A protocol for resuscitation of severe burn patients guided by transpulmonary thermodilution and lactate levels: a 3-year prospective cohort study.

PubMed

Sánchez, Manuel; García-de-Lorenzo, Abelardo; Herrero, Eva; Lopez, Teresa; Galvan, Beatriz; Asensio, María; Cachafeiro, Lucia; Casado, Cesar

2013-08-15

The use of urinary output and vital signs to guide initial burn resuscitation may lead to suboptimal resuscitation. Invasive hemodynamic monitoring may result in over-resuscitation. This study aimed to evaluate the results of a goal-directed burn resuscitation protocol that used standard measures of mean arterial pressure (MAP) and urine output, plus transpulmonary thermodilution (TPTD) and lactate levels to adjust fluid therapy to achieve a minimum level of preload to allow for sufficient vital organ perfusion. We conducted a three-year prospective cohort study of 132 consecutive critically burned patients. These patients underwent resuscitation guided by MAP (>65 mmHg), urinary output (0.5 to 1 ml/kg), TPTD and lactate levels. Fluid therapy was adjusted to achieve a cardiac index (CI) >2.5 L/minute/m² and an intrathoracic blood volume index (ITBVI) >600 ml/m2, and to optimize lactate levels. Statistical analysis was performed using mixed models. We also used Pearson or Spearman methods and the Mann-Whitney U-test. A total of 98 men and 34 women (mean age, 48 ± 18 years) was studied. The mean total body surface area (TBSA) burned was 35% ± 22%. During the early resuscitation phase, lactate levels were elevated (2.58 ± 2.05 mmol/L) and TPTD showed initial hypovolemia by the CI (2.68 ± 1.06 L/minute/m²) and the ITBVI (709 ± 254 mL/m²). At 24 to 32 hours, the CI and lactic levels were normalized, although the ITBVI remained below the normal range (744 ± 276 ml/m²). The mean fluid rate required to achieve protocol targets in the first 8 hours was 4.05 ml/kg/TBSA burned, which slightly increased in the next 16 hours. Patients with a urine output greater than or less than 0.5 ml/kg/hour did not show differences in heart rate, mean arterial pressure, CI, ITBVI or lactate levels. Initial hypovolemia may be detected by TPTD monitoring during the early resuscitation phase. This hypovolemia might not be reflected by blood pressure and hourly urine output. An adequate CI and tissue perfusion can be achieved with below-normal levels of preload. Early resuscitation guided by lactate levels and below-normal preload volume targets appears safe and avoids unnecessary fluid input.

Assessment of Microcirculatory Hemoglobin Levels in Normal and Diabetic Subjects using Diffuse Reflectance Spectroscopy in the Visible Region — a Pilot Study

NASA Astrophysics Data System (ADS)

Sujatha, N.; Anand, B. S. Suresh; Nivetha, K. Bala; Narayanamurthy, V. B.; Seshadri, V.; Poddar, R.

2015-07-01

Light-based diagnostic techniques provide a minimally invasive way for selective biomarker estimation when tissues transform from a normal to a malignant state. Spectroscopic techniques based on diffuse reflectance characterize the changes in tissue hemoglobin/oxygenation levels during the tissue transformation process. Recent clinical investigations have shown that changes in tissue oxygenation and microcirculation are observed in diabetic subjects in the initial and progressive stages. In this pilot study, we discuss the potential of diffuse reflectance spectroscopy (DRS) in the visible (Vis) range to differentiate the skin microcirculatory hemoglobin levels between normal and advanced diabetic subjects with and without neuropathy. Average concentration of hemoglobin as well as hemoglobin oxygen saturation within the probed tissue volume is estimated for a total of four different sites in the foot sole. The results indicate a statistically significant decrease in average total hemoglobin and increase in hemoglobin oxygen saturation levels for diabetic foot compared with a normal foot. The present study demonstrates the ability of reflectance spectroscopy in the Vis range to determine and differentiate the changes in tissue hemoglobin and hemoglobin oxygen saturation levels in normal and diabetic subjects.

Gray Matter-White Matter De-Differentiation on Brain Computed Tomography Predicts Brain Death Occurrence.

PubMed

Vigneron, C; Labeye, V; Cour, M; Hannoun, S; Grember, A; Rampon, F; Cotton, F

2016-01-01

Previous studies have shown that a loss of distinction between gray matter (GM) and white matter (WM) on unenhanced CT scans was predictive of poor outcome after cardiac arrest. The aim of this study was to identify a marker/predictor of imminent brain death. In this retrospective study, 15 brain-dead patients after anoxia and cardiac arrest were included. Patients were paired (1:1) with normal control subjects. Only patients' unenhanced CT scans performed before brain death and during the 24 hours after initial signs were analyzed. WM and GM densities were measured in predefined regions of interest (basal ganglia level, centrum semi-ovale level, high convexity level, brainstem level). At each level, GM and WM density and GM/WM ratio for brain-dead patients and normal control subjects were compared using the Wilcoxon signed-rank test. At each level, a lower GM/WM ratio and decreased GM and WM densities were observed in brain-dead patients' CT scans when compared with normal control subject CT scans. A cut-off value of 1.21 at the basal ganglia level was identified, below which brain death systematically occurred. GM/WM dedifferentiation on unenhanced CT scan is measurable before the occurrence of brain death, highlighting its importance in brain death prediction. The mechanism of GM/WM differentiation loss could be explained by the lack of oxygen caused by ischemia initially affecting the mitochondrial system. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationship between adiponectin levels, acylated ghrelin levels, and short-term body mass index changes in children with diabetes mellitus type 1 at diagnosis and after insulin therapy.

PubMed

Martos-Moreno, Gabriel A; Barrios, Vicente; Soriano-Guillén, Leandro; Argente, Jesús

2006-11-01

To determine the effect of the initial metabolic imbalance and its restoration after insulin therapy on adiponectin and acylated ghrelin levels in children with type 1 diabetes mellitus (T1DM). Twenty prepubertal children with newly diagnosed T1DM were prospectively studied at diagnosis and after 1 and 4 months of therapy. Body mass index (BMI) and serum levels of adiponectin, resistin, total and acylated ghrelin, leptin, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) were determined. The control group comprised 40 healthy prepubertal children. BMI was decreased at diagnosis, normalized at 1 month, and remained so thereafter. Adiponectin levels at diagnosis were similar to controls, increasing significantly after 1 month and normalizing at 4 months. Acylated ghrelin levels were lower at diagnosis, with a significant increase at 1 month and normalizing at 4 months. Resistin levels were normal at all time points. Leptin levels were decreased, while TNF-alpha and IL-6 were increased at diagnosis and normalized at 1 month. These findings suggest that BMI is not the main predictor of acylated ghrelin or adiponectin levels in newly diagnosed T1DM subjects and that these peptides may play an important role in the metabolic adaptation in this disease.

Hyperthyrotropinemia in newly diagnosed cystic fibrosis patients with pancreatic insufficiency reversed by enzyme therapy.

PubMed

Giannakopoulos, Aris; Katelaris, Anni; Noni, Maria; Karakonstantakis, Theodore; Kanaka-Gantenbein, Christina; Doudounakis, Stavros

2018-05-01

Patients with cystic fibrosis (CF) commonly present with an elevated TSH concentration, suggesting subclinical hypothyroidism. Its relation to concomitant pancreatic insufficiency and its natural course upon initiation of enzyme replacement have not been adequately studied. Herein, we investigated the thyroid function in newly diagnosed infants with CF and monitored the course of thyroid function response to pancreatic enzyme substitution treatment. Fourteen, newly diagnosed infants with CF and pancreatic insufficiency, were followed every 6-8 weeks for 6 months ensuing onset of pancreatic enzyme substitution therapy. All infants had normal TSH values on neonatal screening. Ten out of 14 (71%) had hyperthyrotropinemia and normal freeT4 values at presentation. No patient received thyroxine. Upon follow-up, after 6 months, TSH values normalized in 90% of infants with CF and hyperthyrotropinemia. Serum selenium levels were negatively correlated with TSH levels. Mild TSH elevation is a frequent finding in newly diagnosed cystic fibrosis patients with pancreatic insufficiency during infancy. TSH elevation resolves in most cases after initiation of enzyme substitution and improvement of nutritional status without any substitutive therapy with thyroxine. What is Known: • Newly diagnosed infants with cystic fibrosis often present with a state of hyperthyrotropinemia suggesting subclinical hypothyroidism. What is New: • Pancreatic enzyme substitution and improvement of nutrition restores normal TSH levels without the need of thyroxine therapy.

Multi-scale modeling of APC and [Formula: see text]-catenin regulation in the human colonic crypt.

PubMed

Emerick, Brooks; Schleiniger, Gilberto; Boman, Bruce M

2018-06-01

Stem cell renewal and differentiation in the human colonic crypt are linked to the [Formula: see text]-catenin pathway. The spatial balance of Wnt factors in proliferative cells within the crypt maintain an appropriate level of cellular reproduction needed for normal crypt homeostasis. Mutational events at the gene level are responsible for deregulating the balance of Wnt factors along the crypt, causing an overpopulation of proliferative cells, a loss of structure of the crypt domain, and the initiation of colorectal carcinomas. We formulate a PDE model describing cell movement and reproduction in a static crypt domain. We consider a single cell population whose proliferative capabilities are determined by stemness, a quantity defined by intracellular levels of adenomatous polyposis coli (APC) scaffold protein and [Formula: see text]-catenin. We fit APC regulation parameters to biological data that describe normal protein gradients in the crypt. We also fit cell movement and protein flux parameters to normal crypt characteristics such as renewal time, total cell count, and proportion of proliferating cells. The model is used to investigate abnormal crypt dynamics when subjected to a diminished APC gradient, a scenario synonymous to mutations in the APC gene. We find that a 25% decrease in APC synthesis leads to a fraction of 0.88 proliferative, which is reflective of normal-appearing FAP crypts. A 50% drop in APC activity yields a fully proliferative crypt showing a doubling of the level of stemness, which characterizes the initial stages of colorectal cancer development. A sensitivity analysis of APC regulation parameters shows the perturbation of factors that is required to restore crypt dynamics to normal in the case of APC mutations.

Low empathy in deaf and hard of hearing (pre)adolescents compared to normal hearing controls.

PubMed

Netten, Anouk P; Rieffe, Carolien; Theunissen, Stephanie C P M; Soede, Wim; Dirks, Evelien; Briaire, Jeroen J; Frijns, Johan H M

2015-01-01

The purpose of this study was to examine the level of empathy in deaf and hard of hearing (pre)adolescents compared to normal hearing controls and to define the influence of language and various hearing loss characteristics on the development of empathy. The study group (mean age 11.9 years) consisted of 122 deaf and hard of hearing children (52 children with cochlear implants and 70 children with conventional hearing aids) and 162 normal hearing children. The two groups were compared using self-reports, a parent-report and observation tasks to rate the children's level of empathy, their attendance to others' emotions, emotion recognition, and supportive behavior. Deaf and hard of hearing children reported lower levels of cognitive empathy and prosocial motivation than normal hearing children, regardless of their type of hearing device. The level of emotion recognition was equal in both groups. During observations, deaf and hard of hearing children showed more attention to the emotion evoking events but less supportive behavior compared to their normal hearing peers. Deaf and hard of hearing children attending mainstream education or using oral language show higher levels of cognitive empathy and prosocial motivation than deaf and hard of hearing children who use sign (supported) language or attend special education. However, they are still outperformed by normal hearing children. Deaf and hard of hearing children, especially those in special education, show lower levels of empathy than normal hearing children, which can have consequences for initiating and maintaining relationships.

Cerebrospinal fluid neopterin decay characteristics after initiation of antiretroviral therapy

PubMed Central

2013-01-01

Background Neopterin, a biomarker of macrophage activation, is elevated in the cerebrospinal fluid (CSF) of most HIV-infected individuals and decreases after initiation of antiretroviral therapy (ART). We studied decay characteristics of neopterin in CSF and blood after commencement of ART in HIV-infected subjects and estimated the set-point levels of CSF neopterin after ART-mediated viral suppression. Methods CSF and blood neopterin were longitudinally measured in 102 neurologically asymptomatic HIV-infected subjects who were treatment-naïve or had been off ART for ≥ 6 months. We used a non-linear model to estimate neopterin decay in response to ART and a stable neopterin set-point attained after prolonged ART. Seven subjects with HIV-associated dementia (HAD) who initiated ART were studied for comparison. Results Non-HAD patients were followed for a median 84.7 months. Though CSF neopterin concentrations decreased rapidly after ART initiation, it was estimated that set-point levels would be below normal CSF neopterin levels (<5.8 nmol/L) in only 60/102 (59%) of these patients. Pre-ART CSF neopterin was the primary predictor of set-point (P <0.001). HAD subjects had higher baseline median CSF neopterin levels than non-HAD subjects (P <0.0001). Based on the non-HAD model, only 14% of HAD patients were predicted to reach normal levels. Conclusions After virologically suppressive ART, abnormal CSF neopterin levels persisted in 41% of non-HAD and the majority of HAD patients. ART is not fully effective in ameliorating macrophage activation in CNS as well as blood, especially in subjects with higher pre-ART levels of immune activation. PMID:23664008

14 CFR 1274.801 - Adjustments to performance costs.

Code of Federal Regulations, 2010 CFR

2010-01-01

... NASA's initial cost share or funding levels, detailed cost analysis techniques may be applied, which... shall continue to maintain the share ratio requirements (normally 50/50) stated in § 1274.204(b). ...

Lipid monitoring in patients with schizophrenia prescribed second-generation antipsychotics.

PubMed

Weissman, Ellen M; Zhu, Carolyn W; Schooler, Nina R; Goetz, Raymond R; Essock, Susan M

2006-09-01

Treatment with second-generation antipsychotic (SGA) medications has been linked with increased rates of the metabolic syndrome (i.e., dyslipidemia, obesity, and hyperglycemia). Several sets of published recommendations now provide clinicians with guidelines for monitoring metabolic parameters in individuals with schizophrenia treated with SGAs. However, few data are available regarding actual metabolic monitoring practices in this patient population. The objectives of the study were to determine baseline lipid monitoring rates for individuals with schizophrenia prescribed SGAs during the period prior to the publication of monitoring guidelines and to determine whether individuals with abnormal lipid levels received follow-up monitoring sooner than individuals with normal levels. Lipid monitoring rates for 408 individuals with schizophrenia who were prescribed SGAs from October 1999 to October 2003 were examined using administrative data from a Veterans Affairs facility. Survival analysis was used to examine time to follow-up lipid measurement and to compare time to follow-up measure for individuals with normal initial lipid levels versus those with elevated initial lipid levels. Eighty-five percent of individuals had at least 1 measurement for total cholesterol or triglycerides in a 4-year period. Abnormal initial measurements predicted significantly earlier follow-up monitoring (p < .005 for total cholesterol, p < .05 for triglycerides, p < .001 for low-density lipoprotein cholesterol). However, median time to follow-up measure was 304 days (approximately 10 months) for individuals with elevated total cholesterol levels, which is too long for optimal clinical follow-up. Program managers and clinicians should assess adequacy of monitoring and support quality improvement initiatives in this area.

Clinical features of hepatitis B and C virus infections, with high α-fetoprotein levels but not hepatocellular carcinoma

PubMed Central

Kim, Cha Young; Kim, Bo Ra; Lee, Sang Soo; Jeon, Dae-Hong; Lee, Chang Min; Kim, Wan Soo; Cho, Hyun Chin; Kim, Jin Joo; Lee, Jae Min; Kim, Hong Jun; Ha, Chang Yoon; Kim, Hyun Jin; Kim, Tae Hyo; Jung, Woon Tae; Lee, Ok-Jae

2017-01-01

Abstract The appropriate α-fetoprotein (AFP) level to confirm hepatocellular carcinoma (HCC) could be 100 ng/mL; however, the clinical significance of falsely elevated AFP in patients without HCC has not been fully studied. We investigated the clinical features and outcome of patients without HCC but with high AFP levels (100 ng/mL), especially with chronic hepatitis B (CHB) or C (CHC). The sample included 124 consecutive patients with CHB (n = 97) or CHC (n = 27), with AFP levels >100 ng/mL and without HCC at baseline. Multivariate Cox proportional regression analysis was performed to determine the factors associated with AFP normalization and HCC development. During the mean 52-month follow-up, the proportion of patients with CHB with AFP normalization (90.7%) was significantly higher than the proportion of patients with CHC (59.3%, P < 0.001). Initial aspartate aminotransferase levels (hazard ratio [HR] = 1.02 per 10 U/L increase, P = 0.021) and antiviral therapy (HR = 2.89, P < 0.001) were significantly associated with AFP normalization. Of the 16 (12.9%) patients who developed HCC, hepatitis B virus infection (HR = 10.82, P = 0.001), initiation of antiviral treatment postenrollment (HR = 0.23, P = 0.030), and AFP normalization within 12 months (HR = 0.13, P = 0.011) were associated with HCC development. CHB and CHC were the most common causes of falsely elevated AFP (>100 ng/mL). With either CHB or CHC, persistent AFP elevation (>12 months), regardless of antiviral treatment, might be an important marker of HCC development. PMID:28079817

Getting better, but not well: A 1.5 year follow-up of cognitive performance and cortisol levels in clinical and non-Clinical burnout.

PubMed

Oosterholt, Bart G; Maes, Joseph H R; Van der Linden, Dimitri; Verbraak, Marc J P M; Kompier, Michiel A J

2016-05-01

The purpose was to reexamine cognitive performance and cortisol levels of initial clinical burnout patients, non-clinical burnout individuals, and healthy controls. After 1.5-years of the initial measurement, clinical burnout patients showed a reduction of burnout symptoms and general physical and psychological complaints, but these were still elevated compared with controls. Nonetheless, they continued to report cognitive problems and still showed a minor impaired cognitive test performance. However, they no longer reported larger subjective costs associated with cognitive test performance and their cortisol awakening response (CAR) returned to a normal level. Compared with controls, non-clinical burnout individuals still reported the same, elevated, level of burnout symptoms, general physical and psychological complaints, and cognitive problems. Their cognitive test performance and associated subjective costs remained normal. However, they seemed to continue to display a lowered CAR. To conclude, after 1.5-years, clinical burnout patients got better, but not 'well', and non-clinical burnout individuals remained not 'well'. Copyright © 2016 Elsevier B.V. All rights reserved.

A Comparison of the Bounded Derivative and the Normal Mode Initialization Methods Using Real Data

NASA Technical Reports Server (NTRS)

Semazzi, F. H. M.; Navon, I. M.

1985-01-01

Browning et al. (1980) proposed an initialization method called the bounded derivative method (BDI). They used analytical data to test the new method. Kasahara (1982) theoretically demonstrated the equivalence between BDI and the well known nonlinear normal mode initialization method (NMI). The purposes of this study are the extension of the application of BDI to real data and comparison with NMI. The unbalanced initial state (UBD) is data of January, 1979 OOZ which were interpolated from the adjacent sigma levels of the GLAS GCM to the 300 mb surface. The global barotropic model described by Takacs and Balgovind (1983) is used. Orographic forcing is explicitly included in the model. Many comparisons are performed between various quantities. However, we only present a comparison of the time evolution at two grid points A(50 S, 90 E) and B(10 S, 20 E) which represent low and middle latitude locations. To facilitate a more complete comparison an initialization experiment based on the classical balance equation (CBE) was also included.

Low Empathy in Deaf and Hard of Hearing (Pre)Adolescents Compared to Normal Hearing Controls

PubMed Central

Netten, Anouk P.; Rieffe, Carolien; Theunissen, Stephanie C. P. M.; Soede, Wim; Dirks, Evelien; Briaire, Jeroen J.; Frijns, Johan H. M.

2015-01-01

Objective The purpose of this study was to examine the level of empathy in deaf and hard of hearing (pre)adolescents compared to normal hearing controls and to define the influence of language and various hearing loss characteristics on the development of empathy. Methods The study group (mean age 11.9 years) consisted of 122 deaf and hard of hearing children (52 children with cochlear implants and 70 children with conventional hearing aids) and 162 normal hearing children. The two groups were compared using self-reports, a parent-report and observation tasks to rate the children’s level of empathy, their attendance to others’ emotions, emotion recognition, and supportive behavior. Results Deaf and hard of hearing children reported lower levels of cognitive empathy and prosocial motivation than normal hearing children, regardless of their type of hearing device. The level of emotion recognition was equal in both groups. During observations, deaf and hard of hearing children showed more attention to the emotion evoking events but less supportive behavior compared to their normal hearing peers. Deaf and hard of hearing children attending mainstream education or using oral language show higher levels of cognitive empathy and prosocial motivation than deaf and hard of hearing children who use sign (supported) language or attend special education. However, they are still outperformed by normal hearing children. Conclusions Deaf and hard of hearing children, especially those in special education, show lower levels of empathy than normal hearing children, which can have consequences for initiating and maintaining relationships. PMID:25906365

Febuxostat-associated eosinophilic polymyositis in marginal zone lymphoma.

PubMed

Chahine, Georges; Saleh, Khalil; Ghorra, Claude; Khoury, Nathalie; Khalife, Nadine; Fayad, Fouad

2017-03-01

Febuxostat is an orally administered selective inhibitor of xanthine oxidase approved for the treatment of gout and prevention of tumor lysis syndrome. It is a relatively safe medication. Hypersensitivity reactions associated with the use of febuxostat are quite rare with only one reported case of DRESS syndrome. Recently, two case reports of rhabdomyolysis following the initiation of febuxostat were published. We hereby present the first case of rhabdomyolysis with hypereosinophilia following the administration of febuxostat to a 50-year-old patient newly diagnosed with marginal zone lymphoma. Three weeks after the initiation of febuxostat for tumor lysis syndrome prophylaxis, the patient presented with generalized weakness, diffuse myalgia and low-grade fever. Initial studies showed creatinine kinase level of 4471, hypereosinophilia of 1900/mm 3 , and LDH of 2691. All infectious and autoimmune diseases were ruled out. TSH level was normal. Muscle biopsy showed myonecrosis in addition to an eosinophilic inflammatory infiltrate in the endomysium and perimysium. Discontinuation of febuxostat led to prompt symptom resolution and normalization of blood tests eight days later. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Case 252: Acute Hyperammonemic Encephalopathy Resulting from Late-Onset Ornithine Transcarbamylase Deficiency.

PubMed

Hershman, Michelle; Carmody, Raymond; Udayasankar, Unni K

2018-04-01

History A 19-year-old woman with no pertinent medical history was brought to the emergency department after being found unconscious on her bathroom floor by her roommate. In the preceding weeks, she had reported intractable nausea and vomiting, for which she had been taking ondansetron. No other medications had been prescribed. The day prior to presentation, she had contacted her mother and described increasing confusion. Glasgow coma scale score on arrival in the emergency department was 4. Intravenous naloxone was administered, without immediate response. Initial blood glucose level was 232 mg/dL (12.8 mmol/L) (normal range, 79-140 mg/dL [4.4- 7.7 mmol/L]), and other routine laboratory test results were normal. Urine toxicology results were negative. Cerebrospinal fluid evaluation revealed levels were within normal limits. Neurologic examination revealed dilated pupils, which showed a sluggish response to light, and left lower extremity rigidity with intermittent tremors. Initial unenhanced cranial computed tomographic (CT) findings were negative. Magnetic resonance (MR) imaging of the brain was performed. The patient's condition deteriorated, with increasing cerebral edema over the next week, and she was declared brain dead. Her liver was transplanted into an adult recipient, who subsequently developed cerebral edema and elevated plasma ammonia levels, resulting in death in the immediate postoperative period.

Study on the status of thyroid function and thyroid nodules in chinese breast cancer patients

PubMed Central

Xu, Zhou; Zhao, Chunxia; Wu, Yutuan; Wu, He; Chen, Haoran; Li, Hong-Yuan; Wu, Kai-Nan; Kong, Ling-Quan

2017-01-01

We performed a study to investigate the status of thyroid nodules and thyroid functions in Chinese breast cancer women. The clinical data of female patients with breast cancer or benign breast diseases and normal populace were evaluated. The thyroxine(T4) level in initially diagnosed breast cancer patients were significantly higher than those in benign breast diseases patients (7.68±1.51 vs 7.29±1.52ug/dl, p<0.001), while the TSH levels were slightly lower than in benign breast diseases patients(3.23±4.59 vs 3.60±6.74uIU/ml, p=0.302). The overall incidence of hypothyroidism in initially diagnosed breast cancer and benign breast diseases patients were 28.65% and 32.74%(p=0.195). During chemotherapy, the T4(7.08±1.69ug/dl), fT3(2.87±0.48pg/ml) and fT4(0.83±0.15ng/dl) levels were significantly lower than in initially diagnosed breast cancer patients(7.68±1.51ug/dl, 3.07±0.50pg/ml, 0.88±0.20ng/dl, p<0.05). The incidence of thyroid nodules in initially diagnosed breast cancer patients, benign breast diseases patients and healthy population were 56.17%, 43.64%, 34.49%(p<0.001). The incidence of TI-RADS≥4 TN in initially diagnosed breast cancer patients and benign breast diseases patients were significantly higher than in normal population(7.27% vs 9.45% vs 2.87%, p<0.001). The incidence of TI-RADS≥4 thyroid nodules in breast cancer patients receiving chemotherapy was significantly higher than in initially diagnosed breast cancer patients(11.71% vs 7.27%, p<0.05). These data indicate that the incidence of thyroid disease in breast disease patients is higher than in normal population in China, and the breast diseases, especially breast cancer, might be related to the high incidence of thyroid nodules. PMID:29113346

Choline pathways during normal and stimulated renal growth in rats.

PubMed Central

Bean, G H; Lowenstein, L M

1978-01-01

Cellular membrane synthesis occurs during normal and stimulated renal growth. Choline in the kidney is utilized as a precursor for membrane synthesis via the choline kinase reaction. We investigated choline phosphorylation during normal and stimulated renal growth. Rapidly growing neonatal rat kidneys contained relatively high levels of choline kinase activity (61 pmol phosphorylcholine/min per mg protein). Choline kinase activity and phosphorylcholine production then fell gradually over the 1st mo of life; by 1 mo phosphorylcholine production was 34 pmol phosphorylcholine/min per mg protein. Choline kinase activity increased by 27% (P less than 0.001) in 28-day-old rats when renal growth was stimulated by contralateral nephrectomy; the increase occurred within 2 h after surgery. Thus, changes in the activity of this important enzyme in the initiation of membrane synthesis is associated both with normal renal development and with adaptation to nephron loss. The findings further suggest that the cell membrane may be involved in the initiation of compensatory renal growth. PMID:659614

Normal Human Fibroblasts Are Resistant to RAS-Induced Senescence

PubMed Central

Benanti, Jennifer A.; Galloway, Denise A.

2004-01-01

Oncogenic stimuli are thought to induce senescence in normal cells in order to protect against transformation and to induce proliferation in cells with altered p53 and/or retinoblastoma (Rb) pathways. In human fibroblasts, RAS initiates senescence through upregulation of the cyclin-dependent kinase inhibitor p16INK4A. We show here that in contrast to cultured fibroblast strains, freshly isolated normal fibroblasts are resistant to RAS-induced senescence and instead show some characteristics of transformation. RAS did not induce growth arrest or expression of senescence-associated β-galactosidase, and Rb remained hyperphosphorylated despite elevated levels of p16. Instead, RAS promoted anchorage-independent growth of normal fibroblasts, although expression of hTert with RAS increased colony formation and allowed normal fibroblasts to bypass contact inhibition. To test the hypothesis that p16 levels determine how cells respond to RAS, we expressed RAS in freshly isolated fibroblasts that expressed very low levels of p16, in hTert-immortalized fibroblasts that had accumulated intermediate levels of p16, and in IMR90 fibroblasts with high levels of p16. RAS induced growth arrest in cells with higher p16 levels, and this effect was reversed by p16 knockdown in the hTert-immortalized fibroblasts. These findings indicate that culture-imposed stress sensitizes cells to RAS-induced arrest, whereas early passage cells do not arrest in response to RAS. PMID:15024073

Study of patients with Hyper-IgM type IV phenotype who recovered spontaneously during late childhood and review of the literature.

PubMed

Karaca, Neslihan Edeer; Durandy, Anne; Gulez, Nesrin; Aksu, Guzide; Kutukculer, Necil

2011-08-01

Hyper-IgM syndromes are characterized by normal or elevated serum IgM levels with the absence or reduced levels of other immunoglobulins. There are some patients with defective class-switch recombination (CSR) who do not have CD40L, CD40, AID, and UNG defects. The aim of this study is to determine the B-cell functions of patients with Hyper-IgM type 4 phenotype. Ten patients (seven males and three females) 84.2 ± 16.5 months of age with initial low serum IgG and IgA and high or normal IgM levels were included. Clinically, 50% had recurrent upper respiratory tract, 10% urinary tract, 10% lower respiratory tract infections, and 30% had mixed type infections. Lymphoid hyperplasia, overt autoimmune manifestations, or malignancy was not noted. Seven of 10 patients were studied twice; at the age of 34.2 ± 13.7 and at 86.6 ± 12.3 months. Absolute lymphocyte counts and lymphocyte subsets were normal in all cases. All of them had normal expression of CD40 on B cells and CD40L on activated T cells for males. At first examination, all patients had normal in vitro sCD40L+rIL-4-induced B cell proliferation response and somatic hypermutation but CSR towards IgE was absent. AID and UNG genes did not show any abnormalities. All showed improvement in both clinical findings and Ig levels during the follow-up period of 55.8 ± 14.8 months. Ages for normalization of IgG and IgA were 68.2 ± 8.7 and 70.2 ± 21.6 months, respectively. During the second evaluation: In vitro sCD40L+rIL-4-induced B-cell proliferation was normal in all cases, whereas CSR was still abnormal in five of eight patients. Two of the patients had an increase in in vitro CSR response but still low IgG2 subclass levels. Three patients with initially absent in vitro CSR response also normalized. Clinical manifestations and immunoglobulin levels of the patients with Hyper-IgM type 4 phenotype recovered in late childhood at about 6 years of age. There was a transient CSR defect which was not observed in cases with transient hypogammaglobulinemia of infancy. Detection of a non-AID or non-UNG associated CSR defect in infancy should be confirmed later on since spontaneous recovery may occur.

Chemical composition of acid precipitation in central Texas

Treesearch

Hal B. H., Jr. Cooper; Jerry M. Demo

1976-01-01

Studies were undertaken to determine factors affecting composition of acidic precipitation formation in the Austin area of Central Texas. The study was initiated to determine background levels of acid and alkalinity producing constituents in an area with elevated natural dust levels from nearby limestone rock formations. Results showed normal rainfall pH values of 6.5...

The Outcome of Cirrhotic Patients with Ascites Is Improved by the Normalization of the Serum Sodium Level by Tolvaptan

PubMed Central

Kogiso, Tomomi; Kobayashi, Mutsuki; Yamamoto, Kuniko; Ikarashi, Yuichi; Kodama, Kazuhisa; Taniai, Makiko; Torii, Nobuyuki; Hashimoto, Etsuko; Tokushige, Katsutoshi

2017-01-01

Objective Hyponatremia is frequently observed in patients with decompensated liver cirrhosis and it is also related to a poor prognosis. The vasopressin V2-receptor antagonist tolvaptan is used to treat cirrhotic patients with ascites and increases the serum sodium (Na) level. In this study, we investigated (i) whether or not correction of the Na level improves the prognosis of cirrhotic patients with ascites and (ii) predictors of normalization of the serum Na level after tolvaptan therapy. Methods This was a single-center retrospective study. A total of 95 Japanese cirrhotic patients (60 men, median age 63 years) were enrolled and received tolvaptan orally after hospitalization for ascites treatment. The serum Na level was monitored during the period of tolvaptan treatment. The laboratory data and survival rates of patients who achieved serum Na levels of <135 and ≥135 mEq/L after 1 week were compared. Results Patients showed serum Na levels of 136 (121-145) mEq/L, and 42.1% had a serum Na level of <135 mEq/L. Among patients with an initial serum Na level <135 mEq/L, 60.0% achieved a normal level after 1 week, and the survival rate was significantly higher in patients with a normalized serum Na level (p<0.01). The pretreatment brain natriuretic peptide (BNP) level was predictive of achieving a serum Na level of ≥135 mEq/L (odds ratio: 0.87, 95% confidence interval: 0.316-0.987, p<0.05). Conclusion Normalization of the Na level after one week was associated with a favorable outcome of tolvaptan therapy, and Na correction improved the prognosis. PMID:28943585

Origin and initiation mechanisms of neuroblastoma.

PubMed

Tsubota, Shoma; Kadomatsu, Kenji

2018-05-01

Neuroblastoma is an embryonal malignancy that affects normal development of the adrenal medulla and paravertebral sympathetic ganglia in early childhood. Extensive studies have revealed the molecular characteristics of human neuroblastomas, including abnormalities at genome, epigenome and transcriptome levels. However, neuroblastoma initiation mechanisms and even its origin are long-standing mysteries. In this review article, we summarize the current knowledge about normal development of putative neuroblastoma sources, namely sympathoadrenal lineage of neural crest cells and Schwann cell precursors that were recently identified as the source of adrenal chromaffin cells. A plausible origin of enigmatic stage 4S neuroblastoma is also discussed. With regard to the initiation mechanisms, we review genetic abnormalities in neuroblastomas and their possible association to initiation mechanisms. We also summarize evidences of neuroblastoma initiation observed in genetically engineered animal models, in which epigenetic alterations were involved, including transcriptomic upregulation by N-Myc and downregulation by polycomb repressive complex 2. Finally, several in vitro experimental methods are proposed that hopefully will accelerate our comprehension of neuroblastoma initiation. Thus, this review summarizes the state-of-the-art knowledge about the mechanisms of neuroblastoma initiation, which is critical for developing new strategies to cure children with neuroblastoma.

Parafoveal and foveal processing of abbreviations during eye fixations in reading: Making a case for case

PubMed Central

Slattery, Timothy J.; Schotter, Elizabeth R.; Berry, Raymond W.; Rayner, Keith

2011-01-01

The processing of abbreviations in reading was examined with an eye movement experiment. Abbreviations were of two distinct types: Acronyms (abbreviations that can be read with the normal grapheme-phoneme correspondence rules, such as NASA) and initialisms (abbreviations in which the grapheme-phoneme correspondences are letter names, such as NCAA). Parafoveal and foveal processing of these abbreviations was assessed with the use of the boundary change paradigm (Rayner, 1975). Using this paradigm, previews of the abbreviations were either identical to the abbreviation (NASA or NCAA), orthographically legal (NUSO or NOBA), or illegal (NRSB or NRBA). The abbreviations were presented as capital letter strings within normal, predominantly lowercase sentences and also sentences in all capital letters such that the abbreviations would not be visually distinct. The results indicate that acronyms and initialisms undergo different processing during reading, and that readers can modulate their processing based on low-level visual cues (distinct capitalization) in parafoveal vision. In particular, readers may be biased to process capitalized letter strings as initialisms in parafoveal vision when the rest of the sentence is normal, lower case letters. PMID:21480754

Parafoveal and foveal processing of abbreviations during eye fixations in reading: making a case for case.

PubMed

Slattery, Timothy J; Schotter, Elizabeth R; Berry, Raymond W; Rayner, Keith

2011-07-01

The processing of abbreviations in reading was examined with an eye movement experiment. Abbreviations were of 2 distinct types: acronyms (abbreviations that can be read with the normal grapheme-phoneme correspondence [GPC] rules, such as NASA) and initialisms (abbreviations in which the GPCs are letter names, such as NCAA). Parafoveal and foveal processing of these abbreviations was assessed with the use of the boundary change paradigm (K. Rayner, 1975). Using this paradigm, previews of the abbreviations were either identical to the abbreviation (NASA or NCAA), orthographically legal (NUSO or NOBA), or illegal (NRSB or NRBA). The abbreviations were presented as capital letter strings within normal, predominantly lowercase sentences and also sentences in all capital letters such that the abbreviations would not be visually distinct. The results indicate that acronyms and initialisms undergo different processing during reading and that readers can modulate their processing based on low-level visual cues (distinct capitalization) in parafoveal vision. In particular, readers may be biased to process capitalized letter strings as initialisms in parafoveal vision when the rest of the sentence is normal, lowercase letters.

Pituitary gigantism: a retrospective case series.

PubMed

Creo, Ana L; Lteif, Aida N

2016-05-01

Pituitary gigantism (PG) is a rare pediatric disease with poorly defined long-term outcomes. Our aim is to describe the longitudinal clinical course in PG patients using a single-center, retrospective cohort study. Patients younger than 19 years diagnosed with PG were identified. Thirteen cases were confirmed based on histopathology of a GH secreting adenoma or hyperplasia and a height >2 SD for age and gender. Laboratory studies, initial pathology, and imaging were abstracted. Average age at diagnosis was 13 years with an average initial tumor size of 7.4×3.8 mm. Initial transsphenoidal surgery was curative in 3/12 patients. Four of the nine patients who failed the initial surgery required a repeat procedure. Octreotide successfully normalized GH levels in 1/6 patients with disease refractory to surgery (1/6). Two out of five patients received pegvisomant after failing octreotide but only one patient responded to treatment. Five patients were ultimately treated with radiosurgery or radiation patients were followed for an average of 10 years. PG is difficult to treat. In most patients, the initial transsphenoidal surgery failed to normalize GH levels. If the initial surgery was unsuccessful, repeat surgery was unlikely to control GH secretion. Treatment with octreotide or pegvisomant was successful in less than half the patients failing surgery. Radiosurgery was curative, but is not an optimal treatment for pediatric patients. Despite the small sample, our study suggests that the treatment outcome of pediatric PG may be different than adults.

Partial hypopituitarism and Langerhans cell histiocytosis

PubMed Central

Balaguruswamy, S; Chattington, P D

2011-01-01

A case of multisystem Langerhans cell histiocytosis with pituitary involvement nearly 20 years after initial presentation. A 48-year-old man had histiocytosis X 22 years ago initially involving the groin; subsequently his external auditory meatus, scalp, gum, mandibular bone, perineum and axilla were involved and treated. The pituitary gland was involved 4 years ago. A thyrotropin-releasing hormone test showed delayed response suggestive of hypothalamic disease. Prolactin levels were normal. A gonadotropin-releasing hormone test showed impaired testosterone and gonadotrophin response in keeping with pituitary disease. A glucagon stimulation test showed an impaired growth hormone response but a normal cortisol increase. MRI pituitary showed an empty sella. There was no evidence of diabetes insipidus. Bone mineral densitometry was normal. He has partial hypopituitarism needing thyroxine and testosterone replacement. He also developed type 2 diabetes mellitus 9 years ago. He is closely monitored for any development of diabetes insipidus and the need for growth hormone supplementation. PMID:22715201

Thermodynamic models for bounding pressurant mass requirements of cryogenic tanks

NASA Technical Reports Server (NTRS)

Vandresar, Neil T.; Haberbusch, Mark S.

1994-01-01

Thermodynamic models have been formulated to predict lower and upper bounds for the mass of pressurant gas required to pressurize a cryogenic tank and then expel liquid from the tank. Limiting conditions are based on either thermal equilibrium or zero energy exchange between the pressurant gas and initial tank contents. The models are independent of gravity level and allow specification of autogenous or non-condensible pressurants. Partial liquid fill levels may be specified for initial and final conditions. Model predictions are shown to successfully bound results from limited normal-gravity tests with condensable and non-condensable pressurant gases. Representative maximum collapse factor maps are presented for liquid hydrogen to show the effects of initial and final fill level on the range of pressurant gas requirements. Maximum collapse factors occur for partial expulsions with large final liquid fill fractions.

[Protein metabolism in vegans].

PubMed

Okuda, T; Miyoshi-Nishimura, H; Makita, T; Sugawa-Katayama, Y; Hazama, T; Simizu, T; Yamaguchi, Y

1994-11-01

To elucidate the mechanisms of adaptation to a low-energy and low-protein vegan diet, we carried out dietary surveys and nitrogen balance studies five times during one year on two women and a man who ate raw brown rice, raw green vegetables, three kinds of raw roots, fruit and salt daily. Individual subjects modified this vegan diet slightly. The mean daily energy intake of the subjects was 18, 14, and 32 kcal/kg, of body weight. The loss of body weight was about 10% of the initial level. The daily nitrogen balance was -32, -33, and -11 mg N/kg of body weight. In spite of the negative nitrogen balance, the results of routine clinical tests, initially normal, did not change with the vegan diet. Ten months after the start of the vegan diet, the subjects were given 15N urea orally. The incorporation of 15N into serum proteins suggested that these subjects could utilize urea nitrogen for body protein synthesis. The level of 15N in serum proteins was close to the level in other normal adult men on a low-protein diet with adequate energy for 2 weeks.

Optimizing treatment of hypothyroidism.

PubMed

Clarke, Nick; Kabadi, Udaya M

2004-01-01

Several thyroid hormone preparations are currently available, including levothyroxine sodium (thyroxine), liothyronine (triiodothyronine), and desiccated thyroid extract, as well as a combination of levothyroxine sodium and liothyronine. Levothyroxine sodium monotherapy at an appropriate daily dose provides uniform levels of both thyroxine and triiodothyronine in the circulation without diurnal variation. Therefore, it is the preparation of choice in most patients with hypothyroidism of both the primary and central types. A normal thyrotropin (TSH) level of 1-2 mU/L is considered the determinant of optimal daily levothyroxine sodium dose in patients with primary hypothyroidism, whereas normal thyroxine and triiodothyronine levels in the mid or upper normal range may denote optimal replacement in patients with central hypothyroidism. Optimal daily levothyroxine sodium dose may be determined according to serum TSH level at the time of diagnosis of primary hypothyroidism. Initial administration of close to the full calculated dose of levothyroxine sodium is appropriate for younger patients, reducing the need for follow-up visits and repeated laboratory testing for dose titration. In the elderly and in patients with a history of coronary artery disease (CAD), the well established approach of starting with a low dose and gradually titrating to the full calculated dose is always the best option. Levothyroxine sodium can and should be continued in patients receiving treatment for CAD. Even minor over-replacement during initial titration of levothyroxine sodium should be avoided, because of the risk of cardiac events. Chronic over-replacement may induce osteoporosis, particularly in postmenopausal women, and should also be avoided.

Subnormal energy expenditure: a putative causal factor in the weight gain induced by treatment of hyperthyroidism.

PubMed

Jacobsen, R; Lundsgaard, C; Lorenzen, J; Toubro, S; Perrild, H; Krog-Mikkelsen, I; Astrup, A

2006-03-01

To examine the causes of weight gain occurring as an adverse effect of treatment of hyperthyroidism. We measured 24-h energy expenditure (EE), body composition and spontaneous physical activity (SPA) in eight patients before and 1 year after treatment of hyperthyroidism was initiated, and eight controls. One year after initiation of treatment thyrotropin was normalized, thyroid hormones had fallen to the lower end of the reference range and fat mass had increased by 3.5 kg (p < 0.001). Twenty-four hour EE adjusted for fat-free mass (FFM) was 15% higher in hyperthyroid patients before treatment than in controls (p = 0.003), and treatment decreased 24-h EE by 1.9 MJ/day (p = 0.001). After treatment, 24-h EE, adjusted for FFM, was similar to the controls. Multiple regression analyses showed that the suppressed EE could partly be attributed to an iatrogenic suppression of thyroid hormones, resulting in lower sleeping EE. Twenty-four hour SPA was normal in the hyperthyroid state, but decreased after treatment by 21% (p = 0.045), to a level not significantly different, but still below that of the controls. The study suggests that weight gain during treatment of hyperthyroidism might be due to subnormal levels of EE and SPA caused by a suppression of the thyroid hormone to a level in the lower end of the normal range.

[Metabolic activity of neutrophilic granulocytes and possible ways of its correction in patients with acute coronary syndrome].

PubMed

Ryzhkova, N A; Havrylenko, T I; Parkhomenko, O M; Kozhukhov, S M

2011-01-01

The present study aimed to investigate the metabolic activity of neutrocytes and the action of corvitin on the level of superoxide anion and myeloperoxidases of cells in vitro with the calculation of index of consumption of myeloperoxidase in patients with ST-elevation acute coronary syndrome. Patient were divided into 2 groups according to the level of superoxide anion. Group 1 included the patients (68%) with the initially low level of superoxide anion, and adding of corvitin to the cells of such patients promoted normalization of this index. In this group we observed also neutrocytosis, low index of consumption of myeloperoxidase and a high level of this enzyme in general population of neutrocytes. Group 2 included patients (32%) with initially normal level of superoxide anion. In this group, corvitin did not influence substantially this factor. Such patients had a level ofmyeloperoxidase within control values and the index of consumption of this enzyme was also within control values. The analysis of hospital period showed that the patients of group 1 had a higher frequency of ventricular tachycardia/ventricular fibrillation, paroxysms of atrial fibrillation, bundle-branch blocks and worsening of the kidney function. We suppose that a low level of superoxide anion in neutrocytes play a major role in the development of complications in patients with acute coronary syndrome. An intravenous administration of corvitin was effective in restoring the metabolic activity of neutrocytes.

Dental hyponatraemia.

PubMed

Simpson, R M

2011-08-01

A 14-year-old girl developed dental pain and was treated for acute infected pulpitis of her right upper lateral incisor with drilling and filling. The pain continued and was helped by analgesia, sucking ice cubes and drinking cold water. Forty-eight hours later, she became confused and disoriented. She started to vomit and complained of headache. Investigations revealed hyponatraemia with normal serum potassium levels and initially normal urinary sodium excretion. Over the next 24 hours, she passed 5.45 L of urine and her serum sodium rose from 125 to 143 mmol/L. Self-induced water intoxication has been described during drinking games and initiation ceremonies, but this would appear to an unusual cause. Conservative management proved successful in allowing this girl to recover without sequelae.

The membrane mucin MUC4 is elevated in breast tumor lymph node metastases relative to matched primary tumors and confers aggressive properties to breast cancer cells.

PubMed

Workman, Heather C; Miller, Jamie K; Ingalla, Ellen Q; Kaur, Rouminder P; Yamamoto, Diane I; Beckett, Laurel A; Young, Lawrence Jt; Cardiff, Robert D; Borowsky, Alexander D; Carraway, Kermit L; Sweeney, Colleen; Carraway, Kermit L

2009-01-01

Previous studies indicate that overexpression of the membrane-associated mucin MUC4 is potently anti-adhesive to cultured tumor cells, and suppresses cellular apoptotic response to a variety of insults. Such observations raise the possibility that MUC4 expression could contribute to tumor progression or metastasis, but the potential involvement of MUC4 in breast cancer has not been rigorously assessed. The present study aimed to investigate the expression of the membrane mucin MUC4 in normal breast tissue, primary breast tumors and lymph node metastases, and to evaluate the role of MUC4 in promoting the malignant properties of breast tumor cells. MUC4 expression levels in patient-matched normal and tumor breast tissue was initially examined by immunoblotting lysates of fresh frozen tissue samples with a highly specific preparation of anti-MUC4 monoclonal antibody 1G8. Immunohistochemical analysis was then carried out using tissue microarrays encompassing patient-matched normal breast tissue and primary tumors, and patient-matched lymph node metastases and primary tumors. Finally, shRNA-mediated knockdown was employed to assess the contribution of MUC4 to the cellular growth and malignancy properties of JIMT-1 breast cancer cells. Immunoblotting and immunohistochemistry revealed that MUC4 levels are suppressed in the majority (58%, p < 0.001) of primary tumors relative to patient-matched normal tissue. On the other hand, lymph node metastatic lesions from 37% (p < 0.05) of patients expressed higher MUC4 protein levels than patient-matched primary tumors. MUC4-positive tumor emboli were often found in lymphovascular spaces of lymph node metastatic lesions. shRNA-mediated MUC4 knockdown compromised the migration, proliferation and anoikis resistance of JIMT-1 cells, strongly suggesting that MUC4 expression actively contributes to cellular properties associated with breast tumor metastasis. Our observations suggest that after an initial loss of MUC4 levels during the transition of normal breast tissue to primary tumor, the re-establishment of elevated MUC4 levels confers an advantage to metastasizing breast tumor cells by promoting the acquisition of cellular properties associated with malignancy.

RED BLOOD CELL PRESERVATION.

DTIC Science & Technology

red cells were assayed by ion exchange chromatography. The O-day 2,3- diphosphoglycerate concentrations of the ACD-AP bloods were below the normal...adenosine or guanosine. After a small initial increase, the ADP levels remained fairly constant. The AMP values increased as the ATP decreased and in

IGF-1 levels may increase paradoxically with dopamine agonist treatment for prolactinomas.

