this therapeutic technique.

Protective Effect of Free and Bound Polyphenol Extracts from Ginger (Zingiber officinale Roscoe) on the Hepatic Antioxidant and Some Carbohydrate Metabolizing Enzymes of Streptozotocin-Induced Diabetic Rats

PubMed Central

Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin; Ashafa, Anofi Omotayo Tom

2013-01-01

This study investigated the hepatoprotective effects of polyphenols from Zingiber officinale on streptozotocin-induced diabetic rats by assessing liver antioxidant enzymes, carbohydrate-metabolizing enzymes and liver function indices. Initial oral glucose tolerance test was conducted using 125 mg/kg, 250 mg/kg, and 500 mg/kg body weight of both free and bound polyphenols from Z. officinale. 28 day daily oral administration of 500 mg/kg body weight of free and bound polyphenols from Z. officinale to streptozotocin-induced (50 mg/kg) diabetic rats significantly reduced (P < 0.05) the fasting blood glucose compared to control groups. There was significant increase (P < 0.05) in the antioxidant enzymes activities in the animals treated with both polyphenols. Similarly, the polyphenols normalised the activities of some carbohydrate metabolic enzymes (hexokinase and phosphofructokinase) in the liver of the rats treated with it and significantly reduced (P < 0.05) the activities of liver function enzymes. The results from the present study have shown that both free and bound polyphenols from Z. officinale especially the free polyphenol could ameliorate liver disorders caused by diabetes mellitus in rats. This further validates the use of this species as medicinal herb and spice by the larger population of Nigerians. PMID:24367390

Protective Effect of Free and Bound Polyphenol Extracts from Ginger (Zingiber officinale Roscoe) on the Hepatic Antioxidant and Some Carbohydrate Metabolizing Enzymes of Streptozotocin-Induced Diabetic Rats.

PubMed

Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin; Ashafa, Anofi Omotayo Tom

2013-01-01

This study investigated the hepatoprotective effects of polyphenols from Zingiber officinale on streptozotocin-induced diabetic rats by assessing liver antioxidant enzymes, carbohydrate-metabolizing enzymes and liver function indices. Initial oral glucose tolerance test was conducted using 125 mg/kg, 250 mg/kg, and 500 mg/kg body weight of both free and bound polyphenols from Z. officinale. 28 day daily oral administration of 500 mg/kg body weight of free and bound polyphenols from Z. officinale to streptozotocin-induced (50 mg/kg) diabetic rats significantly reduced (P < 0.05) the fasting blood glucose compared to control groups. There was significant increase (P < 0.05) in the antioxidant enzymes activities in the animals treated with both polyphenols. Similarly, the polyphenols normalised the activities of some carbohydrate metabolic enzymes (hexokinase and phosphofructokinase) in the liver of the rats treated with it and significantly reduced (P < 0.05) the activities of liver function enzymes. The results from the present study have shown that both free and bound polyphenols from Z. officinale especially the free polyphenol could ameliorate liver disorders caused by diabetes mellitus in rats. This further validates the use of this species as medicinal herb and spice by the larger population of Nigerians.

Priming of Wheat with the Green Leaf Volatile Z-3-Hexenyl Acetate Enhances Defense against Fusarium graminearum But Boosts Deoxynivalenol Production1

PubMed Central

Ameye, Maarten; Audenaert, Kris; De Zutter, Nathalie; Steppe, Kathy; Van Meulebroek, Lieven; Vanhaecke, Lynn; De Vleesschauwer, David; Haesaert, Geert; Smagghe, Guy

2015-01-01

Priming refers to a mechanism whereby plants are sensitized to respond faster and/or more strongly to future pathogen attack. Here, we demonstrate that preexposure to the green leaf volatile Z-3-hexenyl acetate (Z-3-HAC) primed wheat (Triticum aestivum) for enhanced defense against subsequent infection with the hemibiotrophic fungus Fusarium graminearum. Bioassays showed that, after priming with Z-3-HAC, wheat ears accumulated up to 40% fewer necrotic spikelets. Furthermore, leaves of seedlings showed significantly smaller necrotic lesions compared with nonprimed plants, coinciding with strongly reduced fungal growth in planta. Additionally, we found that F. graminearum produced more deoxynivalenol, a mycotoxin, in the primed treatment. Expression analysis of salicylic acid (SA) and jasmonic acid (JA) biosynthesis genes and exogenous methyl salicylate and methyl jasmonate applications showed that plant defense against F. graminearum is sequentially regulated by SA and JA during the early and later stages of infection, respectively. Interestingly, analysis of the effect of Z-3-HAC pretreatment on SA- and JA-responsive gene expression in hormone-treated and pathogen-inoculated seedlings revealed that Z-3-HAC boosts JA-dependent defenses during the necrotrophic infection stage of F. graminearum but suppresses SA-regulated defense during its biotrophic phase. Together, these findings highlight the importance of temporally separated hormone changes in molding plant health and disease and support a scenario whereby the green leaf volatile Z-3-HAC protects wheat against Fusarium head blight by priming for enhanced JA-dependent defenses during the necrotrophic stages of infection. PMID:25713338

Spontaneous hepatic repopulation in transgenic mice expressing mutant human α1-antitrypsin by wild-type donor hepatocytes.

PubMed

Ding, Jianqiang; Yannam, Govardhana R; Roy-Chowdhury, Namita; Hidvegi, Tunda; Basma, Hesham; Rennard, Stephen I; Wong, Ronald J; Avsar, Yesim; Guha, Chandan; Perlmutter, David H; Fox, Ira J; Roy-Chowdhury, Jayanta

2011-05-01

α1-Antitrypsin deficiency is an inherited condition that causes liver disease and emphysema. The normal function of this protein, which is synthesized by the liver, is to inhibit neutrophil elastase, a protease that degrades connective tissue of the lung. In the classical form of the disease, inefficient secretion of a mutant α1-antitrypsin protein (AAT-Z) results in its accumulation within hepatocytes and reduced protease inhibitor activity, resulting in liver injury and pulmonary emphysema. Because mutant protein accumulation increases hepatocyte cell stress, we investigated whether transplanted hepatocytes expressing wild-type AAT might have a competitive advantage relative to AAT-Z-expressing hepatocytes, using transgenic mice expressing human AAT-Z. Wild-type donor hepatocytes replaced 20%-98% of mutant host hepatocytes, and repopulation was accelerated by injection of an adenovector expressing hepatocyte growth factor. Spontaneous hepatic repopulation with engrafted hepatocytes occurred in the AAT-Z-expressing mice even in the absence of severe liver injury. Donor cells replaced both globule-containing and globule-devoid cells, indicating that both types of host hepatocytes display impaired proliferation relative to wild-type hepatocytes. These results suggest that wild-type hepatocyte transplantation may be therapeutic for AAT-Z liver disease and may provide an alternative to protein replacement for treating emphysema in AAT-ZZ individuals.