PubMed

Akirov, Amit; Greenman, Yona; Glaser, Benjamin; S'chigol, Irena; Mansiterski, Yossi; Eizenberg, Yoav; Shraga-Slutzky, Ilana; Shimon, Ilan

2018-05-04

Hyperprolactinemia is common in acromegaly and in these patients, insulin-like growth factor (IGF)-1 level may decrease with dopamine agonist. We report a series of patients with prolactinoma and a paradoxical increase of IGF-1 levels during cabergoline treatment. Clinical characteristics and response to treatment of patients with prolactinomas, in whom normal or slightly elevated baseline IGF-1 levels increased with cabergoline. The cohort consisted of ten prolactinoma patients (nine males, mean age 48 ± 14 years). Mean adenoma size was 23.8 ± 16.2 mm, with cavernous sinus invasion in eight. In five patients baseline IGF-1 levels were normal and in four levels were 1.2-1.5-fold the upper limit of the normal (ULN). One patient had IGF-1 measured shortly after initiating cabergoline and it was 1.4 × ULN. During cabergoline treatment (dose range 0.5-2 mg/week) PRL normalization was achieved in all and tumor shrinkage occurred in seven patients. The mean IGF-1 increase on cabergoline was 1.7 ± 0.4 × ULN. Cabergoline dose reduction or interruption was attempted in five patients and resulted in decreased IGF-1 levels in all, including normalization in two patients. Three patients were eventually diagnosed with acromegaly, one was referred for pituitary surgery followed by complete remission, another patient was switched to somatostatin analogue, and the third was treated by combination of somatostatin analogues with pegvisomant, with reduction of IGF-1 in all these patients. IGF-1 levels may increase to clinically significant levels during cabergoline treatment for PRL-adenoma. We suggest IGF-1 monitoring in all patients treated with dopamine agonists and not only in those presenting symptoms of acromegaly.

Reference values for maternal total and differential leukocyte counts in different trimesters of pregnancy and the initial postpartum period in western Turkey.

PubMed

Sanci, Muzaffer; Töz, Emrah; Ince, Onur; Özcan, Aykut; Polater, Kevser; Inan, Abdurrahman Hamdi; Beyan, Emrah; Akkaya, Emrah

2017-07-01

The aim of this study was to investigate alterations in the leukocyte and differential leukocyte counts in different trimesters of pregnancy and the initial postpartum period. The study population consisted of 40,325 pregnant women. A full blood count and automated differential leukocyte count were performed and all the haemogram results in the different trimesters of pregnancy were recorded. Percentiles were calculated using statistical software. A total of 82,786 complete blood count evaluations were performed in 40,325 subjects from the 6th to 41st week of pregnancy and in the initial postpartum period. The leukocyte counts increased from the 1st to the 3rd trimester and peaked in the initial postpartum period. Our reference values for the total and differential leukocyte counts may assist clinicians in distinguishing between leukocytosis and pathological elevation of the white blood cell count during pregnancy and the initial postpartum period. Impact statement Pregnancy requires profound adaptation by multiple systems to accommodate the demands of the developing foetus. Similar to all other systems, many haematological changes occur during pregnancy. Studies of normal variation in leukocyte counts were insufficient to distinguish normal from abnormal leukocyte counts during pregnancy and in the initial postpartum period, due to small numbers of patients and a lack of differential leukocyte counts. Without reference leukocyte levels, infections may be more difficult to assess during pregnancy and in the postpartum period. In this study, we report the 3rd, 5th, 10th, 50th, 95th and 99th percentile values for the total and differential leukocyte counts according to trimester in normal pregnancy and the initial postpartum period. Our reference values for the total and differential leukocyte counts in each trimester and the initial postpartum period may assist clinicians in distinguishing between normal leukocytosis and pathological elevation of the white blood cell count during pregnancy and the initial postpartum period. Our results may prevent misdiagnosis of physiological elevated leukocytes as bacterial infection that leads to unnecessary medication use that may compromise the foetus.

Spontaneous normalization of anti-tissue transglutaminase antibody levels is common in children with type 1 diabetes mellitus.

PubMed

Waisbourd-Zinman, Orith; Hojsak, Iva; Rosenbach, Yoram; Mozer-Glassberg, Yael; Shalitin, Shlomit; Phillip, Moshe; Shamir, Raanan

2012-05-01

The prevalence of celiac disease among type 1 diabetes mellitus (T1DM) patients is 5-10 times higher than in the general population. Thus, evaluation of celiac serology is indicated at diagnosis of T1DM and on follow up. This study was prompted by the observation that elevated anti-TTG antibody levels in diabetic children may spontaneously normalize despite continued consumption of gluten. The objective of the study was to investigate the prevalence of this phenomenon and associated factors. The files of all children diagnosed with type 1 diabetes mellitus from 2003-2009 at a tertiary pediatric medical center were reviewed for those with elevated serum levels of anti-TTG antibody. Clinical, medical, laboratory, and treatment data were collected. Findings were compared between patients diagnosed with celiac disease and patients with initially elevated anti-TTG antibody levels that spontaneously normalized. Forty-eight of the 738 patients with type 1 diabetes attending our center (6.5%) had elevated anti-TTG antibody blood levels. Celiac disease was diagnosed in 23, and anti-TTG antibody levels normalized in 17 (35.4%), all of whom consumed gluten. At one-year follow-up, there was no significant difference between the groups in HbA1c level or change in anthropometric measurements. Physicians treating children with type 1 diabetes and mildly elevated anti-TTG antibody levels might consider 12-month serologic follow-up on a gluten-containing diet rather than immediate duodenal biopsy.

EA 18G Growler Aircraft (EA 18G)

DTIC Science & Technology

2015-12-01

10051.9 N/A 13186.9 8636.4 11550.1 15672.4 1 APB Breach Confidence Level Confidence Level of cost estimate for current APB: 50% The current...estimate recommendation aims to provide sufficient resources to execute the program under normal conditions, encountering average levels of technical...TY $M) Initial PAUC Development Estimate Changes PAUC Production Estimate Econ Qty Sch Eng Est Oth Spt Total 93.573 4.150 1.442 -0.319 0.947 -0.348

Eight-year follow-up of a child with a GH/prolactin-secreting adenoma: efficacy of pegvisomant therapy.

PubMed

Bergamaschi, S; Ronchi, C L; Giavoli, C; Ferrante, E; Verrua, E; Ferrari, D I; Lania, A; Rusconi, R; Spada, A; Beck-Peccoz, P

2010-01-01

A 3.4-year-old girl was admitted to the Pediatric Department because of tall stature (116.0 cm, +5.1 SDS) and increased height velocity (16.3 cm/year, +6.1 SDS). Basal hormonal evaluation revealed elevated insulin-like growth factor I (IGF-I) levels (938 ng/ml, nv 40-190), prolactin (PRL) (98.0 ng/ml, nv 1.7-24.0) and mean growth hormone (GH) nocturnal concentration (147 ng/ml). Basal adrenal, gonadal and thyroid functions were normal. Hand-wrist bone age was 3.6 years. Magnetic resonance imaging revealed a macroadenoma with moderate suprasellar invasion. The adenoma was surgically removed and histological characterization confirmed the diagnosis of GH/PRL-secreting adenoma. The patient was admitted to our Endocrine Unit when 7.9 years old, because of the persistence of elevated GH, IGF-I and PRL levels, although there was a slight height velocity reduction and absence of tumor recurrence. Treatment with cabergoline was initiated, but only PRL levels normalized. Afterwards, octreotide long-acting release (LAR) was added without reaching the normalization of GH and IGF-I levels. Thus, treatment with octreotide LAR was discontinued and pegvisomant was added to cabergoline, leading to the normalization of IGF-I levels and height velocity without side effects. Other anterior pituitary functions were always normal. To conclude, treatment of pituitary gigantism with pegvisomant was effective and well tolerated in a young giant unresponsive to combined cabergoline and octreotide treatment.

Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure.

PubMed

Teinturier, C; Hartmann, O; Valteau-Couanet, D; Benhamou, E; Bougneres, P F

1998-11-01

We studied pubertal status and ovarian function in 21 girls aged 11-21 years who had earlier received 1.2-13 years (median 7 years) high-dose chemotherapy and autologous BMT without TBI for malignant tumors. Ten of them were given busulfan (600 mg/m2) and melphalan (140 mg/m2) with or without cyclophosphamide (3.6 g/m2). Eleven others did not receive busulfan. Twelve girls (57%) had clinical and hormonal evidence of ovarian failure. Among nine others who had completed normal puberty, six had normal gonadotropin levels, one had elevated gonadotropin levels and two had gonadotropin levels at the upper limit of normal. The 10 girls who received busulfan all developed severe and persistent ovarian failure. High-dose busulfan is therefore a major cause of ovarian failure even when given in the prepubertal period. These findings emphasize the need for long-term endocrine follow-up of these patients in order to initiate estrogen replacement therapy.

eIF4E Threshold Levels Differ in Governing Normal and Neoplastic Expansion of Mammary Stem and Luminal Progenitor cells

PubMed Central

Avdulov, Svetlana; Herrera, Jeremy; Smith, Karen; Peterson, Mark; Gomez-Garcia, Jose R.; Beadnell, Thomas C.; Schwertfeger, Kathryn L.; Benyumov, Alexey O.; Manivel, J. Carlos; Li, Shunan; Bielinsky, Anja-Katrin; Yee, Douglas; Bitterman, Peter B.; Polunovsky, Vitaly A.

2015-01-01

Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when overexpressed. The mechanisms by which eIF4E directs such distinct biological outputs remains unknown. We found that mouse mammary morphogenesis during pregnancy and lactation is accompanied by increased cap-binding capability of eIF4E and activation of the eIF4E-dependent translational apparatus, but only subtle oscillations in eIF4E abundance. Using a transgenic mouse model engineered so that lactogenic hormones stimulate a sustained increase in eIF4E abundance in stem/progenitor cells of lactogenic mammary epithelium during successive pregnancy/lactation cycles, eIF4E overexpression increased cell self-renewal, triggered DNA replication stress, and induced formation of pre-malignant and malignant lesions. Using complementary in vivo and ex vivo approaches, we found that increasing eIF4E levels rescued cells harboring oncogenic c-Myc or H-RasV12 from DNA replication stress and oncogene-induced replication catastrophe. Our findings indicate that distinct threshold levels of eIF4E govern its biological output in lactating mammary glands, and that eIF4E overexpression in the context of stem/progenitor cell population expansion can initiate malignant transformation by enabling cells to evade DNA damage checkpoints activated by oncogenic stimuli. Maintaining eIF4E levels below its pro-neoplastic threshold is an important anticancer defense in normal cells, with important implications for understanding pregnancy-associated breast cancer. PMID:25524901

eIF4E threshold levels differ in governing normal and neoplastic expansion of mammary stem and luminal progenitor cells.

PubMed

Avdulov, Svetlana; Herrera, Jeremy; Smith, Karen; Peterson, Mark; Gomez-Garcia, Jose R; Beadnell, Thomas C; Schwertfeger, Kathryn L; Benyumov, Alexey O; Manivel, J Carlos; Li, Shunan; Bielinsky, Anja-Katrin; Yee, Douglas; Bitterman, Peter B; Polunovsky, Vitaly A

2015-02-15

Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when overexpressed. The mechanisms by which eIF4E directs such distinct biologic outputs remain unknown. We found that mouse mammary morphogenesis during pregnancy and lactation is accompanied by increased cap-binding capability of eIF4E and activation of the eIF4E-dependent translational apparatus, but only subtle oscillations in eIF4E abundance. Using a transgenic mouse model engineered so that lactogenic hormones stimulate a sustained increase in eIF4E abundance in stem/progenitor cells of lactogenic mammary epithelium during successive pregnancy/lactation cycles, eIF4E overexpression increased self-renewal, triggered DNA replication stress, and induced formation of premalignant and malignant lesions. Using complementary in vivo and ex vivo approaches, we found that increasing eIF4E levels rescued cells harboring oncogenic c-Myc or H-RasV12 from DNA replication stress and oncogene-induced replication catastrophe. Our findings indicate that distinct threshold levels of eIF4E govern its biologic output in lactating mammary glands and that eIF4E overexpression in the context of stem/progenitor cell population expansion can initiate malignant transformation by enabling cells to evade DNA damage checkpoints activated by oncogenic stimuli. Maintaining eIF4E levels below its proneoplastic threshold is an important anticancer defense in normal cells, with important implications for understanding pregnancy-associated breast cancer. ©2014 American Association for Cancer Research.

A mechanical energy analysis of gait initiation

NASA Technical Reports Server (NTRS)

Miller, C. A.; Verstraete, M. C.

1999-01-01

The analysis of gait initiation (the transient state between standing and walking) is an important diagnostic tool to study pathologic gait and to evaluate prosthetic devices. While past studies have quantified mechanical energy of the body during steady-state gait, to date no one has computed the mechanical energy of the body during gait initiation. In this study, gait initiation in seven normal male subjects was studied using a mechanical energy analysis to compute total body energy. The data showed three separate states: quiet standing, gait initiation, and steady-state gait. During gait initiation, the trends in the energy data for the individual segments were similar to those seen during steady-state gait (and in Winter DA, Quanbury AO, Reimer GD. Analysis of instantaneous energy of normal gait. J Biochem 1976;9:253-257), but diminished in amplitude. However, these amplitudes increased to those seen in steady-state during the gait initiation event (GIE), with the greatest increase occurring in the second step due to the push-off of the foundation leg. The baseline level of mechanical energy was due to the potential energy of the individual segments, while the cyclic nature of the data was indicative of the kinetic energy of the particular leg in swing phase during that step. The data presented showed differences in energy trends during gait initiation from those of steady state, thereby demonstrating the importance of this event in the study of locomotion.

Changes in the predominant human Lactobacillus flora during in vitro fertilisation

PubMed Central

Jakobsson, Tell; Forsum, Urban

2008-01-01

Background Signature matching of nucleotide sequences in the V1 and V3 regions 16S rRNA genes using pyrosequencing technology is a powerful tool for typing vaginal Lactobacilli to the species level and has been used for investigating the vaginal microbial niche. Methods This study has characterized the normal cultivable vaginal Lactobacillus flora at varying estradiol levels in plasma; the study comprised 17 patients undergoing ovarian stimulation for In Vitro Fertilization (IVF) treatment. The vaginal status of each participant was initially assessed as normal according to Amsel and Nugent criteria. Results L. crispatus, L. gasseri and/or L. jensenii were present in 10 of the patients throughout the study period, and little variation among these three species was encountered in individual patients. The flora of three women was dominated by L. delbrüeckii, L. rhamnosus or L. vaginalis. One woman exhibited a dominance of L. iners. The flora of the remaining three women were initially dominated by L. rhamnosus or L. reuteri, but as their estrogen levels rose, their flora composition altered, to become dominated by one of the three species most common in a normal, healthy vagina. Conclusion Signature matching of nucleotide sequences in the V1 and V3 regions of 16S rRNA genes is a discriminative tool for the study of vaginal Lactobacilli and can be used to track the Lactobacillus flora under a variety of physiological conditions. PMID:18590533

ERP C250 Shows the Elderly (Cognitively Normal, Alzheimer’s Disease) Store More Stimuli in Short-Term Memory than Young Adults Do

PubMed Central

Chapman, Robert M.; Gardner, Margaret N.; Mapstone, Mark; Klorman, Rafael; Porsteinsson, Anton P.; Dupree, Haley M.; Antonsdottir, Inga M.; Kamalyan, Lily

2016-01-01

Objective To determine how aging and dementia affect the brain’s initial storing of task-relevant and irrelevant information in short-term memory. Methods We used brain Event-Related Potentials (ERPs) to measure short-term memory storage (ERP component C250) in 36 Young Adults, 36 Normal Elderly, and 36 early-stage AD subjects. Participants performed the Number-Letter task, a cognitive paradigm requiring memory storage of a first relevant stimulus to compare it with a second stimulus. Results In Young Adults, C250 was more positive for the first task-relevant stimulus compared to all other stimuli. C250 in Normal Elderly and AD subjects was roughly the same to relevant and irrelevant stimuli in intratrial parts 1–3 but not 4. The AD group had lower C250 to relevant stimuli in part 1. Conclusions Both normal aging and dementia cause less differentiation of relevant from irrelevant information in initial storage. There was a large aging effect involving differences in the pattern of C250 responses of the Young Adult versus the Normal Elderly/AD groups. Also, a potential dementia effect was obtained. Significance C250 is a candidate tool for measuring short-term memory performance on a biological level, as well as a potential marker for memory changes due to normal aging and dementia. PMID:27178862

Dysfunction of protein kinase FA/GSK-3 alpha in lymphocytes of patients with schizophrenic disorder.

PubMed

Yang, S D; Yu, J S; Lee, T T; Yang, C C; Ni, M H; Yang, Y Y

1995-09-01

As compared to normal people, the lymphocytes of patients with schizophrenia were found to have an impairment of ATP.Mg-dependent protein phosphatase activation. More importantly, the impaired protein phosphatase activation in the lymphocytes of schizophrenic patients could be consistently and completely restored to normal by exogenous pure protein kinase FA/glycogen synthase kinase-3 alpha (kinase FA/GSK-3 alpha) (the activating factor of ATP.Mg-dependent protein phosphatase), indicating that the molecular mechanism for the impaired protein phosphatase activation in schizophrenic patients may be due to a functional loss of kinase FA/GSK-3 alpha. Immunoblotting and kinase activity analysis in an anti-kinase FA/GSK-3 alpha immunoprecipitate further demonstrate that both cellular activities and protein levels of kinase FA/GSK-3 alpha in the lymphocytes of schizophrenic patients were greatly impared as compared to normal controls. Statistical analysis revealed that the lymphocytes isolated from 37 normal people contain kinase FA/GSK-3 alpha activity in the high levels of 14.8 +/- 2.4 units/mg of cell protein, whereas the lymphocytes of 48 patients with schizophrenic disorder contain kinase FA/GSK-3 alpha activity in the low levels of 2.8 +/- 1.6 units/mg, indicating that the different levels of kinase FA/GSK-3 alpha activity between schizophrenic patients and normal people are statistically significant. Taken together, the results provide initial evidence that patients with schizophrenic disorder may have a common impairment in the protein levels and cellular activities of kinase FA/GSK-3 alpha, a multisubstrate protein kinase and a multisubstrate protein phosphatase activator in their lymphocytes.

The harmless acute pancreatitis score: a clinical algorithm for rapid initial stratification of nonsevere disease.

PubMed

Lankisch, Paul Georg; Weber-Dany, Bettina; Hebel, Kathrin; Maisonneuve, Patrick; Lowenfels, Albert B

2009-06-01

Only severe acute pancreatitis requires treatment, according to the principles of intensive care medicine in an intensive care or intermediate care unit. The aim of the study was to define and evaluate a simple clinical algorithm for rapid initial identification of patients with a first attack of acute pancreatitis who do not require intensive care. This prospective study included 394 patients who were admitted to the Municipal Clinic of Lüneburg, Germany, between 1987 and 2003. From a number of parameters of disease severity on admission, 3 parameters that showed the strongest prediction of a nonsevere course (no rebound tenderness and/or guarding, normal hematocrit level, and normal serum creatinine level) were combined to form the harmless acute pancreatitis score (HAPS). The score then was validated in a German multicenter study including 452 patients between 2004 and 2006. In both the initial and the validation set, the HAPS correlated with a nonsevere course of the disease (P < .0001). The score correctly identified a harmless course in 200 (98%) of 204 patients. The HAPS enables identification, within approximately 30 minutes after admission, of patients with acute pancreatitis whose disease will run a mild course. The high level of accuracy of this test (98%) will allow physicians to identify patients quickly who do not require intensive care, and potentially those who will not require inpatient treatment at all. Thus, the HAPS may save substantial hospital costs.

Dietary Vitamin K intake and anticoagulation control during the initiation phase of warfarin therapy: A prospective cohort study

USDA-ARS?s Scientific Manuscript database

The effect of varying levels of dietary vitamin K intake on therapeutic International Normalized Ratio (INR) values among patients starting warfarin therapy has not been well studied. We performed a prospective cohort study among 282 patients to explore the independent associations between usual in...

Stress-induced ascorbic acid depletion and cortisol production in two salmonid fishes

USGS Publications Warehouse

Wedemeyer, Gary

1969-01-01

Interrenal ascorbic acid and serum cortisol were measured in non-specificity stressed yearling coho salmon and rainbow trout.Interrenal ascorbate was markedly decreased during stress but increased to normal if adaptation occurred.Serum cortisol was elevated by non-specific stress and remained high after interrenal ascorbate had returned to initial levels.

Subclinical Obsessive-Compulsive Symptoms, Cognitive Processes, School Achievement, and Intelligence-Achievement Relationship in Adolescents

ERIC Educational Resources Information Center

Malakar, Partha; Basu, Jayanti

2017-01-01

The aim of the study was to determine whether the general intelligence, cognitive processes, school achievement, and intelligence-achievement relationship of adolescents with subclinical levels of obsessive-compulsive symptoms differed from those of their normal counterparts. From an initial large pool of 14-year-old Bengali students in eighth…

Effect of a prenatal lifestyle intervention on physical activity level in late pregnancy and the first year postpartum

PubMed Central

Sagedal, Linda Reme; Haakstad, Lene Annette Hagen; Lohne-Seiler, Hilde

2017-01-01

Background Despite documented health benefits for mother and baby, physical activity (PA)-level tends to decline in pregnancy. Overweight/obese and physically inactive women are two selected groups at increased risk of pregnancy complications. Thus, efficient strategies to maintain or increase PA-level in pregnancy and the postpartum period, especially among these women, are warranted. This secondary analysis examined the effect of a prenatal lifestyle-intervention on PA-level in late pregnancy and the first year postpartum, with subanalysis on initially physically active versus inactive and normal-weight versus overweight/obese women. Method The Norwegian Fit for Delivery (NFFD) randomized controlled trial included healthy primiparous women with singleton pregnancies and body mass index (BMI) ≥19 kg/m2 assigned to an intervention group, n = 303 (twice weekly group-exercises and dietary counseling) or a control group, n = 303 (standard prenatal care). The International Physical Activity Questionnaire short-form was used to assess PA-levels at inclusion (mean gestational week (GW) 16), GW 36, and six and 12 months postpartum. Results At GW 36, a positive intervention-effect with a significant between-group difference in total PA-level compared to time of inclusion was found for the total group (530 MET-min/week, p = 0.001) and the subgroups of normal-weight (533 MET-min/week, p = 0.003) and initially active women (717 MET-min/week, p<0.001). Intervention-effect was dependent on exercise-adherence among overweight/obese and inactive women. Compared to time of inclusion, the intervention groups maintained total PA-level at GW 36, while total PA-level decreased in the control groups. The PA-levels increased postpartum, but with no significant differences between the randomization groups. Conclusion The NFFD prenatal combined lifestyle intervention had a significant effect on TPA-level in late pregnancy among women entering pregnancy normal-weight or physically active, thereby preventing the downward trend typically seen during pregnancy. Intervention-effect among overweight/obese and physically inactive women was, however, dependent on exercise-adherence. Long-term intervention-effect was not observed in the postpartum period. PMID:29176762

Effect of a prenatal lifestyle intervention on physical activity level in late pregnancy and the first year postpartum.

PubMed

Sanda, Birgitte; Vistad, Ingvild; Sagedal, Linda Reme; Haakstad, Lene Annette Hagen; Lohne-Seiler, Hilde; Torstveit, Monica Klungland

2017-01-01

Despite documented health benefits for mother and baby, physical activity (PA)-level tends to decline in pregnancy. Overweight/obese and physically inactive women are two selected groups at increased risk of pregnancy complications. Thus, efficient strategies to maintain or increase PA-level in pregnancy and the postpartum period, especially among these women, are warranted. This secondary analysis examined the effect of a prenatal lifestyle-intervention on PA-level in late pregnancy and the first year postpartum, with subanalysis on initially physically active versus inactive and normal-weight versus overweight/obese women. The Norwegian Fit for Delivery (NFFD) randomized controlled trial included healthy primiparous women with singleton pregnancies and body mass index (BMI) ≥19 kg/m2 assigned to an intervention group, n = 303 (twice weekly group-exercises and dietary counseling) or a control group, n = 303 (standard prenatal care). The International Physical Activity Questionnaire short-form was used to assess PA-levels at inclusion (mean gestational week (GW) 16), GW 36, and six and 12 months postpartum. At GW 36, a positive intervention-effect with a significant between-group difference in total PA-level compared to time of inclusion was found for the total group (530 MET-min/week, p = 0.001) and the subgroups of normal-weight (533 MET-min/week, p = 0.003) and initially active women (717 MET-min/week, p<0.001). Intervention-effect was dependent on exercise-adherence among overweight/obese and inactive women. Compared to time of inclusion, the intervention groups maintained total PA-level at GW 36, while total PA-level decreased in the control groups. The PA-levels increased postpartum, but with no significant differences between the randomization groups. The NFFD prenatal combined lifestyle intervention had a significant effect on TPA-level in late pregnancy among women entering pregnancy normal-weight or physically active, thereby preventing the downward trend typically seen during pregnancy. Intervention-effect among overweight/obese and physically inactive women was, however, dependent on exercise-adherence. Long-term intervention-effect was not observed in the postpartum period.

Dietary Management of Hyperthyroidism in a Dog.

PubMed

Looney, Andrea; Wakshlag, Joseph

An 8 yr old female spayed golden retriever presented for a routine exam during which ventral cervical soft tissue masses were identified. History included weight loss, increased activity and appetite, gagging, and occasional diarrhea. Exam findings included a body condition score of 4/9 and palpable ventral cervical nodules. A serum thyroxine (T4) value was 8.0 ug/dL (normal = 0.8-3.5ug/dL). Doppler systolic blood pressure readings ranged from 200-210 mmHg (normal systolic blood pressure <150 mmHg). The diagnosis was hyperthyroidism due to active thyroid masses. Due to financial constraints, the owner elected conservative management. Initial treatment with methimazole resulted in a decreased T4 value of 5.0 ug/dL at approximately 4 mo after initiation of treatment. A commercially available iodine-restricted feline diet was fed and this resulted in further reduction in serum T4 levels, improved sleeping cycles, reduced anxiety, and reduced systolic blood pressure. A temporary suspension of iodine-restricted feline diet for 2 mo resulted in increases in serum T4 concentrations, which, subsequently, decreased with re-introduction of the diet. Roughly 10 mo after initiation of the therapeutic diet and 16 mo after intial diagnosis, the dog remains relatively normal clinically despite active growing cervical masses with T4 concentration of 2.3 ug/dL.

3D geometries of normal faults in a brittle-ductile sedimentary cover: Analogue modelling

NASA Astrophysics Data System (ADS)

Vasquez, Lina; Nalpas, Thierry; Ballard, Jean-François; Le Carlier De Veslud, Christian; Simon, Brendan; Dauteuil, Olivier; Bernard, Xavier Du

2018-07-01

It is well known that ductile layers play a major role in the style and location of deformation. However, at the scale of a single normal fault, the impact of rheological layering is poorly constrained and badly understood, and there is a lack of information regarding the influence of several décollement levels within a sedimentary cover on the single fault geometry under purely extensive deformation. We present small-scale experiments that were built with interbedded layers of brittle and ductile materials and with minimum initial constraints (only a velocity discontinuity at the base of the experiment) on the normal fault geometry in order to investigate the influence of controlled parameters such as extension velocity, rate of extension, ductile thickness and varying stratigraphy on the 3D fault geometry. These experiments showed a broad-spectrum of tectonic features such as grabens, ramp-flat-ramp normal faults and reverse faults. Forced folds are associated with fault flats that develop in the décollement levels (refraction of the fault angle). One of the key points is that the normal fault geometry displays large variations in both direction and dip, despite the imposed homogeneous extension. This result is exclusively related to the presence of décollement levels, and is not associated with any global/regional variation in extension direction and/or inversion.

Fumarate hydratase is a critical metabolic regulator of hematopoietic stem cell functions.

PubMed

Guitart, Amelie V; Panagopoulou, Theano I; Villacreces, Arnaud; Vukovic, Milica; Sepulveda, Catarina; Allen, Lewis; Carter, Roderick N; van de Lagemaat, Louie N; Morgan, Marcos; Giles, Peter; Sas, Zuzanna; Gonzalez, Marta Vila; Lawson, Hannah; Paris, Jasmin; Edwards-Hicks, Joy; Schaak, Katrin; Subramani, Chithra; Gezer, Deniz; Armesilla-Diaz, Alejandro; Wills, Jimi; Easterbrook, Aaron; Coman, David; So, Chi Wai Eric; O'Carroll, Donal; Vernimmen, Douglas; Rodrigues, Neil P; Pollard, Patrick J; Morton, Nicholas M; Finch, Andrew; Kranc, Kamil R

2017-03-06

Strict regulation of stem cell metabolism is essential for tissue functions and tumor suppression. In this study, we investigated the role of fumarate hydratase (Fh1), a key component of the mitochondrial tricarboxylic acid (TCA) cycle and cytosolic fumarate metabolism, in normal and leukemic hematopoiesis. Hematopoiesis-specific Fh1 deletion (resulting in endogenous fumarate accumulation and a genetic TCA cycle block reflected by decreased maximal mitochondrial respiration) caused lethal fetal liver hematopoietic defects and hematopoietic stem cell (HSC) failure. Reexpression of extramitochondrial Fh1 (which normalized fumarate levels but not maximal mitochondrial respiration) rescued these phenotypes, indicating the causal role of cellular fumarate accumulation. However, HSCs lacking mitochondrial Fh1 (which had normal fumarate levels but defective maximal mitochondrial respiration) failed to self-renew and displayed lymphoid differentiation defects. In contrast, leukemia-initiating cells lacking mitochondrial Fh1 efficiently propagated Meis1 / Hoxa9 -driven leukemia. Thus, we identify novel roles for fumarate metabolism in HSC maintenance and hematopoietic differentiation and reveal a differential requirement for mitochondrial Fh1 in normal hematopoiesis and leukemia propagation. © 2017 Guitart et al.

WASP family proteins and formins compete in pseudopod- and bleb-based migration

PubMed Central

2018-01-01

Actin pseudopods induced by SCAR/WAVE drive normal migration and chemotaxis in eukaryotic cells. Cells can also migrate using blebs, in which the edge is driven forward by hydrostatic pressure instead of actin. In Dictyostelium discoideum, loss of SCAR is compensated by WASP moving to the leading edge to generate morphologically normal pseudopods. Here we use an inducible double knockout to show that cells lacking both SCAR and WASP are unable to grow, make pseudopods or, unexpectedly, migrate using blebs. Remarkably, amounts and dynamics of actin polymerization are normal. Pseudopods are replaced in double SCAR/WASP mutants by aberrant filopods, induced by the formin dDia2. Further disruption of the gene for dDia2 restores cells’ ability to initiate blebs and thus migrate, though pseudopods are still lost. Triple knockout cells still contain near-normal F-actin levels. This work shows that SCAR, WASP, and dDia2 compete for actin. Loss of SCAR and WASP causes excessive dDia2 activity, maintaining F-actin levels but blocking pseudopod and bleb formation and migration. PMID:29191847

Resveratrol and Malignancies

PubMed Central

Bunaciu, Rodica P.

2015-01-01

Carcinogenesis is a multifactorial process, frequently encompassing 3 stages: initiation, promotion and progression. It is characterized by multiple deviations from normal both at the cell and organism levels. Although most people have a small number of cells that present deviations from normal, most of those cells will not cause cancer. However, some will. What tips the balance between normal and abnormal is the subject of intense scientific research as well as unfounded speculations. Chronic inflammation is one of the risk factors for cancer. Resveratrol is consumed by the population as a dietary supplement in the hope of decreasing the risk of inflammation and cancer and other chronic diseases such as diabetes and vascular diseases. There is a discrepancy between the doses used in the animal studies showing that resveratrol decreases all three stages of carcinogenesis, and the doses ingested by the population either as supplements or in the diet. While there is health benefit from using high resveratrol doses, it might be also of practical and scientific benefit to focus future effort in understanding the effects of normal dietary resveratrol levels. PMID:26478855

Enforced expression of the c-myc oncogene inhibits cell differentiation by precluding entry into a distinct predifferentiation state in G/sub 0//G/sub 1/

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

Freytag, S.O.

1988-04-01

A broad base of data has implicated a role for the c-myc proto-oncogene in the control of the cell cycle and cell differentiation. To further define the role of myc in these processes, the authors examined the effect of enforced myc expression on several events that are thought to be important steps leading to the terminally differentiated state: (i) the ability to arrest growth in G/sub 0//G/sub 1/, (ii) the ability to replicate the genome upon initiation of the differentiation program, and (iii) the ability to loose responsiveness to mitogens and withdraw from the cell cycle. 3T3-L1 preadipocyte cell linesmore » expressing various levels of myc mRNA were established by transfection with a recombinant myc gene under the transcriptional control of the Rous sarcoma virus (RSV) promoter. Cells that expressed high constitutive levels of pRSV myc mRNA arrested in G/sub 0//G/sub 1/ at densities similar to those of normal cells at confluence. Upon initiation of the differentiation program, such cells traversed the cell cycle with kinetics similar to those of normal cells and subsequently arrested in G/sub 0//G/sub 1/. Thus, enforced expression of myc had no effect on the ability of cells to arrest growth in G/sub 0//G/sub 1/ or to replicate the genome upon initiation of the differentiation program. Cells were then tested for their ability to reenter the cell cycle upon exposure to high concentrations of serum and for their capacity to differentiate. In contrast to normal cells, cells expressing high constitutive levels of myc RNA reentered the cell cycle when challenged with 30% serum and failed to terminally differentiate.« less

Management and surgical treatment of parathyroid crisis secondary to parathyroid tumors: report of four cases.

PubMed

Ameerudden, Shakil; He, Xianghui

2011-01-01

Parathyroid crisis, also known as a parathyroid storm, is a rare and serious complication of primary hyperparathyroidism. Four cases are reported here in which patients presented to hospital with general complaints due to hypercalcemia secondary to hyperparathyroidism. Blood test results upon admission showed high levels of serum calcium and parathyroid hormone, and medical treatment initiated to lower the calcium level was ineffective. After relevant investigations, each patient underwent surgical exploration of the parathyroid glands, followed by excision of a pathological parathyroid tumor. There was a prompt decrease in parathyroid hormone level immediately after surgery. Histology reports revealed that patients had parathyroid adenoma. All patients recovered after surgery, with serum calcium levels restored back to normal and with resolution of all symptoms of hypercalcemia. This report illustrates how often this disease is initially misdiagnosed, and how prompt appropriate surgical treatment provides the best outcome for the patient.

Overexpression of SERBP1 (Plasminogen activator inhibitor 1 RNA binding protein) in human breast cancer is correlated with favourable prognosis.

PubMed

Serce, Nuran Bektas; Boesl, Andreas; Klaman, Irina; von Serényi, Sonja; Noetzel, Erik; Press, Michael F; Dimmler, Arno; Hartmann, Arndt; Sehouli, Jalid; Knuechel, Ruth; Beckmann, Matthias W; Fasching, Peter A; Dahl, Edgar

2012-12-13

Plasminogen activator inhibitor 1 (PAI-1) overexpression is an important prognostic and predictive biomarker in human breast cancer. SERBP1, a protein that is supposed to regulate the stability of PAI-1 mRNA, may play a role in gynaecological cancers as well, since upregulation of SERBP1 was described in ovarian cancer recently. This is the first study to present a systematic characterisation of SERBP1 expression in human breast cancer and normal breast tissue at both the mRNA and the protein level. Using semiquantitative realtime PCR we analysed SERBP1 expression in different normal human tissues (n = 25), and in matched pairs of normal (n = 7) and cancerous breast tissues (n = 7). SERBP1 protein expression was analysed in two independent cohorts on tissue microarrays (TMAs), an initial evaluation set, consisting of 193 breast carcinomas and 48 normal breast tissues, and a second large validation set, consisting of 605 breast carcinomas. In addition, a collection of benign (n = 2) and malignant (n = 6) mammary cell lines as well as breast carcinoma lysates (n = 16) were investigated for SERBP1 expression by Western blot analysis. Furthermore, applying non-radioisotopic in situ hybridisation a subset of normal (n = 10) and cancerous (n = 10) breast tissue specimens from the initial TMA were analysed for SERBP1 mRNA expression. SERBP1 is not differentially expressed in breast carcinoma compared to normal breast tissue, both at the RNA and protein level. However, recurrence-free survival analysis showed a significant correlation (P = 0.008) between abundant SERBP1 expression in breast carcinoma and favourable prognosis. Interestingly, overall survival analysis also displayed a tendency (P = 0.09) towards favourable prognosis when SERBP1 was overexpressed in breast cancer. The RNA-binding protein SERBP1 is abundantly expressed in human breast cancer and may represent a novel breast tumour marker with prognostic significance. Its potential involvement in the plasminogen activator protease cascade warrants further investigation.

Cholecalciferol 20 000 IU Once Weekly in HIV-Positive Patients with Low Vitamin D Levels: Result from a Cohort Study.

PubMed

Noe, Sebastian; Heldwein, Silke; Pascucchi, Rita; Oldenbüttel, Celia; Wiese, C; von Krosigk, Ariane; Jägel-Guedes, Eva; Jäger, Hans; Mayer, Wolfgang; Spinner, Christoph D; Wolf, Eva

To evaluate efficacy and safety of 20 000 IU cholecalciferol weekly in HIV-infected patients. Longitudinal data for 243 HIV-infected patients with paired 25-OH-vitamin D3 values for the same month in 2 consecutive years were stratified by the initiation of supplementation in this retrospective study. After 1 year of administration of cholecalciferol 20 000 IU weekly, about 78% of patients with initial vitamin D level <20 µg/L achieved vitamin D levels >20 µg/L and 42% achieved levels >30 µg/L. Supplemented patients with baseline vitamin D levels <20 µg/L showed a significant risk reduction for hypocalcemia ( P = .006; risk difference: 20.8%) and a significantly lower increase in alkaline phosphatase (AP) compared to those in the nonsubstituted group. The dose of 20 000 IU of cholecalciferol once weekly was found to be safe and effective. Normalization of vitamin D levels within 1 year was observed in 42% to 75% of the patients.

AGM-88E Advanced Anti-Radiation Guided Missile (AGM-88E AARGM)

DTIC Science & Technology

2015-12-01

0.0 0.0 Acq O&M 0.0 0.0 -- 0.0 0.0 0.0 0.0 Total 1528.5 1661.1 N/A 2107.4 1861.4 2026.2 2663.7 1 APB Breach Confidence Level Confidence Level of...normal conditions, encountering average levels of technical, schedule, and programmatic risk and external interference. Based on the rigor in methods...SAR Baseline to Current SAR Baseline (TY $M) Initial PAUC Development Estimate Changes PAUC Production Estimate Econ Qty Sch Eng Est Oth Spt Total

A Novel KCNJ11 Mutation Associated with Transient Neonatal Diabetes

PubMed Central

Gole, Evangelia; Oikonomou, Stavroula; Ellard, Sian; De Franco, Elisa; Karavanaki, Kyriaki

2018-01-01

Neonatal diabetes mellitus (NDM) is a rare type of monogenic diabetes that presents in the first 6 months of life. Activating mutations in the KCNJ11 gene encoding for the Kir6.2 subunit of the ATP-sensitive potassium (KATP ) channel can lead to transient NDM (TNDM) or to permanent NDM (PNDM). A female infant presented on the 22nd day of life with severe hyperglycemia and ketoacidosis (glucose: 907mg/dL, blood gas pH: 6.84, HCO3: 6 mmol/L). She was initially managed with intravenous (IV) fluids and IV insulin. Ketoacidosis resolved within 48 hours and she was started on subcutaneous insulin injections with intermediate acting insulin NPH twice daily requiring initially 0.75-1.35 IU/kg/d. Pre-prandial C-peptide levels were 0.51 ng/mL (normal: 1.77-4.68). Insulin requirements were gradually reduced and insulin administration was discontinued at the age of 10 months with subsequent normal glucose and HbA1c levels. C-peptide levels normalized (pre-prandial: 1.6 ng/mL, postprandial: 2 ng/mL). Genetic analysis identified a novel missense mutation (p.Pro254Gln) in the KCNJ11 gene. We report a novel KCNJ11 mutation in a patient who presented in the first month of life with a phenotype of NDM that subsided at the age of 10 months. It is likely that the novel p.P254Q mutation results in mild impairment of the KATP channel function leading to TNDM. PMID:28943514

Influence of RNase E deficiency on the production of stx2-bearing phages and Shiga toxin in an RNase E-inducible strain of enterohaemorrhagic Escherichia coli (EHEC) O157:H7.

PubMed

Thuraisamy, Thujitha; Lodato, Patricia B

2018-05-01

In enterohaemorrhagic Escherichia coli (EHEC), stx1 or stx2 genes encode Shiga toxin (Stx1 or Stx2, respectively) and are carried by prophages. The production and release of both stx phages and toxin occur upon initiation of the phage lytic cycle. Phages can further disseminate stx genes by infecting naïve bacteria in the intestine. Here, the effect of RNase E deficiency on these two virulence traits was investigated. Cultures of the EHEC strains TEA028-rne containing low versus normal RNase E levels or the parental strain (TEA028) were treated with mitomycin C (MMC) to induce the phage lytic cycle. Phages and Stx2 titres were quantified by the double-agar assay and the receptor ELISA technique, respectively. RNase E deficiency in MMC-treated cells significantly reduced the yield of infectious stx2 phages. Delayed cell lysis and the appearance of encapsidated phage DNA copies suggest a slow onset of the lytic cycle. However, these observations do not entirely explain the decrease of phage yields. stx1 phages were not detected under normal or deficient RNase E levels. After an initial delay, high levels of toxin were finally produced in MMC-treated cultures. RNase E scarcity reduces stx2 phage production but not toxin. Normal concentrations of RNase E are likely required for correct phage morphogenesis. Our future work will address the mechanism of RNase E action on phage morphogenesis.

ERP C250 shows the elderly (cognitively normal, Alzheimer's disease) store more stimuli in short-term memory than Young Adults do.

PubMed

Chapman, Robert M; Gardner, Margaret N; Mapstone, Mark; Klorman, Rafael; Porsteinsson, Anton P; Dupree, Haley M; Antonsdottir, Inga M; Kamalyan, Lily

2016-06-01

To determine how aging and dementia affect the brain's initial storing of task-relevant and irrelevant information in short-term memory. We used brain Event-Related Potentials (ERPs) to measure short-term memory storage (ERP component C250) in 36 Young Adults, 36 Normal Elderly, and 36 early-stage AD subjects. Participants performed the Number-Letter task, a cognitive paradigm requiring memory storage of a first relevant stimulus to compare it with a second stimulus. In Young Adults, C250 was more positive for the first task-relevant stimulus compared to all other stimuli. C250 in Normal Elderly and AD subjects was roughly the same to relevant and irrelevant stimuli in Intratrial Parts 1-3 but not 4. The AD group had lower C250 to relevant stimuli in part 1. Both normal aging and dementia cause less differentiation of relevant from irrelevant information in initial storage. There was a large aging effect involving differences in the pattern of C250 responses of the Young Adult versus the Normal Elderly/AD groups. Also, a potential dementia effect was obtained. C250 is a candidate tool for measuring short-term memory performance on a biological level, as well as a potential marker for memory changes due to normal aging and dementia. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Cholecystokinin Revisited: CCK and the Hunger Trap in Anorexia Nervosa

PubMed Central

Cuntz, Ulrich; Enck, Paul; Frühauf, Erich; Lehnert, Peter; Riepl, Rudolf L.; Fichter, Manfred M.; Otto, Bärbel

2013-01-01

Objective Despite a number of studies in the past decades, the role of Cholecystokinin (CCK) in anorexia nervosa (AN) has remained uncertain. In this study a highly specific assay for the biologically active part of CCK was used in patients with bulimic as well as with the restricting type of AN who were followed over the course of weight gain. Methods Ten patients with restricting and 13 with bulimic AN were investigated upon admission (T0), after a weight gain of at least 2 kg on two consecutive weighting dates (T1), and during the last week before discharge (T2) from inpatient treatment in a specialized clinic. Blood samples were drawn under fasting conditions and 20 and 60 minutes following a standard meal (250 kcal). Data were compared to those of eight controls matched for sex and age. Gastrointestinal complaints of patients were measured by a questionnaire at each of the follow-up time points. Results At admission, AN patients exhibited CCK-levels similar to controls both prior to and after a test meal. Pre and post-meal CCK levels increased significantly after an initial weight gain but decreased again with further weight improvement. CCK release was somewhat lower in bulimic than in restricting type AN but both subgroups showed a similar profile. There was no significant association of CCK release to either initial weight or BMI, or their changes, but CCK levels at admission predicted gastrointestinal symptom improvement during therapy. Conclusions Normal CCK profiles in AN at admission indicates hormonal responses adapted to low food intake while change of eating habits and weight gain results in initially increased CCK release (counteracting the attempts to alter eating behavior) that returns towards normal levels with continuous therapy. PMID:23349895

Exploring Delirium’s Heterogeneity: Association between Arousal Subtypes at Initial Presentation and 6-month Mortality in Older Emergency Department Patients

PubMed Central

Han, Jin H.; Brummel, Nathan E.; Chandrasekhar, Rameela; Wilson, Jo Ellen; Liu, Xulei; Vasilevskis, Eduard E.; Girard, Timothy D.; Carlo, Maria E.; Dittus, Robert S.; Schnelle, John F.; Ely, E. Wesley

2016-01-01

Objectives To determine how delirium subtyped by level of arousal at initial presentation affects 6-month mortality. Design This was a preplanned secondary analysis of two prospective cohort studies. Setting Academic tertiary care emergency department (ED). Participants 1,084 ED patients who were 65 years old or older. Measurements At the time of enrollment, trained research personnel performed the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and Richmond Agitation Sedation Scale (RASS) to determine delirium and level of arousal, respectively. Patients were categorized as having no delirium, delirium with normal arousal, delirium with decreased arousal, or delirium with increased arousal. Death was ascertained by medical record review and the Social Security Death Index. Cox proportional hazard regression was used to analyze the association between delirium arousal subtypes and 6-month mortality. Results Delirium with normal arousal was the only subtype that was significantly associated with increased 6-month mortality (HR=3.1, 95%CI: 1.3 – 7.4) compared with the no delirium group after adjusting for confounders. The HRs for delirium with decreased and increased arousal were 1.4 (95%CI: 0.9 – 2.1) and 1.3 (95%CI: 0.3 – 5.4), respectively. Conclusion Delirious ED patients with normal arousal at initial presentation had a three-fold increased hazard of death within 6-months compared to patients without delirium. There was a trend towards increased hazard of death in delirious ED patients with decreased arousal, but this relationship did not reach statistical significance. These data suggest that subtyping delirium by arousal may have prognostic value but requires confirmation with a larger study. PMID:27623552

Pronounced reversible hyperammonemic encephalopathy associated with combined valproate-topiramate therapy in a 7-year-old girl.

PubMed

Weise, Sebastian; Syrbe, Steffen; Preuss, Matthias; Bertsche, Astrid; Merkenschlager, Andreas; Bernhard, Matthias K

2015-01-01

Valproate is one of the most frequently used anticonvulsive drugs in children and adults. Valproate is a generally well tolerated medication. However, encephalopathy with or without hyperammonemia is one of its rare adverse events. We present a 7-year-old girl who suffered from epilepsy with generalized tonic-clonic seizures and absence epilepsy. She was initially treated with topiramate. Methylprednisolone pulse therapy and long-term therapy with valproate were initiated due to an increase of seizure frequency. At day 5 of therapy, a further increase of seizure frequency was observed followed by lethargy and somnolence. Liver enzymes remained within normal range, but ammonia serum levels increased to a maximum of 544 mmol/l. Discontinuing valproate and starting potassium-benzoate and sodium-phenylbutyrate improved the clinical condition and ammonia serum levels. Haemodialysis was not required. Cranial magnetic resonance imaging ruled out brain edema. The patient was further on successfully treated with a combination of both, topiramate and levetiracetam. Seizures did not recur and development was normal until now (3 years later). To the best of our knowledge, we observed the highest ammonia serum levels ever reported in valproate-induced hyperammonemia with a complete remission of the subsequent encephalopathy. Topiramate might increase the risk of valproate-induced encephalopathy by carbonic anhydrase inhibition.

Changes in Fasting Plasma Glucose Levels with Ribavirin and Pegylated Interferon Treatment in Normal and Impaired Glucose Tolerant Patients with Chronic Hepatitis C

PubMed Central

Sarasombath, Ongkarn; Suwantarat, Nuntra; Tice, Alan D

2012-01-01

Background Patients with Hepatitis C Virus (HCV) infection have increased rates of glucose intolerance, and studies have shown the improvement of fasting plasma glucose (FPG) levels after clearance of HCV infection with standard ribavirin plus pegylated interferon treatment. The purpose of this study was to examine glycemic changes with standard HCV treatment in patients with impaired fasting glucose (IFG) and normal fasting glucose (NFG). Methods A retrospective study of FPG changes in HCV patients with IFG and NFG treated with standard HCV therapy was conducted. Baseline characteristics and viral responses were assessed; FPG levels before treatment, at the end of treatment, and more than one-month post treatment were compared. Results The mean FPG levels increased by 8.68 mg/dl at the end of treatment in the NFG group but decreased by 9.0 mg/dl in the IFG group, a statistically significant difference (P=0.019). The change in FPG levels remained significantly different after adjusting for weight change (P=0.009) and weight changes and initial weight (P=0.039). FPG change from baseline at more than one month after treatment were similar in both groups (P=0.145). The change in FPG levels was not associated with sustained viral response. Conclusions In HCV-infected patients, standard ribavirin plus pegylated interferon treatment reduced FPG levels in patients with IFG and increased FPG levels in NFG individuals; independent of initial weight, weight change, or viral response. Standard HCV treatment modulates fasting plasma glucose levels which supports the need for a prospective study to determine the clinical significance of this finding. PMID:22737650

[Clinical characteristics and analysis of mass spectrometric data in 33 patients with maple syrup urine disease].