SU-E-T-36: An Investigation of the Margin From CTV to PTV Using Retraction Method for Cervical Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, D; Chen, J; Hao, Y

Purpose: This work employs the retraction method to compute and evaluate the margin from CTV to PTV based on the influence of target dosimetry of setup errors during cervical carcinoma patients treatment. Methods: Sixteen patients with cervical cancer were treated by Elekta synergy and received a total of 305 KV-CBCT images. The iso-center of the initial plans were changed according to the setup errors to simulate radiotherapy and then recalculated the dose distribution using leaf sequences and MUs for individual plans. The margin from CTV to PTV will be concluded both by the method of retracting (Fixed the PTV ofmore » the original plan, and retract PTV a certain distance defined as simulative organization CTVnx. The minimum distance value from PTV to CTVnx which get specified doses, namely guarantee at least 99% CTV volume can receive the dose of 95%, is the margin CTV to PTV we found) and the former formula method. Results: (1)The setup errors of 16 patients in X, Y and Z directions were(1.13±2.94) mm,(−1.63±7.13) mm,(−0.65±2.25) mm. (2) The distance between CTVx and PTV was 5, 9 and 3mm in X, Y and Z directions According to 2.5+0.7σ. (3) Transplantation plans displayed 99% of CTVx10- CTVx7 and received 95% of prescription dose, but CTVx6- CTVx3 departed from standard of clinic.In order to protect normal tissues, we selected 7mm as the minimum value of the margin from CTV to PTV. Conclusion: We have test an retraction method for the margin from CTV to PTV evaluation. The retraction method is more reliable than the formula method for calculating the margin from the CTV to the PTV, because it represented practice of treatment, and increasing a new method in this field.« less

Meconium ileus in patients with cystic fibrosis is not a risk factor for clinical deterioration and survival: the Israeli Multicenter Study.

PubMed

Efrati, Ori; Nir, Judith; Fraser, Drora; Cohen-Cymberknoh, Malena; Shoseyov, David; Vilozni, Daphna; Modan-Moses, Dalit; Levy, Ran; Szeinberg, Amir; Kerem, Eitan; Rivlin, Joseph

2010-02-01

Patients with cystic fibrosis (CF) presenting with meconium ileus (MI) tend to have worse outcomes than those without MI. We evaluated the clinical characteristics and survival rates among Israeli patients with CF with and without MI after a prolonged follow-up (15-30 years). A multicenter retrospective study. Forty-nine patients with CF, representing 13.8% of all patients with CF in Israel, presented with MI (current age 17.4 +/- 7.9 years) between 1975 and 2006. They were compared with 38 patients with CF (current age 19.3 +/- 6.5 years) without MI matched by sex and CF transmembrane conductance regulator mutation. A total of 66.2% of patients with MI and 73.6% without MI were followed for a prolonged period (24.9 +/- 2.7 years). Of the patients with MI, 31 were managed operatively, whereas 18 were treated successfully with gastrograffin enema, with similar clinical outcomes. Five patients in the MI group and 3 in the control group died during the study period. Bacterial colonization, z score of body mass index, and pulmonary function tests were similar in patients with and without MI in the long term. In younger patients, many clinical parameters were more prevalent in patients with MI (P = 0.004). However, these differences disappeared after the long-term follow-up (up to 31-years). Patients with CF presenting with MI had similar pulmonary function and nutritional status, as well as survival rates as did the control patients without MI. The distinct genetic mutation found in our population may explain in part the favorable results compared with other studies. In addition, it seems that early diagnosis and treatment of MI in patients with CF may be beneficial, subsequently lowering morbidity, and increasing survival.

Platysma Flap with Z-Plasty for Correction of Post-Thyroidectomy Swallowing Deformity

PubMed Central

Jeon, Min Kyeong; Kang, Seok Joo

2013-01-01

Background Recently, the number of thyroid surgery cases has been increasing; consequently, the number of patients who visit plastic surgery departments with a chief complaint of swallowing deformity has also increased. We performed a scar correction technique on post-thyroidectomy swallowing deformity via platysma flap with Z-plasty and obtained satisfactory aesthetic and functional outcomes. Methods The authors performed operations upon 18 patients who presented a definitive retraction on the swallowing mechanism as an objective sign of swallowing deformity, or throat or neck discomfort on swallowing mechanism such as sensation of throat traction as a subjective sign after thyoridectomy from January 2009 till June 2012. The scar tissue that adhered to the subcutaneous tissue layer was completely excised. A platysma flap as mobile interference was applied to remove the continuity of the scar adhesion, and additionally, Z-plasty for prevention of midline platysma banding was performed. Results The follow-up results of the 18 patients indicated that the definitive retraction on the swallowing mechanism was completely removed. Throat or neck discomfort on the swallowing mechanism such as sensation of throat traction also was alleviated in all 18 patients. When preoperative and postoperative Vancouver scar scales were compared to each other, the scale had decreased significantly after surgery (P<0.05). Conclusions Our simple surgical method involved the formation of a platysma flap with Z-plasty as mobile interference for the correction of post-thyroidectomy swallowing deformity. This method resulted in aesthetically and functionally satisfying outcomes. PMID:23898442

Misregulation effect of a novel allelic variant in the Z promoter region found in cis with the CYP21A2 p.P482S mutation: implications for 21-hydroxylase deficiency.

PubMed

Fernández, Cecilia S; Bruque, Carlos D; Taboas, Melisa; Buzzalino, Noemí D; Espeche, Lucia D; Pasqualini, Titania; Charreau, Eduardo H; Alba, Liliana G; Ghiringhelli, Pablo D; Dain, Liliana

2015-09-01

The aim of the current study was to search for the presence of genetic variants in the CYP21A2 Z promoter regulatory region in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Screening of the 10 most frequent pseudogene-derived mutations was followed by direct sequencing of the entire coding sequence, the proximal promoter, and a distal regulatory region in DNA samples from patients with at least one non-determined allele. We report three non-classical patients that presented a novel genetic variant-g.15626A>G-within the Z promoter regulatory region. In all the patients, the novel variant was found in cis with the mild, less frequent, p.P482S mutation located in the exon 10 of the CYP21A2 gene. The putative pathogenic implication of the novel variant was assessed by in silico analyses and in vitro assays. Topological analyses showed differences in the curvature and bendability of the DNA region bearing the novel variant. By performing functional studies, a significantly decreased activity of a reporter gene placed downstream from the regulatory region was found by the G transition. Our results may suggest that the activity of an allele bearing the p.P482S mutation may be influenced by the misregulated CYP21A2 transcriptional activity exerted by the Z promoter A>G variation.

A dexamethasone-regulated gene signature is prognostic for poor survival in glioblastoma patients

PubMed Central

Luedi, Markus M.; Singh, Sanjay K.; Mosley, Jennifer C.; Hatami, Masumeh; Gumin, Joy; Sulman, Erik P.; Lang, Frederick F.; Stueber, Frank; Zinn, Pascal O.; Colen, Rivka R.

2016-01-01

Background Dexamethasone is reported to induce both tumor-suppressive and tumor-promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. Methods We utilized three independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in TCGA and REMBRANDT databases. In silico connectivity Map analysis identified camptothecin as antagonist to dexamethasone induced negative effects. Results Pathway analyses predicted an activation of dexamethasone network (z-score:2.908). Top activated canonical pathways included ‘role of BRCA1 in DNA damage response’ (p=1.07E-04). GSCs were protected against temozolomide-induced apoptosis when co-incubated with dexamethasone. Altered cellular functions included cell-movement, cell-survival, and apoptosis with z-scores of 2.815, 5.137, and −3.122 respectively. CEBPB was activated in a dose dependent manner specifically in slow-dividing ‘stem-like’ cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk score had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone effects. Conclusions Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects. PMID:27653222

Do self- or parent-reported dietary, physical activity, and sedentary behaviors predict worsening obesity in children?

PubMed

Dorsey, Karen B; Mauldon, Maria; Magraw, Ruth; Yu, Sunkyung; Krumholz, Harlan M

2010-10-01

To determine whether information gathered during routine healthcare visits regarding obesity related risk factors and risk behaviors predicts increases in BMI z-score over time among overweight and obese children. Medical records from 168 overweight and 441 obese patients seen for repeated visits between September 2003 and April 2006 were examined for reported dietary, physical activity, and sedentary behaviors, family history of obesity and diabetes mellitus, documented Acanthosis nigricans, and BMI values. Random-effects regression analysis was done to determine whether demographic, familial, or behavioral data predicted changes in BMI z-score over time. The presence of A nigricans and a family history of obesity were associated with an increase in BMI z-score (beta=0.56, SE=0.09, P<.001 and beta=0.31, SE=0.13, P=.021). These risk factors explained 8% and 7% of the variation in BMI z-score respectively. Self- or parent-reported dietary and physical activity behaviors did not predict change in BMI z-score. Our findings suggest that the risk factors and self- or parent-reported risk behaviors routinely assessed by pediatric clinicians have limited ability to predict future growth trends, demonstrating the difficulty in determining which patients have the greatest risk of progression of obesity. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Treatment of patella baja by a modified Z-plasty.

PubMed

Guido, Wierer; Christian, Hoser; Elmar, Herbst; Elisabeth, Abermann; Christian, Fink

2016-09-01

The purpose of this study was to evaluate the efficiency of a modified Z-plasty for patellar tendon lengthening for the treatment of patella baja. Rather than adapting only two tendon reins according to the conventional Z-plasty method, the modified Z-plasty provides four reins to enable multifold overlapping of the tendon tissue. Between 2010 and 2012, a modified Z-plasty procedure was performed in four patients suffering from patella baja. Physical examinations and standardized scoring instruments served as the evaluation measures. The median preoperative CD ratio of 0.53 (range 0.43-0.62) was corrected to 1.03 (range 1-1.06) after a median follow-up of 34 months (range 23-41 months). The median preoperative flexion of 108° (range 80-135°) improved to 143° (range 110-145°) compared with the flexion of 145° (range 140-145°) of the unaffected knee. No patients showed any signs of extension lag. The median Lysholm score improved from 49 (range 22-80) to 91 (range 67-95), and the Tegner activity level improved from 2 (range 0-6) to 6 (range 2-6). The median VAS status for pain decreased from an average of 8.5 (range 4-10) to 1 (range 0-2). No complications were observed. The modified Z-plasty procedure is a valuable technique for the treatment of patella baja, especially if allografts are not available. This procedure allowed for early mobilization and achieved excellent clinical results. IV.

Management of acute cough by Zataria multiflora Boiss as an alternative treatment.

PubMed

Mahboubi, Mohaddese

2018-01-01

Cough, as a defensive reflux mechanism, removes foreign objects and secretions from bronchi and bronchioles of airways. Zataria multiflora is a popular plant for treatment of cough in Iranian traditional medicine. The aim of this review was to evaluate the potency of Z. multiflora as an alternative treatment in management of acute cough and its possible mechanisms of action. Here the authors compiled information about Z. multiflora in the treatment of cough from all accessible resources and books. The results of this investigation showed that there were five clinical studies that evaluated the efficacy of Z. multiflora essential oil or extract alone (n = 1), in combination with Althaea officinalis (n = 2) or Foeniculum vulgare essential oil (n = 1), in the form of syrup (n = 3), oral drop (n = 1) and soft capsule (n = 1), for the treatment of acute cough in comparison with placebo or synthetic drugs (bromhexine, dextromethorphan and clobutinol). All clinical studies confirmed the efficacy of Z. multiflora in the amelioration of acute cough in pediatric (n = 1) and adult patients (n = 4) without any adverse effects. Different mechanisms, such as anti-inflammatory, analgesic, antimicrobial, relaxant and immune-enhancement, may be responsible for the efficacy of Z. multiflora in cough relief. Other clinical trials can be performed with Z. multiflora in combination with ivy leaf extract or primrose root extract on patients with cough. Copyright © 2017 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

Growth and Obesity Among Older Single Ventricle Patients Presenting for Fontan Conversion.

PubMed

Freud, Lindsay R; Webster, Gregory; Costello, John M; Tsao, Sabrina; Rychlik, Karen; Backer, Carl L; Deal, Barbara J

2015-10-01

Long-term growth outcomes and the prevalence of obesity among older single ventricle (SV) patients have not been well characterized. We investigated these parameters, as well as the impact of obesity on survival, in an older cohort of SV patients presenting for Fontan conversion. We analyzed preoperative height, weight, and body mass index (BMI) of patients who underwent Fontan conversion. Overweight and obese were defined as BMI ≥85 percentile and ≥95 percentile for patients <20 years and BMI 25 to 30 kg/m(2) and ≥30 kg/m(2) for patients ≥20 years, respectively. Postoperative transplant-free survival was assessed among obese, overweight, and normal weight patients. We evaluated 139 patients presenting for Fontan conversion at a median age of 23.2 years. Patients had shorter stature compared to the normal population (mean Z score -0.6, P < .001). Younger patients had lower BMI compared to the normal population (<20 years: mean Z score -0.5, P = .02), while older patients had elevated BMI (≥20 years: mean Z score +0.4, P < .001). The mean BMI among older patients approached overweight at 24.6 kg/m(2). The prevalence of obesity increased with advancing age, with 36% overweight and 14% obese at >30 years. At a median of 8.2 years following Fontan conversion, obesity and overweight status were not associated with transplant-free survival. Older SV patients presenting for Fontan conversion had shorter stature compared to the normal population as well as a high prevalence of overweight and obesity. Although there was no relationship between weight status and early postoperative survival, further investigation of long-term outcomes is warranted. © The Author(s) 2015.