PubMed

Yang, Nan; Han, Lian-shu; Ye, Jun; Qiu, Wen-juan; Zhang, Hui-wen; Gao, Xiao-lan; Wang, Yu; Li, Xiao-yan; Xu, Hao; Gu, Xue-fan

2012-10-30

To explore the clinical characteristics and the diagnostic method of maple syrup urine disease (MSUD). From January 2003 to December 2011, a total of 14 000 patients with suspected inherited metabolism diseases were tested. The blood levels of leucine and valine of these patients were detected by tandem mass spectrometry. The urinary level of branched-chain α-ketoacids was tested by gas chromatography-mass spectrometry. And the diagnosis was based on the elevated levels of leucine and valine in blood and branched-chain α-ketoacids in urine. Thirty-three MSUD patients were confirmed. Their median age of initial visit was 0.17 years old (range: 7 days to 30 years old). The peak onset age of them was 2-30 days old, including 28 cases of neonatal onset (84.8%). The presenting symptoms of 28 cases were feeding difficulties (n=14), poor response, lethargy and seizures. Their median blood levels of leucine and valine (1901 (458-5804) and 600 (315-1617) µmol/L) were significantly higher than their normal levels ((50-300) and (60-250) µmol/L, both P<0.01). Their urinary levels of 2-OH-isovaleric acid, 2-keto-isovaleric acid, 2-keto-3-methylvaleric acid, 2-keto-isocaproic and acetylglycine (262.5 (5.4-624.3), 35.8 (1.9-156.0), 133.8 (7.4-611.5), 518.7 (17.2-2121.2) and 280.5 (11.0-1087.9) respectively) significantly higher than their normal levels (0, <0.1, 0, 0, <0.1 respectively, all P<0.01). In 5 intermittent MSUD patients, their blood levels of leucine and valine (402 (348-958) and 556 (322-808) µmol/L) were significantly higher than their normal levels (both P<0.01). The urinary level of 2-OH-isovaleric acid was significantly higher than its normal levels (P<0.01) while the urinary levels of other α-ketoacids were normal. The confirmation of MSUD remains difficult because of a lack of specific clinical features. The detections of tandem mass spectrometry and gas chromatography-mass spectrometry may aid its early diagnosis.

Computational Micromodel for Epigenetic Mechanisms

PubMed Central

Raghavan, Karthika; Ruskin, Heather J.; Perrin, Dimitri; Goasmat, Francois; Burns, John

2010-01-01

Characterization of the epigenetic profile of humans since the initial breakthrough on the human genome project has strongly established the key role of histone modifications and DNA methylation. These dynamic elements interact to determine the normal level of expression or methylation status of the constituent genes in the genome. Recently, considerable evidence has been put forward to demonstrate that environmental stress implicitly alters epigenetic patterns causing imbalance that can lead to cancer initiation. This chain of consequences has motivated attempts to computationally model the influence of histone modification and DNA methylation in gene expression and investigate their intrinsic interdependency. In this paper, we explore the relation between DNA methylation and transcription and characterize in detail the histone modifications for specific DNA methylation levels using a stochastic approach. PMID:21152421

Mutations in FOXC2 in humans (lymphoedema distichiasis syndrome) cause lymphatic dysfunction on dependency.

PubMed

Mellor, Russell H; Tate, Naomi; Stanton, Anthony W B; Hubert, Charlotte; Mäkinen, Taija; Smith, Alberto; Burnand, Kevin G; Jeffery, Steve; Levick, J Rodney; Mortimer, Peter S

2011-01-01

Human lymphoedema distichiasis syndrome (LDS) results from germline mutations in transcription factor FOXC2. In a mouse model, lack of lymphatic and venous valves is observed plus abnormal smooth muscle cell recruitment to initial lymphatics. We investigated the mechanism of lymphoedema in humans with FOXC2 mutations, specifically the effect of gravitational forces on dermal lymphatic function. We performed (1) quantitative fluorescence microlymphangiography (FML) on the skin of the forearm (non-swollen region) at heart level, and the foot (swollen region) below heart level (dependent) and then at heart level, and (2) immunohistochemical staining of microlymphatics in forearm and foot skin biopsies, using antibodies to podoplanin, LYVE-1 and smooth muscle actin. FML revealed a marked reduction in fluid uptake by initial lymphatics in the LDS foot during dependency, yet normal uptake (similar to controls) in the same foot at heart level and in LDS forearms. In control subjects, dependency did not impair initial lymphatic filling. Immunohistochemical microlymphatic density in forearm and foot did not differ between LDS and controls. FOXC2 mutations cause a functional failure of dermal initial lymphatics during gravitational stress (dependency), but not hypoplasia. The results reveal a pathophysiological mechanism contributing to swelling in LDS. Copyright © 2011 S. Karger AG, Basel.

Translational repression of mouse mu opioid receptor expression via leaky scanning

PubMed Central

Song, Kyu Young; Hwang, Cheol Kyu; Kim, Chun Sung; Choi, Hack Sun; Law, Ping-Yee; Wei, Li-Na; Loh, Horace H.

2007-01-01

Mu opioid receptor (MOR) expression is under temporal and spatial controls, but expression levels of the MOR gene are relatively low in vivo. In addition to transcriptional regulations, upstream AUGs (uAUGs) and open reading frames (uORFs) profoundly affect the translation of the primary ORF and thus the protein levels in several genes. The 5′-untranslated region (UTR) of mouse MOR mRNA contains three uORFs preceding the MOR main initiation codon. In MOR-fused EGFP or MOR promoter/luciferase reporter constructs, mutating each uAUG individually or in combinations increased MOR transient heterologous expression in neuroblastoma NMB and HEK293 cells significantly. Translation of such constructs increased up to 3-fold without altering the mRNA levels if either the third uAUG or both the second and third AUGs were mutated. Additionally, these uAUG-mediated translational inhibitions were independent of their peptide as confirmed by internal mutation analyses in each uORF. Translational studies indicated that protein syntheses were initiated at these uAUG initiation sites, with the third uAUG initiating the highest translation level. These results support the hypothesis that uORFs in mouse MOR mRNA act as negative regulators through a ribosome leaky scanning mechanism. Such leaky scanning resulted in the suppression of mouse MOR under normal conditions. PMID:17284463

The effects of nuclear magnetic resonance on patients with cardiac pacemakers

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

Pavlicek, W.; Geisinger, M.; Castle, L.

1983-04-01

The effect of nuclear magnetic resonance (NMR) imaging on six representative cardiac pacemakers was studied. The results indicate that the threshold for initiating the asynchronous mode of a pacemaker is 17 gauss. Radiofrequency levels are present in an NMR unit and may confuse or possibly inhibit demand pacemakers, although sensing circuitry is normally provided with electromagnetic interference discrimination. Time-varying magnetic fields can generate pulse amplitudes and frequencies to mimic cardiac activity. A serious limitation in the possibility of imaging a patient with a pacemaker would be the alteration of normal pulsing parameters due to time-varying magnetic fields.

Creatin-kinase elevation after accidental ingestion of almotriptan in an 18-month-old girl.

PubMed

Castagno, E; Lupica, M; Viola, S; Savino, F; Miniero, R

2014-02-01

Few studies have been published to demonstrate tolerability and efficacy of almotriptan in adolescents and children with migraine, particularly in the first years of life, though preliminary results are favorable. We report the case of an 18-month-old infant with elevation of serum levels of creatin-kinase after the accidental ingestion of almotriptan. A previously healthy 18-month-old girl (weight: 13 kg) was admitted to our Department four hours after the accidental ingestion of 6.25 mg of almotriptan (0.48 mg/kg), without any specific symptom. The performed investigations showed high serum levels of creatin-kinase (CK) (527 IU/L; normal values: 24-170 IU/L). Transaminase, creatinine, aldolase, myoglobin and troponin T serum levels were normal. The electrocardiogram proved negative. Initial management consisted of parenteral rehydration with saline solution. CK levels lowered significantly at 12 hours (455 IU/L) and at 65 hours (188 IU/L) after the ingestion. No symptoms were observed before discharge and on follow-up.

Prevention of pathology in mdx mice by expression of utrophin: analysis using an inducible transgenic expression system.

PubMed

Squire, S; Raymackers, J M; Vandebrouck, C; Potter, A; Tinsley, J; Fisher, R; Gillis, J M; Davies, K E

2002-12-15

Duchenne muscular dystrophy results from the absence of dystrophin, a cytoskeletal protein. Previously, we have shown in a transgenic mouse model of the disease (mdx) that high levels of expression of the dystrophin-related protein, utrophin can prevent pathology. We developed a new transgenic mouse model where muscle specific utrophin expression was conditioned by addition of tetracycline in water. Transgene expression was turned on at different time points: in utero, at birth, 10 and 30 days after birth. We obtained moderate levels of expression, variable from fibre to fibre (mosaicism) but sufficient to induce a correct localization of the dystro-sarcoglycan complex. Histology revealed a reduction of necrotic foci and of the percentage of centronucleated fibres, which remained still largely above the normal level. Isometric force was not improved but the resistance to eccentric contractions was significantly stronger. When utrophin expression was activated 30 days after birth, improvements were marginal, suggesting that the age at which utrophin therapy is initiated could be an important factor. Our results also provide an unexpected insight into the pathogenesis of the dystrophinopathies. We observed a complete normalization of the characteristics of the mechano-sensitive/voltage-independent Ca(2+) channels (occurrence, open probabilities and Ca(2+) currents), while the classical markers of dystrophy were still abnormal. These observations question the role of increased Ca(2+) channel activity in initiating the dystrophic process. The new model shows that utrophin therapy, initiated after birth, can be effective, but the extent of correction of the various symptoms of dystrophinopathy critically depends on the amount of utrophin expressed.

Finite element analysis of heat load of tungsten relevant to ITER conditions

NASA Astrophysics Data System (ADS)

Zinovev, A.; Terentyev, D.; Delannay, L.

2017-12-01

A computational procedure is proposed in order to predict the initiation of intergranular cracks in tungsten with ITER specification microstructure (i.e. characterised by elongated micrometre-sized grains). Damage is caused by a cyclic heat load, which emerges from plasma instabilities during operation of thermonuclear devices. First, a macroscopic thermo-mechanical simulation is performed in order to obtain temperature- and strain field in the material. The strain path is recorded at a selected point of interest of the macroscopic specimen, and is then applied at the microscopic level to a finite element mesh of a polycrystal. In the microscopic simulation, the stress state at the grain boundaries serves as the marker of cracking initiation. The simulated heat load cycle is a representative of edge-localized modes, which are anticipated during normal operations of ITER. Normal stresses at the grain boundary interfaces were shown to strongly depend on the direction of grain orientation with respect to the heat flux direction and to attain higher values if the flux is perpendicular to the elongated grains, where it apparently promotes crack initiation.

Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

NASA Astrophysics Data System (ADS)

Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

2013-06-01

Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

A Fiberless Seed Mutation in Cotton Is Associated with Lack of Fiber Cell Initiation in Ovule Epidermis and Alterations in Sucrose Synthase Expression and Carbon Partitioning in Developing Seeds1

PubMed Central

Ruan, Yong-Ling; Chourey, Prem S.

1998-01-01

Fiber cell initiation in the epidermal cells of cotton (Gossypium hirsutum L.) ovules represents a unique example of trichome development in higher plants. Little is known about the molecular and metabolic mechanisms controlling this process. Here we report a comparative analysis of a fiberless seed (fls) mutant (lacking fibers) and a normal (FLS) mutant to better understand the initial cytological events in fiber development and to analyze the metabolic changes that are associated with the loss of a major sink for sucrose during cellulose biosynthesis in the mutant seeds. On the day of anthesis (0 DAA), the mutant ovular epidermal cells lacked the typical bud-like projections that are seen in FLS ovules and are required for commitment to the fiber development pathway. Cell-specific gene expression analyses at 0 DAA showed that sucrose synthase (SuSy) RNA and protein were undetectable in fls ovules but were in abundant, steady-state levels in initiating fiber cells of the FLS ovules. Tissue-level analyses of developing seeds 15 to 35 DAA revealed an altered temporal pattern of SuSy expression in the mutant relative to the normal genotype. Whether the altered programming of SuSy expression is the cause or the result of the mutation is unknown. The developing seeds of the fls mutant have also shown several correlated changes that represent altered carbon partitioning in seed coats and cotyledons as compared with the FLS genotype. PMID:9765525

A fiberless seed mutation in cotton is associated with lack of fiber cell initiation in ovule epidermis and alterations in sucrose synthase expression and carbon partitioning in developing seeds

PubMed

Ruan; Chourey

1998-10-01

Fiber cell initiation in the epidermal cells of cotton (Gossypium hirsutum L.) ovules represents a unique example of trichome development in higher plants. Little is known about the molecular and metabolic mechanisms controlling this process. Here we report a comparative analysis of a fiberless seed (fls) mutant (lacking fibers) and a normal (FLS) mutant to better understand the initial cytological events in fiber development and to analyze the metabolic changes that are associated with the loss of a major sink for sucrose during cellulose biosynthesis in the mutant seeds. On the day of anthesis (0 DAA), the mutant ovular epidermal cells lacked the typical bud-like projections that are seen in FLS ovules and are required for commitment to the fiber development pathway. Cell-specific gene expression analyses at 0 DAA showed that sucrose synthase (SuSy) RNA and protein were undetectable in fls ovules but were in abundant, steady-state levels in initiating fiber cells of the FLS ovules. Tissue-level analyses of developing seeds 15 to 35 DAA revealed an altered temporal pattern of SuSy expression in the mutant relative to the normal genotype. Whether the altered programming of SuSy expression is the cause or the result of the mutation is unknown. The developing seeds of the fls mutant have also shown several correlated changes that represent altered carbon partitioning in seed coats and cotyledons as compared with the FLS genotype.

Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings

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

Garcia, J.F.; Ebbe, S.N.; Hollander, L.

1982-05-01

Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 ..mu..l of sample, the assay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples showmore » a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases of circulating Ep levels in physiological and clinical conditions known to be associated with stimulation or suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initial practical value of the Ep RA in the hematology clinic, which will most certainly be expanded with its more extensive use.« less

Cervical spine disease may result in a negative lumbar spinal drainage trial in normal pressure hydrocephalus: case report.

PubMed

Komotar, Ricardo J; Zacharia, Brad E; Mocco, J; Kaiser, Michael G; Frucht, Stephen J; McKhann, Guy M

2008-10-01

In this case report, we present a patient with normal pressure hydrocephalus in whom a lumbar drainage trial yielded a false-negative result secondary to cervical spondylosis. An 80-year-old woman presented with classic symptoms of normal pressure hydrocephalus as well as evidence of cervical myelopathy. Magnetic resonance imaging of the brain and spine showed enlarged ventricles and single-level cervical canal narrowing. An initial lumbar drainage trial was performed, which revealed negative results. The patient then underwent cervical decompression and fusion. Despite this procedure, the patient's symptoms continued to worsen. A repeat lumbar drainage trial was performed with positive results. Subsequently, a ventriculoperitoneal shunt was placed, resulting in significant improvement of her symptoms. This case report illustrates how altered cerebrospinal fluid flow dynamics may impact the accuracy of the lumbar spinal drainage trial in patients with normal pressure hydrocephalus.

Biosynthesis of Bacterial Cell Walls.

DTIC Science & Technology

amino acid accumulation level in Lactobacillus plantarum and Streptococcus faecalis despite a normal initial transport rate. In the course of these...biosynthesis of a dipeptide, D-alanylcysteine; A demonstration that a pantothenic acid deficiency renders L. plantarum unusually sensitive to lysozyme digestion...A quantitative description of the lipid constituents of S. faecalis and L. plantarum ; An investigation of the biochemical basis of a marked lytic

Prognostic significance of normal-sized ovary in advanced serous epithelial ovarian cancer.

PubMed

Paik, E Sun; Kim, Ji Hye; Kim, Tae Joong; Lee, Jeong Won; Kim, Byoung Gie; Bae, Duk Soo; Choi, Chel Hun

2018-01-01

We compared survival outcomes of advanced serous type epithelial ovarian cancer (EOC) patients with normal-sized ovaries and enlarged-ovarian tumors by propensity score matching analysis. The medical records of EOC patients treated at Samsung Medical Center between 2002 and 2015 were reviewed retrospectively. We investigated EOC patients with high grade serous type histology and International Federation of Gynecology and Obstetrics (FIGO) stage IIIB, IIIC, or IV who underwent primary debulking surgery (PDS) and adjuvant chemotherapy to identify patients with normal-sized ovaries. Propensity score matching was performed to compare patients with normal-sized ovaries to patients with enlarged-ovarian tumors (ratio, 1:3) according to age, FIGO stage, initial cancer antigen (CA)-125 level, and residual disease status after PDS. Of the 419 EOC patients, 48 patients had normal-sized ovary. Patients with enlarged-ovarian tumor were younger (54.0±10.3 vs. 58.4±9.2 years, p=0.005) than those with normal-sized ovary, and there was a statistically significant difference in residual disease status between the 2 groups. In total cohort with a median follow-up period of 43 months (range, 3-164 months), inferior overall survival (OS) was shown in the normal-sized ovary group (median OS, 71.2 vs. 41.4 months; p=0.003). After propensity score matching, the group with normal-sized ovary showed inferior OS compared to the group with enlarged-ovarian tumor (median OS, 72.1 vs. 41.4 months; p=0.031). In multivariate analysis for OS, normal-sized ovary remained a significant factor. Normal-sized ovary was associated with poor OS compared with the common presentation of enlarged ovaries in EOC, independent of CA-125 level or residual disease. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

NASA Instrument Cost/Schedule Model

NASA Technical Reports Server (NTRS)

Habib-Agahi, Hamid; Mrozinski, Joe; Fox, George

2011-01-01

NASA's Office of Independent Program and Cost Evaluation (IPCE) has established a number of initiatives to improve its cost and schedule estimating capabilities. 12One of these initiatives has resulted in the JPL developed NASA Instrument Cost Model. NICM is a cost and schedule estimator that contains: A system level cost estimation tool; a subsystem level cost estimation tool; a database of cost and technical parameters of over 140 previously flown remote sensing and in-situ instruments; a schedule estimator; a set of rules to estimate cost and schedule by life cycle phases (B/C/D); and a novel tool for developing joint probability distributions for cost and schedule risk (Joint Confidence Level (JCL)). This paper describes the development and use of NICM, including the data normalization processes, data mining methods (cluster analysis, principal components analysis, regression analysis and bootstrap cross validation), the estimating equations themselves and a demonstration of the NICM tool suite.

Computer-aided detection of initial polyp candidates with level set-based adaptive convolution

NASA Astrophysics Data System (ADS)

Zhu, Hongbin; Duan, Chaijie; Liang, Zhengrong

2009-02-01

In order to eliminate or weaken the interference between different topological structures on the colon wall, adaptive and normalized convolution methods were used to compute the first and second order spatial derivatives of computed tomographic colonography images, which is the beginning of various geometric analyses. However, the performance of such methods greatly depends on the single-layer representation of the colon wall, which is called the starting layer (SL) in the following text. In this paper, we introduce a level set-based adaptive convolution (LSAC) method to compute the spatial derivatives, in which the level set method is employed to determine a more reasonable SL. The LSAC was applied to a computer-aided detection (CAD) scheme to detect the initial polyp candidates, and experiments showed that it benefits the CAD scheme in both the detection sensitivity and specificity as compared to our previous work.

Preparation of acetylated waxy, normal, and high-amylose maize starches with intermediate degrees of substitution in aqueous solution and their properties.

PubMed

Luo, Zhi-Gang; Shi, Yong-Cheng

2012-09-19

Acetylated waxy, normal, and high-amylose maize starches with intermediate degrees of substitution (DS) were prepared in aqueous solution with 20% (w/w) sodium hydroxide as a catalyst. The level of DS was in the order high-amylose maize starch > waxy maize starch > normal maize starch. Settling volume indicated that during the early reaction, normal maize starch swelled to a lesser extent compared with waxy and high-amylose maize starches. The settling volume of all three starches increased initially but decreased after long reaction time. Aggregation of granules was observed as DS increased. The A-type X-ray diffraction pattern of acetylated normal and waxy maize starches weakened as DS increased, whereas the diffraction peaks disappeared in acetylated high-amylose starch when DS was 0.95. Low DS promoted the swelling of the starches in water, but at high DS, the starches became more hydrophobic and the peak viscosity of acetylated starches decreased.

stem fasciated, a Recessive Mutation in Sunflower (Helianthus annuus), Alters Plant Morphology and Auxin Level

PubMed Central

FAMBRINI, MARCO; BONSIGNORI, ELISA; RAPPARINI, FRANCESCA; CIONINI, GIULIANO; MICHELOTTI, VANIA; BERTINI, DANIELE; BARALDI, RITA; PUGLIESI, CLAUDIO

2006-01-01

• Background and Aims Plant lateral organs such as leaves arise from a group of initial cells within the flanks of the shoot apical meristem (SAM). Alterations in the initiation of lateral organs are often associated with changes in the dimension and arrangement of the SAM as well as with abnormal hormonal homeostasis. A mutation named stem fasciated (stf) that affects various aspects of plant development, including SAM shape and auxin level, was characterized in sunflower (Helianthus annuus). • Methods F1, F2 and F3 generations were obtained through reciprocal crosses between stf and normal plants. For the genetic analysis, a χ2 test was used. Phenotypic observations were made in field-grown and potted plants. A histological analysis of SAM, hypocotyl, epicotyl, stem and root apical meristem was also conducted. To evaluate the level of endogenous indole-3-acetic acid (IAA), a capillary gas chromatography–mass spectrometry–selected ion monitoring analysis was performed. • Key Results stf is controlled by a single nuclear recessive gene. stf plants are characterized by a dramatically increased number of leaves and vascular bundles in the stem, as well as by a shortened plastochron and an altered phyllotaxis pattern. By histological analysis, it was demonstrated that the stf phenotype is related to an enlarged vegetative SAM. Microscopy analysis of the mutant's apex also revealed an abnormal enlargement of nuclei in both central and peripheral zones and a disorganized distribution of cells in the L2 layer of the central zone. The stf mutant showed a high endogenous free IAA level, whereas auxin perception appeared normal. • Conclusions The observed phenotype and the high level of auxin detected in stf plants suggest that the STF gene is necessary for the proper initiation of primordia and for the establishment of a phyllotactic pattern through control of both SAM arrangement and hormonal homeostasis. PMID:16845141

A gargantuan acetaminophen level in an acidemic patient treated solely with intravenous N-acetylcysteine.

PubMed

Zell-Kanter, Michele; Coleman, Patrick; Whiteley, Patrick M; Leikin, Jerrold B

2013-01-01

The objective of this report is to describe an acidemic patient with one of the largest recorded acetaminophen ingestions in a patient with acidemia who was treated with supportive care and intravenous (IV) N-acetylcysteine. A 59-year-old female with a history of depression was found comatose. In the Emergency Department, she was obtunded with agonal respirations and immediately intubated. Activated charcoal was given through a nasogastric tube. An initial acetaminophen serum level was 1141 mg/L. The patient was started on IV N-acetylcysteine. The acetaminophen level peaked 2 hours later at 1193 mg/L. She was continued on the IV N-acetylcysteine protocol. The next day her aspartate aminotransferase was 3150 U/L, alanine aminotransferase was 2780 U/L, and creatinine phosphokinase was 16,197 U/L. There was no elevation in bilirubin or international normalized ratio (INR). Transaminase levels decreased on day 3 and normalized by day 4 when she was transferred to a psychiatric unit. Few cases have been reported of strikingly elevated acetaminophen levels in poisoned patients who did not receive hemodialysis. These patients did have increased lactate levels, and some had normal liver function tests. All of these patients received N-acetylcysteine and survived the poisoning without sequelae. This patient in this report was unique in that she had the highest reported serum acetaminophen level with acidosis and was treated successfully with only IV N-acetylcysteine and supportive care.

Auditory maturation in premature infants: a potential pitfall for early cochlear implantation.

PubMed

Hof, Janny R; Stokroos, Robert J; Wix, Eduard; Chenault, Mickey; Gelders, Els; Brokx, Jan

2013-08-01

To describe spontaneous hearing improvement in the first years of life of a number of preterm neonates relative to cochlear implant candidacy. Retrospective case study. Hearing levels of 14 preterm neonates (mean gestational age at birth = 29 weeks) referred after newborn hearing screening were evaluated. Initial hearing thresholds ranged from 40 to 105 dBHL (mean = 85 dBHL). Hearing level improved to normal levels for four neonates and to moderate levels for five, whereas for five neonates, no improvement in hearing thresholds was observed and cochlear implantation was recommended. Three of the four neonates in whom the hearing improved to normal levels were born prior to 28 weeks gestational age. Hearing improvement was mainly observed prior to a gestational age of 80 weeks. Delayed maturation of an immature auditory pathway might be an important reason for referral after newborn hearing screening in premature infants. Caution is advised regarding early cochlear implantation in preterm born infants. Audiological follow-ups until at least 80 weeks gestational age are therefore recommended. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Neuronal Protein 3.1 Deficiency Leads to Reduced Cutaneous Scar Collagen Deposition and Tensile Strength due to Impaired Transforming Growth Factor-β1 to -β3 Translation.

PubMed

Cheng, Tao; Yue, Michael; Aslam, Muhammad Nadeem; Wang, Xin; Shekhawat, Gajendra; Varani, James; Schuger, Lucia

2017-02-01

Neuronal protein 3.1 (P311), a conserved RNA-binding protein, represents the first documented protein known to stimulate transforming growth factor (TGF)-β1 to -β3 translation in vitro and in vivo. Because TGF-βs play critical roles in fibrogenesis, we initiated efforts to define the role of P311 in skin scar formation. Here, we show that P311 is up-regulated in skin wounds and in normal and hypertrophic scars. Genetic ablation of p311 resulted in a significant decrease in skin scar collagen deposition. Lentiviral transfer of P311 corrected the deficits, whereas down-regulation of P311 levels by lentiviral RNA interference reproduced the deficits seen in P311 -/- mice. The decrease in collagen deposition resulted in scars with reduced stiffness but also reduced scar tensile strength. In vitro studies using murine and human dermal fibroblasts showed that P311 stimulated TGF-β1 to -β3 translation, a process that involved eukaryotic translation initiation factor 3 subunit b as a P311 binding partner. This resulted in increased TGF-β levels/activity and increased collagen production. In addition, P311 induced dermal fibroblast activation and proliferation. Finally, exogenous TGF-β1 to -β3, each restituted the normal scar phenotype. These studies demonstrate that P311 is required for the production of normal cutaneous scars and place P311 immediately up-stream of TGF-βs in the process of fibrogenesis. Conditions that decrease P311 levels could result in less tensile scars, which could potentially lead to higher incidence of dehiscence after surgery. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

False elevation of carboxyhemoglobin: case report.

PubMed

Mehrotra, Shruti; Edmonds, Marcia; Lim, Rodrick K

2011-02-01

Carbon monoxide toxicity in infants and children, like adults, produce nonspecific symptoms with normal vital signs necessitating the serum measurement of carboxyhemoglobin (COHb). In infants, the COHb may be falsely elevated. Our goal was to report a case of suspected carbon monoxide toxicity in an infant and the likely cause of the falsely elevated serum COHb. A previously healthy 3-month-old girl presented to the pediatric emergency department (ED) with smoke inhalation from a defective furnace. She was asymptomatic. On examination, she was alert, with Glasgow Coma Scale of 15 and normal vital signs. Cardiorespiratory and neurological examinations were completely normal. Because of concern regarding carbon monoxide poisoning, she was treated with normobaric oxygen therapy. Initial and subsequent serum COHb levels were persistently elevated, despite treatment and the infant appearing clinically well. As such, she had a prolonged stay in the ED. Further investigations found that fetal hemoglobin interferes with the spectrophotometric method used to analyze serum COHb levels. Carboxyhemoglobin serum level, in infants, may be falsely elevated due to the fetal hemoglobin interfering with standard methods of analysis. Knowledge of the false elevation using standard spectrophotometric methods of COHb in clinically well-appearing infants can decrease unnecessary oxygen therapy and monitoring time in the ED.

Pseudohypoparathyroidism: a rare but important cause of hypocalcaemia

PubMed Central

Chong, Pui Lin; Meeking, Darryl R

2013-01-01

We present a 46-year-old Caucasian lady with symptomatic hypocalcaemia. Investigations revealed markedly raised parathyroid hormone (PTH) levels with vitamin D deficiency. A number of conditions causing secondary hyperparathyroidism were ruled out from her medical history and initial investigations. The main differential diagnoses were vitamin D deficiency and PTH resistance (pseudohypoparathyroidism, PHP). With high-normal serum phosphate and normal alkaline phosphatase, and a lack of symptoms associated with osteomalacia, vitamin D deficiency alone was unlikely to be the cause of hypocalcaemia. Given a normal physical appearance, genetic testing was arranged and confirmed the diagnosis of PHP type Ib. She is currently taking activated vitamin D to maintain calcium homeostasis. PTH resistance is the hallmark of PHP, a rare complex genetic disorder, which can be easily missed resulting in potentially serious consequences. PMID:23345494

Visualization of CD44 and CD133 in Normal Pancreas and Pancreatic Ductal Adenocarcinomas

PubMed Central

Immervoll, Heike; Hoem, Dag; Steffensen, Ole Johnny; Miletic, Hrvoje; Molven, Anders

2011-01-01

Tumor-initiating cells of pancreatic ductal adenocarcinoma (PDAC) have been isolated based on expression of either CD133 or CD44. The authors aimed to visualize pancreatic cells simultaneously expressing both these cell surface markers by employing the same antibodies commonly used in cell-sorting studies. Normal and diseased pancreatic tissue, including 51 PDAC cases, were analyzed. CD44 and CD133 expression was determined by immunohistochemical double staining on formalin-fixed material and subcellular protein distribution evaluated by immunofluorescence/confocal microscopy. In the normal pancreas, CD44 and CD133 were coexpressed in the centroacinar regions but in non-overlapping subcellular compartments. As expected, CD44 was found mainly basolaterally, whereas CD133 was present on the apical/endoluminal membrane. This was also the case in chronically inflamed/atrophic pancreatic tissue and in PDAC. In some malignant ducts, CD44 was found at the apical cell membrane adjacent to but never overlapping with CD133 expression. CD44 level was significantly associated with the patient’s lymph node status. In conclusion, a CD44+/CD133+ cell population does exist in the normal and neoplastic pancreas. The preferentially centroacinar localization of the doubly positive cells in the normal parenchyma suggests that this population could be of particular interest in attempts to identify tumor-initiating cells in PDAC. This article contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. PMID:21411814

Analysis of vector wind change with respect to time for Cape Kennedy, Florida

NASA Technical Reports Server (NTRS)

Adelfang, S. I.

1978-01-01

Multivariate analysis was used to determine the joint distribution of the four variables represented by the components of the wind vector at an initial time and after a specified elapsed time is hypothesized to be quadravariate normal; the fourteen statistics of this distribution, calculated from 15 years of twice-daily rawinsonde data are presented by monthly reference periods for each month from 0 to 27 km. The hypotheses that the wind component changes with respect to time is univariate normal, that the joint distribution of wind component change with respect to time is univariate normal, that the joint distribution of wind component changes is bivariate normal, and that the modulus of vector wind change is Rayleigh are tested by comparison with observed distributions. Statistics of the conditional bivariate normal distributions of vector wind at a future time given the vector wind at an initial time are derived. Wind changes over time periods from 1 to 5 hours, calculated from Jimsphere data, are presented. Extension of the theoretical prediction (based on rawinsonde data) of wind component change standard deviation to time periods of 1 to 5 hours falls (with a few exceptions) within the 95 percentile confidence band of the population estimate obtained from the Jimsphere sample data. The joint distributions of wind change components, conditional wind components, and 1 km vector wind shear change components are illustrated by probability ellipses at the 95 percentile level.

Dynamics of testosterone concentration in male steppe lemmings (Lagurus lagurus) in the reproductive cycle reflects the species-specific mating system.

PubMed

Potapova, O F; Potapov, M A; Kondratyuk, E Yu; Evsikov, V I

2016-05-01

In the blood of male steppe lemmings, relatively low background levels of testosterone were detected, this is characteristic of a monogamous species. A significant increase in testosterone level, more expressed in sexually active males, was observed at the initial stage of formation of reproductive couples. Apparently, in the future, the couple will exist in a stable relationship, and, hence, the maintenance of a high testosterone level becomes excessive. The decrease in, and the relative "normalization" of, the hormone level during the existence of the pair, including raising of the young, promotes higher expression of the male paternal care of the offspring at the species level.

The radiation response of human dermal fibroblasts

NASA Astrophysics Data System (ADS)

Mitchell, Stephen Andrew

A clinically reliable predictive assay based on normal-tissue radiosensitivity may lead to improved tumour control through individualised dose prescriptions. In-vitro fibroblast radiosensitivity has been shown, in several studies, to correlate with late radiation morbidity. The aim of this study was to investigate some of the cellular mechanisms underlying the normal-tissue response. In this study, seventeen primary fibroblast strains were established by enzymatic disaggregation of skin biopsies obtained from patients. These comprised seven who experienced acute tissue reactions to radiotherapy, four patients with a normal response and six non-cancer volunteers. An AT cell line was included as a positive control for radiosensitivity. In-vitro radiosensitivity was measured using a clonogenic assay at both high (HDR: 1.6 Gymin-1) and low dose rate (LDR: 0.01 Gymin-1). The radiation parameter HDR SF2 was the most sensitive in discriminating the seven sensitive patients from the remaining ten normal patients (range 0.11-0.19 sensitive patients compared with 0.17-0.34 control patients: p<0.0001). Neither the use of an internal control or LDR radiation protocol increased this discrimination. Pulsed-field gel electrophoresis (PFGE) was used to measure the level of initial and residual double-strand breaks following irradiation. No correlation was found between HDR SF2 and initial DNA damage. However, a strong correlation was found between clonogenic survival and both residual DNA damage (measured over 10-70 Gy, allowing 4 h repair, correlation coefficient: 0.90, <0.0001) and the ratio of residual/initial DNA damage, with the sensitive cell lines generally showing a higher level of residual DNA damage. Cell-cycle delays were found in all 18 cell strains in response to 2 Gy irradiation, but were not found to discriminate between sensitive and normal patients. Associated studies found no mutations of the ATM gene in the five radiosensitive patients studied. However, a coding sequence alteration was found in the XRCC1 gene in one of the radiosensitive patients. These findings indicate that a DNA repair defect may be partly responsible for the extreme reactions to radiotherapy observed in a small percentage of patients and that with further modifications, an assay based on measurement of residual DNA damage may form the basis of a predictive test for radiosensitivity.

Intrathecal enzyme replacement therapy reduces lysosomal storage in the brain and meninges of the canine model of MPS I.

PubMed

Kakkis, E; McEntee, M; Vogler, C; Le, S; Levy, B; Belichenko, P; Mobley, W; Dickson, P; Hanson, S; Passage, M

2004-01-01

Enzyme replacement therapy (ERT) has been developed for several lysosomal storage disorders, including mucopolysaccharidosis I (MPS I), and is effective at reducing lysosomal storage in many tissues and in ameliorating clinical disease. However, intravenous ERT does not adequately treat storage disease in the central nervous system (CNS), presumably due to effects of the blood-brain barrier on enzyme distribution. To circumvent this barrier, we studied whether intrathecal (IT) recombinant human alpha-L-iduronidase (rhIDU) could penetrate and treat the brain and meninges. An initial dose-response study showed that doses of 0.46-4.14 mg of IT rhIDU successfully penetrated the brain of normal dogs and reached tissue levels 5.6 to 18.9-fold normal overall and 2.7 to 5.9-fold normal in deep brain sections lacking CSF contact. To assess the efficacy and safety in treating lysosomal storage disease, four weekly doses of approximately 1 mg of IT rhIDU were administered to MPS I-affected dogs resulting in a mean 23- and 300-fold normal levels of iduronidase in total brain and meninges, respectively. Quantitative glycosaminoglycan (GAG) analysis showed that the IT treatment reduced mean total brain GAG to normal levels and achieved a 57% reduction in meningeal GAG levels accompanied by histologic improvement in lysosomal storage in all cell types. The dogs did develop a dose-dependent immune response against the recombinant human protein and a meningeal lymphocytic/plasmacytic infiltrate. The IT route of ERT administration may be an effective way to treat the CNS disease in MPS I and could be applicable to other lysosomal storage disorders.

Lead poisoning following ingestion of pieces of lead roofing plates: pica-like behavior in an adult.

PubMed

Sabouraud, Sabine; Testud, François; Descotes, Jacques; Benevent, Monique; Soglu, Gilbert

2008-03-01

A 37-year-old man was admitted to hospital after complaining of abdominal pain for the past two weeks. On admission the abdominal radiograph showed multiple radio-opaque flecks dispersed throughout the gastrointestinal tract. Blood testing showed hemoglobin level 8.7 g/dL and a blood lead level of 112.4 microg/dL. The family interview revealed that the patient had pica-like behavior since childhood. He was a site foreman and had been ingesting pieces of roofing plates for a few weeks. The patient was treated with laxatives and CaNa(2)EDTA therapy was initiated. The blood lead level then dropped to 69.9 microg/dL. The patient received two subsequent courses of oral succimer and the blood lead level decreased to 59 microg/dL 21 days after the first course. The follow-up abdominal X-ray 20 days after the first examination was normal. Four months later, an outpatient follow-up visit showed a blood lead level within normal limits (14.5 microg/dL) and a psychiatric follow-up was initiated. Lead poisoning following the ingestion of lead-containing foreign bodies is particularly rare in adults, while it is sometimes observed in children. Pica behavior is a well-identified risk factor of lead intoxication in children but is quite exceptional in adults, where it is usually considered to be a psychiatric condition. Other unusual sources of lead poisoning include the ingestion of lead bullets, ceramic lead glaze or glazed earthenware, lead-contaminated candies, ethnic or herbal remedies.

Antitissue Transglutaminase Normalization Postdiagnosis in Children With Celiac Disease.

PubMed

Isaac, Daniela Migliarese; Rajani, Seema; Yaskina, Maryna; Huynh, Hien Q; Turner, Justine M

2017-08-01

Limited pediatric data exist examining the trend and predictors of antitissue transglutaminase (atTG) normalization over time in children with celiac disease (CD). We aimed to evaluate time to normalization of atTG in children after CD diagnosis, and to assess for independent predictors affecting this duration. A retrospective chart review was completed in pediatric patients with CD diagnosed from 2007 to 2014 at the Stollery Children's Hospital Celiac Clinic (Edmonton, Alberta, Canada). The clinical predictors assessed for impact on time to atTG normalization were initial atTG, Marsh score at diagnosis, gluten-free diet compliance (GFDC), age at diagnosis, sex, ethnicity, medical comorbidities, and family history of CD. Kaplan-Meier survival analysis was completed to assess time to atTG normalization, and Cox regression to assess for independent predictors of this time. A total of 487 patients met inclusion criteria. Approximately 80.5% of patients normalized atTG levels. Median normalization time was 407 days for all patients (95% confidence interval [CI: 361-453]), and 364 days for gluten-free diet compliant patients (95% CI [335-393]). Type 1 diabetes mellitus (T1DM) patients took significantly longer to normalize at 1204 days (95% CI [199-2209], P < 0.001). Cox regression demonstrated T1DM (hazard ratio = 0.36 [0.24-0.55], P < 0.001) and higher baseline atTG (hazard ratio = 0.52 [0.43-0.63], P < 0.001) were significant predictors of longer atTG normalization time. GFDC was a significant predictor of earlier normalization (OR = 13.91 [7.86-24.62], P < 0.001). GFDC and lower atTG at diagnosis are predictors of earlier normalization. Patients with T1DM are less likely to normalize atTG levels, with longer normalization time. Additional research and education for higher-risk populations are needed.

Thinning of heterogeneous lithosphere: insights from field observations and numerical modelling

NASA Astrophysics Data System (ADS)

Petri, B.; Duretz, T.; Mohn, G.; Schmalholz, S. M.

2017-12-01

The nature and mechanisms of formation of extremely thinned continental crust (< 10 km) and lithosphere during rifting remain debated. Observations from present-day and fossil continental passive margins document the heterogeneous nature of the lithosphere characterized, among others, by lithological variations and structural inheritance. This contribution aims at investigating the mechanisms of extreme lithospheric thinning by exploring in particular the role of initial heterogeneities by coupling field observations from fossil passive margins and numerical models of lithospheric extension. Two field examples from the Alpine Tethys margins outcropping in the Eastern Alps (E Switzerland and N Italy) and in the Southern Alps (N Italy) were selected for their exceptional level of preservation of rift-related structures. This situation enables us to characterize (1) the pre-rift architecture of the continental lithosphere, (2) the localization of rift-related deformation in distinct portion of the lithosphere and (3) the interaction between initial heterogeneities of the lithosphere and rift-related structures. In a second stage, these observations are integrated in high-resolution, two-dimensional thermo-mechanical models taking into account various patterns of initial mechanical heterogeneities. Our results show the importance of initial pre-rift architecture of the continental lithosphere during rifting. Key roles are given to high-angle and low-angle normal faults, anastomosing shear-zones and decoupling horizons. We propose that during the first stages of thinning, deformation is strongly controlled by the complex pre-rift architecture of the lithosphere, localized along major structures responsible for the lateral extrusion of mid to lower crustal levels. This extrusion juxtaposes mechanically stronger levels in the hyper-thinned continental crust, being exhumed by subsequent low-angle normal faults. Altogether, these results highlight the critical role of the extraction of mechanically strong layers of the lithosphere during the extreme thinning of the continental lithosphere and allows to propose a new model for the formation of continental passive margins.

40 CFR 63.2862 - What records must I keep?

Code of Federal Regulations, 2012 CFR

2012-07-01

...) initial startup period or the § 63.2850(e)(2) malfunction period. Complete both plans before the... such as normal operation, nonoperating, initial startup period, malfunction period, or exempt operation... inventory. (ii) The operating status of your source such as normal operation, nonoperating, initial startup...

40 CFR 63.2862 - What records must I keep?

Code of Federal Regulations, 2013 CFR

2013-07-01

...) initial startup period or the § 63.2850(e)(2) malfunction period. Complete both plans before the... such as normal operation, nonoperating, initial startup period, malfunction period, or exempt operation... inventory. (ii) The operating status of your source such as normal operation, nonoperating, initial startup...

40 CFR 63.2862 - What records must I keep?

Code of Federal Regulations, 2014 CFR

2014-07-01

...) initial startup period or the § 63.2850(e)(2) malfunction period. Complete both plans before the... such as normal operation, nonoperating, initial startup period, malfunction period, or exempt operation... inventory. (ii) The operating status of your source such as normal operation, nonoperating, initial startup...

40 CFR 63.2862 - What records must I keep?

Code of Federal Regulations, 2011 CFR

2011-07-01

...) initial startup period or the § 63.2850(e)(2) malfunction period. Complete both plans before the... such as normal operation, nonoperating, initial startup period, malfunction period, or exempt operation... inventory. (ii) The operating status of your source such as normal operation, nonoperating, initial startup...

40 CFR 63.2862 - What records must I keep?

Code of Federal Regulations, 2010 CFR

2010-07-01

...) initial startup period or the § 63.2850(e)(2) malfunction period. Complete both plans before the... such as normal operation, nonoperating, initial startup period, malfunction period, or exempt operation... inventory. (ii) The operating status of your source such as normal operation, nonoperating, initial startup...

Characteristics of bone turnover in the long bone metaphysis fractured patients with normal or low Bone Mineral Density (BMD).

PubMed

Wölfl, Christoph; Schweppenhäuser, Daniela; Gühring, Thorsten; Takur, Caner; Höner, Bernd; Kneser, Ulrich; Grützner, Paul Alfred; Kolios, Leila

2014-01-01

The incidence of osteoporotic fractures increases as our population ages. Until now, the exact biochemical processes that occur during the healing of metaphyseal fractures remain unclear. Diagnostic instruments that allow a dynamic insight into the fracture healing process are as yet unavailable. In the present matched pair analysis, we study the time course of the osteoanabolic markers bone specific alkaline phosphatase (BAP) and transforming growth factor β1 (TGFβ1), as well as the osteocatabolic markers crosslinked C-telopeptide of type-I-collagen (β-CTX) and serum band 5 tartrate-resistant acid phosphatase (TRAP5b), during the healing of fractures that have a low level of bone mineral density (BMD) compared with fractures that have a normal BMD. Between March 2007 and February 2009, 30 patients aged older than 50 years who suffered a metaphyseal fracture were included in our study. BMDs were verified by dual energy Xray absorptiometry (DXEA) scans. The levels of BTMs were examined over an 8-week period. Osteoanabolic BAP levels in those with low levels of BMD were significantly different from the BAP levels in those with normal BMD. BAP levels in the former group increased constantly, whereas the latter group showed an initial strong decrease in BAP followed by slowly rising values. Osteocatabolic β-CTX increased in the bone of the normal BMD group constantly, whereas these levels decreased significantly in the bone of the group with low BMD from the first week. TRAP5b was significantly reduced in the low level BMD group. With this work, we conduct first insights into the molecular biology of the fracture healing process in patients with low levels of BMD that explains the mechanism of its fracture healing. The results may be one reason for the reduced healing qualities in bones with low BMD.

Computational aspects of the nonlinear normal mode initialization of the GLAS 4th order GCM

NASA Technical Reports Server (NTRS)

Navon, I. M.; Bloom, S. C.; Takacs, L.

1984-01-01

Using the normal modes of the GLAS 4th Order Model, a Machenhauer nonlinear normal mode initialization (NLNMI) was carried out for the external vertical mode using the GLAS 4th Order shallow water equations model for an equivalent depth corresponding to that associated with the external vertical mode. A simple procedure was devised which was directed at identifying computational modes by following the rate of increase of BAL sub M, the partial (with respect to the zonal wavenumber m) sum of squares of the time change of the normal mode coefficients (for fixed vertical mode index) varying over the latitude index L of symmetric or antisymmetric gravity waves. A working algorithm is presented which speeds up the convergence of the iterative Machenhauer NLNMI. A 24 h integration using the NLNMI state was carried out using both Matsuno and leap-frog time-integration schemes; these runs were then compared to a 24 h integration starting from a non-initialized state. The maximal impact of the nonlinear normal mode initialization was found to occur 6-10 hours after the initial time.

Effects of feeding a diet containing Gymnema sylvestre extract: Attenuating progression of obesity in C57BL/6J mice.

PubMed

Kim, Hyeon-Jeong; Hong, Seong-Ho; Chang, Seung-Hee; Kim, Sanghwa; Lee, Ah Young; Jang, Yoonjeong; Davaadamdin, Orkhonselenge; Yu, Kyeong-Nam; Kim, Ji-Eun; Cho, Myung-Haing

2016-05-01

To investigate the effect of Gymnema sylvestre extract (GS) on initial anti-obesity, liver injury, and glucose homeostasis induced by a high-fat diet (HFD). The dry powder of GS was extracted with methanol, and gymnemic acid was identified by high performance liquid chromatography as deacyl gymnemic acid. Male C57BL/6J mice that fed on either a normal diet, normal diet containing 1 g/kg GS (CON+GS), HFD, or HFD containing 1.0 g/kg GS (HFD + GS) for 4 weeks were used to test the initial anti-obesity effect of GS. Body weight gain and food intake, and serum levels about lipid and liver injury markers were measured. Histopathology of adipose tissue and liver stained with hematoxylin and eosin (H&E) and oil-red O were analyzed. After 4 weeks of GS extract feeding, intraperitoneal glucose tolerance test (IPGTT) was performed. The methanol extracts of GS exerted significant anti-obesity effects in HFD + GS group. They decreased body weight gain, a lower food and energy efficiency ratio, and showed lower serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL)-cholesterol, very-low density lipoprotein (VLDL)-cholesterol and leptin compared with the HFD group. The decreases of abdominal as well as epididymal fat weight and adipocyte hypertrophy, lipid droplets in liver, and serum levels of aspartate aminotransferase (AST) and alanine transaminase (ALT) were also observed. The CON + GS group showed an effect of glucose homeostasis compared to the CON group. This study shows that GS provide the possibility as a key role in an initial anti-obesity effects feeding with a HFD. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Elevated utero/placental GR/NR3C1 is not required for the induction of parturition in the dog.