The effect of ezetimibe-statin combination on steroid hormone production in men with coronary artery disease and low cholesterol levels.

PubMed

Krysiak, Robert; Kowalska, Beata; Żmuda, Witold; Okopień, Bogusław

2015-04-01

Aggressive statin treatment was found to slightly reduce testosterone production. The aim of this study was to compare the effects of ezetimibe-statin combination and high-dose statin therapy on testicular and adrenal cortex function in men with LDL cholesterol levels below 70 mg/dL. The study included 26 adult men with coronary artery disease. Twelve of these patients did not tolerate high-dose statin therapy and were treated with lower doses of a statin plus ezetimibe. Fourteen patients tolerating high-dose simvastatin or rosuvastatin treatment continued high-dose statin therapy throughout the study period. Plasma lipids, glucose homeostasis markers and plasma levels of testosterone, cortisol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, gonadotropins and ACTH, as well as urine free cortisol were assessed at baseline and after 16 weeks of treatment. Replacing high-dose statin therapy with ezetimibe/statin combination therapy reduced plasma levels of LH by 32% (p=0.043), as well as increased plasma levels of testosterone by 20% (p=0.038). Ezetimibe/statin combination did not induce any significant changes in plasma levels or urine excretion of the remaining hormones. At the end of the study, plasma LH levels were higher, while plasma testosterone levels were lower in patients receiving the combination therapy than in those treated only with high-dose statin. Our results indicate that ezetimibe combined with moderate statin dose exerts a less pronounced effect on testicular function in comparison with high-dose statin therapy. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Long-Term Correction of Sandhoff Disease Following Intravenous Delivery of rAAV9 to Mouse Neonates

PubMed Central

Walia, Jagdeep S; Altaleb, Naderah; Bello, Alexander; Kruck, Christa; LaFave, Matthew C; Varshney, Gaurav K; Burgess, Shawn M; Chowdhury, Biswajit; Hurlbut, David; Hemming, Richard; Kobinger, Gary P; Triggs-Raine, Barbara

2015-01-01

GM2 gangliosidoses are severe neurodegenerative disorders resulting from a deficiency in β-hexosaminidase A activity and lacking effective therapies. Using a Sandhoff disease (SD) mouse model (Hexb−/−) of the GM2 gangliosidoses, we tested the potential of systemically delivered adeno-associated virus 9 (AAV9) expressing Hexb cDNA to correct the neurological phenotype. Neonatal or adult SD and normal mice were intravenously injected with AAV9-HexB or –LacZ and monitored for serum β-hexosaminidase activity, motor function, and survival. Brain GM2 ganglioside, β-hexosaminidase activity, and inflammation were assessed at experimental week 43, or an earlier humane end point. SD mice injected with AAV9-LacZ died by 17 weeks of age, whereas all neonatal AAV9-HexB–treated SD mice survived until 43 weeks (P < 0.0001) with only three exhibiting neurological dysfunction. SD mice treated as adults with AAV9-HexB died between 17 and 35 weeks. Neonatal SD-HexB–treated mice had a significant increase in brain β-hexosaminidase activity, and a reduction in GM2 ganglioside storage and neuroinflammation compared to adult SD-HexB– and SD-LacZ–treated groups. However, at 43 weeks, 8 of 10 neonatal-HexB injected control and SD mice exhibited liver or lung tumors. This study demonstrates the potential for long-term correction of SD and other GM2 gangliosidoses through early rAAV9 based systemic gene therapy. PMID:25515709

Modulation of mitochondrial activity in HaCaT keratinocytes by the cell penetrating peptide Z-Gly-RGD(DPhe)-mitoparan.

PubMed

Richardson, Adam; Muir, Lewis; Mousdell, Sasha; Sexton, Darren; Jones, Sarah; Howl, John; Ross, Kehinde

2018-01-30

Biologically active cell penetrating peptides (CPPs) are an emerging class of therapeutic agent. The wasp venom peptide mastoparan is an established CPP that modulates mitochondrial activity and triggers caspase-dependent apoptosis in cancer cells, as does the mastoparan analogue mitoparan (mitP). Mitochondrial depolarisation and activation of the caspase cascade also underpins the action of dithranol, a topical agent for treatment of psoriasis. The effects of a potent mitP analogue on mitochondrial activity were therefore examined to assess its potential as a novel approach for targeting mitochondria for the treatment of psoriasis. In HaCaT keratinocytes treated with the mitP analogue Z-Gly-RGD(DPhe)-mitP for 24 h, a dose-dependent loss of mitochondrial activity was observed using the methyl-thiazolyl-tetrazolium (MTT) assay. At 10 μmol L -1 , MTT activity was less than 30% that observed in untreated cells. Staining with the cationic dye JC-1 suggested that Z-Gly-RGD(DPhe)-mitP also dissipated the mitochondrial membrane potential, with a threefold increase in mitochondrial depolarisation levels. However, caspase activity appeared to be reduced by 24 h exposure to Z-Gly-RGD(DPhe)-mitP treatment. Furthermore, Z-Gly-RGD(DPhe)-mitP treatment had little effect on overall cell viability. Our findings suggest Z-Gly-RGD(DPhe)-mitP promotes the loss of mitochondrial activity but does not appear to evoke apoptosis in HaCaT keratinocytes.

X-LAG: How did they grow so tall?

PubMed

Beckers, Albert; Rostomyan, Liliya; Potorac, Iulia; Beckers, Pablo; Daly, Adrian F

2017-06-01

X-linked acrogigantism (XLAG) is a new, pediatric-onset genetic syndrome, due to Xq26.3 microduplications encompassing the GPR101 gene. XLAG has a remarkably distinct phenotype with disease onset occurring before the age of 5 in all cases described to date, which is significantly younger than in other forms of pituitary gigantism. These patients have mixed GH and prolactin positive adenomas and/or mixed-cell hyperplasia and highly elevated levels of GH/IGF-1 and prolactin. Given their particularly young age of onset, the significant GH hypersecretion can lead to a phenotype of severe gigantism with very advanced age-specific height Z-scores. If not adequately treated in childhood, this condition results in extreme final adult height. XLAG has a clinical course that is highly similar to some of the tallest people with gigantism in history. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Surgical techniques in radiation induced temporal lobe necrosis in nasopharyngeal carcinoma patients.

PubMed

Alfotih, Gobran Taha Ahmed; Zheng, Mei Guang; Cai, Wang Qing; Xu, Xin Ke; Hu, Zhen; Li, Fang Cheng

2016-01-01

Radiation induced brain injury ranges from acute reversible edema to late, irreversible radiation necrosis. Radiation induced temporal lobe necrosis is associated with permanent neurological deficits and occasionally progresses to death. We present our experience with surgery on radiation induced temporal lobe necrosis (RTLN) in nasopharyngeal carcinoma (NPC) patients with special consideration of clinical presentation, surgical technique, and outcomes. This retrospective study includes 12 patients with RTLN treated by the senior author between January 2010 and December 2014. Patients initially sought medical treatment due to headache; other symptoms were hearing loss, visual deterioration, seizure, hemiparesis, vertigo, memory loss and agnosia. A temporal approach through a linear incision was performed for all cases. RTLN was found in one side in 7 patients, and bilaterally in 5. 4 patients underwent resection of necrotic tissue bilaterally and 8 patients on one side. No death occurred in this series of cases. There were no post-operative complications, except 1 patient who developed aseptic meningitis. All 12 patients were free from headache. No seizure occurred in patients with preoperative epilepsy. Other symptoms such as hemiparesis and vertigo improved in all patients. Memory loss, agnosia and hearing loss did not change post-operatively in all cases. The follow-up MR images demonstrated no recurrence of necrotic lesions in all 12 patients. Neurosurgical intervention through a temporal approach with linear incision is warranted in patients with radiation induced temporal lobe necrosis with significant symptoms and signs of increased intracranial pressure, minimum space occupying effect on imaging, or neurological deterioration despite conservative management. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

A New Frontier for Cardiac Monitoring

NASA Technical Reports Server (NTRS)

2001-01-01

CardioDynamics International Corporation (CDIC) has created the BioZ(TM) System through a Small Business Innovation Research (SBIR) award from Johnson Space Center, providing patients and physicians with a cost-effective and highly accurate monitoring system.The BioZ non-invasive heart monitor is based on a technology known as Impedance Cardiography (ICG). BioZ provides the physician with vital information about the heart's ability to deliver blood to the body, the force one's heart exerts with each beat, and the amount of fluid in the chest. Specially designed bioimpedance sensors placed on the neck and chest monitor 12 different parameters, including cardiac output, contractility, systemic vascular resistance, and thoracic fluid content. These sensors monitor the electrical conductivity of the body-information that is converted into blood flow data and is displayed in real time on a monitoring screen. BioZ.com(TM) and BioZ.pc(TM) are two additional products that incorporate the same sensors present in the original BioZ system. The "com" in BioZ.com stands for cardiac output monitor. This fully integrated system is essentially a smaller version of the BioZ, combining the same abilities with a compact, lightweight design, while providing greater portability.

Protein Z efficiently depletes thrombin generation in disseminated intravascular coagulation with poor prognosis.

PubMed

Lee, Nuri; Kim, Ji-Eun; Gu, Ja-Yoon; Yoo, Hyun Ju; Kim, Inho; Yoon, Sung-Soo; Park, Seonyang; Han, Kyou-Sup; Kim, Hyun Kyung

2016-01-01

Disseminated intravascular coagulation (DIC) is characterized by consumption of coagulation factors and anticoagulants. Thrombin generation assay (TGA) gives useful information about global hemostatic status. We developed a new TGA system that anticoagulant addition can deplete thrombin generation in plasma, which may reflect defective anticoagulant system in DIC. TGAs were measured on the calibrated automated thrombogram with and without thrombomodulin or protein Z in 152 patients who were suspected of having DIC, yielding four parameters including lag time, endogenous thrombin potential, peak thrombin and time-to-peak in each experiment. Nonsurvivors showed significantly prolonged lag time and time-to-peak in TGA-protein Z system, which was performed with added protein Z. In multivariate Cox regression analysis, lag time and time-to-peak in TGA system were significant independent prognostic factors. In TGA-protein Z system, lag time and time-to-peak were revealed as independent prognostic factors of DIC. Protein Z addition could potentiate its anticoagulant effect in DIC with poor prognosis, suggesting the presence of defective protein Z system. The prolonged lag time and time-to-peak in both TGA and TGA-protein Z systems are expected to be used as independent prognostic factors of DIC.

Dynamic Contrast-Enhanced Perfusion Area-Detector CT: Preliminary Comparison of Diagnostic Performance for N Stage Assessment With FDG PET/CT in Non-Small Cell Lung Cancer.

PubMed

Ohno, Yoshiharu; Fujisawa, Yasuko; Sugihara, Naoki; Kishida, Yuji; Seki, Shinichiro; Koyama, Hisanobu; Yoshikawa, Takeshi

2017-11-01

The objective of our study was to directly compare the capability of dynamic first-pass contrast-enhanced (CE) perfusion area-detector CT (ADCT) and FDG PET/CT for differentiation of metastatic from nonmetastatic lymph nodes and assessment of N stage in patients with non-small cell lung carcinoma (NSCLC). Seventy-seven consecutive patients, 45 men (mean age ± SD, 70.4 ± 5.9 years) and 32 women (71.2 ± 7.7 years), underwent dynamic first-pass CE-perfusion ADCT at two or three different positions for covering the entire thorax, FDG PET/CT, surgical treatment, and pathologic examination. From all ADCT data for each of the subjects, a whole-chest perfusion map was computationally generated using the dual- and single-input maximum slope and Patlak plot methods. For quantitative N stage assessment, perfusion parameters and the maximum standardized uptake value (SUV max ) for each lymph node were determined by measuring the relevant ROI. ROC curve analyses were performed for comparing the diagnostic capability of each of the methods on a per-node basis. N stages evaluated by each of the indexes were then statistically compared with the final pathologic diagnosis by means of chi-square and kappa statistics. The area under the ROC curve (A z ) values of systemic arterial perfusion (A z = 0.89), permeability surface (A z = 0.78), and SUV max (A z = 0.85) were significantly larger than the A z values of total perfusion (A z = 0.70, p < 0.05) and distribution volume (A z = 0.55, p < 0.05). For each of the threshold values, agreement for systemic arterial perfusion calculated using the dual-input maximum slope model was substantial (κ = 0.70, p < 0.0001), and agreement for SUV max was moderate (κ = 0.60, p < 0.0001). Dynamic first-pass CE-perfusion ADCT is as useful as FDG PET/CT for the differentiation of metastatic from nonmetastatic lymph nodes and assessment of N stage in patients with NSCLC.