PubMed

Gram, Aykut; Trachsel, Alexandra; Boos, Alois; Kowalewski, Mariusz P

2016-10-01

The endocrine mechanisms that lead to initiation of parturition in dogs are still not fully understood. The prepartum luteolysis is associated with increased prostaglandin (PG) F2α secretion; however, there is no pregnancy- or parturition-related increase in estrogens. Moreover, unlike in other mammalian species, in the dog, increased peripartum levels of cortisol measured sporadically in maternal peripheral blood are not mandatory for normal parturition. Nevertheless, auto/paracrine effects of cortisol at the placental feto-maternal level cannot be excluded. Therefore, the aim of this study was to investigate the expression and localization of glucocorticoid receptor (GR/NR3C1) in canine utero/placental (Ut/Pl) units and uterine interplacental sites at selected time points during pregnancy (pre-implantation, post-implantation and mid-gestation), and at normal and antigestagen-induced parturition. The Ut/Pl expression of GR/NR3C1 did not change significantly from pre-implantation until mid-gestation; however, it was strongly induced during the prepartum luteolysis. Within the interplacental samples, expression of GR/NR3C1-mRNA was greater post-implantation than pre-implantation and did not change afterward, i.e. toward mid-gestation. Compartmentalization studies within the Ut/Pl units, involving placenta, endometrium and myometrium separately, performed at the prepartum luteolysis revealed the highest GR/NR3C1-mRNA levels in placenta compared with endometrium and myometrium. Interestingly, in antigestagen-treated mid-pregnancy dogs, Ut/Pl and interplacental GR/NR3C1-mRNA expression remained unaffected. At the cellular level, placental GR/NR3C1 was clearly detectable in placenta fetalis, i.e. in trophoblast cells. In conclusion, increased expression of GR/NR3C1 during normal parturition, but not following antigestagen-treatment, suggest that it is not required for initiating the signaling cascade of PG synthesis leading to the induction of parturition in the dog. © 2016 Society for Reproduction and Fertility.

Overexpression of SERBP1 (Plasminogen activator inhibitor 1 RNA binding protein) in human breast cancer is correlated with favourable prognosis

PubMed Central

2012-01-01

Background Plasminogen activator inhibitor 1 (PAI-1) overexpression is an important prognostic and predictive biomarker in human breast cancer. SERBP1, a protein that is supposed to regulate the stability of PAI-1 mRNA, may play a role in gynaecological cancers as well, since upregulation of SERBP1 was described in ovarian cancer recently. This is the first study to present a systematic characterisation of SERBP1 expression in human breast cancer and normal breast tissue at both the mRNA and the protein level. Methods Using semiquantitative realtime PCR we analysed SERBP1 expression in different normal human tissues (n = 25), and in matched pairs of normal (n = 7) and cancerous breast tissues (n = 7). SERBP1 protein expression was analysed in two independent cohorts on tissue microarrays (TMAs), an initial evaluation set, consisting of 193 breast carcinomas and 48 normal breast tissues, and a second large validation set, consisting of 605 breast carcinomas. In addition, a collection of benign (n = 2) and malignant (n = 6) mammary cell lines as well as breast carcinoma lysates (n = 16) were investigated for SERBP1 expression by Western blot analysis. Furthermore, applying non-radioisotopic in situ hybridisation a subset of normal (n = 10) and cancerous (n = 10) breast tissue specimens from the initial TMA were analysed for SERBP1 mRNA expression. Results SERBP1 is not differentially expressed in breast carcinoma compared to normal breast tissue, both at the RNA and protein level. However, recurrence-free survival analysis showed a significant correlation (P = 0.008) between abundant SERBP1 expression in breast carcinoma and favourable prognosis. Interestingly, overall survival analysis also displayed a tendency (P = 0.09) towards favourable prognosis when SERBP1 was overexpressed in breast cancer. Conclusions The RNA-binding protein SERBP1 is abundantly expressed in human breast cancer and may represent a novel breast tumour marker with prognostic significance. Its potential involvement in the plasminogen activator protease cascade warrants further investigation. PMID:23236990

Leveraging the Cloud for Integrated Network Experimentation

DTIC Science & Technology

2014-03-01

kernel settings, or any of the low-level subcomponents. 3. Scalable Solutions: Businesses can build scalable solutions for their clients , ranging from...values. These values 13 can assume several distributions that include normal, Pareto , uniform, exponential and Poisson, among others [21]. Additionally, D...communication, the web client establishes a connection to the server before traffic begins to flow. Web servers do not initiate connections to clients in

Beta blocker effects on plasma homocysteine levels in patients with hypertension.

PubMed

Atar, Ilyas; Korkmaz, Mehmet Emin; Demircan, Senol; Atar, Inci Asli; Bozbaş, Hüseyin; Aydinalp, Alp; Ozin, Bülent; Yildirir, Aylin; Müderrisoğlu, Haldun

2005-08-01

Recent studies have shown that hyperhomocysteinemia might play a role in the pathogenesis of hypertension. The effects of antihypertensive agents on plasma homocysteine levels have not been tested extensively. We investigated the effects of beta-blocker therapy on homocysteine levels in patients with hypertension. In the study, 120 patients with newly diagnosed hypertension were enrolled. All patients received metoprolol succinate 100 mg/day initially. If blood pressure was above normal on the 15th day of follow-up, the metoprolol dosage was doubled. Before initiation of the antihypertensive medication and after the fourth month of treatment, homocysteine levels were measured. Of the 120 patients enrolled, 39 could not complete the study. Homocysteine levels decreased significantly by the end of the fourth month when compared with basal values (13.5+/-4.5 micromol/l versus 12.4+/-4.9 micromol/l; P = 0.001). There was no relation between homocysteine level and blood pressure control. There was a significant decrease in homocysteine levels in the women treated in this study (P = 0.001); however, this effect was absent in men (P = 0.185). We demonstrate that metoprolol succinate treatment significantly decreases plasma homocysteine levels in patients with hypertension, especially in women.

On the response of superpressure balloons to displacements from equilibrium density level

NASA Technical Reports Server (NTRS)

Levanon, N.; Kushnir, Y.

1976-01-01

The response of a superpressure balloon to an initial displacement from its constant-density floating level is examined. An approximate solution is obtained to the governing vertical equation of motion for constant-density superpressure balloons. This solution is used to filter out neutrally buoyant oscillations in balloon records despite the nonlinear behavior of the balloon. The graph depicting the pressure data after deconvolution between the raw pressure data and the normalized balloon wavelet shows clearly the strong filtering-out of the neutral buoyancy oscillations.

Long-lasting active lifestyle and successful cognitive aging in a healthy elderly population: The PROOF cohort.

PubMed

Saint Martin, M; Sforza, E; Barthélémy, J C; Roche, F; Lefèvre, P; Liénard, G; Thomas-Anterion, C

2017-12-01

The aim of this study was to determine whether cognitive reserve in the elderly affects the evolution of cognitive performance and what its relationship is with active lifestyles in later life. Cognitive performance was evaluated at baseline and 8 years later in 543 participants of the PROOF cohort, initially aged 67 years. Subjects were categorized as Cognitively Elite (CE), Cognitively Normal (CN) or Cognitively Impaired (CI) at each evaluation. At follow-up, demographic data and lifestyle, including social, intellectual and physical behaviors, were collected by questionnaires. As much as 69% (n=375) remained unchanged, while 25.5% (n=138) decreased and 5.5% (n=30) improved. When present, the reduction in cognitive status was most often limited to one level, but was dependent on the initial level, affecting up to 73% of the initially CN, but only 58% of the initially CE. Cognitive stability was significantly associated with the degree of social engagement at follow-up (CE: P=0.009; CN: P=0.025). In the healthy elderly, high cognitive ability predicts both cognitive ability and social involvement in later life. Cognitive decline by only one level may also extend the time to reach impairment, underlining the importance of the so-called cognitive reserve. Copyright © 2017. Published by Elsevier Masson SAS.

Use of allopurinol with low-dose 6-mercaptopurine in inflammatory bowel disease to achieve optimal active metabolite levels: A review of four cases and the literature

PubMed Central

Witte, Todd N; Ginsberg, Allen L

2008-01-01

BACKGROUND: At least one-third of patients with inflammatory bowel disease do not respond or are intolerant to therapy with 6-mercaptopurine (6-MP). A subgroup fails to attain optimal levels of 6-thioguanine nucleotide (6-TGN) and instead shunts to 6-methylmercaptopurine nucleotide (6-MMPN). PATIENTS AND METHODS: A retrospective chart review was conducted, and four patients are described who had been previously unable to achieve optimal 6-TGN metabolite levels until allopurinol was added to their treatment. RESULTS: All four patients achieved optimal 6-TGN levels and undetectable 6-MMPN with a mean 6-MP dose of 0.49 mg/kg. Three achieved steroid-free clinical remission. Two of those three patients had normalization of liver enzymes; one patient had baseline normal liver enzymes despite an initial 6-MMPN level of 27,369 pmol/8×108 red blood cells. Two patients experienced reversible leukopenia. CONCLUSIONS: Combination allopurinol and low-dose 6-MP is an effective means to achieve optimal metabolite levels and steroid-free clinical remission in previously refractory patients. Caution is advised. PMID:18299738

Normal Cognition and Behavior in a Smith-Lemli-Opitz Syndrome Patient Who Presented With Hirschsprung Disease

PubMed Central

Mueller, C.; Patel, S.; Irons, M.; Antshel, K.; Salen, G.; Tint, G.S.; Bay, C.

2005-01-01

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis. It is caused by mutations in the gene encoding the enzyme 7-dehydrocholesterol Δ7-reductase (DHCR7), which catalyzes the final step in cholesterol biosynthesis, usually resulting in cholesterol deficiency. We report a 3.5-year-old girl who has cognition in the low average range and normal behavior, but in whom molecular studies identified two missense mutations in DHCR7: V326L and F284L. She was born at term following an uncomplicated pregnancy and delivery, and presented at 12 days of age with poor feeding, abdominal distention, and jaundice. Colonic biopsy was consistent with Hirschsprung disease. On physical examination she had mild ptosis, a long philtrum, mild micrognathia, a short, upturned nose, and subtle 2,3 syndactyly. Her 7-dehydrocholesterol (7-DHC) level was markedly elevated at 8.7 mg/dl (normal 0.10 ± 0.05), and her cholesterol level was normal at 61 mg/dl (normal for newborn period 50–80 mg/dl). Karyotype analysis was normal, 46,XX. Breast milk feeding was initiated and continued for 18 months. Cholesterol supplementation was implemented at 100 mg/kg/day at 3 months, which resulted in increased cholesterol levels and reduced dehydrocholesterol levels. Neuropsychological testing has shown functioning in the low average range, between the 14th and 18th centiles when compared to peers. This is markedly higher than most children with SLOS. She has no behavioral problems. MRI and MRS testing of the brain revealed no structural abnormalities. This is in contrast to a recently reported case by Prasad et al. [2002: Am J Med Genet 108:64–68] with a mild phenotype, behavioral problems, and abnormal MRI, who is compound heterozygote for both a null and missense mutation. Our case suggests that patients with severe feeding disorders with or without Hirschprung disease and postnatal onset microcephaly may warrant screening for SLOS. PMID:14556255

Symptomatic Hypercalcemia in a Patient with B-cell Chronic Lymphocytic Leukemia - A Case Report and Review of the Literature.

PubMed

Koutroumpakis, Efstratios; Lobe, Montgomery; McCarthy, Lezah; Mehdi, Syed

Hypercalcemia due to malignancy is well described in the literature and a common paraneoplastic finding in certain solid tumors. Hematologic malignancies, however, are less frequently associated with hypercalcemia with the exception of myelomas and T-cell lymphomas. This case report describes a patient with B-cell chronic lymphocytic leukemia (B-CLL) who developed symptomatic hypercalcemia. None of the pathogenetic mechanisms of malignancy-associated hypercalcemia already described in the literature could explain the pathogenesis of hypercalcemia in our patient. Calcium levels were normalized after initial treatment and remained within normal limits following treatment of the underlying B-CLL. The follow-up period was 26 months. The normalization of calcium levels was closely associated with the drop in the absolute lymphocyte count. Symptomatic hypercalcemia in B-CLL is exceedingly rare and only documented a few times in the literature. Hypercalcemia, in the present case, was not caused by any of the mechanisms already described in the literature and responded well to treatment of the underlying B-CLL. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Subgroup of ADNI Normal Controls Characterized by Atrophy and Cognitive Decline Associated With Vascular Damage

PubMed Central

Nettiksimmons, Jasmine; Beckett, Laurel; Schwarz, Christopher; Carmichael, Owen; Fletcher, Evan; DeCarli, Charles

2013-01-01

Previous work examining Alzheimer’s Disease Neuroimaging Initiative (ADNI) normal controls using cluster analysis identified a subgroup characterized by substantial brain atrophy and white matter hyperintensities (WMH). We hypothesized that these effects could be related to vascular damage. Fifty-three individuals in the suspected vascular cluster (Normal 2) were compared with 31 individuals from the cluster characterized as healthy/typical (Normal 1) on a variety of outcomes, including magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers, vascular risk factors and outcomes, cognitive trajectory, and medications for vascular conditions. Normal 2 was significantly older but did not differ on ApoE4+ prevalence. Normal 2 differed significantly from Normal 1 on all MRI measures but not on Amyloid-Beta1-42 or total tau protein. Normal 2 had significantly higher body mass index (BMI), Hachinksi score, and creatinine levels, and took significantly more medications for vascular conditions. Normal 2 had marginally significantly higher triglycerides and blood glucose. Normal 2 had a worse cognitive trajectory on the Rey’s Auditory Verbal Learning Test (RAVLT) 30-min delay test and the Functional Activity Questionnaire (FAQ). Cerebral atrophy associated with multiple vascular risks is common among cognitively normal individuals, forming a distinct subgroup with significantly increased cognitive decline. Further studies are needed to determine the clinical impact of these findings. PMID:23527743

Role of Krüppel-like factor 4 and heat shock protein 27 in cancer of the larynx

PubMed Central

Karam, Jihad; Fadous-Khalifé, Marie Claude; Tannous, Rita; Fakhreddine, Sally; Massoud, Marcel; Hadchity, Joseph; Aftimos, Georges; Hadchity, Elie

2017-01-01

Late detection and lack of standard treatment strategies in larynx cancer patients result in high levels of mortality and poor prognosis. Prognostic stratification of larynx cancer patients based on molecular prognostic tumor biomarkers may lead to more efficient clinical management. Krüppel-like factor 4 (KLF4) and Heat Shock Protein 27 (HSP27) have an important role in tumorigenesis and are considered promising candidate biomarkers for various types of cancer. However, their role in larynx carcinoma remains to be elucidated. The present study aimed to determine KLF4 and HSP27 expression profiles in laryngeal tumors. The protein and mRNA expression levels of KLF4 and HSP27 were evaluated by immunohistochemical and reverse transcription-polymerase chain reaction analyses in 44 larynx carcinoma samples and 21 normal tissue samples, and then correlated with clinical characteristics. A differential expression of KLF4 and HSP27 was observed between normal and tumor tissues. The protein and mRNA expression levels of KLF4 were significantly decreased in larynx squamous cell carcinoma (LSCC) compared with normal tissue, whereas HSP27 was significantly overexpressed in tumor tissues compared with normal tissues, at the protein and mRNA levels. KLF4 expression decreased gradually with tumor progression whereas HSP27 expression increased. A significant difference was observed between stages I and IV. KLF4 and HSP27 exhibit opposite functions and roles in the carcinogenic process of LSCC. Their role in laryngeal cancer initiation and progression emphasizes their use as potential future targets for prognosis and treatment. KLF4 and HSP27 expression levels may act as potential biomarkers in patients with cancer of the larynx. PMID:29181170

Drinking water and sanitation: progress in 73 countries in relation to socioeconomic indicators

PubMed Central

Bartram, Jamie

2016-01-01

Abstract Objective To assess progress in the provision of drinking water and sanitation in relation to national socioeconomic indicators. Methods We used household survey data for 73 countries – collected between 2000 and 2012 – to calculate linear rates of change in population access to improved drinking water (n = 67) and/or sanitation (n = 61). To enable comparison of progress between countries with different initial levels of access, the calculated rates of change were normalized to fall between –1 and 1. In regression analyses, we investigated associations between the normalized rates of change in population access and national socioeconomic indicators: gross national income per capita, government effectiveness, official development assistance, freshwater resources, education, poverty, Gini coefficient, child mortality and the human development index. Findings The normalized rates of change indicated that most of the investigated countries were making progress towards achieving universal access to improved drinking water and sanitation. However, only about a third showed a level of progress that was at least half the maximum achievable level. The normalized rates of change did not appear to be correlated with any of the national indicators that we investigated. Conclusion In many countries, the progress being made towards universal access to improved drinking water and sanitation is falling well short of the maximum achievable level. Progress does not appear to be correlated with a country’s social and economic characteristics. The between-country variations observed in such progress may be linked to variations in government policies and in the institutional commitment and capacity needed to execute such policies effectively. PMID:26957676

Molecular analysis of a phytohemagglutinin-defective cultivar of Phaseolus vulgaris L.

PubMed

Vitale, A; Ceriotti, A; Bollini, R

1985-10-01

The seeds of Phaseolus vulgaris cv. Pinto III are known to lack detectable amounts of phytohemagglutinin (PHA) and to accumulate very reduced levels of PHA mRNA compared with normal cultivars. Using PHA complementary-DNA clones and monospecific antibodies we analyzed cv. Pinto III genomic DNA and cotyledonary proteins synthesized both in vitro and in vivo. We detected genomic DNA sequences that hybridize with complementary-DNA clones for the two different classes of PHA polypeptides (PHA-E and PHA-L), at levels comparable to a normal bean cultivar. This indicates that the cv. Pinto III phenotype is not the result of a large deletion of the PHA structural genes. Messenger RNA isolated from cv. Pinto III developing cotyledons synthesizes in vitro very small amounts of a protein which is recognized by antibodies specific for PHA, and gives, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a single band with molecular weight similar but not identical to that of PHA-L polypeptides. This protein is also synthesized in vivo at a very reduced level, less than 1% compared with PHA in normal cultivars, and has mitogenic activity comparable to that of the PHA-L subunit, while it shows very weak erythroagglutinating activity. The initial steps in the synthesis and processing of this protein are identical to those already identified for PHA polypeptides. The cv. Pinto III protein could be either a PHA-L polypeptide whose synthesis is not affected by the mutation or a PHA-like lectin present normally at low levels in P. vulgaris.

Drinking water and sanitation: progress in 73 countries in relation to socioeconomic indicators.

PubMed

Luh, Jeanne; Bartram, Jamie

2016-02-01

To assess progress in the provision of drinking water and sanitation in relation to national socioeconomic indicators. We used household survey data for 73 countries - collected between 2000 and 2012 - to calculate linear rates of change in population access to improved drinking water (n = 67) and/or sanitation (n = 61). To enable comparison of progress between countries with different initial levels of access, the calculated rates of change were normalized to fall between -1 and 1. In regression analyses, we investigated associations between the normalized rates of change in population access and national socioeconomic indicators: gross national income per capita, government effectiveness, official development assistance, freshwater resources, education, poverty, Gini coefficient, child mortality and the human development index. The normalized rates of change indicated that most of the investigated countries were making progress towards achieving universal access to improved drinking water and sanitation. However, only about a third showed a level of progress that was at least half the maximum achievable level. The normalized rates of change did not appear to be correlated with any of the national indicators that we investigated. In many countries, the progress being made towards universal access to improved drinking water and sanitation is falling well short of the maximum achievable level. Progress does not appear to be correlated with a country's social and economic characteristics. The between-country variations observed in such progress may be linked to variations in government policies and in the institutional commitment and capacity needed to execute such policies effectively.

Early Speech Production of Children with Cleft Palate.

ERIC Educational Resources Information Center

Estrem, Theresa; Broen, Patricia A.

1989-01-01

The study comparing word-initial target phonemes and phoneme production of five toddlers with cleft palate and five normal toddlers found that the cleft palate children tended to target more words with word-initial nasals, approximants, and vowels and fewer words with word-initial stops, fricatives, and affricates than normal children. (Author/DB)

[Hypothyreodism. From the latent functional disorder up to coma].

PubMed

Hintze, G; Derwahl, M

2010-05-01

An autoimmune thyroiditis represents the main reason of hypothyroidism, defined as a lack of thyroid hormone. This autoimmune process results in destruction of functioning thyroid follicles. While subclinical or latent hypothyroidism is defined on the basis of laboratory values (an elevation of TSH with normal peripheral hormone levels), the typical signs and symptoms are associated with hypothyroidism. In about 80% of cases antibodies against thyroid peroxidase can be measured, but only in about 40-50% of cases antibodies against thyroglobulin are detectable. If hypothyrodism has been diagnosed, substitution with levothyroxine should be initiated, with the therapeutic goal to decrease TSH level to the lower normal range. In cases of subclinical hypothyroidism, levothyroxine medication should be started in patients with a high TSH value, positive antibodies and/or the typical ultrasound of autoimmune thyroiditis. However, substitution with levothyroxine in any case of elevated TSH values should be avoided.

Primary central nervous system lymphoma in childhood presenting as progressive panhypopituitarism.

PubMed

Silfen, M E; Garvin, J H; Hays, A P; Starkman, H S; Aranoff, G S; Levine, L S; Feldstein, N A; Wong, B; Oberfield, S E

2001-02-01

We report a 15-year-old boy who had isolated central diabetes insipidus initially diagnosed at age 11 years. A brain magnetic resonance imaging (MRI) was normal at the time. At age 12 years, growth hormone (GH) testing was performed because of a decline in linear growth rate and demonstrated GH deficiency. After a repeat normal brain MRI, GH therapy was begun. Three years later, hormonal testing revealed prepubertal gonadotropins and low testosterone levels, free thyroxine index, and morning cortisol levels. Repeat brain MRI demonstrated a 9-mm enhancing lesion in the region of the pituitary stalk. The pathologic diagnosis was that of a high-grade malignant B-cell lymphoma, suggestive of Burkitt Lymphoma. Growth hormone therapy has not been associated with an increased incidence of lymphoma. This report underscores the need for vigilance in follow-up brain imaging and hormonal evaluation in children with diabetes insipidus, especially those with evolving anterior hormone deficiencies.

Evaluating the 'Focus on Normal Birth and Reducing Caesarean section Rates Rapid Improvement Programme': A mixed method study in England.

PubMed

Marshall, Joyce L; Spiby, Helen; McCormick, Felicia

2015-02-01

caesarean section plays an important role in ensuring safety of mother and infant but rising rates are not accompanied by measurable improvements in maternal or neonatal mortality or morbidity. The 'Focus on Normal Birth and Reducing Caesarean section Rates Rapid Improvement Programme' was a facilitative initiative developed to promote opportunities for normal birth and reduce caesarean section rates in England. to evaluate the 'Focus on Normal Birth and Reducing Caesarean section Rates' programme, by assessment of: impact on caesarean section rates, use of service improvements tools and participants׳ perceptions of factors that sustain or hinder work within participating maternity units. a mixed methods approach included analysis of mode of birth data, web-based questionnaires and in-depth semi-structured telephone interviews. twenty Hospital Trusts in England (selected from 68 who applied) took part in the 'Focus on Normal Birth and Reducing Caesarean section Rates Rapid Improvement Programme' initiative. In each hospital Trust, the head of midwifery, an obstetrician, the relevant lead for organisational development, a supervisor of midwives, or a clinical midwife and a service user representative were invited to participate in the independent evaluation. collection and analysis of mode of birth data from 20 participating hospital Trusts, web-based questionnaires administered to key individuals in all 20 Trusts and in-depth semi-structured telephone interviews conducted with key individuals in a sample of six Trusts. there was a marginal decline of 0.5% (25.9% from 26.4%) in mean total caesarean section rate in the period 1 January 2009 to 31 January 2010 compared to the baseline period (1 July-31 December 2008). Reduced total caesarean section rates were achieved in eight trusts, all with higher rates at the beginning of the initiative. Features associated with lower caesarean section rates included a shared philosophy prioritising normal birth, clear communication across disciplines and strong leadership at a range of levels, including executive support and clinical leaders within each discipline. it is important that the philosophy and organisational context of care are examined to identify potential barriers and facilitative factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

A low cost igniter utilizing an SCB and titanium sub-hydride potassium perchlorate pyrotechnic

NASA Technical Reports Server (NTRS)

Bickes, R. W., Jr.; Grubelich, M. C.; Hartman, J. K.; McCampbell, C. B.; Churchill, J. K.

1994-01-01

A conventional NSI (NASA Standard Initiator) normally employs a hot-wire ignition element to ignite ZPP (zirconium potassium perchlorate). With minor modifications to the interior of a header similar to an NSI device to accommodate an SCB (semiconductor bridge), a low cost initiator was obtained. In addition, the ZPP was replaced with THKP (titanium sub-hydride potassium perchlorate) to obtain increased overall gas production and reduced static-charge sensitivity. This paper reports on the all-fire and no-fire levels obtained and on a dual mix device that uses THKP as the igniter mix and a thermite as the output mix.

Ion Movements in Shock in Relation to Survival and Its Modifications

DTIC Science & Technology

1985-01-01

from normal to irreversibly injured are initiated and modified by primary and/or secondary effects of ion redistributions taking place between the...reactions to injury by the shock state has become possible. However, spcclflc aspects concerning effects at the cellular and subcellular levels need...to be further clarified. Therefore, the aim of this study was to characterize the cellular and subcellular effects of hemorrhagic and bacteremic shock

Deliberate total parathyroidectomy: a potentially novel therapy for tumor-induced hypophosphatemic osteomalacia.

PubMed

Bhadada, Sanjay K; Palnitkar, Saroj; Qiu, Shijing; Parikh, Nayana; Talpos, Gary B; Rao, Sudhaker D

2013-11-01

Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic metabolic bone disorder that can be cured by removing or ablating the offending tumor. However, when the tumor cannot be localized, lifelong therapy with oral phosphate and calcitriol or cinacalcet with close monitoring is required. A 56-year-old man was diagnosed with TIO in 1990. Initial therapy consisted of oral phosphate and calcitriol with symptomatic and biochemical improvement and healing of osteomalacia. Eight years later, hypercalcemic hyperparathyroidism developed, requiring subtotal parathyroidectomy with a transient increase in serum phosphate and normalization of serum calcium and PTH. Recurrent hypercalcemic hyperparathyroidism developed after 10 years of medical therapy. A deliberate total parathyroidectomy produced a prompt rise in serum phosphate into the normal range > 3.0 mg/dL and remained normal during the next 4 years of follow-up, despite continued very high serum fibroblast growth factor-23 levels throughout the 23-year follow-up. We report an unusual case of a TIO patient with long-term follow-up who developed recurrent hypercalcemic hyperparathyroidism on long-term oral phosphate therapy. Deliberate total parathyroidectomy normalized serum phosphate despite persistently elevated fibroblast growth factor-23 levels. Total parathyroidectomy offers a potentially novel therapy in some patients with TIO in whom medical therapy is not feasible or the tumor is unresectable.

Individualized cost-effective conventional ovulation induction treatment in normogonadotrophic anovulatory infertility (WHO group 2).

PubMed

Eijkemans, Marinus J C; Polinder, Suzanne; Mulders, Annemarie G M G J; Laven, Joop S E; Habbema, J Dik F; Fauser, Bart C J M

2005-10-01

Conventional treatment in normogonadotrophic anovulatory infertility (WHO 2) consists of clomiphene citrate (CC), followed by exogenous gonadotrophins (FSH) and IVF. Response to these treatments may be predicted on the basis of individual patient characteristics. We aimed to devise a patient-tailored, cost-effective treatment algorithm involving the above-mentioned treatment modalities, based on individual patient characteristics. Sixteen prognostic groups are defined, according to the presence or absence of: age >30 years, amenorrhea, elevated androgen levels and obesity. The chances of response with each of the three treatments were calculated using prediction models. Treatment costs were based on the data of 240 patients visiting a specialist academic fertility unit. Outcome was an ongoing pregnancy within 12 months after initiation of treatment. The costs per pregnancy of three different strategies were compared, with a threshold for cost-effectiveness of 10 000. The strategy CC + FSH + IVF compared with FSH + IVF generated more pregnancies against lower costs. Compared with CC + IVF, it also produced more pregnancies, but at higher costs. For <30 years of age with normal androgen levels, costs per pregnancy were less than 10 000. For women >30 years old, costs per pregnancy were 25 000 and over 200 000, when presenting with normal or elevated androgen levels, respectively. The conventional treatment protocol is efficient for women aged <30 years with normal androgen levels. For women >30 years old with elevated androgen levels, FSH may be skipped.

Vitamin D supplementation, bone turnover, and inflammation in HIV-infected patients.

PubMed

Benguella, L; Arbault, A; Fillion, A; Blot, M; Piroth, C; Denimal, D; Duvillard, L; Ornetti, P; Chavanet, P; Maillefert, J-F; Piroth, L

2018-04-13

To assess whether vitamin D supplementation could be associated with a modification of inflammatory markers and bone turnover in HIV-1-infected patients. Patients who participated in an initial survey in 2010 and who were followed in the same department were included in a new study in 2012. Between 2010 and 2012, vitamin D supplementation was offered to patients presenting with hypovitaminosis D as per appropriate guidelines. Clinical examinations were performed, and fasting blood samples were taken for inflammation and bone marker evaluations. Of the 263 patients who participated in the 2010 study, 198 were included in the 2012 study. Hypovitaminosis D was observed in 47% (36/77) of participants supplemented as per appropriate guidelines, in 78% (75/97) of transiently or incompletely supplemented participants, and in 71% (17/24) of non-supplemented participants (mainly because vitamin D levels in 2010 were normal). No significant correlation between vitamin D supplementation and the 2-year inflammation outcome (IL-6 and hsCRP) or C-terminal telopeptide levels was observed. However, a decrease in IL6 levels over the 2 years significantly correlated with reaching a normal vitamin D level (OR=0.89 per+1pg/mL IL6 increase, 95% CI=0.81-0.97, P=0.015). Vitamin D supplementation decreases the risk of hypovitaminosis D but does not decrease the risk of inflammation nor bone turnover, unless normal 25-OH vitamin D levels are reached. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Induction of insulin secretion by a component of Urtica dioica leave extract in perifused Islets of Langerhans and its in vivo effects in normal and streptozotocin diabetic rats.

PubMed

Farzami, Bijan; Ahmadvand, D; Vardasbi, S; Majin, F J; Khaghani, Sh

2003-11-01

The blood glucose lowering effect of Urtica dioica (Stinging Nettle) as a medicinal plant has been noted in old writings such as those of Avicenna. Recently, there has also been other investigators that indicated the hypoglycemic effect of Urtica dioica. But so far, the mechanism of this effect has not been deduced. In this report, a perifusion system is arranged in which an exact number of Langerhans Islets were exposed to several fractions of extracts of Urtica dioica by TLC. The active ingredient fraction named F(1), caused a marked increase in insulin secretion. A simultaneous assay of glucose showed that the increase in insulin level was associated with a decrease in glucose level. Furthermore, the active component of Urtica dioica was found to increase the insulin content of blood sera in normal and streptozotocin diabetic rats that were injected intraperitoneally (i.p.) with the active ingredient of the extract. The in vivo studies presented in this report show that not only an increase in insulin level of blood sera was observed in rats after 30 min from the initial point of injection but a simultaneous decrease of blood sugar was detected when similar sera was tested for glucose. The increase in insulin level was six times during the 120 min of our determination. The decrease in blood sugar was found to be similar both in the level and time of initiation. On the basis of our findings, we assume that F(1) is the active ingredient of plant leaves extract. The results show that the blood lowering effect of the extract was due to the enhancement of insulin secretion by Langerhance Isletes.

A kinetic model to study the regulation of β-catenin, APC, and Axin in the human colonic crypt.

PubMed

Emerick, Brooks; Schleiniger, Gilberto; Boman, Bruce M

2017-11-01

The Wnt/[Formula: see text]-catenin pathway plays a crucial role in stem cell renewal and differentiation in the normal human colonic crypt. The balance between [Formula: see text]-catenin and APC along the crypt axis determines its normal functionality. The mechanism that deregulates this balance may give insight into the initiation of colorectal cancer. This is significant because the spatial dysregulation of [Formula: see text]-catenin by the mutated tumor suppressor gene/protein APC in human colonic crypts is responsible for the initiation and growth of colorectal cancer. We consider a regulatory function that promotes APC synthesis within the cell and its effect on the accumulation of the Wnt target protein, [Formula: see text]-catenin. It is evident that an APC gradient exists along the crypt axis; however, the mechanism by which APC expression is regulated within the cell is not well known. We investigate the dynamics of an APC regulatory mechanism with an increased level of Axin at the subcellular level. Model output shows an increase of APC for a diminished Wnt signal, which explains the APC gradient along the crypt. We find that the dynamic interplay between [Formula: see text]-catenin, APC, and Axin produces oscillatory behavior, which is controlled by the Wnt stimulus. In the presence of reduced functional APC, the oscillations are amplified, which suggests that the cell remains in a more proliferative state for longer periods of time. Increased Axin levels (typical of mammalian cells) reduce oscillatory behavior and minimize the levels of [Formula: see text]-catenin within the cell while raising the levels of APC.

Assessment of Oral Conditions and Quality of Life in Morbid Obese and Normal Weight Individuals: A Cross-Sectional Study.

PubMed

Yamashita, Joselene Martinelli; Moura-Grec, Patrícia Garcia de; Freitas, Adriana Rodrigues de; Sales-Peres, Arsênio; Groppo, Francisco Carlos; Ceneviva, Reginaldo; Sales-Peres, Sílvia Helena de Carvalho

2015-01-01

The aim of this study was to identify the impact of oral disease on the quality of life of morbid obese and normal weight individuals. Cohort was composed of 100 morbid-obese and 50 normal-weight subjects. Dental caries, community periodontal index, gingival bleeding on probing (BOP), calculus, probing pocket depth, clinical attachment level, dental wear, stimulated salivary flow, and salivary pH were used to evaluate oral diseases. Socioeconomic and the oral impacts on daily performances (OIDP) questionnaires showed the quality of life in both groups. Unpaired Student, Fisher's Exact, Chi-Square, Mann-Whitney, and Multiple Regression tests were used (p<0.05). Obese showed lower socio-economic level than control group, but no differences were found considering OIDP. No significant differences were observed between groups considering the number of absent teeth, bruxism, difficult mastication, calculus, initial caries lesion, and caries. However, saliva flow was low, and the salivary pH was changed in the obese group. Enamel wear was lower and dentine wear was higher in obese. More BOP, insertion loss, and periodontal pocket, especially the deeper ones, were found in obese subjects. The regression model showed gender, smoking, salivary pH, socio-economic level, periodontal pocket, and periodontal insertion loss significantly associated to obesity. However, both OIDP and BOP did not show significant contribution to the model. The quality of life of morbid obese was more negatively influenced by oral disease and socio-economic factors than in normal weight subjects.

Induced vasodilation as treatment for Raynaud's disease.

PubMed

Jobe, J B; Sampson, J B; Roberts, D E; Beetham, W P

1982-11-01

We examined the efficacy of induced vasodilation as a treatment of idiopathic Raynaud's disease. Eight persons with Raynaud's disease and seven normal persons each received 27 simultaneous pairings of hand immersion in warm water (43 degrees C) for 10 minutes with exposure of the whole body to cold (0 degrees C). A second group of seven normal persons and nine persons with Raynaud's disease received no treatments. All subjects had cold test exposures (0 degrees C) at the start and end of the study. Subjects with Raynaud's disease who received treatments showed significant increases in digital temperatures (2.2 degrees C) during the cold test compared with the values of untreated subjects with Raynaud's disease (p less than 0.05); normal subjects who had received treatments showed no difference from those who had not. Digital temperatures of subjects with Raynaud's disease after treatment increased to levels approaching those of normal subjects, although they showed lower digital temperatures during initial exposure to cold (p less than 0.01). This therapy offers a practical alternative to traditional treatments.

Normalized levels of red blood cells expressing phosphatidylserine, their microparticles, and activated platelets in young patients with β-thalassemia following bone marrow transplantation.

PubMed

Klaihmon, Phatchanat; Vimonpatranon, Sinmanus; Noulsri, Egarit; Lertthammakiat, Surapong; Anurathapan, Usanarat; Sirachainan, Nongnuch; Hongeng, Suradej; Pattanapanyasat, Kovit

2017-10-01

Bone marrow transplantation (BMT) serves as the only curative treatment for patients with β-thalassemia major; however, hemostatic changes have been observed in these BMT patients. Aggregability of thalassemic red blood cells (RBCs) and increased red blood cell-derived microparticles (RMPs) expressing phosphatidylserine (PS) are thought to participate in thromboembolic events by initially triggering platelet activation. To our knowledge, there has been no report providing quantitation of these circulating PS-expressing RBCs and RMPs in young β-thalassemia patients after BMT. Whole blood from each subject was fluorescently labeled to detect RBC markers (CD235a) and annexin-V together with the known number TruCount™ beads. PS-expressing RBCs, RMPs, and activated platelets were identified by flow cytometry. In our randomized study, we found the decreased levels of three aforementioned factors compared to levels in patients receiving regular blood transfusion (RT). This study showed that BMT in β-thalassemia patients decreases the levels of circulating PS-expressing RBCs, their MPs, and procoagulant platelets when compared to patients who received RT. Normalized levels of these coagulation markers may provide the supportive evidence of the effectiveness of BMT for curing thalassemia.

Reduction of damage initiation density in fused silica optics via UV laser conditioning

DOEpatents

Peterson, John E.; Maricle, Stephen M.; Brusasco, Raymond M.; Penetrante, Bernardino M.

2004-03-16

The present invention provides a method for reducing the density of sites on the surface of fused silica optics that are prone to the initiation of laser-induced damage, resulting in optics which have far fewer catastrophic defects and are better capable of resisting optical deterioration upon exposure for a long period of time to a high-power laser beam having a wavelength of about 360 nm or less. The initiation of laser-induced damage is reduced by conditioning the optic at low fluences below levels that normally lead to catastrophic growth of damage. When the optic is then irradiated at its high fluence design limit, the concentration of catastrophic damage sites that form on the surface of the optic is greatly reduced.

Effects of Janus kinase inhibitor tofacitinib on circulating serum amyloid A and interleukin-6 during treatment for rheumatoid arthritis

PubMed Central

Migita, K; Izumi, Y; Jiuchi, Y; Kozuru, H; Kawahara, C; Izumi, M; Sakai, T; Nakamura, M; Motokawa, S; Nakamura, T; Kawakami, A

2014-01-01

The Janus kinase inhibitor tofacitinib is currently being investigated as a disease-modifying agent in rheumatoid arthritis (RA). We investigated the in-vivo effects of tofacitinib treatment for 4 weeks on elevated circulating acute-phase serum amyloid (SAA) levels in 14 Japanese patients with RA. SAA levels fell from 110·5 ± 118·5 μg/ml (mean ± standard deviation) at treatment initiation to 15·3 ± 13·3 μg/ml after 4 weeks treatment with tofacitinib. The reduction in SAA levels was greater in patients receiving tofacitinib plus methotrexate compared with those receiving tofacitinib monotherapy. Tofacitinib was also associated with reduced serum interleukin (IL)-6, but had no effect on serum levels of soluble IL-6 receptor. Patients were divided into groups with adequate (normalization) and inadequate SAA responses (without normalization). Serum IL-6 levels were reduced more in the group with adequate SAA response compared with those with inadequate SAA response. These results suggest that tofacitinib down-regulates the proinflammatory cytokine, IL-6, accompanied by reduced serum SAA levels in patients with active RA. The ability to regulate elevated serum IL-6 and SAA levels may explain the anti-inflammatory activity of tofacitinib. PMID:24665995

ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players.

PubMed

Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

2016-09-15

The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca(2+)) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca(2+) regulates cell death both at the early and late stages of apoptosis. Severe Ca(2+) dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca(2+) (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca(2+) and action potential in ER stress-mediated apoptosis.

Management of Listeria monocytogenes in fermented sausages using the Food Safety Objective concept underpinned by stochastic modeling and meta-analysis.

PubMed

Mataragas, M; Alessandria, V; Rantsiou, K; Cocolin, L

2015-08-01

In the present work, a demonstration is made on how the risk from the presence of Listeria monocytogenes in fermented sausages can be managed using the concept of Food Safety Objective (FSO) aided by stochastic modeling (Bayesian analysis and Monte Carlo simulation) and meta-analysis. For this purpose, the ICMSF equation was used, which combines the initial level (H0) of the hazard and its subsequent reduction (ΣR) and/or increase (ΣI) along the production chain. Each element of the equation was described by a distribution to investigate the effect not only of the level of the hazard, but also the effect of the accompanying variability. The distribution of each element was determined by Bayesian modeling (H0) and meta-analysis (ΣR and ΣI). The output was a normal distribution N(-5.36, 2.56) (log cfu/g) from which the percentage of the non-conforming products, i.e. the fraction above the FSO of 2 log cfu/g, was estimated at 0.202%. Different control measures were examined such as lowering initial L. monocytogenes level and inclusion of an additional killing step along the process resulting in reduction of the non-conforming products from 0.195% to 0.003% based on the mean and/or square-root change of the normal distribution, and 0.001%, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

SCADA Protocol Anomaly Detection Utilizing Compression (SPADUC) 2013

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

Gordon Rueff; Lyle Roybal; Denis Vollmer

2013-01-01

There is a significant need to protect the nation’s energy infrastructures from malicious actors using cyber methods. Supervisory, Control, and Data Acquisition (SCADA) systems may be vulnerable due to the insufficient security implemented during the design and deployment of these control systems. This is particularly true in older legacy SCADA systems that are still commonly in use. The purpose of INL’s research on the SCADA Protocol Anomaly Detection Utilizing Compression (SPADUC) project was to determine if and how data compression techniques could be used to identify and protect SCADA systems from cyber attacks. Initially, the concept was centered on howmore » to train a compression algorithm to recognize normal control system traffic versus hostile network traffic. Because large portions of the TCP/IP message traffic (called packets) are repetitive, the concept of using compression techniques to differentiate “non-normal” traffic was proposed. In this manner, malicious SCADA traffic could be identified at the packet level prior to completing its payload. Previous research has shown that SCADA network traffic has traits desirable for compression analysis. This work investigated three different approaches to identify malicious SCADA network traffic using compression techniques. The preliminary analyses and results presented herein are clearly able to differentiate normal from malicious network traffic at the packet level at a very high confidence level for the conditions tested. Additionally, the master dictionary approach used in this research appears to initially provide a meaningful way to categorize and compare packets within a communication channel.« less

Effects of an advanced temperature cycle on smolt development and endocrinology indicate that temperature is not a zeitgeber for smolting in Atlantic salmon

USGS Publications Warehouse

McCormick, S.D.; Shrimpton, J.M.; Moriyama, S.; Bjornsson, Bjorn Thrandur

2002-01-01

Atlantic salmon (Salmo salar) juveniles were reared under simulated conditions of normal photoperiod (LDN) or short days (LD 9:15) and ambient temperature (AMB: normal temperature increases in April) or an advanced temperature cycle (ADV: temperature increases in February). Under both photoperiod conditions, the timing of increased and peak levels of gill Na+,K+-ATPase activity were not altered by temperature, although the rate of increase was initially greater under ADV. ADV/LD 9:15 resulted in peak gill Na+,K+-ATPase activity that was half of that seen under normal photoperiod and temperature conditions. Plasma growth hormone (GH) levels increased threefold in late March under ADV/LDN, but not under ADV/LD 9:15, indicating that there is a photoperiod-dependent effect of temperature on levels of this hormone. Plasma insulin-like growth factor I (IGF-I) increased in spring in all groups, with increases occurring significantly earlier in the ADV/LDN group. In each photoperiod condition, the advanced temperature cycle resulted in large decreases in plasma thyroxine (T4) levels in March, which subsequently recovered, whereas plasma 3,5,3???-triiodo-L-thyronine (T3) levels were not substantially affected by either photoperiod or temperature. There was no consistent pattern of change in plasma cortisol levels. The results do not provide support for the role of temperature as a zeitgeber, but do indicate that temperature has a role in the timing of smolting by affecting the rate of development and interacting with the photoperiod.

[Antibodies against TSH receptors (TRAb) as indicators in prognosing the effectiveness of Tiamazol therapy for Grave's Disease].

PubMed

Bojarska-Szmygin, Anna; Ciechanek, Roman

2003-01-01

The aim of the study was to evaluate the usefulness of TRAb determinations in prognosing and monitoring the efficacy of conservative treatment in Graves' disease. The examinations were performed in 54 patients. During the 18-month observation all the patients were treated with Tiamazol. The control group consisted of 20 healthy volunteers. The TRAb levels were determined before as well as 12 and 18 months after thyrostatic treatment. Simultaneously, the levels of TSH and FT4 were analysed. Moreover, all the patients underwent ultrasound examinations to assess the size of the thyroid gland. The findings of the 18-month follow up showed that in 31 patients (57%) the thyroid function became normal (group I--euthyreosis), in 23 patients (43%) hyperactivity persisted (group II--hyperthyreosis). The TRAb levels were analysed in both groups of patients. An increased initial level of TRAb was found in the hyperactivity group mean -54.39 + 31.21 U/l which was statistically significantly different from the TRAb levels in the euthyreosis group mean -29.13 +/- 19.14 U/l and in controls mean -2.75 +/- 2.06 U/l (p < 0.001 for both parameters). After 12-month treatment increased values of antibodies were still observed in this group of patients (mean -39.96 +/- 33.40 U/l) in comparison with the euthyreosis group (mean -9.87 +/- 8.33 U/l) and controls (mean -2.75 +/- 2.06 U/l) (p < 0.001 for both parameters). After 18-month treatment the TRAb levels in group II remained increased (mean -40.17 +/- 33.06) while in group I normal levels were achieved. The sizes of the thyroid gland were compared between the individual groups. In the hyperactivity group after 18-month treatment, the thyroid size was the biggest (mean -41.09 +/- 13.94 ml) and was statistically significantly different when compared to the average size in the euthyreosis group mean -31.65 +/- 11.74 ml (p < 0.01) and in controls mean -14.45 +/- 2.37 ml (p < 0.001). The levels of antibodies against TSH receptors are useful parameters in prognosis and monitoring the treatment effectiveness in Graves' disease. High initial levels of antibodies are the poor prognostic factors. The TRAb determinations are of some prognostic value not only before but also 12 months since the onset of therapy. The lack of antibody level normalization during treatment is connected with persisting hyperactivity. The TRAb concentration correlates with the thyroid size.

Changes in body weight after treatment of primary hypothyroidism with levothyroxine.

PubMed

Lee, Sun Y; Braverman, Lewis E; Pearce, Elizabeth N

2014-11-01

Surprisingly few studies have examined weight change in hypothyroid patients after initiation of levothyroxine (LT4) therapy. Our study aimed to investigate weight change after initiation of LT4 treatment for primary hypothyroidism. Using electronic medical records from Boston Medical Center, Boston, Massachusetts, we performed a retrospective cohort study between January 1, 2003, and February 1, 2011. Adults ≥18 years of age with newly diagnosed primary hypothyroidism with an initial thyroid-stimulating hormone (TSH) level ≥10 mIU/L were identified. Patients with postsurgical hypothyroidism, thyroid cancer, and a history of radioactive iodine or head/neck irradiation, congestive heart failure, anorexia nervosa, end-stage renal disease, cirrhosis, pregnancy, or use of prescription weight-loss medications were excluded. TSH and weight at diagnosis and up to 24 months after LT4 initiation were collected. Weight change was assessed at the first posttreatment serum TSH level <5 mIU/L. A total of 101 patients (mean age, 48 ± 15 years; 71% women) were included. Initial median TSH was 18.3 mIU/L (range, 10.1 to 710.5 mIU/L) and initial median weight was 79.6 kg (range 41.5 to 167.5 kg). Posttreatment median TSH level was 2.3 mIU/L (range, 0.04 to 5 mIU/L), and weight change at a median of 5 months (range, 1.1 to 25.6 months) was -0.1 kg (range, -20.6 to 7.7 kg). Initial median body mass index (BMI) of 95 of the patients was 29.3 kg/m2 (range, 19.5 to 56.1 kg/m2), and the median change in BMI was -0.1 kg/m2 (range, -7.1 to 3.3 kg/m2). Only 52% of patients lost weight, with a mean weight loss of 3.8 ± 4.4 kg. Gender, race, education, insurance type, age, initial TSH level, time to normalization of TSH, and initial weight were not associated with changes in weight or BMI. Contrary to popular belief, our study of 101 patients with primary hypothyroidism showed that no significant weight change occurs after initiation of LT4 treatment.

Severe hypocalcemia following bisphosphonate treatment in a patient with Paget's disease of bone.

PubMed

Whitson, Heather E; Lobaugh, Bruce; Lyles, Kenneth W

2006-10-01

Bisphosphonate therapy is a common and effective treatment for Paget's disease of bone, osteoporosis, hypercalcemia of malignancy and cancer metastatic to bone. Clinically significant hypocalcemia has not been reported in patients with Paget's disease of bone and normal parathyroid function treated with an aminobisphosphonate. We treated a 52-year-old woman with polyostotic Paget's disease of bone (serum alkaline phosphatase level-1971 IU/L [normal 31-110 IU/L]), who had not previously received bisphosphonates, with daily oral 30 mg risedronate, oral 1000 mg elemental calcium and oral 400 IU cholecalciferol. After 10 days of treatment, she developed severe hypocalcemia (5.4 mg/dL [normal 8.7-10.2 mg/dL]), requiring hospitalization and support with 5 days of intravenous calcium gluconate. On the day risedronate treatment began, her PTH was low normal at 14 pg/mL (normal 12-72 pg/mL), consistent with a relatively suppressed PTH axis due to high bone turnover. Her vitamin D level was within normal limits (serum 25(OH)D 19 ng/mL [normal 8-38 ng/mL]), although possibly not optimally repleted. We hypothesize that this case represents an example of hungry bone syndrome in a patient with extensive Paget's disease of bone who received risedronate, causing acute suppression of bone resorption while elevated bone formation rates continued. In the year following her recovery, the patient was successfully treated with slowly titrated anti-resorptive therapy (subcutaneous calcitonin followed by titrated doses of risedronate), and is now clinically well. Physicians should be aware of the potential for hypocalcemia when patients with polyostotic Paget's disease and markedly elevated indicators of bone remodeling are initiated on powerful anti-resorptive therapy.