ATZ11 Recognizes Not Only Z-α1-Antitrypsin-Polymers and Complexed Forms of Non-Z-α1-Antitrypsin but Also the von Willebrand Factor

PubMed Central

Yadegari, Hamideh; Driesen, Julia; Kirfel, Jutta; Neuhaus, Thomas; Steiner, Susanne; Esch, Christiane; Bedorf, Jörg; Hertfelder, Hans-Jörg; Fischer, Hans-Peter

2014-01-01

Aims The ATZ11 antibody has been well established for the identification of α1-anti-trypsin (AAT) molecule type PiZ (Z-AAT) in blood samples and liver tissue. In this study, we systematically analyzed the antibody for additional binding sites in human tissue. Methods and Results Ultrastructural ATZ11 binding was investigated immunoelectron microscopically in human umbilical vein endothelial cells (HUVECs) and in platelets of a healthy individual. Human embryonic kidney (HEK293) cells were transiently transfected with Von Willebrand factor (VWF) and analyzed immunocytochemically using confocal microscopy and SDS-PAGE electrophoresis followed by western blotting (WB). Platelets and serum samples of VWF-competent and VWF-deficient patients were investigated using native PAGE and SDS-PAGE electrophoresis followed by WB. The specificity of the ATZ11 reaction was tested immunohistochemically by extensive antibody-mediated blocking of AAT- and VWF-antigens. ATZ11-positive epitopes could be detected in Weibel-Palade bodies (WPBs) of HUVECs and α-granules of platelets. ATZ11 stains pseudo-WBP containing recombinant wild-type VWF (rVWF-WT) in HEK293 cells. In SDS-PAGE electrophoresis followed by WB, anti-VWF and ATZ11 both identified rVWF-WT. However, neither rVWF-WT-multimers, human VWF-multimers, nor serum proteins of VWF-deficient patients were detected using ATZ11 by WB, whereas anti-VWF antibody (anti-VWF) detected rVWF-WT-multimers as well as human VWF-multimers. In human tissue specimens, AAT-antigen blockade using anti-AAT antibody abolished ATZ11 staining of Z-AAT in a heterozygous AAT-deficient patient, whereas VWF-antigen blockade using anti-VWF abolished ATZ11 staining of endothelial cells and megakaryocytes. Conclusions ATZ11 reacts with cellular bound and denatured rVWF-WT and human VWF as shown using immunocytochemistry and subsequent confocal imaging, immunoelectron microscopy, SDS-PAGE and WB, and immunohistology. These immunoreactions are independent of the binding of Z-AAT-molecules and non-Z-AAT complexes. PMID:24646657

Fluid Mosaic Membranes and the Light Reactions of Photosynthesis.

ERIC Educational Resources Information Center

Hannay, Jack

1985-01-01

Discusses: (1) the fluid mosaic membrane structure and light reactions of photosynthesis as exemplified by the Hill and Bendall "Z-scheme"; (2) the arrangement of light-harvesting pigments, electron transport components, and ATP synthesis on chloroplast membranes; and (3) how these topics are treated in A-level textbooks. (JN)

Animal Models of Congenital Cardiomyopathies Associated With Mutations in Z-Line Proteins.

PubMed

Bang, Marie-Louise

2017-01-01

The cardiac Z-line at the boundary between sarcomeres is a multiprotein complex connecting the contractile apparatus with the cytoskeleton and the extracellular matrix. The Z-line is important for efficient force generation and transmission as well as the maintenance of structural stability and integrity. Furthermore, it is a nodal point for intracellular signaling, in particular mechanosensing and mechanotransduction. Mutations in various genes encoding Z-line proteins have been associated with different cardiomyopathies, including dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, and left ventricular noncompaction, and mutations even within the same gene can cause widely different pathologies. Animal models have contributed to a great advancement in the understanding of the physiological function of Z-line proteins and the pathways leading from mutations in Z-line proteins to cardiomyopathy, although genotype-phenotype prediction remains a great challenge. This review presents an overview of the currently available animal models for Z-line and Z-line associated proteins involved in human cardiomyopathies with special emphasis on knock-in and transgenic mouse models recapitulating the clinical phenotypes of human cardiomyopathy patients carrying mutations in Z-line proteins. Pros and cons of mouse models will be discussed and a future outlook will be given. J. Cell. Physiol. 232: 38-52, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Multiparametric magnetic resonance imaging for the assessment of extracapsular invasion and other staging parameters in patients with prostate cancer candidates for radical prostatectomy.

PubMed

Lista, F; Gimbernat, H; Cáceres, F; Rodríguez-Barbero, J M; Castillo, E; Angulo, J C

2014-06-01

the proper evaluation of the extracapsular extension (ECE), the invasion of seminal vesicles and regional lymph nodes are necessary to plan the treatment of localized prostate cancer. A model that assesses the risk of ECE in the specimen considering the clinical, histological and imaging findings is defined. prospective study in 85 patients with prostate cancer treated with radical prostatectomy. Prostate biopsy was performed 4 weeks before multiparametric study (mpMRI). mpMRI included T2-weighted endorectal magnetic resonance imaging (T2W-MRI), diffusion-weighted magnetic resonance imaging (DW-MRI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The apparent diffusion coefficient (ADC) was also measured. A study of consistency (k) was assessed comparing receiver operating characteristic (ROC) curve and area under the curve (AUC), which were obtained in each case (Z). Finally, a regression model was performed to predict ECE. the mean age was 63.7 ± 6.9 years and the mean value of PSA 12.6 ± 13.8. In 31.7% of cases, digital rectal examination was suspicious for malignancy. Prostatectomy specimen showed pT2a in 12 cases (14%), pT2b in 3 (3%), pT2c in 37 (43%), pT3a in 19(22%) and pT3b 14 cases (17%). ECE was evidenced in 33 (39%) of the specimens, seminal vesicle invasion in 14 (16.5%) and pelvic node involvement in 5 patients (6%). The consistency in the evaluation of ECE (image and pathological studies) was .35 for MRI (sensitivity .33, specificity .96) and .62 for mpMRI (sensitivity .58, specificity .98). Mean value of ADC was .76 ± .2 in patients with ECE. This value was not associated with Gleason score (P = .2) or with PSA value (P = .6). AUC value as predictor of ECE was of 65% for MRI, 78% for mpMRI and 50% ADC (Z = .008). Univariate analysis demonstrated that ECE probability increases with each Gleason score point, whilst this probability increases 1.06 times with each PSA point, and decreases .3 times with each point of ADC. Multivariate analysis confirmed that ADC value is a slight protective factor against ECE (OR = .01; CI 95% .002-.14). The consistency in the evaluation of seminal vesicles was .43 for MRI and .67 for mpMRI. AUC was 69% and 82% respectively (Z = .02). The consistency in the evaluation of positive lymph nodes was .4 for MRI and .7 for mpMRI. AUC was 68% and 88% respectively (Z = .36). multiparametric study allows to carry out a more proper preoperative evaluation of ECE than convectional MRI. The most reliable predictors of ECE are DW-MRI combined with DCE-MRI, ADC coefficient and Gleason score. The superiority of mpMRI is also demonstrated for detection of seminal vesicles invasion, but not for the evaluation of lymph nodes invasion. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Cross-regulation by CrcZ RNA controls anoxic biofilm formation in Pseudomonas aeruginosa

NASA Astrophysics Data System (ADS)

Pusic, Petra; Tata, Muralidhar; Wolfinger, Michael T.; Sonnleitner, Elisabeth; Häussler, Susanne; Bläsi, Udo