Induced Abnormality In Mir- and Earth-Grown Super Dwarf Wheat

NASA Technical Reports Server (NTRS)

Bubenheim, David L.; Stieber, Joseph; Campbell, William F.; Salisbury, Frank B.; Levinski, Margarita; Sytchev, Vladimir; Podolsky, Igor; Chernova, Lola; Ivanova, Irene; Kliss, Mark (Technical Monitor)

1998-01-01

Super-dwarf wheat grown on the Mir space station using the Svet "Greenhouse" exhibited morphological, metabolic and reproductive abnormalities compared with normal wheat. Of prominent importance were the abnormalities associated with reproductive ontogeny and the total absence of seed formation on Mir. Changes in the apical meristem associated with transition from the vegetative phase to floral initiation and development of the reproductive spike were all typical of 'Super Dwarf' wheat up to the point of anthesis. Observation of ruptured anthers from the Mir-grown plants revealed what appeared to be normally developed pollen. These pollen grains however, contain only one nucleus, while normal viable pollen is trinucleate. A potentially important difference in the flight experiment, compared with ground reference studies, was identified - a high level of atmospheric ethylene (1200 ppb). Ground studies conducted exposing "Super-dwarf" wheat to ethylene at just prior to anthesis resulted in manifestation of the same abnormalities observed in the space flight samples.

Clinical NMR imaging of the brain in children: normal and neurologic disease

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

Johnson, M.A,; Pennock, J.M.; Bydder, G.M.

1983-11-01

The results of initial clinical nuclear magnetic resonance imaging of the brain in eight normal and 52 children with a wide variety of neurologic diseases were reviewed. The high level of gray-white matter contrast available with inversion-recovery sequences provided a basis for visualizing normal myelination as well as delays or deficits in this process. The appearances seen in cases of parenchymal hemorrhage, cerebral infarction, and proencephalic cysts are described. Ventricular enlargement was readily identified and marginal edema was demonstrated with spin-echo sequences. Abnormalities were seen in cerebral palsy, congenital malformations, Hallervorden-Spatz disease, aminoaciduria, and meningitis. Space-occupying lesions were identified bymore » virtue of their increased relaxation times and mass effects. Nuclear magnetic resonance imaging has considerable potential in pediatric neuroradiologic practice, in some conditions supplying information not available by computed tomography or sonography.« less

Longitudinal change of biomarkers in cognitive decline.

PubMed

Lo, Raymond Y; Hubbard, Alan E; Shaw, Leslie M; Trojanowski, John Q; Petersen, Ronald C; Aisen, Paul S; Weiner, Michael W; Jagust, William J

2011-10-01

To delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD). Cohort study. The 59 study sites for the Alzheimer's Disease Neuroimaging Initiative. A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007. Rates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease's Assessment Scale-cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker. Reductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease's Assessment Scale-cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD. Trajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent.

Lithium overdose and delayed severe neurotoxicity: timing for renal replacement therapy and restarting of lithium.

PubMed

de Cates, Angharad N; Morlet, Julien; Antoun Reyad, Ayman; Tadros, George

2017-10-25

This is a case report of a man in his 60s who presented to an English hospital following a significant lithium overdose. He was monitored for 24 hours, and then renal replacement therapy was initiated after assessment by the renal team. As soon as the lithium level returned to normal therapeutic levels (from 4.7 mEq/L to 0.67 mEq/L), lithium was restarted by the medical team. At this point, the patient developed new slurred speech and later catatonia. In this case report, we discuss the factors that could determine which patients are at risk of neurotoxicity following lithium overdose and the appropriate decision regarding when and how to consider initiation of renal replacement therapy and restarting of lithium. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Neuropsychiatric manifestations in late-onset urea cycle disorder patients.

PubMed

Serrano, Mercedes; Martins, Cecilia; Pérez-Dueñas, Belén; Gómez-López, Lilian; Murgui, Empar; Fons, Carmen; García-Cazorla, Angels; Artuch, Rafael; Jara, Fernando; Arranz, José A; Häberle, Johannes; Briones, Paz; Campistol, Jaume; Pineda, Mercedes; Vilaseca, Maria A

2010-03-01

Inherited urea cycle disorders represent one of the most common groups of inborn errors of metabolism. Late-onset urea cycle disorders caused by partial enzyme deficiencies may present with unexpected clinical phenotypes. We report 9 patients followed up in our hospital presenting late-onset urea cycle disorders who initially manifested neuropsychiatric/neurodevelopmental symptoms (the most prevalent neuropsychiatric/neurodevelopmental diagnoses were mental retardation, attention-deficit hyperactivity disorder [ADHD], language disorder, and delirium). Generally, these clinical pictures did not benefit from pharmacological treatment. Conversely, dietary treatment improved the symptoms. Regarding biochemical data, 2 patients showed normal ammonium but high glutamine levels. This study highlights the fact that neuropsychiatric/neurodevelopmental findings are common among the initial symptomatology of late-onset urea cycle disorders. The authors recommend that unexplained or nonresponsive neuropsychiatric/neurodevelopmental symptoms appearing during childhood or adolescence be followed by a study of ammonia and amino acid plasmatic levels to rule out a urea cycle disorder.

Factors affecting the persistence of drug-induced reprogramming of the cancer methylome

PubMed Central

Bell, Joshua S. K.; Kagey, Jacob D.; Barwick, Benjamin G.; Dwivedi, Bhakti; McCabe, Michael T.; Kowalski, Jeanne; Vertino, Paula M.

2016-01-01

ABSTRACT Aberrant DNA methylation is a critical feature of cancer. Epigenetic therapy seeks to reverse these changes to restore normal gene expression. DNA demethylating agents, including 5-aza-2′-deoxycytidine (DAC), are currently used to treat certain leukemias, and can sensitize solid tumors to chemotherapy and immunotherapy. However, it has been difficult to pin the clinical efficacy of these agents to specific demethylation events, and the factors that contribute to the durability of response remain largely unknown. Here we examined the genome-wide kinetics of DAC-induced DNA demethylation and subsequent remethylation after drug withdrawal in breast cancer cells. We find that CpGs differ in both their susceptibility to demethylation and propensity for remethylation after drug removal. DAC-induced demethylation was most apparent at CpGs with higher initial methylation levels and further from CpG islands. Once demethylated, such sites exhibited varied remethylation potentials. The most rapidly remethylating CpGs regained >75% of their starting methylation within a month of drug withdrawal. These sites had higher pretreatment methylation levels, were enriched in gene bodies, marked by H3K36me3, and tended to be methylated in normal breast cells. In contrast, a more resistant class of CpG sites failed to regain even 20% of their initial methylation after 3 months. These sites had lower pretreatment methylation levels, were within or near CpG islands, marked by H3K79me2 or H3K4me2/3, and were overrepresented in sites that become aberrantly hypermethylated in breast cancers. Thus, whereas DAC-induced demethylation affects both endogenous and aberrantly methylated sites, tumor-specific hypermethylation is more slowly regained, even as normal methylation promptly recovers. Taken together, these data suggest that the durability of DAC response is linked to its selective ability to stably reset at least a portion of the cancer methylome. PMID:27082926

Automatic Rooftop Extraction in Stereo Imagery Using Distance and Building Shape Regularized Level Set Evolution

NASA Astrophysics Data System (ADS)

Tian, J.; Krauß, T.; d'Angelo, P.

2017-05-01

Automatic rooftop extraction is one of the most challenging problems in remote sensing image analysis. Classical 2D image processing techniques are expensive due to the high amount of features required to locate buildings. This problem can be avoided when 3D information is available. In this paper, we show how to fuse the spectral and height information of stereo imagery to achieve an efficient and robust rooftop extraction. In the first step, the digital terrain model (DTM) and in turn the normalized digital surface model (nDSM) is generated by using a newly step-edge approach. In the second step, the initial building locations and rooftop boundaries are derived by removing the low-level pixels and high-level pixels with higher probability to be trees and shadows. This boundary is then served as the initial level set function, which is further refined to fit the best possible boundaries through distance regularized level-set curve evolution. During the fitting procedure, the edge-based active contour model is adopted and implemented by using the edges indicators extracted from panchromatic image. The performance of the proposed approach is tested by using the WorldView-2 satellite data captured over Munich.

Self-pressurization of a flightweight liquid hydrogen tank: Effects of fill level at low wall heat flux

NASA Technical Reports Server (NTRS)

Vandresar, N. T.; Hasan, M. M.; Lin, C.-S.

1991-01-01

Experimental results are presented for the self pressurization and thermal stratification of a 4.89 cu m liquid hydrogen storage tank subjected to low heat flux (2.0 and 3.5 W/sq m) in normal gravity. The test tank was representative of future spacecraft tankage, having a low mass to volume ratio and high performance multilayer thermal insulation. Tests were performed at fill levels of 29 and 49 pcts. (by volume) and complement previous tests at 83 pct. fill. As the heat flux increases, the pressure rise rate at each fill level exceeds the homogeneous rate by an increasing ratio. Herein, this ratio did not exceed a value of 2. The slowest pressure rise rate was observed for the 49 pct. fill level at both heat fluxes. This result is attributed to the oblate spheroidal tank geometry which introduces the variables of wetted wall area, liquid-vapor interfacial area, and ratio of side wall to bottom heating as a function of fill level or liquid depth. Initial tank thermal conditions were found to affect the initial pressure rise rate. Quasi steady pressure rise rates are independent of starting conditions.

Weight gain in insulin-treated patients by body mass index category at treatment initiation: new evidence from real-world data in patients with type 2 diabetes.

PubMed

Paul, S K; Shaw, J E; Montvida, O; Klein, K

2016-12-01

To evaluate, in patients with type 2 diabetes (T2DM) treated with insulin, the extent of weight gain over 2 years of insulin treatment, and the dynamics of weight gain in relation to glycaemic achievements over time according to adiposity levels at insulin initiation. Patients with T2DM (n = 155 917), who commenced insulin therapy and continued it for at least 6 months, were selected from a large database of electronic medical records in the USA. Longitudinal changes in body weight and glycated haemoglobin (HbA1c) according to body mass index (BMI) category were estimated. Patients had a mean age of 59 years, a mean HbA1c level of 9.5%, and a mean BMI of 35 kg/m 2 at insulin initiation. The HbA1c levels at insulin initiation were significantly lower (9.2-9.4%) in the obese patients than in patients with normal body weight (10.0%); however, the proportions of patients with HbA1c >7.5% or >8.0% were similar across the BMI categories. The adjusted weight gain fell progressively with increasing baseline BMI category over 6, 12 and 24 months (p < .01). The adjusted changes in HbA1c were similar across BMI categories. A 1% decrease in HbA1c was associated with progressively less weight gain as pretreatment BMI rose, ranging from a 1.24 kg gain in those with a BMI <25 kg/m 2 to a 0.32 kg loss in those with a BMI > 40 kg/m 2 . During 24 months of insulin treatment, obese patients gained significantly less body weight than normal-weight and overweight patients, while achieving clinically similar glycaemic benefits. These data provide reassurance with regard to the use of insulin in obese patients. © 2016 John Wiley & Sons Ltd.

Attenuation of Diabetic Conditions by Sida rhombifolia in Moderately Diabetic Rats and Inability to Produce Similar Effects in Severely Diabetic in Rats.

PubMed

Chaturvedi, Padmaja; Kwape, Tebogo Elvis

2015-12-01

This study was done out to evaluate the effects of Sida rhombifolia methanol extract (SRM) on diabetes in moderately diabetic (MD) and severely diabetic (SD) Sprague-Dawley rats. SRM was prepared by soaking the powdered plant material in 70% methanol and rota evaporating the methanol from the extract. Effective hypoglycemic doses were established by performing oral glucose tolerance tests (OGTTs) in normal rats. Hourly effects of SRM on glucose were observed in the MD and the SD rats. Rats were grouped, five rats to a group, into normal control 1 (NC1), MD control 1 (MDC1), MD experimental 1 (MDE1), SD control 1 (SDC1), and SD experimental 1 (SDE1) groups. All rats in the control groups were administered 1 mL of distilled water (DW). The rats in the MDE1 and the SDE1 groups were administered SRM orally at 200 and 300 mg/kg body weight (BW), respectively, dissolved in 1 mL of DW. Blood was collected initially and at intervals of 1 hour for 6 hours to measure blood glucose. A similar experimental design was followed for the 30-day long-term trial. Finally, rats were sacrificed, and blood was collected to measure blood glucose, lipid profiles, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH). OGTTs indicated that two doses (200 and 300 mg/kg BW) were effective hypoglycemic doses in normal rats. Both doses reduced glucose levels after 1 hour in the MDE1 and the SDE1 groups. A long-term trial of SRM in the MD group showed a reduced glucose level, a normal lipid profile, and normal GSH and TBARS levels. In SD rats, SRM had no statistically significant effects on these parameters. Normal weight was achieved in the MD rats, but the SD rats showed reduced BW. The study demonstrates that SRM has potential to alleviate the conditions of moderate diabetic, but not severe diabetes.

Adaptation of the walking pattern to uphill walking in normal and spinal-cord injured subjects.

PubMed

Leroux, A; Fung, J; Barbeau, H

1999-06-01

Lower-limb movements and muscle-activity patterns were assessed from seven normal and seven ambulatory subjects with incomplete spinal-cord injury (SCI) during level and uphill treadmill walking (5, 10 and 15 degrees). Increasing the treadmill grade from 0 degrees to 15 degrees induced an increasingly flexed posture of the hip, knee and ankle during initial contact in all normal subjects, resulting in a larger excursion throughout stance. This adaptation process actually began in mid-swing with a graded increase in hip flexion and ankle dorsiflexion as well as a gradual decrease in knee extension. In SCI subjects, a similar trend was found at the hip joint for both swing and stance phases, whereas the knee angle showed very limited changes and the ankle angle showed large variations with grade throughout the walking cycle. A distinct coordination pattern between the hip and knee was observed in normal subjects, but not in SCI subjects during level walking. The same coordination pattern was preserved in all normal subjects and in five of seven SCI subjects during uphill walking. The duration of electromyographic (EMG) activity of thigh muscles was progressively increased during uphill walking, whereas no significant changes occurred in leg muscles. In SCI subjects, EMG durations of both thigh and leg muscles, which were already active throughout stance during level walking, were not significantly affected by uphill walking. The peak amplitude of EMG activity of the vastus lateralis, medial hamstrings, soleus, medial gastrocnemius and tibialis anterior was progressively increased during uphill walking in normal subjects. In SCI subjects, the peak amplitude of EMG activity of the medial hamstrings was adapted in a similar fashion, whereas the vastus lateralis, soleus and medial gastrocnemius showed very limited adaptation during uphill walking. We conclude that SCI subjects can adapt to uphill treadmill walking within certain limits, but they use different strategies to adapt to the changing locomotor demands.

Real-Time SCADA Cyber Protection Using Compression Techniques

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

Lyle G. Roybal; Gordon H Rueff

2013-11-01

The Department of Energy’s Office of Electricity Delivery and Energy Reliability (DOE-OE) has a critical mission to secure the energy infrastructure from cyber attack. Through DOE-OE’s Cybersecurity for Energy Delivery Systems (CEDS) program, the Idaho National Laboratory (INL) has developed a method to detect malicious traffic on Supervisory, Control, and Data Acquisition (SCADA) network using a data compression technique. SCADA network traffic is often repetitive with only minor differences between packets. Research performed at the INL showed that SCADA network traffic has traits desirable for using compression analysis to identify abnormal network traffic. An open source implementation of a Lempel-Ziv-Welchmore » (LZW) lossless data compression algorithm was used to compress and analyze surrogate SCADA traffic. Infected SCADA traffic was found to have statistically significant differences in compression when compared against normal SCADA traffic at the packet level. The initial analyses and results are clearly able to identify malicious network traffic from normal traffic at the packet level with a very high confidence level across multiple ports and traffic streams. Statistical differentiation between infected and normal traffic level was possible using a modified data compression technique at the 99% probability level for all data analyzed. However, the conditions tested were rather limited in scope and need to be expanded into more realistic simulations of hacking events using techniques and approaches that are better representative of a real-world attack on a SCADA system. Nonetheless, the use of compression techniques to identify malicious traffic on SCADA networks in real time appears to have significant merit for infrastructure protection.« less

Influence of weight and body fat distribution on bone density in postmenopausal women.

PubMed

Murillo-Uribe, A; Carranza-Lira, S; Martínez-Trejo, N; Santos-González, J

2000-01-01

To determine whether obesity or body fat distribution induces a greater modification on bone remodeling biochemistry (BRB) and bone density in postmenopausal women. One hundred and thirteen postmenopausal patients were studied. They were initially divided according to body mass index (BMI), and afterwards by waist-hip ratio (WHR) as well as combinations of the two factors. Hormone measurements and assessments of BRB were also done. Dual-emission X-ray absorptiometry from the lumbar column and hip was performed with Lunar DPXL equipment, and the standard deviation in relation to young adult (T) and age-matched subjects (Z) was calculated. Statistical analysis was done by the Mann-Whitney U test. The relation of BMI and WHR with the variables was calculated by simple regression analysis. When divided according to BMI, there was greater bone density in the femoral neck in those with normal weight. After dividing according to WHR, the Z scores had a trend to a lesser decrease in those with upper level body fat distribution. Divided according to BMI and WHR, obese patients with upper-level body fat distribution had greater bone density in the lumbar column than those with normal weight and lower-level body fat distribution. With the same WHR, those with normal weight had greater bone density than those who were obese. A beneficial effect of upper-level body fat distribution on bone density was found. It is greater than that from obesity alone, and obesity and upper-level body fat distribution have an additive effect on bone density.

Continuing C3 breakdown after bilateral nephrectomy in patients with membrano-proliferative glomerulonephritis.

PubMed

Vallota, E H; Forristal, J; Spitzer, R E; Davis, N C; West, C D

1971-03-01

Serum levels of complement components and of C3 nephritic factor (C3NeF) were measured serially in two patients with membrano-proliferative glomerulonephritis who were subjected to bilateral nephrectomy and maintained by peritoneal dialysis for 2 wk before renal transplantation. In both patients, low levels of C3 and high levels of preformed alpha 2D, a C3 breakdown product, were present before nephrectomy and remained essentially unchanged during the anephric period. With transplantation, C3 levels rose towards normal and alpha 2D disappeared from the serum. The serum of both patients contained detectable amounts of C3NeF, a factor which has been shown to react with a cofactor found in normal serum to form an enzyme, designated C3 lytic nephritic factor (C3LyNeF), which will cleave C3 to form the breakdown products, beta1A and alpha 2D. The level of C3NeF was high in one patient before nephrectomy, increased somewhat during the anephric period, and fell after transplantation. In the other patient, the C3NeF level was initially lower, remained relatively constant during the anephric period, and was not significantly affected by transplantation. In both patients, levels of C4 and C5 were either normal or elevated over the period of the study and bore no relationship to the C3 level. The following conclusions can be drawn from the data. The high levels of alpha 2D during the anephric period and the disappearance of this protein as C3 levels approach normal at the time of transplantation indicate that the low C3 levels were largely the result of C3 breakdown rather than diminished synthesis. The presence of C3NeF in detectable amounts in both patients suggest that C3LyNeF, formed by the reaction of C3NeF and cofactor, was responsible for the low C3 levels. Finally, the lack of effect of nephrectomy on C3, alpha 2D, and C3NeF levels indicate that the site of C3 breakdown was extrarenal and that C3NeF and cofactor are at least in large part of extrarenal origin.

[Anti-tissue transglutaminase antibodies not related to gluten intake].

PubMed

Garcia-Peris, Mónica; Donat Aliaga, Ester; Roca Llorens, María; Masip Simó, Etna; Polo Miquel, Begoña; Ribes Koninckx, Carmen

2018-03-16

Anti-tissue transglutaminase antibodies (tTG) have high specificity for coeliac disease (CD). However, positive anti-tTG antibodies have been described in non-coeliac patients. Aim To assess positive anti-tTG antibodies not related to gluten intake. Retrospective review and follow up conducted on patients with suspected CD (increase anti-tTG levels and gastrointestinal symptoms) but with atypical serology results, positive anti-tTG with gluten free diet and a decrease in anti-tTG levels despite gluten intake. A total of 9 cases were reviewed in which 5 cases had Marsh 3 involvement in the initial biopsy, and were diagnosed with CD (Group A). They began a gluten free diet and also a cow's milk protein (CMP) free diet because of their nutritional status. When CMP was re-introduced, anti-tTG increased, and returned to normal after the CMP was withdrawn again. The other 4 patients had a normal initial biopsy (Group B). Gluten was not removed from their diet, but they started a CMP free diet because a non IgE mediated CMP allergy was suspected. Symptoms disappeared, and anti-tTG was normal after CMP free diet with gluten intake. All the patients had susceptibility haplotype HLA DQ2/DQ8. CMP ingestion after an exclusion diet can induce an increase in anti-tTG in some coeliac subjects. CMP can produce this immune response if there were no gluten transgressions. This response has also been observed in non-IgE mediated CMP allergy patients with the susceptibility haplotype HLA DQ2/DQ8. Copyright © 2018. Publicado por Elsevier España, S.L.U.

Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism

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

Finkelstein, J.S.; Klibanski, A.; Neer, R.M.

To assess the effects of gonadal steroid replacement on bone density in men with osteoporosis due to severe hypogonadism, we measured cortical bone density in the distal radius by 125I photon absorptiometry and trabecular bone density in the lumbar spine by quantitative computed tomography in 21 men with isolated GnRH deficiency while serum testosterone levels were maintained in the normal adult male range for 12-31 months (mean +/- SE, 23.7 +/- 1.1). In men who initially had fused epiphyses (n = 15), cortical bone density increased from 0.71 +/- 0.02 to 0.74 +/- 0.01 g/cm2 (P less than 0.01), whilemore » trabecular bone density did not change (116 +/- 9 compared with 119 +/- 7 mg/cm3). In men who initially had open epiphyses (n = 6), cortical bone density increased from 0.62 +/- 0.01 to 0.70 +/- 0.03 g/cm2 (P less than 0.01), while trabecular bone density increased from 96 +/- 13 to 109 +/- 12 mg/cm3 (P less than 0.01). Cortical bone density increased 0.03 +/- 0.01 g/cm2 in men with fused epiphyses and 0.08 +/- 0.02 g/cm2 in men with open epiphyses (P less than 0.05). Despite these increases, neither cortical nor trabecular bone density returned to normal levels. Histomorphometric analyses of iliac crest bone biopsies demonstrated that most of the men had low turnover osteoporosis, although some men had normal to high turnover osteoporosis. We conclude that bone density increases during gonadal steroid replacement of GnRH-deficient men, particularly in men who are skeletally immature.« less

VLBI-SLR Combination Solution Using GEODYN

NASA Technical Reports Server (NTRS)

MacMillan, Dan; Pavlis, Despina; Lemoine, Frank; Chinn, Douglas; Rowlands, David

2010-01-01

We would like to generate a multi-technique solution combining all of the geodetic techniques (VLBI, SLR, GPS, and DORIS) using the same software and using the same a priori models. Here we use GEODYN software and consider only the VLBI-SLR combination. Here we report initial results of our work on the combination. We first performed solutions with GEODYN using only VLBI data and found that VLBI EOP solution results produced with GEODYN agree with results using CALC/SOLVE at the 1-sigma level. We then combined the VLBI normal equations in GEODYN with weekly SLR normal equations for the period 2007-2008. Agreement of estimated Earth orientation parameters with IERS C04 were not significantly different for the VLBI-only, SLR-only, and VLBI+SLR solutions

Assessment of Oral Conditions and Quality of Life in Morbid Obese and Normal Weight Individuals: A Cross-Sectional Study

PubMed Central

de Freitas, Adriana Rodrigues; Sales-Peres, Arsênio; Ceneviva, Reginaldo

2015-01-01

The aim of this study was to identify the impact of oral disease on the quality of life of morbid obese and normal weight individuals. Cohort was composed of 100 morbid-obese and 50 normal-weight subjects. Dental caries, community periodontal index, gingival bleeding on probing (BOP), calculus, probing pocket depth, clinical attachment level, dental wear, stimulated salivary flow, and salivary pH were used to evaluate oral diseases. Socioeconomic and the oral impacts on daily performances (OIDP) questionnaires showed the quality of life in both groups. Unpaired Student, Fisher’s Exact, Chi-Square, Mann-Whitney, and Multiple Regression tests were used (p<0.05). Obese showed lower socio-economic level than control group, but no differences were found considering OIDP. No significant differences were observed between groups considering the number of absent teeth, bruxism, difficult mastication, calculus, initial caries lesion, and caries. However, saliva flow was low, and the salivary pH was changed in the obese group. Enamel wear was lower and dentine wear was higher in obese. More BOP, insertion loss, and periodontal pocket, especially the deeper ones, were found in obese subjects. The regression model showed gender, smoking, salivary pH, socio-economic level, periodontal pocket, and periodontal insertion loss significantly associated to obesity. However, both OIDP and BOP did not show significant contribution to the model. The quality of life of morbid obese was more negatively influenced by oral disease and socio-economic factors than in normal weight subjects. PMID:26177268

¹H MRS characterization of neurochemical profiles in orthotopic mouse models of human brain tumors.

PubMed

Hulsey, Keith M; Mashimo, Tomoyuki; Banerjee, Abhishek; Soesbe, Todd C; Spence, Jeffrey S; Vemireddy, Vamsidhara; Maher, Elizabeth A; Bachoo, Robert M; Choi, Changho

2015-01-01

Glioblastoma (GBM), the most common primary brain tumor, is resistant to currently available treatments. The development of mouse models of human GBM has provided a tool for studying mechanisms involved in tumor initiation and growth as well as a platform for preclinical investigation of new drugs. In this study we used (1) H MR spectroscopy to study the neurochemical profile of a human orthotopic tumor (HOT) mouse model of human GBM. The goal of this study was to evaluate differences in metabolite concentrations in the GBM HOT mice when compared with normal mouse brain in order to determine if MRS could reliably differentiate tumor from normal brain. A TE =19 ms PRESS sequence at 9.4 T was used for measuring metabolite levels in 12 GBM mice and 8 healthy mice. Levels for 12 metabolites and for lipids/macromolecules at 0.9 ppm and at 1.3 ppm were reliably detected in all mouse spectra. The tumors had significantly lower concentrations of total creatine, GABA, glutamate, total N-acetylaspartate, aspartate, lipids/macromolecules at 0.9 ppm, and lipids/macromolecules at 1.3 ppm than did the brains of normal mice. The concentrations of glycine and lactate, however, were significantly higher in tumors than in normal brain. Copyright © 2014 John Wiley & Sons, Ltd.

Beclin-1 Expression in Normal Bladder and in Cd+2 and As+3 Exposed and Transformed Human Urothelial Cells (UROtsa)

PubMed Central

Larson, Jennifer L.; Somji, Seema; Zhou, Xu Dong; Sens, Mary Ann; Garrett, Scott H.; Sens, Donald A.; Dunlevy, Jane R.

2010-01-01

The expression of beclin-1 in normal human bladder and in Cd+2 and As+3 exposed and transformed urothelial cells (UROtsa) was examined in this study. It was shown using a combination of real time PCR, western analysis and immunohistochemistry that beclin-1 was expressed in the urothelial cells of the normal bladder. It was also demonstrated that the parental UROtsa cell line expressed beclin-1 mRNA and protein at levels similar to that of the in situ urothelium. The level of beclin-1 expression underwent only modest alterations when the UROtsa cells were malignantly transformed by Cd+2 or As+3 or when the parental cells were exposed acutely to Cd+2 or As+3. While there were instances of significant alterations at individual time points and within cell line-to-cell line comparisons there was no evidence of a dose response relationship or correlations to the phenotypic properties of the cell lines. Similar results were obtained for the expression of the Atg-5, Atg-7, Atg-12 and LC3B autophagy-related proteins. The findings provide initial evidence for beclin-1 expression in normal bladder and that large alterations in the expression of beclin-1 and associated proteins do not occur when human urothelial cells are malignantly transformed with, or exposed to, either Cd+2 or As+3. PMID:20206246

New genetic associations detected in a host response study to hepatitis B vaccine.

PubMed

Davila, S; Froeling, F E M; Tan, A; Bonnard, C; Boland, G J; Snippe, H; Hibberd, M L; Seielstad, M

2010-04-01

The immune response to hepatitis B vaccination differs greatly among individuals, with 5-10% of healthy people failing to produce protective levels of antibodies. Several factors have been implicated in determining this response, chiefly individual genetic variation and age. Aiming to identify genes involved in the response to hepatitis B vaccination, a two-stage investigation of 6091 single-nucleotide polymorphisms (SNPs) in 914 immune genes was performed in an Indonesian cohort of 981 individuals showing normal levels of anti-HBs versus 665 individuals displaying undetectable levels of anti-HBs 18 months after initial dose of the vaccine. Of 275 SNPs identified in the first stage (476 normal/372 nonresponders) with P<0.05, significant associations were replicated for 25 polymorphisms in 15 genes (503 normal/295 nonresponders). We validated previous findings (HLA-DRA, rs5000563, P-value combined=5.57 x 10(-10); OR (95%CI)=0.61 (0.52-0.71)). In addition, we detected a new association outside of the human leukocyte antigen loci region that passed correction for multiple testing. This SNP is in the 3' downstream region of FOXP1, a transcription factor involved in B-cell development (P-value combined=9.2 x 10(-6); OR (95%CI)=1.38 (1.2-1.6)).These findings might help to understand the biological reasons behind vaccine failure and other aspects of variation in the immune responses of healthy individuals.

Affect intensity and processing fluency of deterrents.

PubMed

Holman, Andrei

2013-01-01

The theory of emotional intensity (Brehm, 1999) suggests that the intensity of affective states depends on the magnitude of their current deterrents. Our study investigated the role that fluency--the subjective experience of ease of information processing--plays in the emotional intensity modulations as reactions to deterrents. Following an induction phase of good mood, we manipulated both the magnitude of deterrents (using sets of photographs with pre-tested potential to instigate an emotion incompatible with the pre-existent affective state--pity) and their processing fluency (normal vs. enhanced through subliminal priming). Current affective state and perception of deterrents were then measured. In the normal processing conditions, the results revealed the cubic effect predicted by the emotional intensity theory, with the initial affective state being replaced by the one appropriate to the deterrent only in participants exposed to the high magnitude deterrence. In the enhanced fluency conditions the emotional intensity pattern was drastically altered; also, the replacement of the initial affective state occurred at a lower level of deterrence magnitude (moderate instead of high), suggesting the strengthening of deterrence emotional impact by enhanced fluency.

Shear Strength and Cracking Process of Non-persistent Jointed Rocks: An Extensive Experimental Investigation

NASA Astrophysics Data System (ADS)

Asadizadeh, Mostafa; Moosavi, Mahdi; Hossaini, Mohammad Farouq; Masoumi, Hossein

2018-02-01

In this paper, a number of artificial rock specimens with two parallel (stepped and coplanar) non-persistent joints were subjected to direct shearing. The effects of bridge length ( L), bridge angle ( γ), joint roughness coefficient (JRC) and normal stress ( σ n) on shear strength and cracking process of non-persistent jointed rock were studied extensively. The experimental program was designed based on Taguchi method, and the validity of the resulting data was assessed using analysis of variance. The results revealed that σ n and γ have the maximum and minimum effects on shear strength, respectively. Also, increase in L from 10 to 60 mm led to decrease in shear strength where high level of JRC profile and σ n led to the initiation of tensile cracks due to asperity interlocking. Such tensile cracks are known as "interlocking cracks" which normally initiate from the asperity and then propagate toward the specimen boundaries. Finally, the cracking process of specimens was classified into three categories, namely tensile cracking, shear cracking and combination of tension and shear or mixed mode tensile-shear cracking.

A seven-year review of measured hearing levels in male manual steelworkers with high initial thresholds

PubMed Central

Howell, R. W.

1978-01-01

ABSTRACT Audiometric records of 449 male manual steelworkers were reviewed to see whether the hearing of men with high initial threshold levels deteriorated more rapidly than that of those men with more normal thresholds when exposed to similar noise levels. Subjects were between 15 and 54 years old at the time of initial examination, and had a repeat audiogram 6-8 years later. They were classified into three occupational noise exposure groups: below 90 dB(A), 90-99 dB(A), and 100 dB(A) or over, without knowledge of their audiometric threshold levels, age, or aural history. Measurements at 0·5, 1, 2, 3, 4 and 6 kHz for the right ear were considered, first as the mean for all six frequencies, then for 0·5, 1 and 2 kHz only, and finally for 6 kHz only. After standardisation for age, it was found that those in the high initial threshold groups deteriorated no faster than the remainder of the series. At the 90-99 dB(A) noise exposure level, χ2 tests showed that the differences between the groups, in terms of mean measured hearing loss, were not significant at the 0·05 probability level. The age-standardised mean threshold shifts for the 0·5-6 kHz range of frequencies over the seven-year review period were 7·5, 8·7 and 7·1 dB at a noise exposure level of 100 dB(A) or more, for workers with an initial threshold level of <12 dB, 12-26 dB and > 26 dB respectively; for those exposed to noise of 90-99 dB(A) the corresponding mean shifts were 7·8, 6·8 and 7·3 dB respectively; while for those exposed to noise of less than 90 dB(A) the mean shifts were 6·2, 5·0 and 5·2 dB respectively. PMID:629886

Case report: a rare cause of metabolic alkalosis

PubMed Central

Gebara, Otávio C.E.; Callas, Silvia H.V.; Hoff, Ana O.; Hoff, Paulo M.; Galvão, P.C.A.

2011-01-01

A case of a 66-year-old white man with recent onset of oedema, hypertension, metabolic alkalosis and profound hypokalaemia is described. The initial laboratorial workup showed that urinary chloride concentration and potassium excretion were increased, suggesting a state of hyperaldosteronism. Nonetheless, renin activity was low and aldosterone levels were normal. The metabolic alkalosis seen in this case was due to a rare cause, the ectopic adrenocorticotropic hormone syndrome. A literature review in the subject is presented. PMID:25984146

Alterations of Mental Status and Thyroid Hormones after Thermal Injury

DTIC Science & Technology

1985-01-01

steroid, dopamine, or iodine treatment . At to weeks before death, this association N~ing~ndependent ofeach sa pling, the level of obtundation (LO...was deter ined on treatment with drugs dcting on mental s as or thyroi func- a 6-point scale from normal to deep coma. Whereas initially low tion. (J...other types of nonthyroidal illnes,. of wounds were performed when indicated. Treatment did not (NTI) (4, 5). Previous studies of a variety of NTI

Temporal evolution of urate crystal deposition over articular cartilage after successful urate-lowering therapy in patients with gout: An ultrasonographic perspective.

PubMed

Das, Shyamashis; Goswami, Rudra Prosad; Ghosh, Alakendu; Ghosh, Parasar; Lahiri, Debasish; Basu, Kaushik

2017-05-01

To detect evolution of ultrasonographic signs of deposition of monosodium urate crystals (MSUC) in gouty joints by serial ultrasonography after initiation of urate-lowering therapy (ULT). Adult gout patients were examined by serial ultrasonography after initiation of ULT with target serum uric acid (SUA) < 6 mg/dL. Thirty-eight male patients with gout with mean age of 50 ± 11 years, median disease duration of 48 months and baseline mean SUA level of 8.8 ± 1.5 mg/dL were recruited. Ultrasonographic evidence of MSUC deposition was detected in 89.74% of first metatarsophalangeal (MTP) joints and 27.63% of knee joints. Double contour sign (DCS), tophi, and hyperechoic spots (HES) were detected in 77.63%, 43.42%, and 19.74% of first MTPs, respectively. SUA level normalizes and plateaus after fourth month of follow-up. DCS thickness reduced significantly throughout the follow-up period. Overall, 86.25% DCS and 100% HES disappeared with median time of 6 months and 5.7 months, respectively. SUA normalization was the only significant predictor of DCS disappearance. Serial ultrasonographic determination of DCS, tophi, or HES during hypouricemic therapy is a noninvasive, effective method to detect the lowering of burden of urate load in gouty joints.

In vivo effect of staphylococcal enterotoxin A on peripheral blood lymphocytes.

PubMed Central

Zehavi-Willner, T; Shenberg, E; Barnea, A

1984-01-01

Staphylococcal enterotoxin A (SEA) administration to monkeys produced an initial lymphocytic leukopenia lasting approximately 24 h. Lymphocytes isolated from blood circulation (PBL) during this stage had normal or decreased [3H]thymidine incorporating activity. After 48 h, however, a significant increase (five- to sixfold) in [3H]thymidine incorporating activity into PBL was apparent. The peak of incorporating activity (seven- to eightfold) was reached 3 to 4 days after SEA administration, followed by a gradual decline, reaching the baseline after 2 weeks. The increased levels of [3H] thymidine incorporation in PBL were concomitant with the conversion of lymphopenia into lymphocytosis, accompanied by the release of many immature cells into the circulation. Lymphocytes isolated 24 h after SEA administration in vivo did not respond to the mitogenic action of SEA in vitro. Lymphocytes isolated at later stages after SEA challenge were fully activated by toxin. From a series of studies, it was concluded that SEA administered to monkeys caused, during the initial 24 h, the removal of a great proportion of lymphocytes from the circulation, followed by the release of new immature cells with augmented DNA synthesis activity. The lymphocytic leukocytosis state declined gradually and reached normal levels between 3 and 4 weeks after the SEA challenge. The biological implications of the hematological changes occurring after SEA challenge in vivo are discussed. PMID:6715041

Effect of levo-thyroxine treatment on weight and body mass index in children with acquired hypothyroidism.

PubMed

Lomenick, Jefferson P; El-Sayyid, Maysa; Smith, W Jackson

2008-01-01

To determine whether normalization of thyroid-stimulating hormone (TSH) in children with acquired hypothyroidism is associated with a decrease in weight or body mass index (BMI). We retrospectively identified 68 subjects with acquired hypothyroidism who were seen at least once in our center in follow-up between 1995 and 2006. Treatment with levo-thyroxine decreased the mean TSH level from 147 microU/mL initially to 5.0 microU/mL at the second visit 4.4 months later. This was not associated with a significant change in weight or BMI. Of the 68 subjects, 31% lost weight by the second visit (mean 2.3 kg). The mean initial TSH level of this group was 349 microU/mL. Thirty of the 68 children had at least 2 years of follow-up, and 19/68 had at least 4 years of follow-up. Over those intervals, weight and BMI percentiles and z scores did not change significantly from baseline values. Most children treated for acquired hypothyroidism exhibited little short-term or long-term change in weight or BMI despite near-normalization of TSH. Those children who lost weight tended to have severe hypothyroidism and to have only a small weight loss. Consequently, practitioners should not expect significant decreases in weight after treatment in most children with hypothyroidism.

Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency

PubMed Central

Barna, Maria; Pusic, Aya; Zollo, Ornella; Costa, Maria; Kondrashov, Nadya; Rego, Eduardo; Rao, Pulivarthi H; Ruggero, Davide

2008-01-01

The Myc oncogene regulates the expression of multiple components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, Pol III, and rDNA1,2. An outstanding question is whether and how increasing the cellular protein synthesis capacity can affect the multi-step process leading to cancer. We utilized ribosomal protein heterozygote mice as a genetic tool to restore increased protein synthesis in Eμ–Myc/+ transgenic mice to normal levels and show that in this context Myc's oncogenic potential is suppressed. Our findings demonstrate that the ability of Myc to increase protein synthesis directly augments cell size and is sufficient to accelerate cell cycle progression independently of known cell cycle targets transcriptionally regulated by Myc. In addition, when protein synthesis is restored to normal levels, Myc overexpressing precancerous cells are more efficiently eliminated by programmed cell death. Our findings reveal a novel paradigm that links increases in general protein synthesis rates downstream of an oncogenic signal to a specific molecular impairment in the modality of translation initiation employed to regulate the expression of selective mRNAs. We show that an aberrant increase in cap-dependent translation downstream Myc hyperactivation specifically impairs the translational switch to internal ribosomal entry site (IRES)-dependent translation required for accurate mitotic progression. Failure of this translational switch results in reduced mitotic-specific expression of the endogenous IRES-dependent form of Cdk11 (p58-PITSLRE)3-5, which leads to cytokinesis defects and is associated with increased centrosome numbers and genome instability in Eμ–Myc/+ mice. When accurate translational control is re-established in Eμ–Myc/+ mice, genome instability is suppressed. Our findings reveal how perturbations in translational control provide a highly specific outcome on gene expression, genome stability, and cancer initiation that have important implications for understanding the molecular mechanism of cancer formation at the post-genomic level. PMID:19011615

Association of Low Levels of Vitamin D with Chronic Stable Angina: A Prospective Case-Control Study

PubMed Central

Raina, Ab Hameed; Allai, Mohammad Sultan; Shah, Zafar Amin; Changal, Khalid Hamid; Raina, Manzoor Ahmad; Bhat, Fayaz Ahmad

2016-01-01

Background: Coronary artery disease (CAD) is a major cause of death and disability in developed countries. Chronic stable angina is the initial manifestation of CAD in approximately 50% of the patients. Recent evidence suggests that vitamin D is crucial for cardiovascular health. The prevalence of vitamin D deficiency in our region is 83%. A low level of vitamin D is associated with chronic stable angina. Aim: This study was aimed at supporting or refuting this hypothesis in our population. Materials and Methods: The study was a prospective case-control study. We studied 100 cases of chronic stable angina and compared them with 100 matched controls. Vitamin D deficiency was defined as <20 ng/mL, vitamin D insufficiency as 20-30 ng/mL and normal vitamin D level as 31-150 ng/mL. Results: The prevalence of vitamin D deficiency among cases and controls was 75% and 10%, respectively. 75% of the cases were vitamin D-deficient (<20 ng/mL); 12% were vitamin D-insufficient (20-30 ng/mL), and 13% had normal vitamin D levels (31-150 ng/mL). None had a toxic level of vitamin D. Among the controls, 10% were vitamin D-deficient, 33% were vitamin D-insufficient, and 57% had normal vitamin D levels. The mean vitamin level among cases and controls was 15.53 ng/mL and 40.95 ng/mL, respectively, with the difference being statistically significant (P ≤ 0.0001). There was no statistically significant relation between the disease severities, i.e., on coronary angiography (CAG) with vitamin D level. Among the cases, we found that an increasing age was inversely related to vitamin D levels (P = 0.027). Conclusion: Our study indicates a correlation between vitamin D deficiency and chronic stable angina. Low levels may be an independent, potentially modifiable cardiovascular risk factor. PMID:27114971

Spontaneous circulation of myeloid-lymphoid-initiating cells and SCID-repopulating cells in sickle cell crisis.

PubMed

Lamming, Christopher E D; Augustin, Lance; Blackstad, Mark; Lund, Troy C; Hebbel, Robert P; Verfaillie, Catherine M

2003-03-01

The only curative therapy for sickle cell disease (SCD) is allogeneic hematopoietic stem cell (HSC) transplantation. Gene therapy approaches for autologous HSC transplantation are being developed. Although earlier engraftment is seen when cells from GCSF-mobilized blood are transplanted than when bone marrow is transplanted, administration of GCSF to patients with SCD can cause significant morbidity. We tested whether primitive hematopoietic progenitors are spontaneously mobilized in the blood of patients with SCD during acute crisis (AC-SCD patients). The frequency of myeloid-lymphoid-initiating cells (ML-ICs) and SCID-repopulating cells (SRCs) was significantly higher in blood from AC-SCD patients than in blood from patients with steady-state SCD or from normal donors. The presence of SRCs in peripheral blood was not associated with detection of long-term culture-initiating cells, consistent with the notion that SRCs are more primitive than long-term culture-initiating cells. As ML-ICs and SRCs were both detected in blood of AC-SCD patients only, these assays may both measure primitive progenitors. The frequency of ML-ICs also correlated with increases in stem cell factor, GCSF, and IL-8 levels in AC-SCD compared with steady-state SCD and normal-donor sera. Because significant numbers of ML-ICs and SRCs are mobilized in the blood without exogenous cytokine treatment during acute crisis of SCD, collection of peripheral blood progenitors during crisis may yield a source of autologous HSCs suitable for ex-vivo correction by gene therapy approaches and subsequent transplantation.

Spontaneous rectus sheath hematoma in pregnancy and a systematic anatomical workup of rectus sheath hematoma: a case report.

PubMed

Eckhoff, Kerstin; Wedel, Thilo; Both, Marcus; Bas, Kayhan; Maass, Nicolai; Alkatout, Ibrahim

2016-10-19

Rectus sheath hematoma is a rare clinical diagnosis, particularly in pregnancy. Due to unspecific symptoms, misdiagnosis is likely and could potentially endanger a patient as well as her fetus. A 26-year-old white woman presented with mild right-sided abdominal pain, which increased during palpation and movement, at 26 + 3 weeks' gestational age. Ultrasound imaging initially showed a round and well-demarcated structure, which appeared to be in contact with her uterine wall, leading to a suspected diagnosis of an infarcted leiomyoma. However, she reported increasing levels of pain and laboratory tests showed a significant drop in her initially normal hemoglobin level. A magnetic resonance imaging scan finally revealed a large type III rectus sheath hematoma on the right side. Because of progressive blood loss into her rectus sheath under conservative therapy, with a significant further decrease in her hemoglobin levels, surgical treatment via right-sided paramedian laparotomy was initiated. During the operation the arterial bleed could be ligated. She eventually achieved complete convalescence and delivered a healthy newborn spontaneously after 40 weeks of gestation. This case report highlights the clinical and diagnostic features of rectus sheath hematoma and shows the anatomical aspects of the rectus sheath, simplifying early and correct diagnosis.

A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

PubMed Central

2011-01-01

Background Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. Methods We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm3. For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. Results TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Conclusion Using the first transgenic animal model to elevate circulating levels of IGF-I to those comparable to women at increased risk of breast cancer, we showed that moderately high levels of systemic IGF-I have no effect on pubertal mammary gland development, initiating mammary tumorigenesis or promoting ErbB2 driven mammary carcinogenesis. Our work suggests that ErbB2-induced mammary tumorigenesis is independent of the normal variation in circulating levels of IGF-I. PMID:21867536

Therapeutic suppression of translation initiation factor eIF4E expression reduces tumor growth without toxicity

PubMed Central

Graff, Jeremy R.; Konicek, Bruce W.; Vincent, Thomas M.; Lynch, Rebecca L.; Monteith, David; Weir, Spring N.; Schwier, Phil; Capen, Andrew; Goode, Robin L.; Dowless, Michele S.; Chen, Yuefeng; Zhang, Hong; Sissons, Sean; Cox, Karen; McNulty, Ann M.; Parsons, Stephen H.; Wang, Tao; Sams, Lillian; Geeganage, Sandaruwan; Douglass, Larry E.; Neubauer, Blake Lee; Dean, Nicholas M.; Blanchard, Kerry; Shou, Jianyong; Stancato, Louis F.; Carter, Julia H.; Marcusson, Eric G.

2007-01-01

Expression of eukaryotic translation initiation factor 4E (eIF4E) is commonly elevated in human and experimental cancers, promoting angiogenesis and tumor growth. Elevated eIF4E levels selectively increase translation of growth factors important in malignancy (e.g., VEGF, cyclin D1) and is thereby an attractive anticancer therapeutic target. Yet to date, no eIF4E-specific therapy has been developed. Herein we report development of eIF4E-specific antisense oligonucleotides (ASOs) designed to have the necessary tissue stability and nuclease resistance required for systemic anticancer therapy. In mammalian cultured cells, these ASOs specifically targeted the eIF4E mRNA for destruction, repressing expression of eIF4E-regulated proteins (e.g., VEGF, cyclin D1, survivin, c-myc, Bcl-2), inducing apoptosis, and preventing endothelial cells from forming vessel-like structures. Most importantly, intravenous ASO administration selectively and significantly reduced eIF4E expression in human tumor xenografts, significantly suppressing tumor growth. Because these ASOs also target murine eIF4E, we assessed the impact of eIF4E reduction in normal tissues. Despite reducing eIF4E levels by 80% in mouse liver, eIF4E-specific ASO administration did not affect body weight, organ weight, or liver transaminase levels, thereby providing the first in vivo evidence that cancers may be more susceptible to eIF4E inhibition than normal tissues. These data have prompted eIF4E-specific ASO clinical trials for the treatment of human cancers. PMID:17786246

An evaluation of deficits in semantic cueing and proactive and retroactive interference as early features of Alzheimer's disease.

PubMed

Crocco, Elizabeth; Curiel, Rosie E; Acevedo, Amarilis; Czaja, Sara J; Loewenstein, David A

2014-09-01

To determine the degree to which susceptibility to different types of semantic interference may reflect the initial manifestations of early Alzheimer's disease (AD) beyond the effects of global memory impairment. Normal elderly (NE) subjects (n = 47), subjects with amnestic mild cognitive impairment (aMCI; n = 34), and subjects with probable AD (n = 40) were evaluated by using a unique cued recall paradigm that allowed for evaluation of both proactive and retroactive interference effects while controlling for global memory impairment (i.e., Loewenstein-Acevedo Scales of Semantic Interference and Learning [LASSI-L] procedure). Controlling for overall memory impairment, aMCI subjects had much greater proactive and retroactive interference effects than NE subjects. LASSI-L indices of learning by using cued recall revealed high levels of sensitivity and specificity, with an overall correct classification rate of 90%. These measures provided better discrimination than traditional neuropsychological measures of memory function. The LASSI-L paradigm is unique and unlike other assessments of memory in that items posed for cued recall are explicitly presented, and semantic interference and cueing effects can be assessed while controlling for initial level of memory impairment. This is a powerful procedure that allows the participant to serve as his or her own control. The high levels of discrimination between subjects with aMCI and normal cognition that exceeded traditional neuropsychological measures makes the LASSI-L worthy of further research in the detection of early AD. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Everolimus induces rapid plasma glucose normalization in insulinoma patients by effects on tumor as well as normal tissues.

PubMed

Fiebrich, Helle-Brit; Siemerink, Ester J M; Brouwers, Adrienne H; Links, Thera P; Remkes, Wouter S; Hospers, Geke A P; de Vries, Elisabeth G E

2011-01-01

Mammalian target of rapamycin inhibitor everolimus administered to four insulinoma patients rapidly controlled hypoglycemia (Kulke et al., N Engl J Med 2009;360:195-197). We wanted to identify the kinetics of everolimus effects on controlling hypoglycemia and understand underlying mechanisms. Three consecutive patients with a metastasized symptomatic insulinoma were started on 100 μg of octreotide subcutaneously three times daily. Because of persisting hypoglycemias, treatment with daily 10 mg of oral everolimus was initiated. Serial plasma glucose levels and serum insulin levels were measured. Computer tomography (CT) scans were performed before and after 2 and 5 months of treatment. [¹⁸F]fluoro-2-deoxy-d-glucose positron emission tomography (¹⁸F-FDG-PET) scans, to visualize glucose metabolism, were made before and after 2 weeks, 5 weeks, and 5 months of treatment. The ¹⁸F-FDG uptake was quantified as the maximum standardized uptake value. All patients achieved control of hypoglycemia on everolimus within 14 days. Insulin levels were 2.5- to 6.3-fold elevated before start of treatment and declined 14%-64% after 4 weeks of treatment. CT scans showed stable disease at 2 months in all patients, with progressive disease after 5 months in one. Before treatment, both the tumor lesions and the muscles and myocardium showed high ¹⁸F-FDG uptake. Everolimus reduced tumor and muscle ¹⁸F-FDG uptake after 2 weeks by 26% ± 14% and 19% ± 41%, and after 5 months by 31% ± 13% and 27% ± 41%. Everolimus normalizes plasma glucose levels in metastatic insulinoma within 14 days, coinciding with a lower glucose uptake in tumor and muscles and declining (pro)insulin levels. This effect on tumor as well as normal tissues explains the rapid controlling of hypoglycemia.

Genetics and blood pressure response to exercise, and its interactions with adiposity.

PubMed

Rankinen, T; Bouchard, C

2002-01-01

Regular aerobic exercise has the potential to induce several beneficial health effects, including a decrease in blood pressure level, especially in hypertensive patients and in subjects with high-normal blood pressure. However, it is also well documented that some people show more pronounced blood pressure responses to endurance training than others, despite identical training programs and similar initial blood pressure levels. This kind of variation is an example of normal biologic diversity and most likely originates from interactions with genetic factors. Data from genetic epidemiologic studies indicate that there is a genetic component that affects both resting blood pressure and blood pressure responses to acute exercise. Evidence from molecular genetic studies is scarce, but the first reports suggest that DNA sequence variation in the hypertension candidate genes, such as angiotensinogen, also modify blood pressure responses to endurance training. The current knowledge regarding the role of genetic factors in the modification of blood pressure responses to endurance training will be summarized and discussed. Copyright 2002 CHF, Inc.

Normal carboxyhaemoglobin level in carbon monoxide poisoning treated with hyperbaric oxygen therapy.

PubMed

Helgeson, Scott A; Wilson, Michael E; Guru, Pramod K

2017-07-24

Throughout the world both intentional and inadvertent exposure to carbon monoxide (CO) remains an important public health issue. While CO poisoning can be lethal, the morbidity is predominantly due to nervous system injury. A previously healthy 22-year-old woman was found unconscious at home by her sister. Her parents were found dead in the house with a recent history of a dysfunctional furnace. She was presumed to have CO poisoning despite an initial carboxyhaemoglobin level of 2.5%. Patient had both clinical and radiological evidence of neurological damage. However, with multiple sessions of hyperbaric oxygen (HBO) therapy she recovered to a near normal functional status. There is no consensus that exists among treating physicians about the role of hyperbaric oxygen in management of neurological injury. The case described here has significant neurological damage related to CO exposure but improved after HBO therapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A Method for Preparation, Storage and Activation of Large Populations of Immotile Sea Urchin Sperm

NASA Technical Reports Server (NTRS)

Bracho, Geracimo E.; Fritch, Jennifer J.; Tash, Joseph S.

1997-01-01

Reversible protein phosphorylation is associated with initiation and modulation of sperm flagellar motility. Many studies aimed at examining the signal transduction mechanisms underlying the expression of motility have relied on detergent-permeabilized sperm reactivated with exogenous 32 P-ATP. However, the reactivation conditions allow variable levels of motility to be expressed and phosphorylation of many proteins that appear to be unrelated to sperm motility. Thus, identification of the few relevant proteins is difficult. We have developed a method to collect and keep sperm immotile until reactivated for analysis to normal motility levels. Artificial sea water (ASW) buffered with 5 mM 2-[N-morpholino]ethanesulfonic acid at pH 6.0 and containing 50 mM KCI, allows collection and storage of immotile sea urchin sperm for up to 96 h at 4-5 C. Motility under these conditions is essentially zero, but sperm is rapidly reactivated to normal motility by diluting with ASW to standard pH (8.0) and KCI concentration (10 mM).

Acoustic properties of naturally produced clear speech at normal speaking rates

NASA Astrophysics Data System (ADS)

Krause, Jean C.; Braida, Louis D.

2004-01-01

Sentences spoken ``clearly'' are significantly more intelligible than those spoken ``conversationally'' for hearing-impaired listeners in a variety of backgrounds [Picheny et al., J. Speech Hear. Res. 28, 96-103 (1985); Uchanski et al., ibid. 39, 494-509 (1996); Payton et al., J. Acoust. Soc. Am. 95, 1581-1592 (1994)]. While producing clear speech, however, talkers often reduce their speaking rate significantly [Picheny et al., J. Speech Hear. Res. 29, 434-446 (1986); Uchanski et al., ibid. 39, 494-509 (1996)]. Yet speaking slowly is not solely responsible for the intelligibility benefit of clear speech (over conversational speech), since a recent study [Krause and Braida, J. Acoust. Soc. Am. 112, 2165-2172 (2002)] showed that talkers can produce clear speech at normal rates with training. This finding suggests that clear speech has inherent acoustic properties, independent of rate, that contribute to improved intelligibility. Identifying these acoustic properties could lead to improved signal processing schemes for hearing aids. To gain insight into these acoustical properties, conversational and clear speech produced at normal speaking rates were analyzed at three levels of detail (global, phonological, and phonetic). Although results suggest that talkers may have employed different strategies to achieve clear speech at normal rates, two global-level properties were identified that appear likely to be linked to the improvements in intelligibility provided by clear/normal speech: increased energy in the 1000-3000-Hz range of long-term spectra and increased modulation depth of low frequency modulations of the intensity envelope. Other phonological and phonetic differences associated with clear/normal speech include changes in (1) frequency of stop burst releases, (2) VOT of word-initial voiceless stop consonants, and (3) short-term vowel spectra.

Partial reconstitution of humoral immunity and fewer infections in patients with chronic lymphocytic leukemia treated with ibrutinib.

PubMed

Sun, Clare; Tian, Xin; Lee, Yuh Shan; Gunti, Sreenivasulu; Lipsky, Andrew; Herman, Sarah E M; Salem, Dalia; Stetler-Stevenson, Maryalice; Yuan, Constance; Kardava, Lela; Moir, Susan; Maric, Irina; Valdez, Janet; Soto, Susan; Marti, Gerald E; Farooqui, Mohammed Z; Notkins, Abner L; Wiestner, Adrian; Aue, Georg

2015-11-05

Chronic lymphocytic leukemia (CLL) is characterized by immune dysregulation, often including hypogammaglobulinemia, which contributes to a high rate of infections and morbidity. Ibrutinib, a covalent inhibitor of Bruton tyrosine kinase (BTK), inhibits B-cell receptor signaling and is an effective, US Food and Drug Administration (FDA)-approved treatment of CLL. Inactivating germline mutations in BTK cause a severe B-cell defect and agammaglobulinemia. Therefore, we assessed the impact of ibrutinib on immunoglobulin levels, normal B cells, and infection rate in patients with CLL treated with single-agent ibrutinib on a phase 2 investigator-initiated trial. Consistent with previous reports, immunoglobulin G (IgG) levels remained stable during the first 6 months on treatment, but decreased thereafter. In contrast, there were a transient increase in IgM and a sustained increase in IgA (median increase 45% at 12 months, P < .0001). To distinguish the effects on clonal B cells from normal B cells, we measured serum free light chains (FLCs). In κ-clonal CLL cases, clonal (κ) FLCs were elevated at baseline and normalized by 6 months. Nonclonal (λ) FLCs, which were often depressed at baseline, increased, suggesting the recovery of normal B cells. Consistently, we observed normal B-cell precursors in the bone marrow and an increase in normal B-cell numbers in the peripheral blood. Patients with superior immune reconstitution, as defined by an increase in serum IgA of ≥50% from baseline to 12 months, had a significantly lower rate of infections (P = .03). These data indicate that ibrutinib allows for a clinically meaningful recovery of humoral immune function in patients with CLL. This trial was registered at www.clinicaltrials.gov as #NCT015007330.

Partial reconstitution of humoral immunity and fewer infections in patients with chronic lymphocytic leukemia treated with ibrutinib

PubMed Central

Sun, Clare; Tian, Xin; Lee, Yuh Shan; Gunti, Sreenivasulu; Lipsky, Andrew; Herman, Sarah E. M.; Salem, Dalia; Stetler-Stevenson, Maryalice; Yuan, Constance; Kardava, Lela; Moir, Susan; Maric, Irina; Valdez, Janet; Soto, Susan; Marti, Gerald E.; Farooqui, Mohammed Z.; Notkins, Abner L.; Aue, Georg

2015-01-01

Chronic lymphocytic leukemia (CLL) is characterized by immune dysregulation, often including hypogammaglobulinemia, which contributes to a high rate of infections and morbidity. Ibrutinib, a covalent inhibitor of Bruton tyrosine kinase (BTK), inhibits B-cell receptor signaling and is an effective, US Food and Drug Administration (FDA)-approved treatment of CLL. Inactivating germline mutations in BTK cause a severe B-cell defect and agammaglobulinemia. Therefore, we assessed the impact of ibrutinib on immunoglobulin levels, normal B cells, and infection rate in patients with CLL treated with single-agent ibrutinib on a phase 2 investigator-initiated trial. Consistent with previous reports, immunoglobulin G (IgG) levels remained stable during the first 6 months on treatment, but decreased thereafter. In contrast, there were a transient increase in IgM and a sustained increase in IgA (median increase 45% at 12 months, P < .0001). To distinguish the effects on clonal B cells from normal B cells, we measured serum free light chains (FLCs). In κ-clonal CLL cases, clonal (κ) FLCs were elevated at baseline and normalized by 6 months. Nonclonal (λ) FLCs, which were often depressed at baseline, increased, suggesting the recovery of normal B cells. Consistently, we observed normal B-cell precursors in the bone marrow and an increase in normal B-cell numbers in the peripheral blood. Patients with superior immune reconstitution, as defined by an increase in serum IgA of ≥50% from baseline to 12 months, had a significantly lower rate of infections (P = .03). These data indicate that ibrutinib allows for a clinically meaningful recovery of humoral immune function in patients with CLL. This trial was registered at www.clinicaltrials.gov as #NCT015007330. PMID:26337493

Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy.

PubMed

Rahimy, Elham; Li, Fang-Yong; Hagberg, Lars; Fuchs, Dietmar; Robertson, Kevin; Meyerhoff, Dieter J; Zetterberg, Henrik; Price, Richard W; Gisslén, Magnus; Spudich, Serena

2017-04-01

We explored the establishment of abnormal blood-brain barrier (BBB) permeability and its relationship to neuropathogenesis during primary human immunodeficiency virus (HIV) infection by evaluating the cerebrospinal fluid (CSF) to serum albumin quotient (QAlb) in patients with primary HIV infection. We also analyzed effects of initiating combination antiretroviral therapy (cART). The QAlb was measured in longitudinal observational studies of primary HIV infection. We analyzed trajectories of the QAlb before and after cART initiation, using mixed-effects models, and associations between the QAlb and the CSF level of neurofilament light chain (NFL), the ratio of N-acetylaspartate to creatinine levels (a magnetic resonance spectroscopy neuronal integrity biomarker), and neuropsychological performance. The baseline age-adjusted QAlb was elevated in 106 patients with primary HIV infection (median time of measurement, 91 days after infection), compared with that in 64 controls (P = .02). Before cART initiation, the QAlb increased over time in 84 participants with a normal baseline QAlb (P = .006) and decreased in 22 with a high baseline QAlb (P = .011). The QAlb did not change after a median cART duration of 398 days, initiated at a median interval of 225 days after infection (P = .174). The QAlb correlated with the NFL level at baseline (r = 0.497 and P < .001) and longitudinally (r = 0.555 and P < .001) and with the ratio of N-acetylaspartate to creatinine levels in parietal gray matter (r = -0.352 and P < .001 at baseline and r = -0.387 and P = .008 longitudinally) but not with neuropsychological performance. The QAlb rises during primary HIV infection, associates with neuronal injury, and does not significantly improve over a year of treatment. BBB-associated neuropathogenesis in HIV-infected patients may initiate during primary infection. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy

PubMed Central

Rahimy, Elham; Li, Fang-Yong; Hagberg, Lars; Fuchs, Dietmar; Robertson, Kevin; Meyerhoff, Dieter J.; Zetterberg, Henrik; Price, Richard W.; Gisslén, Magnus

2017-01-01

Abstract Background. We explored the establishment of abnormal blood-brain barrier (BBB) permeability and its relationship to neuropathogenesis during primary human immunodeficiency virus (HIV) infection by evaluating the cerebrospinal fluid (CSF) to serum albumin quotient (QAlb) in patients with primary HIV infection. We also analyzed effects of initiating combination antiretroviral therapy (cART). Methods. The QAlb was measured in longitudinal observational studies of primary HIV infection. We analyzed trajectories of the QAlb before and after cART initiation, using mixed-effects models, and associations between the QAlb and the CSF level of neurofilament light chain (NFL), the ratio of N-acetylaspartate to creatinine levels (a magnetic resonance spectroscopy neuronal integrity biomarker), and neuropsychological performance. Results. The baseline age-adjusted QAlb was elevated in 106 patients with primary HIV infection (median time of measurement, 91 days after infection), compared with that in 64 controls (P = .02). Before cART initiation, the QAlb increased over time in 84 participants with a normal baseline QAlb (P = .006) and decreased in 22 with a high baseline QAlb (P = .011). The QAlb did not change after a median cART duration of 398 days, initiated at a median interval of 225 days after infection (P = .174). The QAlb correlated with the NFL level at baseline (r = 0.497 and P < .001) and longitudinally (r = 0.555 and P < .001) and with the ratio of N-acetylaspartate to creatinine levels in parietal gray matter (r = −0.352 and P < .001 at baseline and r = −0.387 and P = .008 longitudinally) but not with neuropsychological performance. Conclusion. The QAlb rises during primary HIV infection, associates with neuronal injury, and does not significantly improve over a year of treatment. BBB-associated neuropathogenesis in HIV-infected patients may initiate during primary infection. PMID:28368497

Spinal myoclonus associated with vitamin B12 deficiency.

PubMed

Dogan, Ebru Apaydin; Yuruten, Betigul

2007-11-01

We report a 85-year-old female patient with involuntary and regular movements restricted to abdominal muscles, resembling belly dance, with additional clinical features; ataxia, impaired cognition, neuropathy and glossitis. We initially excluded the possible cortical and spinal structural abnormalities with magnetic resonance imagings and performed routine blood analysis which revealed that serum vitamin B12 (vB12) level was under normal ranges. The relation of low serum vB12 level and myoclonus is speculative and very few studies have demonstrated such patients. In this case report, serum vB12 deficiency is discussed in the context of its probable role in the generation of spinal myoclonus.

Self-pressurization of a flightweight liquid hydrogen storage tank subjected to low heat flux

NASA Technical Reports Server (NTRS)

Hasan, M. M.; Lin, C. S.; Vandresar, N. T.

1991-01-01

Results are presented for an experimental investigation of self-pressurization and thermal stratification of a 4.89 cu m liquid hydrogen (LH2) storage tank subjected to low heat flux (0.35, 2.0, and 3.5 W/sq m) under normal gravity conditions. Tests were performed at fill levels of 83 to 84 percent (by volume). The LH2 tank was representative of future spacecraft tankage, having a low mass-to-volume ratio and high performance multilayer thermal insulation. Results show that the pressure rise rate and thermal stratification increase with increasing heat flux. At the lowest heat flux, the pressure rise rate is comparable to the homogenous rate, while at the highest heat flux, the rate is more than three times the homogeneous rate. It was found that initial conditions have a significant impact on the initial pressure rise rate. The quasi-steady pressure rise rates are nearly independent of the initial condition after an initial transient period has passed.

Management of minor head injury in patients receiving oral anticoagulant therapy: a prospective study of a 24-hour observation protocol.

PubMed

Menditto, Vincenzo G; Lucci, Moira; Polonara, Stefano; Pomponio, Giovanni; Gabrielli, Armando

2012-06-01

Patients receiving warfarin who experience minor head injury are at risk of intracranial hemorrhage, and optimal management after a single head computed tomography (CT) scan is unclear. We evaluate a protocol of 24-hour observation followed by a second head CT scan. In this prospective case series, we enrolled consecutive patients receiving warfarin and showing no intracranial lesions on a first CT scan after minor head injury treated at a Level II trauma center. We implemented a structured clinical pathway, including 24-hour observation and a CT scan performed before discharge. We then evaluated the frequency of death, admission, neurosurgery, and delayed intracranial hemorrhage. We enrolled and observed 97 consecutive patients. Ten refused the second CT scan and were well during 30-day follow-up. Repeated CT scanning in the remaining 87 patients revealed a new hemorrhage lesion in 5 (6%), with 3 subsequently hospitalized and 1 receiving craniotomy. Two patients discharged after completing the study protocol with 2 negative CT scan results were admitted 2 and 8 days later with symptomatic subdural hematomas; neither received surgery. Two of the 5 patients with delayed bleeding at 24 hours had an initial international normalized ratio greater than 3.0, as did both patients with delayed bleeding beyond 24 hours. The relative risk of delayed hemorrhage with an initial international normalized ratio greater than 3.0 was 14 (95% confidence interval 4 to 49). For patients receiving warfarin who experience minor head injury and have a negative initial head CT scan result, a protocol of 24-hour observation followed by a second CT scan will identify most occurrences of delayed bleeding. An initial international normalized ratio greater than 3 suggests higher risk. Copyright © 2011 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

Long-Term Effects of Highly Active Antiretroviral Therapy on CD4+ Cell Evolution among Children and Adolescents Infected with HIV: 5 Years and Counting

PubMed Central

Patel, Kunjal; Hernán, Miguel A.; Williams, Paige L.; Seeger, John D.; McIntosh, Kenneth; Van Dyke, Russell B.; Seage, George R.

2011-01-01

Background Lower percentages of CD4+ T lymphocytes are associated with adverse clinical outcomes among children and adolescents infected with human immunodeficiency virus (HIV). CD4+ lymphocyte percentage generally increases with receipt of highly active antiretroviral therapy (HAART), but long-term follow-up is required to assess whether these increases in CD4+ cell percentage are maintained and whether they lead to normal CD4+ cell percentages in children with severe immunosuppression. Methods The study population included 1236 children and adolescents perinatally infected with HIV who were enrolled in a US-based multicenter prospective cohort study (Pediatric AIDS Clinical Trials Group 219/219C) and who were not receiving HAART at study initiation. We estimated the effects of HAART, HAART with protease inhibitors, and HAART with nonnucleoside reverse-transcriptase inhibitors on CD4+ cell percentage, using marginal structural models to account for confounding by severity. Results Initiation of any type of HAART increased CD4+ cell percentage by 2.34% (95% confidence interval, 1.35%–3.33%) in the first year, relative to noninitiation of HAART. The substantial increases in CD4+ cell percentage observed after the first year of experience with these combination therapies were followed by relatively smaller increases that continued for 5 years after initiation. Although larger increases in CD4+ cell percentage were observed among children with a greater degree of immunosuppression at baseline, the mean CD4+ cell percentage after 5 years of HAART did not reach normal levels. Conclusions Our study supports the initiation of HAART in children before severe immunosuppression occurs for long-term maintenance of normal CD4+ cell percentages. This beneficial result must be weighed against the evidence of potential adverse events associated with the prolonged use of such therapy. PMID:18426371

Minimum requirements for the function of eukaryotic translation initiation factor 2.

PubMed Central

Erickson, F L; Nika, J; Rippel, S; Hannig, E M

2001-01-01

Eukaryotic translation initiation factor 2 (eIF2) is a G protein heterotrimer required for GTP-dependent delivery of initiator tRNA to the ribosome. eIF2B, the nucleotide exchange factor for eIF2, is a heteropentamer that, in yeast, is encoded by four essential genes and one nonessential gene. We found that increased levels of wild-type eIF2, in the presence of sufficient levels of initiator tRNA, overcome the requirement for eIF2B in vivo. Consistent with bypassing eIF2B, these conditions also suppress the lethal effect of overexpressing the mammalian tumor suppressor PKR, an eIF2alpha kinase. The effects described are further enhanced in the presence of a mutation in the G protein (gamma) subunit of eIF2, gcd11-K250R, which mimics the function of eIF2B in vitro. Interestingly, the same conditions that bypass eIF2B also overcome the requirement for the normally essential eIF2alpha structural gene (SUI2). Our results suggest that the eIF2betagamma complex is capable of carrying out the essential function(s) of eIF2 in the absence of eIF2alpha and eIF2B and are consistent with the idea that the latter function primarily to regulate the level of eIF2.GTP.Met-tRNA(i)(Met) ternary complexes in vivo. PMID:11333223

Ferritin: a zinc detoxicant and a zinc ion donor.

PubMed Central

Price, D; Joshi, J G

1982-01-01

Rats were injected with 1 mg of Zn2+ as zinc sulfate or 2 mg of Cd2+ as cadmium sulfate per kg of body weight on a daily basis. After seven injections, ferritin and metallothionein were isolated from the livers of the rats. Significant amounts of zinc were associated with ferritin. Incubation of such ferritin with apoenzymes of calf intestinal alkaline phosphatase, yeast phosphoglucomutase, and yeast aldolase restored their enzymic activity. The amount of zinc injected was insufficient to stimulate significant synthesis of metallothionein, but similar experiments with injection of cadmium did stimulate the synthesis of metallothionein. The amount of Zn2+ in ferritin of Cd-injected rats was greater than that in ferritin in Zn-injected rats, which was greater than that in ferritin of normal rats. Thus at comparable protein concentration ferritin from Cd-injected rats was a better Zn2+ donor than was ferritin from Zn-injected or normal animals. Ferritin is a normal constituent of several tissues, whereas metallothionein is synthesized under metabolic stress. Thus ferritin may function as a "metal storage and transferring agent" for iron and for zinc. It is suggested that ferritin probably serves as the initial chelator for Zn2+ and perhaps other metal ions as well and that under very high toxic levels of metal ions the synthesis of metallothionein is initiated as the second line of defense. PMID:6212927

Adaptive changes in translation initiation activities for rat pancreatic protein synthesis with feeding of a high-protein diet.

PubMed

Hashi, Masaru; Yoshizawa, Fumiaki; Onozuka, Emi; Ogata, Momoko; Hara, Hiroshi

2005-08-01

We have previously demonstrated that dietary protein induced pancreatic hypergrowth in pancreaticobiliary diverted (PBD) rats. Dietary protein and dietary amino acids stimulate protein synthesis by regulating translation initiation in the rat skeletal muscle and liver. The aim of the present study was to determine whether feeding a high-protein diet induces activation of translation initiation for protein synthesis in the rat pancreas. In PBD rats in which the bile-pancreatic juice was surgically diverted to the upper ileum for 11-13 days, pancreatic dry weight and protein content were doubled compared with those in sham rats and further increased with feeding of a high-protein diet (60% casein diet) for 2 days. These pancreatic growth parameters were maintained at high levels for the next 5 days and were much higher than those of sham rats fed a high-protein diet. In both sham and PBD rats, feeding of a high-protein diet for 2 days induced phosphorylation of eukaryotic initiation factor 4E-binding protein 1 and 70-kDa ribosomal protein S6 kinase, indicating the activation of the initiation phase of translation for pancreatic protein synthesis. However, this increased phosphorylation returned to normal levels on Day 7 in PBD but not in sham rats. We concluded that feeding a high-protein diet induced pancreatic growth with increases in the translation initiation activities for pancreatic protein synthesis within 2 days and that prolonged feeding of a high-protein diet changed the initiation activities differently in sham and PBD rats.

Environmental lead exposure accelerates progressive diabetic nephropathy in type II diabetic patients.

PubMed

Huang, Wen-Hung; Lin, Ja-Liang; Lin-Tan, Dan-Tzu; Hsu, Ching-Wei; Chen, Kuan-Hsing; Yen, Tzung-Hai

2013-01-01

Whether environmental lead exposure has a long-term effect on progressive diabetic nephropathy in type II diabetic patients remains unclear. A total of 107 type II diabetic patients with stage 3 diabetic nephropathy (estimated glomerular filtration rate (eGFR) range, 30-60 mL/min/1.73 m(2)) with normal body lead burden (BLB) (<600  μ g/72 hr in EDTA mobilization tests) and no history of exposure to lead were prospectively followed for 2 years. Patients were divided into high-normal BLB (>80  μ g) and low-normal BLB (<80  μ g) groups. The primary outcome was a 2-fold increase in the initial creatinine levels, long-term dialysis, or death. The secondary outcome was a change in eGFR over time. Forty-five patients reached the primary outcome within 2 years. Although there were no differences in baseline data and renal function, progressive nephropathy was slower in the low-normal BLB group than that in the high-normal BLB group. During the study period, we demonstrated that each 100  μ g increment in BLB and each 10  μ g increment in blood lead levels could decrease GFR by 2.2 mL/min/1.72 m(2) and 3.0 mL/min/1.72 m(2) (P = 0.005), respectively, as estimated by generalized equations. Moreover, BLB was associated with increased risk of achieving primary outcome. Environmental exposure to lead may have a long-term effect on progressive diabetic nephropathy in type II diabetic patients.

Conventional and digital radiographic assessment of tooth enamel de-/remineralization processes: an experimental study.

PubMed

Leite-Ribeiro, Patrícia; de Oliveira, Thais Feitosa Leitão; Mathias, Paula; Campo, Elisângela de Jesus; Sarmento, Viviane Almeida

2014-01-01

This study aimed to compare digital techniques for evaluating dental enamel de-/remineralization. Sixty extracted molars were subjected to a process of de- and remineralization. Radiographs were taken before and after each stage. These radiographs were evaluated by the conventional method and were then scanned and analyzed either with or without the use of image enhancement. Moreover, the gray levels (GLs) of the affected areas were measured. All methods exhibited low sensitivity and identical levels of specificity (99.4%). Analysis of the grayscale levels found statistically significant differences between the initial radiographs (P < 0.05). The mean GL of the carious group was significantly lower than that of the remineralized group. The GL did not differ significantly between the initial and final radiographs of the remineralized group, although the mean of the first group was lower than that of the second, which demonstrated that the remineralization process restored the normal density of the dental enamel. Measurement of the mean GL was sufficiently sensitive to detect small alterations in the surface of the enamel.

Tau elevations in the brain extracellular space correlate with reduced amyloid-β levels and predict adverse clinical outcomes after severe traumatic brain injury.

PubMed

Magnoni, Sandra; Esparza, Thomas J; Conte, Valeria; Carbonara, Marco; Carrabba, Giorgio; Holtzman, David M; Zipfel, Greg J; Stocchetti, Nino; Brody, David L

2012-04-01

Axonal injury is believed to be a major determinant of adverse outcomes following traumatic brain injury. However, it has been difficult to assess acutely the severity of axonal injury in human traumatic brain injury patients. We hypothesized that microdialysis-based measurements of the brain extracellular fluid levels of tau and neurofilament light chain, two low molecular weight axonal proteins, could be helpful in this regard. To test this hypothesis, 100 kDa cut-off microdialysis catheters were placed in 16 patients with severe traumatic brain injury at two neurological/neurosurgical intensive care units. Tau levels in the microdialysis samples were highest early and fell over time in all patients. Initial tau levels were >3-fold higher in patients with microdialysis catheters placed in pericontusional regions than in patients in whom catheters were placed in normal-appearing right frontal lobe tissue (P = 0.005). Tau levels and neurofilament light-chain levels were positively correlated (r = 0.6, P = 0.013). Neurofilament light-chain levels were also higher in patients with pericontusional catheters (P = 0.04). Interestingly, initial tau levels were inversely correlated with initial amyloid-β levels measured in the same samples (r = -0.87, P = 0.000023). This could be due to reduced synaptic activity in areas with substantial axonal injury, as amyloid-β release is closely coupled with synaptic activity. Importantly, high initial tau levels correlated with worse clinical outcomes, as assessed using the Glasgow Outcome Scale 6 months after injury (r = -0.6, P = 0.018). Taken together, our data add support for the hypothesis that axonal injury may be related to long-term impairments following traumatic brain injury. Microdialysis-based measurement of tau levels in the brain extracellular space may be a useful way to assess the severity of axonal injury acutely in the intensive care unit. Further studies with larger numbers of patients will be required to assess the reproducibility of these findings and to determine whether this approach provides added value when combined with clinical and radiological information.

Clinical and Genetic Determinants of Warfarin Pharmacokinetics and Pharmacodynamics during Treatment Initiation

PubMed Central

Gong, Inna Y.; Schwarz, Ute I.; Crown, Natalie; Dresser, George K.; Lazo-Langner, Alejandro; Zou, GuangYong; Roden, Dan M.; Stein, C. Michael; Rodger, Marc; Wells, Philip S.; Kim, Richard B.; Tirona, Rommel G.

2011-01-01

Variable warfarin response during treatment initiation poses a significant challenge to providing optimal anticoagulation therapy. We investigated the determinants of initial warfarin response in a cohort of 167 patients. During the first nine days of treatment with pharmacogenetics-guided dosing, S-warfarin plasma levels and international normalized ratio were obtained to serve as inputs to a pharmacokinetic-pharmacodynamic (PK-PD) model. Individual PK (S-warfarin clearance) and PD (Imax) parameter values were estimated. Regression analysis demonstrated that CYP2C9 genotype, kidney function, and gender were independent determinants of S-warfarin clearance. The values for Imax were dependent on VKORC1 and CYP4F2 genotypes, vitamin K status (as measured by plasma concentrations of proteins induced by vitamin K absence, PIVKA-II) and weight. Importantly, indication for warfarin was a major independent determinant of Imax during initiation, where PD sensitivity was greater in atrial fibrillation than venous thromboembolism. To demonstrate the utility of the global PK-PD model, we compared the predicted initial anticoagulation responses with previously established warfarin dosing algorithms. These insights and modeling approaches have application to personalized warfarin therapy. PMID:22114699

Hierarchical Diagnosis of Vocal Fold Disorders

NASA Astrophysics Data System (ADS)

Nikkhah-Bahrami, Mansour; Ahmadi-Noubari, Hossein; Seyed Aghazadeh, Babak; Khadivi Heris, Hossein

This paper explores the use of hierarchical structure for diagnosis of vocal fold disorders. The hierarchical structure is initially used to train different second-level classifiers. At the first level normal and pathological signals have been distinguished. Next, pathological signals have been classified into neurogenic and organic vocal fold disorders. At the final level, vocal fold nodules have been distinguished from polyps in organic disorders category. For feature selection at each level of hierarchy, the reconstructed signal at each wavelet packet decomposition sub-band in 5 levels of decomposition with mother wavelet of (db10) is used to extract the nonlinear features of self-similarity and approximate entropy. Also, wavelet packet coefficients are used to measure energy and Shannon entropy features at different spectral sub-bands. Davies-Bouldin criterion has been employed to find the most discriminant features. Finally, support vector machines have been adopted as classifiers at each level of hierarchy resulting in the diagnosis accuracy of 92%.

Mechanics of graben formation in crustal rocks - A finite element analysis

NASA Technical Reports Server (NTRS)

Melosh, H. J.; Williams, C. A., Jr.

1989-01-01

The mechanics of the initial stages of graben formation are examined, showing that the configuration of a graben (a pair of antithetically dipping normal faults) is the most energetically favorable fault configuration in elastic-brittle rocks subjected to pure extension. The stress field in the vicinity of a single initial normal fault is computed with a two-dimensional FEM. It is concluded that the major factor controlling graben width is the depth of the initial fault.

Replication of the Escherichia coli chromosome in RNase HI-deficient cells: multiple initiation regions and fork dynamics.

PubMed

Maduike, Nkabuije Z; Tehranchi, Ashley K; Wang, Jue D; Kreuzer, Kenneth N

2014-01-01

DNA replication in Escherichia coli is normally initiated at a single origin, oriC, dependent on initiation protein DnaA. However, replication can be initiated elsewhere on the chromosome at multiple ectopic oriK sites. Genetic evidence indicates that initiation from oriK depends on RNA-DNA hybrids (R-loops), which are normally removed by enzymes such as RNase HI to prevent oriK from misfiring during normal growth. Initiation from oriK sites occurs in RNase HI-deficient mutants, and possibly in wild-type cells under certain unusual conditions. Despite previous work, the locations of oriK and their impact on genome stability remain unclear. We combined 2D gel electrophoresis and whole genome approaches to map genome-wide oriK locations. The DNA copy number profiles of various RNase HI-deficient strains contained multiple peaks, often in consistent locations, identifying candidate oriK sites. Removal of RNase HI protein also leads to global alterations of replication fork migration patterns, often opposite to normal replication directions, and presumably eukaryote-like replication fork merging. Our results have implications for genome stability, offering a new understanding of how RNase HI deficiency results in R-loop-mediated transcription-replication conflict, as well as inappropriate replication stalling or blockage at Ter sites outside of the terminus trap region and at ribosomal operons. © 2013 John Wiley & Sons Ltd.

The impact of protease inhibitors on maternal serum screening analyte levels in pregnant women who are HIV positive.

PubMed

Einstein, Francine H; Wright, Rodney L; Trentacoste, Stephanie; Gross, Susan; Merkatz, Irwin R; Bernstein, Peter S

2004-09-01

The purpose of this study was to compare alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol levels in women who take protease inhibitors and those women who do not. This retrospective review from August 2000 to May 2003 was performed for maternal serum screen results, medication use, pregnancy, and perinatal outcomes. Thirty-nine women met study criteria. Sixteen women were treated with protease inhibitors, and 23 women were not treated with protease inhibitors. There was no difference in initial viral load or initial CD4 count between the groups. No difference was found for human chorionic gonadotropin and estriol levels; significantly lower alpha-fetoprotein multiples of the median were found for the women who were treated with protease inhibitors compared with the women who were not (0.97 +/- 0.32 [SD] MoM vs 1.2 +/- 0.4 MoM, respectively; P = .04). Six of 39 women (15%) had positive maternal serum screens. All the babies were normal at birth, and there were no cases of perinatal transmission of human immunodeficiency virus. Protease inhibitors are associated with lower alpha-fetoprotein levels in women who are infected with human immunodeficiency virus.

Sensitivity and validity of psychometric tests for assessing driving impairment: effects of sleep deprivation.

PubMed

Jongen, Stefan; Perrier, Joy; Vuurman, Eric F; Ramaekers, Johannes G; Vermeeren, Annemiek

2015-01-01

To assess drug induced driving impairment, initial screening is needed. However, no consensus has been reached about which initial screening tools have to be used. The present study aims to determine the ability of a battery of psychometric tests to detect performance impairing effects of clinically relevant levels of drowsiness as induced by one night of sleep deprivation. Twenty four healthy volunteers participated in a 2-period crossover study in which the highway driving test was conducted twice: once after normal sleep and once after one night of sleep deprivation. The psychometric tests were conducted on 4 occasions: once after normal sleep (at 11 am) and three times during a single night of sleep deprivation (at 1 am, 5 am, and 11 am). On-the-road driving performance was significantly impaired after sleep deprivation, as measured by an increase in Standard Deviation of Lateral Position (SDLP) of 3.1 cm compared to performance after a normal night of sleep. At 5 am, performance in most psychometric tests showed significant impairment. As expected, largest effect sizes were found on performance in the Psychomotor Vigilance Test (PVT). Large effects sizes were also found in the Divided Attention Test (DAT), the Attention Network Test (ANT), and the test for Useful Field of View (UFOV) at 5 and 11 am during sleep deprivation. Effects of sleep deprivation on SDLP correlated significantly with performance changes in the PVT and the DAT, but not with performance changes in the UFOV. From the psychometric tests used in this study, the PVT and DAT seem most promising for initial evaluation of drug impairment based on sensitivity and correlations with driving impairment. Further studies are needed to assess the sensitivity and validity of these psychometric tests after benchmark sedative drug use.

Numerical investigation of contact stresses for fretting fatigue damage initiation

NASA Astrophysics Data System (ADS)

Bhatti, N. A.; Abdel Wahab, M.

2017-05-01

Fretting fatigue phenomena occurs due to interaction between contacting bodies under application of cyclic and normal loads. In addition to environmental conditions and material properties, the response at the contact interface highly depends on the combination of applied loads. High stress concentration is present at the contact interface, which can start the damage nucleation process. At the culmination of nucleation process several micro cracks are initiated, ultimately leading to the structural failure. In this study, effect of ratio of tangential to normal load on contact stresses, slip amplitude and damage initiation is studied using finite element analysis. The results are evaluated for Ruiz parameter as it involves the slip amplitude which in an important factor in fretting fatigue conditions. It is observed that tangential to normal load ratio influences the stick zone size and damage initiation life. Furthermore, it is observed that tensile stress is the most important factor that drives the damage initiation to failure for the cases where failure occurs predominantly in mode I manner.

[Atorvastatin improves reflow after percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction by decreasing serum uric acid level].

PubMed

Yan, Ling; Ye, Lu; Wang, Kun; Zhou, Jie; Zhu, Chunjia

2016-05-25

Objective: To investigate the effect of atorvastatin on reflow in patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and its relation to serum uric acid levels. Methods: One hundred and fourteen STEMI patients undergoing primary PCI were enrolled and randomly divided into two groups:55 cases received oral atorvastatin 20 mg before PCI (routine dose group) and 59 cases received oral atorvastatin 80 mg before PCI (high dose group). According to the initial serum uric acid level, patients in two groups were further divided into normal uric acid subgroup and hyperuricemia subgroup. The changes of uric acid level and coronary artery blood flow after PCI were observed. Correlations between the decrease of uric acid, the dose of atorvastatin and the blood flow of coronary artery after PCI were analyzed. Results: Serum uric acid levels were decreased after treatment in both groups (all P <0.05), and patients with hyperuricemia showed more significant decrease in serum uric acid level ( P <0.05). Compared with the routine dose group, serum uric acid level in patients with hyperuricemia decreased more significantly in the high dose group ( P <0.05), but no significant difference was observed between patients with normal serum uric acid levels in two groups ( P >0.05). Among 114 patients, there were 19 cases without reflow after PCI (16.7%). In the routine dose group, there were 12 patients without reflow, in which 3 had normal uric acid and 9 had high uric acid levels ( P <0.01). In the high dose group, there were 7 patients without reflow, in which 2 had normal uric acid and 5 had high uric acid ( P <0.05). Logistic regression analysis showed that hyperuricemia was one of independent risk factors for no-reflow after PCI ( OR =1.01, 95% CI :1.01-1.11, P <0.01). The incidence of no-flow after PCI in the routine dose group was 21.8% (12/55), and that in the high dose group was 11.9% (7/59) ( P <0.01). Conclusion: High dose atorvastatin can decrease serum uric acid levels and improve reflow after PCI in patients with STEMI.

LAM-1 and FAT Genes Control Development of the Leaf Blade in Nicotiana sylvestris.

PubMed Central

McHale, NA

1993-01-01

Leaf primordia of the lam-1 mutant of Nicotiana sylvestris grow normally in length but remain bladeless throughout development. The blade initiation site is established at the normal time and position in lam-1 primordia. Anticlinal divisions proceed normally in the outer L1 and L2 layers, but the inner L3 cells fail to establish the periclinal divisions that normally generate the middle mesophyll core. The lam-1 mutation also blocks formation of blade mesophyll from distal L2 cells. This suggests that LAM-1 controls a common step in initiation of blade tissue from the L2 and L3 lineage of the primordium. Another recessive mutation (fat) was isolated in N. sylvestris that induces abnormal periclinal divisions in the mesophyll during blade initiation and expansion. This generates a blade approximately twice its normal thickness by doubling the number of mesophyll cell layers from four to approximately eight. Presumably, the fat mutation defines a negative regulator involved in repression of periclinal divisions in the blade. The lam-1 fat double mutant shows radial proliferation of mesophyll cells at the blade initiation site. This produces a highly disorganized, club-shaped blade that appears to represent an additive effect of the lam-1 and fat mutations on blade founder cells. PMID:12271096

Prognosis of patients excluded by the definition of septic shock based on their lactate levels after initial fluid resuscitation: a prospective multi-center observational study.

PubMed

Ko, Byuk Sung; Kim, Kyuseok; Choi, Sung-Hyuk; Kang, Gu Hyun; Shin, Tae Gun; Jo, You Hwan; Ryoo, Seung Mok; Beom, Jin Ho; Kwon, Woon Yong; Han, Kap Su; Choi, Han Sung; Chung, Sung Phil; Suh, Gil Joon; Lim, Tae Ho; Kim, Won Young

2018-02-24

Septic shock can be defined both by the presence of hyperlactatemia and need of vasopressors. Lactate levels should be measured after volume resuscitation (as per the Sepsis-3 definition). However, currently, no studies have evaluated patients who have been excluded by the new criteria for septic shock. The aim of this study was to determine the clinical characteristics and prognosis of these patients, based on their lactate levels after initial fluid resuscitation. This observational study was performed using a prospective, multi-center registry of septic shock, with the participation of 10 hospitals in the Korean Shock Society, between October 2015 and February 2017. We compared the 28-day mortality between patients who were excluded from the new definition (defined as lactate level <2 mmol/L after volume resuscitation) and those who were not (≥2 mmol/L after volume resuscitation), from among a cohort of patients with refractory hypotension, and requiring the use of vasopressors. Other outcome variables such as in-hospital mortality, intensive care unit (ICU) stay (days), Sequential Organ Failure Assessment (SOFA) scores and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were also analyzed. Of 567 patients with refractory hypotension, requiring the use of vasopressors, 435 had elevated lactate levels, while 83 did not have elevated lactate levels (either initially or after volume resuscitation), and 49 (8.2%) had elevated lactate levels initially, which normalized after fluid resuscitation. Thus, these 49 patients were excluded by the new definition of septic shock. These patients, in whom perfusion was restored, demonstrated significantly lower age, platelet count, and initial and subsequent lactate levels (all p < 0.01). Similarly, significantly lower 28-day mortality was observed in these patients than in those who had not been excluded (8.2% vs 25.5%, p = 0.02). In-hospital mortality and the maximum SOFA score were also significantly lower in the excluded patients group (p = 0.03, both). It seems reasonable for septic shock to be defined by the lactate levels after volume resuscitation. However, owing to the small number of patients in whom lactate levels were improved, further study is warranted.

Initial assessment of facial nerve paralysis based on motion analysis using an optical flow method.

PubMed

Samsudin, Wan Syahirah W; Sundaraj, Kenneth; Ahmad, Amirozi; Salleh, Hasriah

2016-01-01

An initial assessment method that can classify as well as categorize the severity of paralysis into one of six levels according to the House-Brackmann (HB) system based on facial landmarks motion using an Optical Flow (OF) algorithm is proposed. The desired landmarks were obtained from the video recordings of 5 normal and 3 Bell's Palsy subjects and tracked using the Kanade-Lucas-Tomasi (KLT) method. A new scoring system based on the motion analysis using area measurement is proposed. This scoring system uses the individual scores from the facial exercises and grades the paralysis based on the HB system. The proposed method has obtained promising results and may play a pivotal role towards improved rehabilitation programs for patients.

Outcomes after an excisional procedure for cervical intraepithelial neoplasia in HIV-infected women

PubMed Central

Reimers, Laura L.; Sotardi, Susan; Daniel, David; Chiu, Lydia G.; Arsdale, Anne Van; Wieland, Daryl L.; Leider, Jason M.; Xue, Xiaonan; Strickler, Howard D.; Garry, David J.; Goldberg, Gary L.; Einstein, Mark H.

2011-01-01

Objective To determine predictors of treatment failure and recurrence after surgical excisional procedures for CIN in HIV-infected women. Methods A retrospective cohort study was conducted in which 136 eligible HIV-infected women treated for CIN between 1999 and 2005 were included. Data were abstracted from charts and computer databases. Treatment failures were defined as the presence of CIN 1+ at initial follow-up. Recurrences were defined as the presence of CIN 1+ subsequent to initial normal follow-up. Results Treatment failure at initial follow-up was common, occurring in 51% of CIN 1 and 55% of CIN 2+. Most lesions detected at treatment failure were high grade (>70%), regardless of the grade of initial lesion. Significant risk factors for treatment failure were loop electrosurgical excision procedure (LEEP) compared to cold knife conization (RR=1.76; 95% CI: 1.15–2.64), and low CD4+ count (p = 0.04). Among those with an initial normal clinical evaluation, 55% eventually recurred. As with treatment failure, most lesions detected at recurrence were high grade. Risk factors for recurrence included use of LEEP (hazard ratio [HR] = 3.38; 95% CI: 1.55–7.39), higher HIV RNA level, and the presence of positive margins at treatment (HR = 6.12; 95% CI: 1.90–19.73). Conclusions Most CIN treatment of HIV-infected women studied either failed or resulted in recurrence. Of particular concern, many of these subsequent lesions were high grade. Conization, however, was associated with significantly less failure/recurrence than LEEP. Clinicians treating CIN in HIV-infected women should avoid raising expectations of cure and instead focus on the achievable goal of cancer prevention until there are better therapies for this patient population. PMID:20605046

Intrauterine myelomeningocele repair postnatal results and follow-up at 3.5 years of age--initial experience from a single reference service in Brazil.

PubMed

Hisaba, Wagner Jou; Cavalheiro, Sérgio; Almodim, Carlos Gilberto; Borges, Carolina Peixoto; de Faria, Tereza Cristina Carbonari; Araujo Júnior, Edward; Nardozza, Luciano Marcondes Machado; Moron, Antonio Fernandes

2012-03-01

Present the outcomes of six cases submitted to intrauterine myelomeningocele (MMC) repair. Descriptive observational study of six children submitted to antenatal surgical repair of MMC between 26 and 27 weeks gestation. All deliveries were through cesarean section. The following neonatal variables were assessed: gestational age at delivery, birth weight, Apgar scores, need for intubation, duration of hospital stay and need for postnatal shunt procedures. After 3.5 years, the children were evaluated using the Columbia Mental Maturity Scale or Denver II tests and the Hoffer Ambulation Scale. All deliveries were preterm at a mean gestational age of 32 + 4 weeks and mean birth weight was 1,942 g. Two infants had Apgar scores <7 at 1 min and 1 at 5 min. Ventricular-peritoneal shunts were placed in two cases. All six children are alive: five have normal cognitive development and one has a neuropsychomotor developmental delay. Two children had normal leg movements, a sacral functional level and are community ambulators. Three children had upper lumbar anatomical level lesions and one had a lower thoracic level lesion at the time of fetal surgery. One child, with an L1-L2 anatomical level lesion, in noambulatory and fully dependent on a wheelchair for mobility. Antenatal surgical repair of MMC reduced the need for postnatal shunt placements. Despite preterm delivery, the cognitive development of most children at 3.5 years was normal. Antenatal surgery seemed to improve lower limb motor function in these cases.