2016-12-01

Pseudomonas aeruginosa (PA) can thrive in anaerobic biofilms in the lungs of cystic fibrosis (CF) patients. Here, we show that CrcZ is the most abundant PA14 RNA bound to the global regulator Hfq in anoxic biofilms grown in cystic fibrosis sputum medium. Hfq was crucial for anoxic biofilm formation. This observation complied with an RNAseq based transcriptome analysis and follow up studies that implicated Hfq in regulation of a central step preceding denitrification. CrcZ is known to act as a decoy that sequesters Hfq during relief of carbon catabolite repression, which in turn alleviates Hfq-mediated translational repression of catabolic genes. We therefore inferred that CrcZ indirectly impacts on biofilm formation by competing for Hfq. This hypothesis was supported by the findings that over-production of CrcZ mirrored the biofilm phenotype of the hfq deletion mutant, and that deletion of the crcZ gene augmented biofilm formation. To our knowledge, this is the first example where competition for Hfq by CrcZ cross-regulates an Hfq-dependent physiological process unrelated to carbon metabolism.

Z-Guggulsterone Improves the Scopolamine-Induced Memory Impairments Through Enhancement of the BDNF Signal in C57BL/6J Mice.

PubMed

Chen, Zhuo; Huang, Chao; Ding, Wenbin

2016-12-01

Memory impairment is a common symptom in patients with neurodegenerative disorders, and its suppression could be beneficial to improve the quality of life of those patients. Z-guggulsterone, a compound extracted from the resin of plant Commiphora whighitii, exhibits numerous pharmacological effects in clinical practice, such as treatment of inflammation, arthritis, obesity and lipid metabolism disorders. However, the role and possible mechanism of Z-guggulsterone on brain-associated memory impairments are largely unknown. This issue was addressed in the present study in a memory impairment model induced by scopolamine, a muscarinic acetylcholine receptor antagonist, using the passive avoidance, Y-maze and Morris water maze tests. Results showed that scopolamine significantly decreased the step-through latency and spontaneous alternation of C57BL/6J mice in passive avoidance and Y-maze test, whereas increased the mean escape latency and decreased the swimming time in target quadrant in Morris water maze test. Pretreatment of mice with Z-guggulsterone at doses of 30 and 60 mg/kg effectively reversed the scopolamine-induced memory impairments. Mechanistic studies revealed that Z-guggulsterone pretreatment reversed the scopolamine-induced increase in acetylcholinesterase (AchE) activity, as well as decreases in brain-derived neurotrophic factor (BDNF) protein expression and cAMP response element-binding protein (CREB), extracellular regulated kinase 1/2 (ERK1/2) and protein kinase B (Akt) phosphorylation levels in the hippocampus and cortex. Inhibition of the BDNF signal, however, blocked the memory-enhancing effect of Z-guggulsterone. Therefore, these findings demonstrate that Z-guggulsterone attenuates the scopolamine-induced memory impairments mainly through activation of the CREB-BDNF signaling pathway, thereby exhibiting memory-improving effects.

Nutritional status of patients with ataxia-telangiectasia: A case for early and ongoing nutrition support and intervention.

PubMed

Ross, Lynda J; Capra, Sandra; Baguley, Brenton; Sinclair, Kate; Munro, Kate; Lewindon, Peter; Lavin, Martin

2015-08-01

Ataxia-telangiectasia (A-T) is a rare genomic syndrome resulting in severe disability. Chronic childhood disorders can profoundly influence growth and development. Nutrition-related issues in A-T are not well described, and there are no nutritional guidelines. This study investigated the nutrition-related characteristics and behaviours of Australian A-T patients attending a national clinic. A cross-sectional analysis of 13 A-T patients (nine females; aged: 4-23 years): nutritional status was assessed by anthropometric and body cell mass (BCM) calculations. Parents reported their child's diet history and physical and behavioural factors that affect nutrition including fatigue and need for assistance. Ten (77%) had short stature (height for age z scores <-1), and seven (54%) were underweight for height (weight/height z scores <-1). Significant malnutrition (BCM z scores <-2) was detected in nine (69%) including the one adult who was severely malnourished. Malnutrition increased significantly with age (BCM for height z scores and age, r = -0.937, P < 0.001). Eight (62%) patients ate poorly compared with estimated energy requirement for weight. Poor diet quality was characterised by high fat and sugar choices. Parents reported significant nutritional barriers as chronic tiredness and the need for care giver assistance with meals. This study confirms profound malnutrition in Australian A-T patients. Poor intakes and diet quality suggest the need for early nutrition intervention. Ongoing support for families and early discussions on tube feeding are required to address changing needs in childhood and likely nutritional decline into adulthood. A prospective study is required to assess feasibility and effectiveness of nutrition interventions in young people with A-T. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Diet and Anthropometrics of Children With Inflammatory Bowel Disease: A Comparison With the General Population.

PubMed

Diederen, Kay; Krom, Hilde; Koole, Jeffrey C D; Benninga, Marc A; Kindermann, Angelika

2018-04-25

There is a lack of knowledge regarding the diet of children with inflammatory bowel disease (IBD). Therefore, we investigated dietary intake in pediatric IBD compared to the general population and assessed anthropometrics and food avoidance. In this cross-sectional cohort study, patients younger than 18 years with IBD were included (2014-2017). Dietary intake (total energy, macro nutrients, food types) was assessed using a Food Frequency Questionnaire (FFQ) and compared with a matched reference population (n = 306). There were 102 patients included (55% male, median age 15.0 years). Median height Z-score was -0.39 (interquartile range [IQR]: -1.17 to 0.26). Growth failure (height Z-scores<-1.64) was present in 11% of patients. Median BMI Z-score was 0.36 (IQR: -0.70 to 0.96). Acute malnutrition (weight-for-height Z-score<-2) was present in 3% of patients. Energy intake was lower in pediatric IBD compared to the reference population (mean kilojoule/day: 8286 vs 9794, P < 0.001). Protein intake did not differ, while fat intake was higher in pediatric IBD (mean gram/day: 101 vs 91, P < 0.001), with higher intake of vegetable oils/fats. Carbohydrate intake was lower in pediatric IBD (mean gram/day: 267 vs 305, P < 0.001), with lower intake of food types high in sugar. Food avoidance was reported in 53% of patients, with frequent avoidance of spicy (46%), high-fat food (30%), and dairy (30%). The diet of children with IBD differs from the general pediatric population, with lower energy intake and high rates of food avoidance. Evaluation of the dietary intake alongside anthropometrics may be important to prevent nutrition deficiencies and promote health.

Power spectrum scale invariance identifies prefrontal dysregulation in paranoid schizophrenia.