Chondroitin Sulfate N-Acetylgalactosaminyltransferase 1 Is Necessary for Normal Endochondral Ossification and Aggrecan Metabolism*

PubMed Central

Sato, Takashi; Kudo, Takashi; Ikehara, Yuzuru; Ogawa, Hiroyasu; Hirano, Tomoko; Kiyohara, Katsue; Hagiwara, Kozue; Togayachi, Akira; Ema, Masatsugu; Takahashi, Satoru; Kimata, Koji; Watanabe, Hideto; Narimatsu, Hisashi

2011-01-01

Chondroitin sulfate (CS) is a glycosaminoglycan, consisting of repeating disaccharide units of N-acetylgalactosamine and glucuronic acid residues, and plays important roles in development and homeostasis of organs and tissues. Here, we generated and analyzed mice lacking chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGalNAcT-1). Csgalnact1−/− mice were viable and fertile but exhibited slight dwarfism. Biochemically, the level of CS in Csgalnact1−/− cartilage was reduced to ∼50% that of wild-type cartilage, whereas its chain length was similar to wild-type mice, indicating that CSGalNAcT-1 participates in the CS chain initiation as suggested in the previous study (Sakai, K., Kimata, K., Sato, T., Gotoh, M., Narimatsu, H., Shinomiya, K., and Watanabe, H. (2007) J. Biol. Chem. 282, 4152–4161). Histologically, the growth plate of Csgalnact1−/− mice contained shorter and slightly disorganized chondrocyte columns with a reduced volume of the extracellular matrix principally in the proliferative layer. Immunohistochemical analysis revealed that the level of both aggrecan and link protein 1 were decreased in Csgalnact1−/− cartilage. Western blot analysis demonstrated an increase in processed forms of aggrecan core protein. These results suggest that CSGalNAcT-1 is required for normal levels of CS biosynthesis in cartilage. Our observations suggest that CSGalNAcT-1 is necessary for normal levels of endochondral ossification, and the decrease in CS amount in the growth plate by its absence causes a rapid catabolism of aggrecan. PMID:21148564

Acute chloroform ingestion successfully treated with intravenously administered N-acetylcysteine.

PubMed

Dell'Aglio, Damon M; Sutter, Mark E; Schwartz, Michael D; Koch, David D; Algren, D A; Morgan, Brent W

2010-06-01

Chloroform, a halogenated hydrocarbon, causes central nervous system depression, cardiac arrhythmias, and hepatotoxicity. We describe a case of chloroform ingestion with a confirmatory serum level and resultant hepatotoxicity successfully treated with intravenously administered N-acetylcysteine (NAC). A 19-year-old man attempting suicide ingested approximately 75 mL of chloroform. He was unresponsive and intubated upon arrival. Intravenously administered NAC was started after initial stabilization was complete. His vital signs were normal. Admission laboratory values revealed normal serum electrolytes, AST, ALT, PT, BUN, creatinine, and bilirubin. Serum ethanol level was 15 mg/dL, and aspirin and acetaminophen were undetectable. The patient was extubated but developed liver function abnormalities with a peak AST of 224 IU/L, ALT of 583 IU/L, and bilirubin level reaching 16.3 mg/dL. NAC was continued through hospital day 6. Serum chloroform level obtained on admission was 91 μg/mL. The patient was discharged to psychiatry without known sequelae and normal liver function tests. The average serum chloroform level in fatal cases of inhalational chloroform poisoning was 64 μg/mL, significantly lower than our patient. The toxicity is believed to be similar in both inhalation and ingestion routes of exposure, with mortality predominantly resulting from anoxia secondary to central nervous system depression. Hepatocellular toxicity is thought to result from free radical-induced oxidative damage. Previous reports describe survival after treatment with orally administered NAC, we report the first use of intravenously administered NAC for chloroform ingestion. Acute oral ingestion of chloroform is extremely rare. Our case illustrates that with appropriate supportive care, patients can recover from chloroform ingestion, and intravenously administered NAC may be of benefit in such cases.

Differential regulation of glutathione peroxidase by selenomethionine and hyperoxia in endothelial cells.

PubMed Central

Jornot, L; Junod, A F

1995-01-01

We have studied the effect of selenomethionine (SeMet) and hyperoxia on the expression of glutathione peroxidase (GP) in human umbilical vein endothelial cells. Incubation of HUVEC with 1 x 10(-6) M SeMet for 24 h and 48 h caused a 65% and 86% increase in GP activity respectively. The same treatment did not result in significant changes in GP gene transcription and mRNA levels. Pactamycin, a specific inhibitor of the initiation step of translation, prevented the rise in GP activity induced by SeMet and caused an increase in GP mRNA in both cells grown in normal and SeMet-supplemented medium. Interestingly, SeMet supplementation stimulated the recruitment of GP mRNA from an untranslatable pool on to polyribosomes, so that the concentration of GP mRNA in polyribosomal translatable pools was 50% higher in cells grown in SeMet-supplemented medium than in cells grown in normal medium. On the other hand, cells exposed to 95% O2 for 3 days in normal medium showed a 60%, 394% and 81% increase in GP gene transcription rate, mRNA levels and activity respectively. Hyperoxia also stabilized GP mRNA. Hyperoxic cells grown in SeMet-supplemented medium did not show any change in GP gene transcription and mRNA levels, but expressed an 81% and 100% increase in GP activity and amount of GP mRNA associated with polyribosomes respectively, when compared with hyperoxic cells maintained in normal medium. Thus, GP appeared to be regulated post-transcriptionally, most probably co-translationally, in response to selenium availability, and transcriptionally and post-transcriptionally in response to oxygen. Images Figure 1 Figure 2 Figure 4 Figure 7 Figure 8 PMID:7887914

Four SNPs and Systemic Level of FOXP3 in Smokers and Patients with Chronic Obstructive Pulmonary Disease.

PubMed

Chu, Shuyuan; Zhong, Xiaoning; Zhang, Jianquan; Lai, Xiaoying; Xie, Jiajun; Li, Yu

2016-12-01

Forkhead box P3 (FOXP3) is the essential transcription factor for the function of regulatory T-cell (Treg). However, the gene mutation of FOXP3 in patients with chronic obstructive pulmonary disease (COPD) at different stages has not been reported. We aim to investigate four single nucleotide polymorphisms (SNPs) and the mRNA expression of FOXP3 in smokers with normal lung function and smokers with COPD at different stages. FOXP3 mRNA expression and SNPs in FOXP3 were assessed in nonsmokers with normal lung function (N), smokers with normal lung function (S), smokers with COPD in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 or 2 grade (COPD 1-2), and smokers with COPD in GOLD 3 or 4 grade (COPD 3-4). In peripheral blood sample, FOXP3 mRNA was assessed using real-time quantitative PCR and SNPs were analyzed by TaqMan PCR. FOXP3 mRNA level in peripheral blood sample was decreased when COPD was aggravated. The frequency of FOXP3 rs5902434 genotype del/del and allele del are lower in COPD 1-2 and COPD 3-4 than that in N or S. The rs5902434 genotype del/del and allele del were, respectively, associated with decreased risk of COPD and lung function decline. The rs5902434 genotypic distribution was correlated with FOXP3 mRNA level. In conclusion, both FOXP3 rs5902434 genotypes and alleles were differently distributed in COPD patients and smokers with normal lung function. The distribution of del/del genotype was associated with systemic expression of FOXP3 mRNA. More research is needed to explore the role of FOXP3 gene polymorphism in immunoinflammation of COPD.

uAUG-mediated translational initiations are responsible for human mu opioid receptor gene expression

PubMed Central

Song, Kyu Young; Kim, Chun Sung; Hwang, Cheol Kyu; Choi, Hack Sun; Law, Ping-Yee; Wei, Li-Na; Loh, Horace H

2010-01-01

Abstract Mu opioid receptor (MOR) is the main site of interaction for major clinical analgesics, particularly morphine. MOR expression is regulated at the transcriptional and post-transcriptional levels. However, the protein expression of the MOR gene is relatively low and the translational control of MOR gene has not been well studied. The 5′-untranslated region (UTR) of the human MOR (OPRM1) mRNA contains four upstream AUG codons (uAUG) preceding the main translation initiation site. We mutated the four uAUGs individually and in combination. Mutations of the third uAUG, containing the same open reading frame, had the strongest inhibitory effect. The inhibitory effect caused by the third in-frame uAUG was confirmed by in vitro translation and receptor-binding assays. Toeprinting results showed that OPRM1 ribosomes initiated efficiently at the first uAUG, and subsequently re-initiated at the in-frame #3 uAUG and the physiological AUG site. This re-initiation resulted in negative expression of OPRM1 under normal conditions. These results indicate that re-initiation in MOR gene expression could play an important role in OPRM1 regulation. PMID:19438807

Persistence of thyrotropin (TSH) receptor antibodies in children and adolescents with Graves' disease treated using antithyroid medication.

PubMed

Smith, Jessica; Brown, Rosalind S

2007-11-01

To determine the course of thyrotropin (thyroid-stimulating hormone [TSH]) receptor antibodies (TRAbs) in children and adolescents with Graves' disease treated using antithyroid drugs (ATDs). Retrospective, cross-sectional study of 86 children and adolescents with Graves' disease treated medically for >3 years. Patients with Hashimoto's thyroiditis and idiopathic short stature (n = 30) served as controls. A second-generation enzyme-linked immunosorbent assay (ELISA) for TRAbs was used. Twenty-two out of 23 (95.7%) patients with newly diagnosed Graves' disease, but 0/30 controls, had detectable TRAbs (22.0 +/- 13.5 U/L [mean +/- SD] vs. 0.9 +/- 0.9 U/L, p < 0.0001). Mean TRAb levels decreased with duration of therapy, but even after 13-24 months, TRAbs had normalized in only 3/16 (18.8%) patients. The initial TRAb titer correlated significantly with severity of the initial hyperthyroidism, but did not predict the response to therapy as indicated by the dosage of ATD required to control the hyperthyroidism at 6 and 12 months. Unlike adults, most children and adolescents with Graves' disease require >2 years of ATD treatment before TRAbs are normalized. Although initial TRAb activity reflects disease severity, it does not predict the response to medical therapy. Recommendations as to treatment duration developed for adult patients should not be applied to the young.

Auditory-nerve responses predict pitch attributes related to musical consonance-dissonance for normal and impaired hearinga

PubMed Central

Bidelman, Gavin M.; Heinz, Michael G.

2011-01-01

Human listeners prefer consonant over dissonant musical intervals and the perceived contrast between these classes is reduced with cochlear hearing loss. Population-level activity of normal and impaired model auditory-nerve (AN) fibers was examined to determine (1) if peripheral auditory neurons exhibit correlates of consonance and dissonance and (2) if the reduced perceptual difference between these qualities observed for hearing-impaired listeners can be explained by impaired AN responses. In addition, acoustical correlates of consonance-dissonance were also explored including periodicity and roughness. Among the chromatic pitch combinations of music, consonant intervals∕chords yielded more robust neural pitch-salience magnitudes (determined by harmonicity∕periodicity) than dissonant intervals∕chords. In addition, AN pitch-salience magnitudes correctly predicted the ordering of hierarchical pitch and chordal sonorities described by Western music theory. Cochlear hearing impairment compressed pitch salience estimates between consonant and dissonant pitch relationships. The reduction in contrast of neural responses following cochlear hearing loss may explain the inability of hearing-impaired listeners to distinguish musical qualia as clearly as normal-hearing individuals. Of the neural and acoustic correlates explored, AN pitch salience was the best predictor of behavioral data. Results ultimately show that basic pitch relationships governing music are already present in initial stages of neural processing at the AN level. PMID:21895089

Phosphorus bioavailability and digestibility of normal and genetically modified low-phytate corn for pigs.

PubMed

Spencer, J D; Allee, G L; Sauber, T E

2000-03-01

We conducted two studies to determine the bioavailability and apparent digestibility of P in a low-phytate corn hybrid (.28% total P, .10% phytate P) genetically modified to be homozygous for the 1pa1-1 allele and a nearly isogenic corn hybrid (normal) (.25% total P, .20% phytate P). Additionally, we conducted an in vitro assay involving a peptic and pancreatin digestion to estimate P availability. The first study used 50 individually penned pigs (initial body weight 9 kg) and 10 treatments in a randomized complete block design. A cornstarch-soybean meal basal diet (.6% Ca, .2% P) was used. Treatments consisted of the basal diet and the basal diet plus .05, .10, or .15% P from monosodium phosphate (MSP), low-phytate corn, or normal corn. After a 35-d feeding period, pigs were killed to collect the fourth metacarpal for measurements of ash and breaking load. Breaking load was regressed on added P intake, and the bioavailability of P was determined by the slope ratio method. The bioavailabilities of P (relative to MSP) for low-phytate and normal corn were 62 and 9%, respectively. These were similar to the determined in vitro values of 57 and 11% for low-phytate and normal corn, respectively. In the second study, 20 pigs (initial BW 20 kg) were used in a randomized complete block design with a 2 x 2 factorial arrangement of treatments. Two corn lines (low-phytate and normal) and two levels of supplemental P (0 and .2%) from dicalcium phosphate were used. Diets with no added P were formulated to contain .9% lysine, .6% Ca, and .34% P. Apparent nutrient digestibilities were calculated from total collection of urine and feces for 5 d. There were no differences among treatments for energy and nitrogen digestibility. Pigs fed low-phytate corn with no added P had increased digestibility and retention of P and reduced total P excretion (P < .05). We conclude that low-phytate corn contains at least five times as much available P as normal corn. The use oflow-phytate corn greatly reduced the amount of P excreted by the pig and increased the N:P ratio in the manure.

Hypocalcaemia following total thyroidectomy: early post-operative parathyroid hormone assay as a risk stratification and management tool.

PubMed

Islam, S; Al Maqbali, T; Howe, D; Campbell, J

2014-03-01

To develop a practical, efficient and predictive algorithm to manage potential or actual post-operative hypocalcaemia after complete thyroidectomy, using a single post-operative parathyroid hormone assay. This paper reports a prospective study of 59 patients who underwent total or completion thyroidectomy over a period of 24 months. Parathyroid hormone levels were checked post-operatively on the day of surgery, and all patients were evaluated for hypocalcaemia both clinically and biochemically with serial corrected calcium measurements. No patient with an early post-operative parathyroid hormone level of 23 ng/l or more (i.e. approximately twice the lower limit of the normal range) developed hypocalcaemia. All the patients who initially had post-operative hypocalcaemia but had an early parathyroid hormone level of 8 ng/l or more (i.e. approximately two-thirds of the lower limit of the normal range) had complete resolution of their hypocalcaemia within three months. Early post-operative parathyroid hormone measurement can reliably predict patients at risk of post-thyroidectomy hypocalcaemia, and predict those patients expected to recover from temporary hypocalcaemia. A suggested post-operative management algorithm is presented.

Effects of an intervention to promote socioemotional development in terms of attachment security: a study in early institutionalization in Chile.

PubMed

Lecannelier, Felipe; Silva, Jaime R; Hoffmann, Marianela; Melo, Rolando; Morales, Raquel

2014-01-01

The Chilean government commissioned a quasi-experimental study with a pre-/postintervention design that had two general aims: (a) to assess infants' psychoaffective developmental levels (pre-intervention phase) and (b) to evaluate whether an intervention based on the promotion of socioemotional development modifies the infant's psychoaffective development. Sixty-two institutionalized infants and their alternative caregivers were evaluated at a pre-intervention stage. An intervention then took place, with the caregivers trained according to an "attachment sensitivity manual." Results showed normal ranges of psychomotor development (64% normal, 9% delayed) and a very high frequency of attachment insecurity, as compared to the normative population (53%).The intervention significantly improved social orientation and object orientation as well as activity and reactivity levels. We conclude that although institutionalized infants in Chile do not exhibit high levels of atypical attachment, socioemotional deterioration may lead to vulnerability in present and future development. Finally, the scope of this study affected public policies regarding children, initiating a change to a foster family system and a variety of modifications in the strategies for adopting institutionalized infants. © 2014 Michigan Association for Infant Mental Health.

Assessment of sperm DNA in patients submitted the assisted reproduction technology procedures.

PubMed

Tsuribe, Patrícia Miyuki; Lima Neto, João Ferreira; Golim, Marjorie de Assis; Dell'Aqua, Camila de Paula Freitas; Issa, João Paulo; Gobbo, Carlos Alberto Monte

2016-03-01

This study aimed to produce data on sperm quality while maintaining the integrity of sperm DNA samples taken from patients submitted to in vitro fertilization (IVF) procedures at our center, and determine whether increased levels of histones were associated with sperm DNA damage and decreased fertilization, cleavage, and pregnancy rates. Such findings might shed light on the physiology and outcomes of pregnancy. Semen samples from 27 patients divided into two groups were analyzed. The case group included individuals offered IVF; the control group had subjects with normal spermograms. Sperm DNA structure was assessed through phosphorylated histone H2AX analysis by flow cytometry. The patients with altered sperm parameters had more histones in sperm chromatin than the individuals with normal sperm parameters. Results indicated that increased levels of histone in sperm chromatin do not affect embryo production, but affect the cleavage rate, embryo quality, and might thus reduce pregnancy rates. The integrity of the paternal genome is of paramount importance in the initiation and maintenance of a viable pregnancy in patients treated with assisted reproduction technology procedures. Further studies on sperm diagnostic tests at a nuclear level might improve the treatment offered to infertile couples.

Sildenafil citrate (Viagra) enhances vasodilatation by atrial natriuretic peptide in normal dogs.

PubMed

Ishikura, Fuminobu; Beppu, Shintaro; Asanuma, Toshihiko; Seward, James B; Khandheria, Bijoy K

2007-12-01

Sildenafil citrate (Viagra) is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5, which might enhance the vasorelaxant and natriuretic actions of atrial natriuretic peptide (ANP) in patients with heart failure. The objective of this study was to examine the combined effect of Viagra on hemodynamic changes during infusion of exogenous ANP. Healthy male beagles were used to assess systemic blood pressure, pulmonary artery pressure (PAP), and plasma levels of cGMP. After hemodynamic variables were measured, 0.1 microg.kg(-1).min(-1) of ANP was given during this study. One hour after initiating infusion of ANP, 2 mg/kg of sildenafil citrate or vehicle was given orally via a nasogastric tube. Hemodynamic changes were measured before and 1 h after these administrations. Mean systemic and PAP decreased during infusion of ANP, and further decreased after sildenafil citrate administration, however, mean systemic blood pressure decreased within 10 mmHg. Plasma levels of cGMP also increased after sildenafil citrate administration. In normal dogs, sildenafil citrate enhances the vasodilator effect of ANP by increasing the cGMP level, however, the concomitant use of sildenafil citrate with ANP will not induce severe hypotension.

Outcome of prolactinoma after pregnancy and lactation: a study on 73 patients.

PubMed

Domingue, Marie-Eve; Devuyst, France; Alexopoulou, Orsalia; Corvilain, Bernard; Maiter, Dominique

2014-05-01

Prolactinoma is the most frequent pituitary tumour among women of child-bearing age. Only a few studies have addressed the outcome of prolactinoma after pregnancy. To study remission, defined as prolactin normalization without medical treatment, after pregnancy and lactation in women with prolactinoma. A retrospective study conducted in 2 Belgian academic centres including 73 patients (54 microprolactinomas and 19 macroprolactinomas) with 104 pregnancies continuing beyond first trimester. Dopamine agonists were stopped in early pregnancy in all treated cases. Prolactin level and adenoma size at pituitary magnetic resonance imaging (MRI) were recorded before pregnancy and throughout follow-up. Thirty of 73 women (41%) were in remission after a median follow-up of 22 months after delivery or cessation of lactation. Adenoma size at diagnosis was smaller in women in remission (5 vs 8 mm). There was a nonsignificant higher rate of remission for microprolactinomas than for macroprolactinoma (46% vs 26%). The first pituitary MRI after pregnancy and lactation showed no tumour and a decreased adenoma size in 23% and 39% of women, respectively. MRI normalization was associated with remission. The number of pregnancies per woman as well as breastfeeding and its duration did not influence remission rate. More than 40% of women with previous diagnosis of prolactinoma have normal PRL level without medical treatment for a median follow-up of 22 months after pregnancy and lactation. The likelihood of remission is associated with a smaller initial adenoma size and normalization of pituitary MRI after pregnancy. © 2013 John Wiley & Sons Ltd.

Expression profile of undifferentiated cell transcription factor 1 in normal and cancerous human epithelia.

PubMed

Mouallif, Mustapha; Albert, Adelin; Zeddou, Mustapha; Ennaji, My Mustapha; Delvenne, Philippe; Guenin, Samuel

2014-08-01

Undifferentiated cell Transcription Factor 1 (UTF1) is a chromatin-bound protein involved in stem cell differentiation. It was initially reported to be restricted to stem cells or germinal tissues. However, recent work suggests that UTF1 is also expressed in somatic cells and that its expression may increase during carcinogenesis. To further clarify the expression profile of UTF1, we evaluated UTF1 expression levels immunohistochemically in eight normal human epithelia (from breast, prostate, endometrium, bladder, colon, oesophagus, lung and kidney) and their corresponding tumours as well as in several epithelial cell lines. We showed UTF1 staining in normal and tumour epithelial tissues, but with varying intensities according to the tissue location. In vitro analyses also revealed that UTF1 is expressed in somatic epithelial cell lines even in the absence of Oct4A and Sox2, its two main known regulators. The comparison of UTF1 levels in normal and tumoral tissues revealed significant overexpression in endometrial and prostatic adenocarcinomas, whereas lower intensity of the staining was observed in renal and colic tumours, suggesting a potential tissue-specific function of UTF1. Altogether, these results highlight a potential dual role for UTF1, acting either as an oncogene or as a tumour suppressor depending on the tissue. These findings also question its role as a specific marker for stem cells. © 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.

[Perifolliculitis capitis abscedens et suffodiens (case report)].

PubMed

Tsiskarishvili, N V; Katsitadze, A G; Tsiskarishvili, Ts I

2012-04-01

Perifolliculitis capitis abscedens et suffodiens (PCAS) is rare chronic, suppurative and inflammatory scalp disease. Its aetiology and pathogenesis is not completely understood. The treatment is usually difficult and often disappointing. We report a case of 25-year-old male who presented with tender, fluctuant nodules and abscesses, with draining pus and patchy alopecia on his scalp for 3 years. A skin biopsy from scalp lesions revealed features that are characteristic of perifolliculitis. Initially, the patient was treated with periodic incision and drainage of the scalp abscesses. The answer was very poor. When admitted to our department, isotretinoin was started at daily dose of 30 mg, because initially his cholesterol and triglyceride levels were mildly increased. When dose was reduced to 10 mg the levels of cholesterol and triglyceride remained normal. A response to treatment was excellent and rapid. The treatment of PCAS represents usually difficulties and frustration for both the patient and the physician. A long course of isotretinoin can be considered as one of the most effective treatment for PCAS.

Cochlear transducer operating point adaptation.

PubMed

Zou, Yuan; Zheng, Jiefu; Ren, Tianying; Nuttall, Alfred

2006-04-01

The operating point (OP) of outer hair cell (OHC) mechanotransduction can be defined as any shift away from the center position on the transduction function. It is a dc offset that can be described by percentage of the maximum transduction current or as an equivalent dc pressure in the ear canal. The change of OP can be determined from the changes of the second and third harmonics of the cochlear microphonic (CM) following a calibration of its initial value. We found that the initial OP was dependent on sound level and cochlear sensitivity. From CM generated by a lower sound level at 74 dB SPL to avoid saturation and suppression of basal turn cochlear amplification, the OHC OP was at constant 57% of the maximum transduction current (an ear canal pressure of -0.1 Pa). To perturb the OP, a constant force was applied to the bony shell of the cochlea at the 18 kHz best frequency location using a blunt probe. The force applied over the scala tympani induced an OP change as if the organ of Corti moved toward the scala vestibuli (SV) direction. During an application of the constant force, the second harmonic of the CM partially recovered toward the initial level, which could be described by two time constants. Removing the force induced recovery of the second harmonic to its normal level described by a single time constant. The force applied over the SV caused an opposite result. These data indicate an active mechanism for OHC transduction OP.

Longitudinal Change of Biomarkers in Cognitive Decline

PubMed Central

Lo, Raymond Y.; Hubbard, Alan E.; Shaw, Leslie M.; Trojanowski, John Q.; Petersen, Ronald C.; Aisen, Paul S.; Weiner, Michael W.; Jagust, William J.

2017-01-01

Objective To delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD). Design Cohort study. Setting The 59 study sites for the Alzheimer’s Disease Neuroimaging Initiative. Participants A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007. Main Outcome Measures Rates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease’s Assessment Scale–cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker. Results Reductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease’s Assessment Scale–cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD. Conclusion Trajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent. PMID:21670386

SU-E-J-55: End-To-End Effectiveness Analysis of 3D Surface Image Guided Voluntary Breath-Holding Radiotherapy for Left Breast

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

Lin, M; Feigenberg, S

Purpose To evaluate the effectiveness of using 3D-surface-image to guide breath-holding (BH) left-side breast treatment. Methods Two 3D surface image guided BH procedures were implemented and evaluated: normal-BH, taking BH at a comfortable level, and deep-inspiration-breath-holding (DIBH). A total of 20 patients (10 Normal-BH and 10 DIBH) were recruited. Patients received a BH evaluation using a commercialized 3D-surface- tracking-system (VisionRT, London, UK) to quantify the reproducibility of BH positions prior to CT scan. Tangential 3D/IMRT plans were conducted. Patients were initially setup under free-breathing (FB) condition using the FB surface obtained from the untaged CT to ensure a correct patientmore » position. Patients were then guided to reach the planned BH position using the BH surface obtained from the BH CT. Action-levels were set at each phase of treatment process based on the information provided by the 3D-surface-tracking-system for proper interventions (eliminate/re-setup/ re-coaching). We reviewed the frequency of interventions to evaluate its effectiveness. The FB-CBCT and port-film were utilized to evaluate the accuracy of 3D-surface-guided setups. Results 25% of BH candidates with BH positioning uncertainty > 2mm are eliminated prior to CT scan. For >90% of fractions, based on the setup deltas from3D-surface-trackingsystem, adjustments of patient setup are needed after the initial-setup using laser. 3D-surface-guided-setup accuracy is comparable as CBCT. For the BH guidance, frequency of interventions (a re-coaching/re-setup) is 40%(Normal-BH)/91%(DIBH) of treatments for the first 5-fractions and then drops to 16%(Normal-BH)/46%(DIBH). The necessity of re-setup is highly patient-specific for Normal-BH but highly random among patients for DIBH. Overall, a −0.8±2.4 mm accuracy of the anterior pericardial shadow position was achieved. Conclusion 3D-surface-image technology provides effective intervention to the treatment process and ensures favorable day-to-day setup accuracy. DIBH setup appears to be more uncertain and this would be the patient group who will definitely benefit from the extra information of 3D surface setup.« less

Sex steroid-induced changes in circulating monocyte chemoattractant protein-1 levels may contribute to metabolic dysfunction in obese men.

PubMed

Ruige, Johannes B; Bekaert, Marlies; Lapauw, Bruno; Fiers, Tom; Lehr, Stefan; Hartwig, Sonja; Herzfeld de Wiza, Daniella; Schiller, Martina; Passlack, Waltraud; Van Nieuwenhove, Yves; Pattyn, Piet; Cuvelier, Claude; Taes, Youri E; Sell, Henrike; Eckel, Juergen; Kaufman, Jean-Marc; Ouwens, D Margriet

2012-07-01

Low testosterone accompanied by elevated estradiol associates with the development of metabolic dysfunction in men. The aim of the study was to explore the hypothesis that alterations in sex steroid levels induce metabolic dysfunction through adipokines. Circulating levels of sex steroids and 28 adipokines were determined in a cross-sectional study of morbidly obese men and aged-matched controls, as well as in a randomized clinical trial with healthy young men in which obesity-related alterations in sex steroid levels were mimicked by treatment with an aromatase inhibitor plus estradiol patches. Morbidly obese men had lower testosterone levels than normal-weight controls. Estradiol levels were increased in morbidly obese men (without DM2) as compared to normal-weight controls. Circulating levels of multiple proinflammatory cytokines, including IL-1Ra, IL-5, IL-6, IL-10, leptin, monocyte chemoattractant protein 1 (MCP1), and macrophage inflammatory protein 1α, positively associated with estradiol and negatively with testosterone. The associations with estradiol, but not with testosterone, remained significant after adjusting for adipocyte cell size. In a separate clinical trial, the direct adverse effects of lowering testosterone and raising estradiol on MCP1 were substantiated in vivo. Initial alterations in sex steroid levels may contribute to metabolic dysfunction through adverse effects on adipokine levels in obese men. The direct adverse effects on MCP1, a chemokine highly linked to the development of metabolic dysfunction, were substantiated in a trial mimicking obesity-related alterations of sex steroid levels in healthy young males.

A multilevel-ROI-features-based machine learning method for detection of morphometric biomarkers in Parkinson's disease.

PubMed

Peng, Bo; Wang, Suhong; Zhou, Zhiyong; Liu, Yan; Tong, Baotong; Zhang, Tao; Dai, Yakang

2017-06-09

Machine learning methods have been widely used in recent years for detection of neuroimaging biomarkers in regions of interest (ROIs) and assisting diagnosis of neurodegenerative diseases. The innovation of this study is to use multilevel-ROI-features-based machine learning method to detect sensitive morphometric biomarkers in Parkinson's disease (PD). Specifically, the low-level ROI features (gray matter volume, cortical thickness, etc.) and high-level correlative features (connectivity between ROIs) are integrated to construct the multilevel ROI features. Filter- and wrapper- based feature selection method and multi-kernel support vector machine (SVM) are used in the classification algorithm. T1-weighted brain magnetic resonance (MR) images of 69 PD patients and 103 normal controls from the Parkinson's Progression Markers Initiative (PPMI) dataset are included in the study. The machine learning method performs well in classification between PD patients and normal controls with an accuracy of 85.78%, a specificity of 87.79%, and a sensitivity of 87.64%. The most sensitive biomarkers between PD patients and normal controls are mainly distributed in frontal lobe, parental lobe, limbic lobe, temporal lobe, and central region. The classification performance of our method with multilevel ROI features is significantly improved comparing with other classification methods using single-level features. The proposed method shows promising identification ability for detecting morphometric biomarkers in PD, thus confirming the potentiality of our method in assisting diagnosis of the disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Coagulation activation in autoimmune bullous diseases

PubMed Central

Marzano, A V; Tedeschi, A; Spinelli, D; Fanoni, D; Crosti, C; Cugno, M

2009-01-01

The main autoimmune blistering skin disorders are pemphigus vulgaris (PV) and bullous pemphigoid (BP). They differ in the inflammatory infiltrate, which is more intense in BP. Inflammation is known to activate coagulation in several disorders. Local and systemic activation of coagulation was evaluated in BP and PV. We studied 20 BP patients (10 active and 10 remittent), 23 PV patients (13 active and 10 remittent) and 10 healthy subjects. The coagulation markers prothrombin fragment F1+2 and D-dimer were measured by enzyme-immunoassays in plasma. The presence of tissue factor (TF), the main initiator of blood coagulation, was evaluated immunohistochemically in skin specimens from 10 patients with active PV, 10 patients with active BP and 10 controls. Plasma F1+2 and D-dimer levels were significantly high in active BP (P = 0·001), whereas in active PV the levels were normal. During remission, F1+2 and D-dimer plasma levels were normal in both BP and PV. TF immunoreactivity was found in active BP but neither in active PV nor in normal skin. TF reactivity scores were higher in active BP than in controls or active PV (P = 0·0001). No difference in TF scores was found between active PV and controls. BP is associated with coagulation activation, which is lacking in PV. This suggests that BP but not PV patients have an increased thrombotic risk. The observation that thrombotic complications occur more frequently in BP than in PV further supports this view. PMID:19737228

The alteration of autophagy and apoptosis in the hippocampus of rats with natural aging-dependent cognitive deficits.

PubMed

Yu, Yang; Feng, Linjing; Li, Junnan; Lan, Xiaoxin; A, Lixiang; Lv, Xiaoyan; Zhang, Ming; Chen, Li

2017-09-15

The present study was aim to explore aging-dependent changes in hippocampal autophagy and apoptosis in a natural aging rat model from adult to old stages and to discover a suitable age for treating neurodegenerative diseases. Wistar rats at 5, 18 and 24months of age were used to mimic the adulthood, initial old, and old phases, respectively. The learning and cognitive ability of the rats was detected by the Morris water maze test. Morphological changes in the hippocampus were observed. Expressions of apoptosis and autophagy-related proteins were examined by Western blot. The adult group (5months) exhibited high levels of autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II and cell survival, maintaining normal learning and cognitive function and integrated hippocampal morphology. The initial old group (18 months) presented a reduced number of neurons and cognitive deficits, and exhibited high levels of apoptosis related Bax/Bcl-2 ratio, Caspase-3 activation and autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II compared to the adult group. The old group (24 months) exhibited a high level of apoptosis related Bax/Bcl-2 ratio, Caspase-3 activation and a low level of autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II compared to its younger group, as well as significant neuronal death and cognitive deficits. The degree of autophagy was generally consistent with its negative regulator, the PI3K/Akt/mTOR axis, in all groups. Our data suggest that cognitive deficits are first observed in the initial old stage. The levels of autophagy and apoptosis tend to be opposite in the adult and old phases. High levels of autophagy and apoptosis coexist in the initial old stage. Our study indicates that up-regulation of autophagy in the initial old phase to anti-cognitive deficits must be further evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

Spontaneous circulation of myeloid-lymphoid–initiating cells and SCID-repopulating cells in sickle cell crisis

PubMed Central

Lamming, Christopher E.D.; Augustin, Lance; Blackstad, Mark; Lund, Troy C.; Hebbel, Robert P.; Verfaillie, Catherine M.

2003-01-01

The only curative therapy for sickle cell disease (SCD) is allogeneic hematopoietic stem cell (HSC) transplantation. Gene therapy approaches for autologous HSC transplantation are being developed. Although earlier engraftment is seen when cells from GCSF-mobilized blood are transplanted than when bone marrow is transplanted, administration of GCSF to patients with SCD can cause significant morbidity. We tested whether primitive hematopoietic progenitors are spontaneously mobilized in the blood of patients with SCD during acute crisis (AC-SCD patients). The frequency of myeloid-lymphoid–initiating cells (ML-ICs) and SCID-repopulating cells (SRCs) was significantly higher in blood from AC-SCD patients than in blood from patients with steady-state SCD or from normal donors. The presence of SRCs in peripheral blood was not associated with detection of long-term culture–initiating cells, consistent with the notion that SRCs are more primitive than long-term culture–initiating cells. As ML-ICs and SRCs were both detected in blood of AC-SCD patients only, these assays may both measure primitive progenitors. The frequency of ML-ICs also correlated with increases in stem cell factor, GCSF, and IL-8 levels in AC-SCD compared with steady-state SCD and normal-donor sera. Because significant numbers of ML-ICs and SRCs are mobilized in the blood without exogenous cytokine treatment during acute crisis of SCD, collection of peripheral blood progenitors during crisis may yield a source of autologous HSCs suitable for ex-vivo correction by gene therapy approaches and subsequent transplantation. PMID:12639987

Antiretroviral Regimens and CD4/CD8 Ratio Normalization in HIV-Infected Patients during the Initial Year of Treatment: A Cohort Study

PubMed Central

De Salvador-Guillouët, F.; Sakarovitch, C.; Durant, J.; Risso, K.; Demonchy, E.; Roger, P. M.; Fontas, E.

2015-01-01

Background As CD4/CD8 ratio inversion has been associated with non-AIDS morbidity and mortality, predictors of ratio normalization after cART need to be studied. Here, we aimed to investigate the association of antiretroviral regimens with CD4/CD8 ratio normalization within an observational cohort. Methods We selected, from a French cohort at the Nice University Hospital, HIV-1 positive treatment-naive patients who initiated cART between 2000 and 2011 with a CD4/CD8 ratio <1. Association between cART and ratio normalization (>1) in the first year was assessed using multivariate logistic regression models. Specific association with INSTI-containing regimens was examined. Results 567 patients were included in the analyses; the median CD4/CD8 ratio was 0.36. Respectively, 52.9%, 29.6% and 10.4% initiated a PI-based, NNRTI-based or NRTI-based cART regimens. About 8% of the population started an INSTI-containing regimen. 62 (10.9%) patients achieved a CD4/CD8 ratio ≥1 (N group). cART regimen was not associated with normalization when coded as PI-, NNRTI- or NRTI-based regimen. However, when considering INSTI-containing regimens alone, there was a strong association with normalization [OR, 7.67 (2.54–23.2)]. Conclusions Our findings suggest an association between initiation of an INSTI-containing regimen and CD4/CD8 ratio normalization at one year in naïve patients. Should it be confirmed in a larger population, it would be another argument for their use as first-line regimen as it is recommended in the recent update of the “Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents”. PMID:26485149

Effects of strabismic amblyopia and strabismus without amblyopia on visuomotor behavior: III. Temporal eye-hand coordination during reaching.

PubMed

Niechwiej-Szwedo, Ewa; Goltz, Herbert C; Chandrakumar, Manokaraananthan; Wong, Agnes M F

2014-11-11

To examine the effects of strabismic amblyopia and strabismus only, without amblyopia, on the temporal patterns of eye-hand coordination during both the planning and execution stages of visually-guided reaching. Forty-six adults (16 with strabismic amblyopia, 14 with strabismus only, and 16 visually normal) executed reach-to-touch movements toward targets presented randomly 5° or 10° to the left or right of central fixation. Viewing conditions were binocular, monocular viewing with the amblyopic eye, and monocular viewing with the fellow eye (dominant and nondominant viewing for participants without amblyopia). Temporal coordination between eye and hand movements was examined during reach planning (interval between the initiation of saccade and reaching, i.e., saccade-to-reach planning interval) and reach execution (interval between the initiation of saccade and reach peak velocity [PV], i.e., saccade-to-reach PV interval). The frequency and dynamics of secondary reach-related saccades were also examined. The temporal patterns of eye-hand coordination prior to reach initiation were comparable among participants with strabismic amblyopia, strabismus only, and visually normal adults. However, the reach acceleration phase of participants with strabismic amblyopia and those with strabismus only were longer following target fixation (saccade-to-reach PV interval) than that of visually normal participants (P < 0.05). This effect was evident under all viewing conditions. The saccade-to-reach planning interval and the saccade-to-reach PV interval were not significantly different among participants with amblyopia with different levels of acuity and stereo acuity loss. Participants with strabismic amblyopia and strabismus only initiated secondary reach-related saccades significantly more frequently than visually normal participants. The amplitude and peak velocity of these saccades were significantly greater during amblyopic eye viewing in participants with amblyopia who also had negative stereopsis. Adults with strabismic amblyopia and strabismus only showed an altered pattern of temporal eye-hand coordination during the reach acceleration phase, which might affect their ability to modify reach trajectory using early online control. Secondary reach-related saccades may provide a compensatory mechanism with which to facilitate the late online control process in order to ensure relatively good reaching performance during binocular and fellow eye viewing. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Hypogonadism and erectile dysfunction associated with soy product consumption.

PubMed

Siepmann, Timo; Roofeh, Joseph; Kiefer, Florian W; Edelson, David G

2011-01-01

Previous research has focused on the beneficial effects of soy and its active ingredients, isoflavones. For instance, soy consumption has been associated with lower cardiovascular and breast cancer risks. However, the number of reports demonstrating adverse effects of isoflavones due to their estrogenlike properties has increased. We present the case of a 19-y-old type 1 diabetic but otherwise healthy man with sudden onset of loss of libido and erectile dysfunction after the ingestion of large quantities of soy-based products in a vegan-style diet. Blood levels of free and total testosterone and dehydroepiandrosterone (DHEA) were taken at the initial presentation for examination and continuously monitored up to 2 y after discontinuation of the vegan diet. Blood concentrations of free and total testosterone were initially decreased, whereas DHEA was increased. These parameters normalized within 1 y after cessation of the vegan diet. Normalization of testosterone and DHEA levels was paralleled by a constant improvement of symptoms; full sexual function was regained 1 y after cessation of the vegan diet. This case indicates that soy product consumption is related to hypogonadism and erectile dysfunction. To the best of our knowledge, this is the first report of a combination of decreased free testosterone and increased DHEA blood concentrations after consuming a soy-rich diet. Hence, this case emphasizes the impact of isoflavones in the regulation of sex hormones and associated physical alterations. Copyright © 2011 Elsevier Inc. All rights reserved.

Population dynamics of aberrant chromosome 1 in mice.

PubMed

Sabantsev, I; Spitsin, O; Agulnik, S; Ruvinsky, A

1993-05-01

Natural populations of two semispecies of house mouse, Mus musculus domesticus and M.m. musculus, were found to be polymorphic for an aberrant chromosome 1 bearing a large inserted block of homogeneously staining heterochromatin. Strong meiotic drive for the aberrant chromosome from M.m. musculus was previously observed in heterozygous female mice. There are at least three meiotic drive levels determined by different allelic variants of distorter. Homozygotes had low viability and females showed low fertility. Both homo- and heterozygous males had normal fertility and their segregation patterns did not deviate from normal. Computer simulations were performed of the dynamics of aberrant chromosome 1 in demes and populations. The data demonstrate that a spontaneous mutation (inversion) of an aberrant chromosome 1, once arisen, has a high probability of spreading in a population at high coefficients of meiotic drive and migration. In the long-term, the population attains a stationary state which is determined by the drive level and migration intensity. The state of stable genotypic equilibrium is independent of deme and population size, as well as of the initial concentration of the aberrant chromosome. As populations initially polymorphic for the distorters approach the stationary state, the stronger distorter is eliminated. The frequencies of the aberrant chromosome determined by computer analysis agree well with those obtained for the studied Asian M.m. musculus populations. The evolutionary pathways for the origin and fixation of the aberrant chromosome in natural populations are considered.

High normal urine albumin-to-creatinine ratio predicts development of hypertension in Korean men.

PubMed

Park, Sung Keun; Moon, Soo Young; Oh, Chang-Mo; Ryoo, Jae-Hong; Park, Min Suk

2014-01-01

Microalbuminuria is known as a risk factor for hypertension. Recently it was suggested that urine albumin-to-creatinine ratio (UACR), even within the normal range, can be associated with hypertension, but the temporal relationship between normal range UACR and hypertension was not confirmed. Therefore the aim of this study was to verify an association between normal range UACR and the development of hypertension in Korean men. This prospective cohort study was performed on 1,284 initially non-hypertensive Korean men. The total follow-up period was 4,109.5 person-years and the mean follow-up period was 3.2±1.51 years. Cox proportional hazards model was used to estimate the hazard ratios (HR) for the risk of hypertension development. After adjusting for multiple covariates, the HR (95% confidence interval [CI]) for incident hypertension, comparing the second to the fourth quartiles of UACR level to the first quartile, were 1.35 (95% CI: 0.93-1.97), 1.55 (95% CI: 1.07-2.25) and 1.89 (95% CI: 1.31-2.71), respectively (P for trend=0.001). High UACR within the normal range was significantly associated with hypertension development. Furthermore, this association remained significant after adjusting for multiple baseline covariates. 

A Markov chain model to evaluate the effect of CYP3A5 and ABCB1 polymorphisms on adverse events associated with tacrolimus in pediatric renal transplantation.

PubMed

Sy, Sherwin K B; Heuberger, Jules; Shilbayeh, Sireen; Conrado, Daniela J; Derendorf, Hartmut

2013-10-01

The SNP A6986G of the CYP3A5 gene (*3) results in a non-functional protein due to a splicing defect whereas the C3435T was associated with variable expression of the ABCB1 gene, due to protein instability. Part of the large interindividual variability in tacrolimus efficacy and toxicity can be accounted for by these genetic factors. Seventy-two individuals were examined for A6986G and C3435T polymorphism using a PCR-RFLP-based technique to estimate genotype and allele frequencies in the Jordanian population. The association of age, hematocrit, platelet count, CYP3A5, and ABCB1 polymorphisms with tacrolimus dose- and body-weight-normalized levels in the subset of 38 pediatric renal transplant patients was evaluated. A Markov model was used to evaluate the time-dependent probability of an adverse event occurrence by CYP3A5 phenotypes and ABCB1 genotypes. The time-dependent probability of adverse event was about double in CYP3A5 non-expressors compared to the expressors for the first 12 months of therapy. The CYP3A5 non-expressors had higher corresponding normalized tacrolimus levels compared to the expressors in the first 3 months. The correlation trend between probability of adverse events and normalized tacrolimus concentrations for the two CYP3A5 phenotypes persisted for the first 9 months of therapy. The differences among ABCB1 genotypes in terms of adverse events and normalized tacrolimus levels were only observed in the first 3 months of therapy. The information on CYP3A5 genotypes and tacrolimus dose requirement is important in designing effective programs toward management of tacrolimus side effects particularly for the initial dose when tacrolimus blood levels are not available for therapeutic drug monitoring.

Influence of Mixed Mode I-Mode II Loading on Fatigue Delamination Growth Characteristics of a Graphite Epoxy Tape Laminate

NASA Technical Reports Server (NTRS)

Ratcliffe, James G.; Johnston, William M., Jr.

2014-01-01

Mixed mode I-mode II interlaminar tests were conducted on IM7/8552 tape laminates using the mixed-mode bending test. Three mixed mode ratios, G(sub II)/G(sub T) = 0.2, 0.5, and 0.8, were considered. Tests were performed at all three mixed-mode ratios under quasi-static and cyclic loading conditions, where the former static tests were used to determine initial loading levels for the latter fatigue tests. Fatigue tests at each mixed-mode ratio were performed at four loading levels, Gmax, equal to 0.5G(sub c), 0.4G(sub c), 0.3G(sub c), and 0.2G(sub c), where G(sub c) is the interlaminar fracture toughness of the corresponding mixed-mode ratio at which a test was performed. All fatigue tests were performed using constant-amplitude load control and delamination growth was automatically documented using compliance solutions obtained from the corresponding quasi-static tests. Static fracture toughness data yielded a mixed-mode delamination criterion that exhibited monotonic increase in Gc with mixed-mode ratio, G(sub II)/G(sub T). Fatigue delamination onset parameters varied monotonically with G(sub II)/G(sub T), which was expected based on the fracture toughness data. Analysis of non-normalized data yielded a monotonic change in Paris law exponent with mode ratio. This was not the case when normalized data were analyzed. Fatigue data normalized by the static R-curve were most affected in specimens tested at G(sub II)/G(sub T)=0.2 (this process has little influence on the other data). In this case, the normalized data yielded a higher delamination growth rate compared to the raw data for a given loading level. Overall, fiber bridging appeared to be the dominant mechanism, affecting delamination growth rates in specimens tested at different load levels and differing mixed-mode ratios.

Changes of poststimulatory plasma renin activity in women with hyperthyroidism or hypothyroidism in relation to therapy.

PubMed

Marcisz, Czeslaw; Kucharz, Eugene J; Marcisz-Orzel, Magdalena; Poręba, Ryszard; Orzel, Arkadiusz; Sioma-Markowska, Urszula

2011-01-01

The influence of thyroid hormones upon renin-angiotensin-aldosterone system is poorly understood. Under basal conditions, individuals belong to normal, low or high plasma renin activity (PRA) subjects. The study was designed to evaluate basal and poststimulatory PRA and serum aldosterone (Aldo) level in patients with hyperthyroidism or hypothyroidism during therapy. We examined 73 women with hyperthyroidism, 27 women with hypothyroidism and 36 healthy controls. The patients were investigated before initiation of therapy and after attainment of euthyroid state. All subjects were investigated under basal conditions (normal-sodium diet) and after application of a low-sodium diet for three days and upright position for 3 hr. PRA, serum Aldo level, blood pressure, serum sodium, potassium and thyroid hormone levels were determined in all subjects. The subjects were classified as low PRA (<1.0 ng/ml/h), normal PRA (1.0-4.0 ng/ml/h) and high PRA (>4.0 ng/ml/h) individuals according to results obtained under basal conditions. Relatively higher poststimulatory enhancement in PRA was found in patients with hyperthyroidism, especially those with low basal PRA, than in those with hypothyroidism. In women with thyroid dysfunctions poststimulatory increase in Aldo were relative lower than poststimulatory enhancement of PRA. After therapy these difference disappeared. The poststimulatory changes in PRA depended on the basal PRA. Poststimulatory PRA is higher in hyperthyroid women, especially those with low basal PRA. In women with hypothyroidism, basal and poststimulatory PRA is low. Blood pressure and severity of thyroid dysfunction was found to be similar in the patients with low, normal or high basic PRA. In women with thyroid dysfunctions, serum Aldo level and its relative poststimulatory increments are inadequate to changes of PRA; it is suggested that the dissociation in the renin-angiotensin-aldosterone system occurs in hyperthyroid and hypothyroid women.