PubMed

Radulescu, Anca R; Rubin, Denis; Strey, Helmut H; Mujica-Parodi, Lilianne R

2012-07-01

Theory and experimental evidence suggest that complex living systems function close to the boundary of chaos, with erroneous organization to an improper dynamical range (too stiff or chaotic) underlying system-wide dysregulation and disease. We hypothesized that erroneous organization might therefore also characterize paranoid schizophrenia, via optimization abnormalities in the prefrontal-limbic circuit regulating emotion. To test this, we acquired fMRI scans from 35 subjects (N = 9 patients with paranoid schizophrenia and N = 26 healthy controls), while they viewed affect-valent stimuli. To quantify dynamic regulation, we analyzed the power spectrum scale invariance (PSSI) of fMRI time-courses and computed the geometry of time-delay (Poincaré) maps, a measure of variability. Patients and controls showed distinct PSSI in two clusters (k(1) : Z = 4.3215, P = 0.00002 and k(2) : Z = 3.9441, P = 0.00008), localized to the orbitofrontal/medial prefrontal cortex (Brodmann Area 10), represented by β close to white noise in patients (β ≈ 0) and in the pink noise range in controls (β ≈ -1). Interpreting the meaning of PSSI differences, the Poincaré maps indicated less variability in patients than controls (Z = -1.9437, P = 0.05 for k(1) ; Z = -2.5099, P = 0.01 for k(2) ). That the dynamics identified Brodmann Area 10 is consistent with previous schizophrenia research, which implicates this area in deficits of working memory, executive functioning, emotional regulation and underlying biological abnormalities in synaptic (glutamatergic) transmission. Our results additionally cohere with a large body of work finding pink noise to be the normal range of central function at the synaptic, cellular, and small network levels, and suggest that patients show less supple responsivity of this region. Copyright © 2011 Wiley-Liss, Inc.

[Low bone mineral density in juvenile idiopathic arthritis: Prevalence and related factors].

PubMed

Galindo Zavala, Rocío; Núñez Cuadros, Esmeralda; Martín Pedraz, Laura; Díaz-Cordovés Rego, Gisela; Sierra Salinas, Carlos; Urda Cardona, Antonio

2017-10-01

Height adjustment is currently recommended for Z-score bone mineral density (BMD) assessed by dual energy X-ray absorptiometry. At present there are no studies that evaluate the prevalence of low BMD in paediatric patients with Juvenile Idiopathic Arthritis (JIA) in Spain following current recommendations. To evaluate low BMD in JIA in paediatric patients with JIA in Spain following the latest recommendations, as well as to assess associated factors. Observational cross-sectional study of Spanish JIA patients from 5 to 16 years-old, followed-up in a Paediatric Rheumatology Unit between July 2014 and July 2015. Anthropometric, clinical and treatment data were recorded. Dual energy X-ray absorptiometry, and bone metabolism parameters were collected, and a completed diet and exercise questionnaire was obtained. A total of 92 children participated. The population prevalence estimation of low BMD was less than 5% (95% CI). A significant positive correlation was found in the multiple linear regression analysis between the body mass index percentile (B: 0.021; P<.001) and lean mass index (B: 0.0002; P=.012), and BMD Z-score adjusted for height (Z-SAH). A significant negative correlation was found between fat mass index (B: -0.0001; P=.018) and serum type I collagen N-propeptide (B: -0,0006; P=.036) and Z-SAH. Low BMD prevalence in JIA patients in our population is low. An adequate nutritional status and the prevalence of lean over fat mass seem to promote the acquisition of bone mass. Those JIA patients with lower BMD could be subjected to an increase of bone turnover. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Automated structure and flow measurement - a promising tool in nailfold capillaroscopy.

PubMed

Berks, Michael; Dinsdale, Graham; Murray, Andrea; Moore, Tonia; Manning, Joanne; Taylor, Chris; Herrick, Ariane L

2018-07-01

Despite increasing interest in nailfold capillaroscopy, objective measures of capillary structure and blood flow have been little studied. We aimed to test the hypothesis that structural measurements, capillary flow, and a combined measure have the predictive power to separate patients with systemic sclerosis (SSc) from those with primary Raynaud's phenomenon (PRP) and healthy controls (HC). 50 patients with SSc, 12 with PRP, and 50 HC were imaged using a novel capillaroscopy system that generates high-quality nailfold images and provides fully-automated measurements of capillary structure and blood flow (capillary density, mean width, maximum width, shape score, derangement and mean flow velocity). Population statistics summarise the differences between the three groups. Areas under ROC curves (A Z ) were used to measure classification accuracy when assigning individuals to SSc and HC/PRP groups. Statistically significant differences in group means were found between patients with SSc and both HC and patients with PRP, for all measurements, e.g. mean width (μm) ± SE: 15.0 ± 0.71, 12.7 ± 0.74 and 11.8 ± 0.23 for SSc, PRP and HC respectively. Combining the five structural measurements gave better classification (A Z  = 0.919 ± 0.026) than the best single measurement (mean width, A Z  = 0.874 ± 0.043), whilst adding flow further improved classification (A Z  = 0.930 ± 0.024). Structural and blood flow measurements are both able to distinguish patients with SSc from those with PRP/HC. Importantly, these hold promise as clinical trial outcome measures for treatments aimed at improving finger blood flow or microvascular remodelling. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

A randomised crossover trial of minimising medical terminology in secondary care correspondence in patients with chronic health conditions: impact on understanding and patient reported outcomes.

PubMed

Wernick, M; Hale, P; Anticich, N; Busch, S; Merriman, L; King, B; Pegg, T

2016-05-01

There is little existing research on the role that secondary care letters have in ensuring patient understanding of chronic health conditions. To determine whether minimising the use of medical terminology in medical correspondence improved patient understanding and anxiety/depression scores. A single-centre, non-blinded, randomised crossover design assessed health literacy, EQ-5D scores and the impact of the 'translated' letter on the doctor's professionalism, the patient's relationship with their general practitioner (GP) and their perceived impact on chronic disease management. Patients were crossed over between their 'translated' and original letter. Sixty patients were recruited. Use of a 'translated' letter reduced mean terms not understood from 7.78 to 1.76 (t(58) = 4.706, P < 0.001). Most patients (78.0%) preferred the 'translated' letter, with 69.5% patients perceiving an enhancement in their doctor's professionalism (z = 2.864, P = 0.004), 69.0% reporting a positive influence on relationship with their GP (z = 2.943, P = 0.003) and 79.7% reporting an increase in perceived ability to manage their chronic health condition with the 'translated' letter (z = 4.601, P < 0.001). There was no effect on EQ-5D depression/anxiety scores. Minimising the use of medical terminology in medical correspondence significantly improved patient understanding and perception of their ability to manage their chronic health condition. Although there was no impact on EQ-5D depression/anxiety scores, overwhelming patient preference for the 'translated' letter indicates a need for minimisation of medical terminology in medical correspondence for patients with chronic health conditions. © 2016 Royal Australasian College of Physicians.