Comparative Study of Regulatory Circuits in Two Sea Urchin Species Reveals Tight Control of Timing and High Conservation of Expression Dynamics

PubMed Central

Gildor, Tsvia; Ben-Tabou de-Leon, Smadar

2015-01-01

Accurate temporal control of gene expression is essential for normal development and must be robust to natural genetic and environmental variation. Studying gene expression variation within and between related species can delineate the level of expression variability that development can tolerate. Here we exploit the comprehensive model of sea urchin gene regulatory networks and generate high-density expression profiles of key regulatory genes of the Mediterranean sea urchin, Paracentrotus lividus (Pl). The high resolution of our studies reveals highly reproducible gene initiation times that have lower variation than those of maximal mRNA levels between different individuals of the same species. This observation supports a threshold behavior of gene activation that is less sensitive to input concentrations. We then compare Mediterranean sea urchin gene expression profiles to those of its Pacific Ocean relative, Strongylocentrotus purpuratus (Sp). These species shared a common ancestor about 40 million years ago and show highly similar embryonic morphologies. Our comparative analyses of five regulatory circuits operating in different embryonic territories reveal a high conservation of the temporal order of gene activation but also some cases of divergence. A linear ratio of 1.3-fold between gene initiation times in Pl and Sp is partially explained by scaling of the developmental rates with temperature. Scaling the developmental rates according to the estimated Sp-Pl ratio and normalizing the expression levels reveals a striking conservation of relative dynamics of gene expression between the species. Overall, our findings demonstrate the ability of biological developmental systems to tightly control the timing of gene activation and relative dynamics and overcome expression noise induced by genetic variation and growth conditions. PMID:26230518

Therapeutic Ultrasound in Navicular Stress Injuries in Elite Track and Field Athletes.

PubMed

Malliaropoulos, Nikolaos; Alaseirlis, Dimosthenis; Konstantinidis, George; Papalada, Agapi; Tsifountoudis, Ioannis; Petras, Kosmas; Maffulli, Nicola

2017-05-01

To ascertain whether therapeutic ultrasound (TUS) can be used to assess the progression of conservative management in navicular stress injuries. This is a prospective, clinical case series. Level of evidence IV. All participants were examined and followed up in a private Sports Injury Clinic. Ten elite track and field athletes with severe dorsal midfoot pain over the navicular bone participated in this study. All patients underwent both TUS and magnetic resonance imaging (MRI) evaluation. The painful threshold of TUS on initial evaluation was a mean of 0.707 ± 149 W/cm, and MRI detected a navicular stress injury in all patients. The athletes received conservative treatment and underwent sequential TUS evaluations at 4, 8, 12 and 16 weeks. Therapeutic ultrasound pain threshold values were recorded, and the patients were additionally asked to grade local tenderness on a Visual Analogue Scale. Time to return to play was also recorded. The level of pain produced by the application of TUS on a navicular stress fracture seemed to correlate well with Visual Analogue Scale scores and the grade of fracture demonstrated on MRI. The initial low TUS painful mean value increased to a normal mean value of 1.97 ± 0.067 W/cm by 16 weeks. When clinical and TUS findings had returned to normal, the patients were allowed to return to sports activities, with no recurrences experienced during the study period. The production of pain associated with the application of TUS on a navicular stress fracture is a safe and reproducible method of monitoring the resolution of these fractures. We have used it successfully in making return-to-play decisions for elite level track and field athletes.

The initial time-course of headache in patients with spontaneous subarachnoid hemorrhage.

PubMed

Čomić, Hata; Rinkel, Gabriel J E; Vergouwen, Mervyn D I

2017-08-15

If acute severe headache disappears early after its onset, the question arises whether subarachnoid hemorrhage (SAH) should still be ruled out. We studied the initial time-course and minimal duration of headache in a consecutive series of neurologically intact patients with spontaneous SAH. We included patients admitted between 2012 and 2015 within 48h after spontaneous SAH with a normal level of consciousness and no focal deficits. We retrieved data on headache severity, measured with a Numeric Rating Scale (NRS), <48h after ictus. We analyzed the proportion of patients with a first NRS 0 and NRS <3 within 48h after ictus and minimal headache duration. Patients were censored in case of a decrease in level of consciousness, aneurysm treatment, or early discharge. We included 106 patients (62 aneurysmal SAH, 33 perimesencephalic hemorrhage, 11 other spontaneous SAH). All patients were treated with analgesics. Within 48h after ictus, a first NRS 0 was reported by 9 patients (8%;95%CI:3%-14%) and a first NRS <3 by 22 patients (21%;95%CI:13%-28%). Shortest time lapse until NRS 0 was 10h in a patient with aneurysmal SAH who had been on acetaminophen and tramadol since 2:35h after ictus. In a cohort of SAH patients with a normal level of consciousness and no focal deficits who all used analgetics, headache disappeared in around 10% within 48h after ictus. Our data indicate that a diagnostic work-up for SAH is also needed in patients using analgesics in whom headache has disappeared after 10h. Copyright © 2017 Elsevier B.V. All rights reserved.

Alterations in a Unique Class of Cortical Chandelier Cell Axon Cartridges in Schizophrenia.

PubMed

Rocco, Brad R; DeDionisio, Adam M; Lewis, David A; Fish, Kenneth N

2017-07-01

The axons of chandelier cells (ChCs) target the axon initial segment of pyramidal neurons, forming an array of boutons termed a cartridge. In schizophrenia, the density of cartridges detectable by gamma-aminobutyric acid (GABA) membrane transporter 1 immunoreactivity is lower, whereas the density of axon initial segments detectable by immunoreactivity for the α2 subunit of the GABA A receptor is higher in layers 2/superficial 3 of the prefrontal cortex. These findings were interpreted as compensatory responses to lower GABA levels in ChCs. However, we recently found that in schizophrenia, ChC cartridge boutons contain normal levels of the 67 kDa isoform of glutamic acid decarboxylase (GAD67) protein, the enzyme responsible for GABA synthesis in these boutons. To understand these findings we quantified the densities of ChC cartridges immunoreactive for vesicular GABA transporter (vGAT+), which is present in all cartridge boutons, and the subset of cartridges that contain calbindin (CB+). Prefrontal cortex tissue sections from 20 matched pairs of schizophrenia and unaffected comparison subjects were immunolabeled for vGAT, GAD67, and CB. The mean density of vGAT+/CB+ cartridges was 2.7-fold higher, exclusively in layer 2 of schizophrenia subjects, whereas the density of vGAT+/CB- cartridges did not differ between subject groups. Neither vGAT, CB, or GAD67 protein levels per ChC bouton nor the number of boutons per cartridge differed between subject groups. Our findings of a greater density of CB+ ChC cartridges in prefrontal cortex layer 2 from schizophrenia subjects suggests that the normal developmental pruning of these cartridges is blunted in the illness. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Factors Affecting Inlet-Engine Compatibility During Aircraft Departures at High Angle of Attack for an F/A -18A Aircraft

NASA Technical Reports Server (NTRS)

Steenken, W. G.; Williams, J. G.; Yuhas, A. J.; Walsh, K. R.

1999-01-01

The F404-GE-400 engine powered F/A- 18A High Alpha Research Vehicle (HARV) was used to examine the quality of inlet airflow during departed flight maneuvers, that is, during flight outside the normal maneuvering envelope where control surfaces have little or no effectiveness. A series of six nose-left and six nose-right departures were initiated at Mach numbers between 0.3 and 0.4 at an altitude of 35 kft. The yaw rates at departure recovery were in the range of 40 to 90 degrees per second. Engine surges were encountered during three of the nose-left and one of the nose-right departures. Time-variant inlet-total-pressure distortion levels at the engine face were determined to not significantly exceed those measured at maximum angle-of-attack and - sideslip maneuvers during controlled flight. Surges as a result of inlet distortion levels were anticipated to initiate in the fan. Analysis revealed that the surges initiated in the compressor and were the result of a combination of high levels of inlet distortion and rapid changes in aircraft motion. These rapid changes in aircraft motion are indicative of a combination of engine mount and gyroscopic loads being applied to the engine structure that impact the aerodynamic stability of the compressor through changes in the rotor-to-case clearances.

Phenomenological characteristic of the electron component in gamma-quanta initiated showers

NASA Technical Reports Server (NTRS)

Nikolsky, S. I.; Stamenov, J. N.; Ushev, S. Z.

1985-01-01

The phenomenological characteristics of the electron component in showers initiated by primary gamma-quanta were analyzed on the basis of the Tien Shan experimental data. It is shown that the lateral distribution of the electrons ion gamma-quanta initiated showers can be described with NKG - function with age parameters bar S equals 0, 76 plus or minus 0, 02, different from the same parameter for normal showers with the same size bar S equals 0, 85 plus or minus 0, 01. The lateral distribution of the correspondent electron energy flux in gamma-quanta initiated showers is steeper as in normal cosmic ray showers.

Cyclic AMP system in muscle tissue during prolonged hypokinesia

NASA Technical Reports Server (NTRS)

Antipenko, Y. A.; Bubeyev, Y. A.; Korovkin, B. F.; Mikhaleva, N. P.

1980-01-01

Components of the cyclic Adenosine-cyclic-35-monophosphate (AMP) system in the muscle tissue of white rats were studied during 70-75 days of hypokinesia, created by placing the animals in small booths which restricted their movements, and during the readaptation period. In the initial period, cyclic AMP levels and the activities of phosphodiesterase and adenylate cyclase in muscle tissue were increased. The values for these indices were roughly equal for controls and experimental animals during the adaptation period, but on the 70th day of the experiment cAMP levels dropped, phosphodiesterase activity increased, and the stimulative effect of epinephrine on the activity of adenylate cyclase decreased. The indices under study normalized during the readaptation period.

Ontogeny of flight initiation in the fly Drosophila melanogaster: implications for the giant fibre system.

PubMed

Hammond, Sarah; O'Shea, Michael

2007-11-01

There are two modes of flight initiation in Drosophila melanogaster-escape and voluntary. Although the circuitry underlying escape is accounted for by the Giant fibre (GF) system, the system underlying voluntary flight initiation is unknown. The GF system is functionally complete before the adult fly ecloses, but immature adults initially fail to react to a stimulus known to reliably evoke escape in mature adults. This suggests that escape in early adulthood, approximately 2-h post-eclosion, is not automatically triggered by the hard-wired GF system. Indeed, we reveal that escape behaviour displays a staged emergence during the first hour post-eclosion, suggesting that the GF system is subject to declining levels of suppression. Voluntary flight initiations are not observed at all during the period when the GF system is released from its suppression, nor indeed for some time after. We addressed the question whether voluntary flight initiation requires the GF system by observing take-off in Shak-B ( 2 ) mutant flies, in which the GF system is defunct. While the escape response is severely impaired in these mutants, they displayed normal voluntary flight initiation. Thus, the escape mechanism is subject to developmental modulation following eclosion and the GF system does not underlie voluntary flight.

Attenuation of Diabetic Conditions by Sida rhombifolia in Moderately Diabetic Rats and Inability to Produce Similar Effects in Severely Diabetic in Rats

PubMed Central

Chaturvedi, Padmaja; Kwape, Tebogo Elvis

2015-01-01

Objectives: This study was done out to evaluate the effects of Sida rhombifolia methanol extract (SRM) on diabetes in moderately diabetic (MD) and severely diabetic (SD) Sprague-Dawley rats. Methods: SRM was prepared by soaking the powdered plant material in 70% methanol and rota evaporating the methanol from the extract. Effective hypoglycemic doses were established by performing oral glucose tolerance tests (OGTTs) in normal rats. Hourly effects of SRM on glucose were observed in the MD and the SD rats. Rats were grouped, five rats to a group, into normal control 1 (NC1), MD control 1 (MDC1), MD experimental 1 (MDE1), SD control 1 (SDC1), and SD experimental 1 (SDE1) groups. All rats in the control groups were administered 1 mL of distilled water (DW). The rats in the MDE1 and the SDE1 groups were administered SRM orally at 200 and 300 mg/kg body weight (BW), respectively, dissolved in 1 mL of DW. Blood was collected initially and at intervals of 1 hour for 6 hours to measure blood glucose. A similar experimental design was followed for the 30-day long-term trial. Finally, rats were sacrificed, and blood was collected to measure blood glucose, lipid profiles, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH). Results: OGTTs indicated that two doses (200 and 300 mg/kg BW) were effective hypoglycemic doses in normal rats. Both doses reduced glucose levels after 1 hour in the MDE1 and the SDE1 groups. A long-term trial of SRM in the MD group showed a reduced glucose level, a normal lipid profile, and normal GSH and TBARS levels. In SD rats, SRM had no statistically significant effects on these parameters. Normal weight was achieved in the MD rats, but the SD rats showed reduced BW. Conclusion: The study demonstrates that SRM has potential to alleviate the conditions of moderate diabetic, but not severe diabetes. PMID:26998385

Predictive factors for rebleeding and death in alcoholic cirrhotic patients with acute variceal bleeding: a multivariate analysis.

PubMed

Krige, Jake E J; Kotze, Urda K; Distiller, Greg; Shaw, John M; Bornman, Philippus C

2009-10-01

Bleeding from esophageal varices is a leading cause of death in alcoholic cirrhotic patients. The aim of the present single-center study was to identify risk factors predictive of variceal rebleeding and death within 6 weeks of initial treatment. Univariate and multivariate analyses were performed on 310 prospectively documented alcoholic cirrhotic patients with acute variceal hemorrhage (AVH) who underwent 786 endoscopic variceal injection treatments between January 1984 and December 2006. All injections were administered during the first 6 weeks after the patients were treated for their first variceal bleed. Seventy-five (24.2%) patients experienced a rebleed, 38 within 5 days of the initial treatment and 37 within 6 weeks of their initial treatment. Of the 15 variables studied and included in a multivariate analysis using a logistic regression model, a bilirubin level >51 mmol/l and transfusion of >6 units of blood during the initial hospital admission were predictors of variceal rebleeding within the first 6 weeks. Seventy-seven (24.8%) patients died, 29 (9.3%) within 5 days and 48 (15.4%) between 6 and 42 days after the initial treatment. Stepwise multivariate logistic regression analysis showed that six variables were predictors of death within the first 6 weeks: encephalopathy, ascites, bilirubin level >51 mmol/l, international normalized ratio (INR) >2.3, albumin <25 g/l, and the need for balloon tube tamponade. Survival was influenced by the severity of liver failure, with most deaths occurring in Child-Pugh grade C patients. Patients with AVH and encephalopathy, ascites, bilirubin levels >51 mmol/l, INR >2.3, albumin <25 g/l and who require balloon tube tamponade are at increased risk of dying within the first 6 weeks. Bilirubin levels >51 mmol/l and transfusion of >6 units of blood were predictors of variceal rebleeding.

Necessity of the glossopharyngeal nerve in the maintenance of normal intake and ingestive bout size of corn oil by rats.

PubMed

Treesukosol, Yada; Blonde, Ginger D; Jiang, Enshe; Gonzalez, Dani; Smith, James C; Spector, Alan C

2010-10-01

Recent evidence in the literature suggests that signals carried by the glossopharyngeal nerve (GL), which supplies sensory and parasympathetic innervation of the posterior tongue, might be essential in the maintenance of normal gustatory responses to fat stimuli. Here, we report that GL transection (GLX) significantly decreased corn oil intake and preference in 23-h two-bottle tests relative to sham-operated controls (Sham). Drinking-pattern analysis of corn oil licking revealed that bout size, rather than the number of bouts initiated, was smaller in GLX than Sham rats. We also tested a range of glucose concentrations and found that total licks over daily 23-h sessions significantly decreased in GLX compared with Sham rats, but this difference failed to reach significance when intake or any bout parameter was measured. These results show that the signals in the GL normally contribute to processes involved with corn oil bout termination as opposed to bout initiation. GL-derived signals could potentially provide input to "reward" circuits in the ventral forebrain that could serve to maintain ingestion during a meal or, alternatively, could act at the level of the brain stem to attenuate the inhibitory potency of vagal signals, thus delaying the onset of satiation, or perhaps contribute to a cephalic phase reflex modulation of the gut. Parasympathetic efferents in the GL innervating the von Ebner's glands, which secrete lingual lipase, which is thought to break down corn oil into detectable ligands, could also be playing a role in driving corn oil intake. Whatever the mechanism, an intact GL is clearly necessary in maintaining normal intake of corn oil.

Neurodevelopmental and body composition outcomes in children with congenital hypothyroidism treated with high-dose initial replacement and close monitoring.

PubMed

Albert, Benjamin B; Heather, Natasha; Derraik, José G B; Cutfield, Wayne S; Wouldes, Trecia; Tregurtha, Sheryl; Mathai, Sarah; Webster, Dianne; Jefferies, Craig; Gunn, Alistair J; Hofman, Paul L

2013-09-01

Despite newborn screening and early levothyroxine replacement, there are continued reports of mild neurocognitive impairment in children with congenital hypothyroidism (CHT). In Auckland, New Zealand, cases are identified by a neonatal screening program with rapid institution of high-dose levothyroxine replacement (10-15 μg/kg·d), producing prompt normalization of thyroid function. Subsequently, frequent monitoring and dose alterations are performed for 2 years. We aimed to assess whether the Auckland treatment strategy prevents impairment of intellectual and motor development. This study encompassed all children with CHT born in 1993-2006 in Auckland and their siblings. Neurocognitive assessments included the following: 1) intelligence quotient via Weschler Preschool and Primary Scale of Intelligence III or Weschler Intelligence Scale for Children IV; 2) Movement Assessment Battery for Children; and 3) Beery Developmental Test of Visual-Motor Integration. Body composition was assessed by dual-energy x-ray absorptiometry. Forty-four CHT cases and 53 sibling controls aged 9.6 ± 3.9 years were studied. Overall intelligence quotient was similar among CHT cases and controls (95.2 vs 98.6; P = .20), and there were also no differences in motor function. Severity of CHT did not influence outcome, but greater time to normalize free T4 was associated with worse motor balance. There were no differences in anthropometry or body composition between groups. These findings suggest that a strategy of rapidly identifying and treating infants with CHT using high-dose levothyroxine replacement is associated with normal intellectual and motor development. The subtle negative impact on motor function associated with time to normalize free T4 levels is consistent with benefit from rapid initial correction.

Current state of type 2 diabetes management.

PubMed

Molitch, Mark E

2013-06-01

Type 2 diabetes mellitus (T2DM) and its associated comorbidities are a major public health issue in the United States. Although a sizable pharmacotherapeutic armamentarium exists to combat this disease and several sources have published evidence-based management guidelines, the management of patients with T2DM remains complex and suboptimal. Currently available medications target various organs in an attempt to normalize hyperglycemia; however, newer agents targeting additional organ systems are in development. Among these, a class of medications that inhibit the sodium glucose cotransporter 2 (SGLT2) in the kidney show promise in their ability to decrease glucose reabsorption and increase glucose excretion. In particular, one of these compounds, canagliflozin, recently was approved by the US Food and Drug Administration. Despite such advances, the natural course of T2DM often eventually leads to the initiation of insulin therapy. A working knowledge of management guidelines, particularly concerning when and how to initiate monotherapies, combination therapies, and complex insulin regimens, is essential for optimal patient management. Insulin therapies should mimic normal physiologic levels of insulin through the use of both basal and bolus insulin analogues. Recognition of the various factors influencing therapeutic choices is also critical for improved patient management.

Japanese and North American Alzheimer's Disease Neuroimaging Initiative studies: Harmonization for international trials.

PubMed

Iwatsubo, Takeshi; Iwata, Atsushi; Suzuki, Kazushi; Ihara, Ryoko; Arai, Hiroyuki; Ishii, Kenji; Senda, Michio; Ito, Kengo; Ikeuchi, Takeshi; Kuwano, Ryozo; Matsuda, Hiroshi; Sun, Chung-Kai; Beckett, Laurel A; Petersen, Ronald C; Weiner, Michael W; Aisen, Paul S; Donohue, Michael C

2018-05-08

We conducted Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) and compared the basic characteristics and progression profiles with those of ADNI in North America. A total of 537 Japanese subjects with normal cognition, late amnestic mild cognitive impairment (LMCI), or mild Alzheimer's disease (AD) were enrolled using the same criteria as ADNI. Rates of changes in representative cognitive or functional measures were compared for amyloid positron emission tomography- or cerebrospinal fluid amyloid β(1-42)-positive LMCI and mild AD between J-ADNI and ADNI. Amyloid positivity rates were significantly higher in normal cognition of ADNI but at similar levels in LMCI and mild AD between J-ADNI and ADNI. Profiles of decline in cognitive or functional measures in amyloid-positive LMCI in J-ADNI (n = 75) and ADNI (n = 269) were remarkably similar, whereas those in mild AD were milder in J-ADNI (n = 73) compared with ADNI (n = 230). These results support the feasibility of bridging of clinical trials in the prodromal stage of AD between Asia and western countries. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Potential prostate cancer drug target: bioactivation of androstanediol by conversion to dihydrotestosterone.

PubMed

Mohler, James L; Titus, Mark A; Wilson, Elizabeth M

2011-09-15

High-affinity binding of dihydrotestosterone (DHT) to the androgen receptor (AR) initiates androgen-dependent gene activation, required for normal male sex development in utero, and contributes to prostate cancer development and progression in men. Under normal physiologic conditions, DHT is synthesized predominantly by 5α-reduction of testosterone, the major circulating androgen produced by the testis. During androgen deprivation therapy, intratumoral androgen production is sufficient for AR activation and prostate cancer growth, even though circulating testicular androgen levels are low. Recent studies indicate that the metabolism of 5α-androstane-3α, 17β-diol by 17β-hydroxysteroid dehydrogenase 6 in benign prostate and prostate cancer cells is a major biosynthetic pathway for intratumoral synthesis of DHT, which binds AR and initiates transactivation to promote prostate cancer growth during androgen deprivation therapy. Drugs that target the so-called backdoor pathway of DHT synthesis provide an opportunity to enhance clinical response to luteinizing-hormone-releasing hormone (LHRH) agonists or antagonists, AR antagonists, and inhibitors of 5α-reductase enzymes (finasteride or dutasteride), and other steroid metabolism enzyme inhibitors (ketoconazole or the recently available abiraterone acetate). ©2011 AACR.

Progesterone Therapy, Endothelial Function and Cardiovascular Risk Factors: A 3-Month Randomized, Placebo-Controlled Trial in Healthy Early Postmenopausal Women

PubMed Central

Prior, Jerilynn C.; Elliott, Thomas G.; Norman, Eric; Stajic, Vesna; Hitchcock, Christine L.

2014-01-01

Background Progesterone is effective treatment for hot flushes/night sweats. The cardiovascular effects of progesterone therapy are unknown but evidence suggests that premenopausal normal estradiol with also normal progesterone levels may provide later cardiovascular protection. We compared the effects of progesterone to placebo on endothelial function, weight, blood pressure, metabolism, lipids, inflammation and coagulation. Methods and Results We conducted a randomized, double-blind, 3-month placebo-controlled trial of progesterone (300 mg daily) among 133 healthy postmenopausal women in Vancouver, Canada from 2003–2009. Endothelial function by venous occlusion plethysmography was a planned primary outcome. Enrolled women were 1–11 y since last menstruation, not using hormones (for >6 months), non-smoking, without diabetes, hypertension, heart disease or their medications. Randomized (1∶1) women (55±4 years, body mass index 25±3) initially had normal blood pressure, fasting lipid, glucose and electrocardiogram results. Endothelial function (% forearm blood flow above saline) was not changed with progesterone (487±189%, n = 18) compared with placebo (408±278%, n = 16) (95% CI diff [−74 to 232], P = 0.30). Progesterone (n = 65) and placebo (n = 47) groups had similar changes in systolic and diastolic blood pressure, resting heart rate, weight, body mass index, waist circumference, total cholesterol, low-density lipoprotein cholesterol and triglyceride levels. High-density lipoprotein was lower (−0.14 mmol/L, P = 0.001) on progesterone compared with placebo. Fasting glucose, hs-C-reactive protein, albumin and D-dimer changes were all comparable to placebo. Framingham General Cardiovascular Risk Profile scores were initially low and remained low with progesterone therapy and not statistically different from placebo. Conclusions Results indicate that progesterone has short-term cardiovascular safety. Endothelial function, weight, blood pressure, waist circumference, inflammation and coagulation were unchanged as were lipids except for HDL-C. The statistically significant decrease in HDL-C levels was not clinically important (based on lack of Cardiovascular Risk Profile change). Trial Registration ClinicalTrials.gov NCT00152438 PMID:24465425

Trace elemental correlation study in malignant and normal breast tissue by PIXE technique

NASA Astrophysics Data System (ADS)

Raju, G. J. Naga; Sarita, P.; Kumar, M. Ravi; Murty, G. A. V. Ramana; Reddy, B. Seetharami; Lakshminarayana, S.; Vijayan, V.; Lakshmi, P. V. B. Rama; Gavarasana, Satyanarayana; Reddy, S. Bhuloka

2006-06-01

Particle induced X-ray emission technique was used to study the variations in trace elemental concentrations between normal and malignant human breast tissue specimens and to understand the effects of altered homeostasis of these elements in the etiology of breast cancer. A 3 MeV proton beam was used to excite the biological samples of normal and malignant breast tissues. The elements Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb and Sr were identified and their relative concentrations were estimated. Almost all the elements were found to be elevated (p < 0.05, Wilcoxon signed-ranks test) in the cancerous tissues when compared with normal tissues. The excess levels of trace elements observed in the cancerous breast tissues could either be a cause or a consequence of breast cancer. Regarding their role in the initiation or promotion of breast cancer, one possible interpretation is that the elevated levels of Cu, Fe and Cr could have led to the formation of free radicals or other reactive oxygen species (ROS) that adversely affect DNA thereby causing breast cancer, which is mainly attributed to genetic abnormalities. Moreover, since Cu and Fe are required for angiogenesis, elevated concentrations of these elements are likely to promote breast cancer by increasing the blood supply for tumor growth. On the other hand elevated concentrations of elements in breast cancer tissues might also be a consequence of the cancer. This can be understood in terms of the biochemical and histological differences between normal and cancerous breast tissues. Tumors, characterized by unregulated multiplication of cells, need an ever-increasing supply of essential nutrients including trace elements. This probably results in an increased vascularity of malignant tissues, which in turn leads to enhancement of elemental concentrations in tumors.

Impact of baseline body mass index status on glucose lowering and weight change during sitagliptin treatment for type 2 diabetics.

PubMed

Chen, Jung-Fu; Chang, Chih-Min; Kuo, Ming-Chun; Tung, Shih-Chen; Tsao, Cheng-Feng; Tsai, Chia-Jen

2016-10-01

This study was designed to evaluate the efficacy of sitagliptin in Taiwanese diabetic subjects with different baseline BMI status. This was a single-center, hospital-based, retrospective chart review in subjects (n=1874) with type 2 diabetes who received sitagliptin. Subjects were classified into subgroups depending upon their baseline BMI by Taiwan national weight classification: normal (BMI<24kg/m(2)) (n=504), overweight (BMI: 24-27kg/m(2)) (n=615), and obese (BMI⩾27kg/m(2)) (n=755). Changes in HbA1c and weight were evaluated over a 12month treatment period. For all three groups, the HbA1c levels declined over the first three months by about 8%, and subsequently plateaued for the next nine months. Obese subjects were slower in reducing HbA1c compared with normal and overweight subjects (P<0.05), but at nine months the reduction was similar across groups. Mean body weight increased over the first nine months of sitagliptin therapy in subjects with normal BMI (57.12-58.30kg), but there was no change in mean body weight in the overweight group. After three months the obese groups had significantly greater loss in body weight compared with the normal group. Baseline BMI status may influence the reduction of HbA1c levels within the first six months of sitagliptin therapy and affect weight change after three months. Being obese was associated with an initial lag in HbA1c reduction and greater weight loss compared with normal and overweight subjects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Calculation of Resistive Loads for Elastic Resistive Exercises.

PubMed

Picha, Kelsey; Uhl, Tim

2018-03-14

What is the correct resistive load to start resistive training with elastic resistance to gain strength? This question is typically answered by the clinician's best estimate and patient's level of discomfort without objective evidence. To determine the average level of resistance to initiate a strengthening routine with elastic resistance following isometric strength testing. Cohort. Clinical. 34 subjects (31 ± 13 y, 73 ± 17 kg, 170 ± 12 cm). The force produced was measured in Newtons (N) with an isometric dynamometer. The force distance was the distance from center of joint to location of force applied was measured in meters to calculate torque that was called "Test Torque" for the purposes of this report. This torque data was converted to "Exercise Load" in pounds based on the location where the resistance was applied, specifically the distance away from the center of rotation of the exercising limb. The average amount of exercise load as percentage of initial Test Torque for each individual for each exercise was recorded to determine what the average level of resistance that could be used for elastic resistance strengthening program. The percentage of initial test torque calculated for the exercise was recorded for each exercise and torque produced was normalized to body weight. The average percentage of maximal isometric force that was used to initiate exercises was 30 ± 7% of test torque. This provides clinicians with an objective target load to start elastic resistance training. Individual variations will occur but utilization of a load cell during elastic resistance provides objective documentation of exercise progression.

Initiation to street life: a qualitative examination of the physical, social, and psychological practices in becoming an accepted member of the street youth community in Western Kenya.

PubMed

Wachira, Juddy; Kamanda, Allan; Embleton, Lonnie; Naanyu, Violet; Winston, Susanna; Ayuku, David; Braitstein, Paula

2015-06-20

The objective of this study was to describe the physical, social, and psychological initiation practices of street connected children and youths, in Eldoret, western Kenya. This qualitative study was conducted from August 2013 to February 2014. A total of 65 SCCY aged 11-24 years were purposively sampled from the three referral points: 1) A dedicated study clinic for vulnerable children and youth at Moi Teaching and Referral Hospital (MTRH); 2) Primary locations in which street children reside "bases/barracks"; 3) Street youth community-based organizations. In-depth interviews and focus group discussions were used to collect data. All data were audio recorded, transcribed, translated to English, and a content analysis performed. The overall median age was 18 years (IQR 14-20.5 years) and 69.2% of participants were male. None had gone beyond primary level of education. The majority (81.5%) reported to be sexually active. The street community had well-defined structures and rules that were protective of members and ensured survival on the streets. To be fully accepted children had to go through an initiation ritual that had important gender differences. Common rituals between males and females included interrogation, smearing of black soot, and payment of tax. Ritual practices unique to boys were physical abuse, theft of personal possessions, volatile substance use, being forced to eat garbage, and sodomy among the physically weak. Rituals unique to girls were being forced to 'become a wife or sexual partner', rape, and gang rape. Physical and psychological abuse during initiation was normalized and there were no clear mechanisms of dealing with these forms of abuse. There were important gender differences in the initiation practices of SCCY. Normalization of physical and psychological abuse during initiation contributes to the high health risks faced by these SCCY. Appropriate interventions need to be developed in collaboration with SCCY.

Lyme disease presenting with facial palsy and myocarditis mimicking myocardial infarction.

PubMed

Gilson, Julieta; Khalighi, Koroush; Elmi, Farhad; Krishnamurthy, Mahesh; Talebian, Amirsina; Toor, Rubinder S

2017-01-01

A 45-year-old woman presented with a sudden episode of typical chest pain, radiating to her neck. The patient denied premature coronary artery disease in the family. Initial EKG showed normal sinus rhythm with a 1 mm ST-elevation involving lead II and lead aVF and a 1 mm ST-depression in lead V1 with associated T-wave inversion. Initial Troponin I (normal <0.4 ng/mL) and CK-MB (normal <7.7 ng/mL) were elevated at 7.82 ng/mL and 55.2 ng/mL, respectively. Six hours later, Troponin I increased to 13.44 ng/mL and CK-MB to 75.7 ng/mL. The patient underwent cardiac catheterization which did not show any significant obstructive coronary artery disease. Two days later the patient developed right-sided facial palsy. Diagnosis of Lyme disease was confirmed by ELISA with positive IgM and IgG antibodies. Treatment with intravenous ceftriaxone and oral steroids was started. Eventually resolution of symptoms and, normalization of cardiac markers and EKG changes, were achieved. This is a rare case of Lyme myocarditis associated with markedly elevated Troponin I, normal left ventricle function, and an absence of conduction abnormalities. To the best of our knowledge, Lyme myocarditis mimicking acute coronary syndrome with such high levels of Troponin I and neurologic compromise has not been previously described. Lyme myocarditis may be a challenging diagnosis in endemic areas especially in patients with coronary artery disease risk factors, presenting with typical chest pain, EKG changes and positive cardiac biomarkers. Therefore, it should be considered a differential diagnosis in patients presenting with clinical symptoms suggestive of acute coronary syndrome. Abbreviations AV: Atrioventricular; CK-MB: Creatinine Kinase-MB; EKG: Electrocardiogram; ELISA: Enzyme-Linked Immunosorbent Assay; IgG: Immunoglobulin G; IgM: Immunoglobulin M.

Sample entropy predicts lifesaving interventions in trauma patients with normal vital signs.

PubMed

Naraghi, L; Mejaddam, A Y; Birkhan, O A; Chang, Y; Cropano, C M; Mesar, T; Larentzakis, A; Peev, M; Sideris, A C; Van der Wilden, G M; Imam, A M; Hwabejire, J O; Velmahos, G C; Fagenholz, P J; Yeh, D; de Moya, M A; King, D R

2015-08-01

Heart rate complexity, commonly described as a "new vital sign," has shown promise in predicting injury severity, but its use in clinical practice is not yet widely adopted. We previously demonstrated the ability of this noninvasive technology to predict lifesaving interventions (LSIs) in trauma patients. This study was conducted to prospectively evaluate the utility of real-time, automated, noninvasive, instantaneous sample entropy (SampEn) analysis to predict the need for an LSI in a trauma alert population presenting with normal vital signs. Prospective enrollment of patients who met criteria for trauma team activation and presented with normal vital signs was conducted at a level I trauma center. High-fidelity electrocardiogram recording was used to calculate SampEn and SD of the normal-to-normal R-R interval (SDNN) continuously in real time for 2 hours with a portable, handheld device. Patients who received an LSI were compared to patients without any intervention (non-LSI). Multivariable analysis was performed to control for differences between the groups. Treating clinicians were blinded to results. Of 129 patients enrolled, 38 (29%) received 136 LSIs within 24 hours of hospital arrival. Initial systolic blood pressure was similar in both groups. Lifesaving intervention patients had a lower Glasgow Coma Scale. The mean SampEn on presentation was 0.7 (0.4-1.2) in the LSI group compared to 1.5 (1.1-2.0) in the non-LSI group (P < .0001). The area under the curve with initial SampEn alone was 0.73 (95% confidence interval [CI], 0.64-0.81) and increased to 0.93 (95% CI, 0.89-0.98) after adding sedation to the model. Sample entropy of less than 0.8 yields sensitivity, specificity, negative predictive value, and positive predictive value of 58%, 86%, 82%, and 65%, respectively, with an overall accuracy of 76% for predicting an LSI. SD of the normal-to-normal R-R interval had no predictive value. In trauma patients with normal presenting vital signs, decreased SampEn is an independent predictor of the need for LSI. Real-time SampEn analysis may be a useful adjunct to standard vital signs monitoring. Adoption of real-time, instantaneous SampEn monitoring for trauma patients, especially in resource-constrained environments, should be considered. Copyright © 2015 Elsevier Inc. All rights reserved.

Manganese intoxication: the cause of an inexplicable epileptic syndrome in a 3 year old child.

PubMed

Herrero Hernandez, Elena; Discalzi, Gianluigi; Dassi, Patrizia; Jarre, Laura; Pira, Enrico

2003-08-01

Excess manganese (Mn) can cause several neurotoxic effects, however only a few studies have reported epileptic syndromes related to manganese intoxication. We describe an epileptic syndrome due to manganese intoxication in a 3 year old male child. His blood manganese was elevated, but no other abnormal values or toxic substances were found in blood or urine. The electroencephalogram (EEG) showed a picture of progressive encephalopathy, while brain magnetic resonance was normal. The patient's conditions rapidly worsened to epileptic status despite the use of antiepileptic drugs. Chelating treatment with CaNa(2)EDTA was initiated to remove excess manganese and promptly succeeded in reverting epileptic symptoms. Concurrently, manganese blood levels and electroencephalogram progressively normalized. Thereafter it has been possible to discontinue antiepileptic treatment, and the patient remains in excellent conditions without any treatment.

Predictors of recurrence in pheochromocytoma.

PubMed

Press, Danielle; Akyuz, Muhammet; Dural, Cem; Aliyev, Shamil; Monteiro, Rosebel; Mino, Jeff; Mitchell, Jamie; Hamrahian, Amir; Siperstein, Allan; Berber, Eren

2014-12-01

The recurrence rate of pheochromocytoma after adrenalectomy is 6.5-16.5%. This study aims to identify predictors of recurrence and optimal biochemical testing and imaging for detecting the recurrence of pheochromocytoma. In this retrospective study we reviewed all patients who underwent adrenalectomy for pheochromocytoma during a 14-year period at a single institution. One hundred thirty-five patients had adrenalectomy for pheochromocytoma. Eight patients (6%) developed recurrent disease. The median time from initial operation to diagnosis of recurrence was 35 months. On multivariate analysis, tumor size >5 cm was an independent predictor of recurrence. One patient with recurrence died, 4 had stable disease, 2 had progression of disease, and 1 was cured. Recurrence was diagnosed by increases in plasma and/or urinary metanephrines and positive imaging in 6 patients (75%), and by positive imaging and normal biochemical levels in 2 patients (25%). Patients with large tumors (>5 cm) should be followed vigilantly for recurrence. Because 25% of patients with recurrence had normal biochemical levels, we recommend routine imaging and testing of plasma or urinary metanephrines for prompt diagnosis of recurrence. Copyright © 2014 Elsevier Inc. All rights reserved.

Espousing melodic intonation therapy in aphasia rehabilitation: a case study.

PubMed

Goldfarb, R; Bader, E

1979-01-01

A program of Melodic Intonation Therapy (MIT) was adapted as a home training procedure to enable a severely affected aphasic adult to respond to 52 simple questions bearing relevance to his daily life. MIT involves embedding short phrases or sentences in a simple, non-distinct melody pattern. As the patient progresses through the program, the melodic aspect is faded and the program eventually leads to production of the target phrase or sentence in normal speech prosody. The present procedure consisted of three levels of training designed to advance the subject from an initial level of intoning responses in a simple melody to producing the responses in normal speech prosody. The subject's wife was trained to administer MIT both in the clinical and home settings. Considerable improvement was obtained in imitation and in context related responses to questions. These findings lend support to the proposal that the music dominance to the right hemisphere assists, and perhaps diminishes the language dominance of, the damaged left hemisphere. The limitations of use of Melodic Intonation Therapy were discussed.

On a Heat Exchange Problem under Sharply Changing External Conditions

NASA Astrophysics Data System (ADS)

Khishchenko, K. V.; Charakhch'yan, A. A.; Shurshalov, L. V.

2018-02-01

The heat exchange problem between carbon particles and an external environment (water) is stated and investigated based on the equations of heat conducting compressible fluid. The environment parameters are supposed to undergo large and fast variations. In the time of about 100 μs, the temperature of the environment first increases from the normal one to 2400 K, is preserved at this level for about 60 μs, and then decreases to 300 K during approximately 50 μs. At the same periods of time, the pressure of the external environment increases from the normal one to 67 GPa, is preserved at this level, and then decreases to zero. Under such external conditions, the heating of graphite particles of various sizes, their phase transition to the diamond phase, and the subsequent unloading and cooling almost to the initial values of the pressure and temperature without the reverse transition from the diamond to the graphite phase are investigated. Conclusions about the maximal size of diamond particles that can be obtained in experiments on the shock compression of the mixture of graphite with water are drawn.

Retinal degeneration in cats fed casein. IV. The early receptor potential.

PubMed

Berson, E L; Watson, G; Grasse, K L; Szamier, R B

1981-08-01

Electroretinographic studies of casein-fed cats with retinal taurine deficiency revealed that the early receptor potential (ERP) was initially normal in amplitude at a time when the a-wave and b-wave of the electroretinogram were substantially reduced or even nondetectable. The preserved ERP's in these taurine-deficient cats could be correlated with the histologic finding that their outer segments were relatively intact over 90% of the retinal area subtended by the test flash. The sequence of electroretinographic changes in these taurine-deficient cats was also consistent with previous biochemical studies on the normal cat retina that have shown a relatively low concentration of taurine at the level of the outer segments and a higher concentration at the level of the inner segments. The responses in early stages from taurine-deficient cats differed from the responses obtained from vitamin A--deficient cats but resembled those from cats that received an intravitreal injection of ouabain. Similarities and a difference between the responses of taurine-deficient cats and those of patients with early retinitis pigmentosa are considered.

Ice Action on Pairs of Cylindrical and Conical Structures,

DTIC Science & Technology

1983-09-01

correlation because the forces generated ficult to pick a distinct peak in the autospectra for between the structure and the ice sheet are af- the...against two conical structures ...... 20 24. Normalized maximum ice force versus ice velocity ................. 20 25. Normalized initial peak force...versus ice velocity .................. 21 26. Ratio of initial peak ice force to theoretical ice force versus ratio of center-to-center distance

Elevation of CSF tumor necrosis factor alpha levels in new daily persistent headache and treatment refractory chronic migraine.

PubMed

Rozen, Todd; Swidan, Sahar Z

2007-01-01

To determine if patients with new daily persistent headache (NDPH) have elevated levels of tumor necrosis factor alpha (TNF alpha) in the CSF. NDPH is considered one of the most treatment resistant of all headache syndromes. This reflects a lack of understanding of its pathogenesis. As a certain percentage of NDPH patients have their headaches start after an infection, the possibility of a persistent state of systemic or CNS inflammation comes into question. TNF alpha is a proinflammatory cytokine involved in brain immune and inflammatory activities, as well as in pain initiation. The goal of this study was to look at TNF alpha levels in the CSF of NDPH patients, to determine if CNS inflammation may play some role in the pathogenesis of this condition. CSF TNF alpha levels were studied in 38 patients: 20 with NDPH and a control population of 16 patients with chronic migraine (CM), and 2 with post-traumatic headache (PT). CSF TNF alpha levels were elevated in 19 of 20 NDPH patients, 16 of 16 CM patients, and both PT patients. Serum TNF alpha levels were normal in most of the study subjects. An elevation of CSF TNF alpha levels was found in almost all NDPH patients and suggest a role for TNF alpha in the pathogenesis of this condition. Surprisingly, all CM and PT patients tested had elevated CSF TNF alpha levels. In most patients with elevated CSF levels, serum TNF alpha levels were normal. All of these syndromes may be manifestations of CNS inflammation. As most of the positive-tested patients showed minimal to no improvement during aggressive inpatient treatment, persistent elevation of CSF TNF alpha levels may be one of the causes of treatment refractory CDH.

Organ distribution of 13N following intravenous injection of [13N]ammonia into portacaval-shunted rats

PubMed Central

Cruz, Nancy F.; Dienel, Gerald A.; Patrick, Tricia A.; Cooper, Arthur J. L.

2016-01-01

Ammonia is neurotoxic, and chronic hyperammonemia is thought to be a major contributing factor to hepatic encephalopathy in patients with liver disease. Portacaval shunting of rats is used as an animal model to study the detrimental metabolic effects of elevated ammonia levels on body tissues, particularly brain and testes that are deleteriously targeted by high blood ammonia. In normal adult rats, the initial uptake of label (expressed as relative concentration) in these organs was relatively low following a bolus intravenous injection of [13N]ammonia compared with lungs, kidneys, liver, and some other organs. The objective of the present study was to determine the distribution of label following intravenous administration of [13N]ammonia among 14 organs in portacaval-shunted rats at 12 weeks after shunt construction. At an early time point (12 sec) following administration of [13N]ammonia the relative concentration of label was highest in lung with lower, but still appreciable relative concentrations in kidney and heart. Clearance of 13N from blood and kidney tended to be slower in portacaval-shunted rats versus normal rats during the 2–10 min interval after the injection. At later times post injection, brain and testes tended to have higher-than-normal 13N levels, whereas many other tissues had similar levels in both groups. Thus, reduced removal of ammonia from circulating blood by the liver diverts more ammonia to extrahepatic tissues, including brain and testes, and alters the nitrogen homeostasis in these tissues. These results emphasize the importance of treatment paradigms designed to reduce blood ammonia levels in patients with liver disease. PMID:27822667

Organ Distribution of 13N Following Intravenous Injection of [13N]Ammonia into Portacaval-Shunted Rats.

PubMed

Cruz, Nancy F; Dienel, Gerald A; Patrick, Patricia A; Cooper, Arthur J L

2017-06-01

Ammonia is neurotoxic, and chronic hyperammonemia is thought to be a major contributing factor to hepatic encephalopathy in patients with liver disease. Portacaval shunting of rats is used as an animal model to study the detrimental metabolic effects of elevated ammonia levels on body tissues, particularly brain and testes that are deleteriously targeted by high blood ammonia. In normal adult rats, the initial uptake of label (expressed as relative concentration) in these organs was relatively low following a bolus intravenous injection of [ 13 N]ammonia compared with lungs, kidneys, liver, and some other organs. The objective of the present study was to determine the distribution of label following intravenous administration of [ 13 N]ammonia among 14 organs in portacaval-shunted rats at 12 weeks after shunt construction. At an early time point (12 s) following administration of [ 13 N]ammonia the relative concentration of label was highest in lung with lower, but still appreciable relative concentrations in kidney and heart. Clearance of 13 N from blood and kidney tended to be slower in portacaval-shunted rats versus normal rats during the 2-10 min interval after the injection. At later times post injection, brain and testes tended to have higher-than-normal 13 N levels, whereas many other tissues had similar levels in both groups. Thus, reduced removal of ammonia from circulating blood by the liver diverts more ammonia to extrahepatic tissues, including brain and testes, and alters the nitrogen homeostasis in these tissues. These results emphasize the importance of treatment paradigms designed to reduce blood ammonia levels in patients with liver disease.

Thyrotropin-producing pituitary adenoma simultaneously existing with Graves' disease: a case report.

PubMed

Arai, Nobuhiko; Inaba, Makoto; Ichijyo, Takamasa; Kagami, Hiroshi; Mine, Yutaka

2017-01-06

Thyrotropin-producing pituitary tumor is relatively rare. In particular, concurrent cases associated with Graves' disease are extremely rare and only nine cases have been reported so far. We describe a case of a thyrotropin-producing pituitary adenoma concomitant with Graves' disease, which was successfully treated. A 40-year-old Japanese woman presented with mild signs of hyperthyroidism. She had positive anti-thyroid-stimulating hormone receptor antibody, anti-thyroglobulin antibody, and anti-thyroid peroxidase antibody. Her levels of serum thyroid-stimulating hormone, which ranged from low to normal in the presence of high levels of serum free thyroid hormones, were considered to be close to a state of syndrome of inappropriate secretion of thyroid-stimulating hormone. Magnetic resonance imaging showed a macropituitary tumor. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease was suspected. Initial therapy included anti-thyroid medication, which was immediately discontinued due to worsening symptoms. Subsequently, surgical therapy for the pituitary tumor was conducted, and her levels of free thyroid hormones, including the thyroid-stimulating hormone, became normal. On postoperative examination, her anti-thyroid-stimulating hormone receptor antibody levels decreased, and the anti-thyroglobulin antibody became negative. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease is rarely reported. The diagnosis of this condition is complicated, and the appropriate treatment strategy has not been clearly established. This case suggests that physicians should consider the coexistence of thyrotropin-producing pituitary adenoma with Graves' disease in cases in which thyroid-stimulating hormone values range from low to normal in the presence of thyrotoxicosis, and the surgical treatment of thyrotropin-producing pituitary adenoma could be the first-line therapy in patients with both thyrotropin-producing pituitary adenoma and Graves' disease.

Elevated Cell Wall Chitin in Candida albicans Confers Echinocandin Resistance In Vivo

PubMed Central

Lee, Keunsook K.; MacCallum, Donna M.; Jacobsen, Mette D.; Walker, Louise A.; Odds, Frank C.

2012-01-01

Candida albicans cells with increased cell wall chitin have reduced echinocandin susceptibility in vitro. The aim of this study was to investigate whether C. albicans cells with elevated chitin levels have reduced echinocandin susceptibility in vivo. BALB/c mice were infected with C. albicans cells with normal chitin levels and compared to mice infected with high-chitin cells. Caspofungin therapy was initiated at 24 h postinfection. Mice infected with chitin-normal cells were successfully treated with caspofungin, as indicated by reduced kidney fungal burdens, reduced weight loss, and decreased C. albicans density in kidney lesions. In contrast, mice infected with high-chitin C. albicans cells were less susceptible to caspofungin, as they had higher kidney fungal burdens and greater weight loss during early infection. Cells recovered from mouse kidneys at 24 h postinfection with high-chitin cells had 1.6-fold higher chitin levels than cells from mice infected with chitin-normal cells and maintained a significantly reduced susceptibility to caspofungin when tested in vitro. At 48 h postinfection, caspofungin treatment induced a further increase in chitin content of C. albicans cells harvested from kidneys compared to saline treatment. Some of the recovered clones had acquired, at a low frequency, a point mutation in FKS1 resulting in a S645Y amino acid substitution, a mutation known to confer echinocandin resistance. This occurred even in cells that had not been exposed to caspofungin. Our results suggest that the efficacy of caspofungin against C. albicans was reduced in vivo due to either elevation of chitin levels in the cell wall or acquisition of FKS1 point mutations. PMID:21986821

Higher Ratio of Serum Alpha-Fetoprotein Could Predict Outcomes in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma and Normal Alanine Aminotransferase

PubMed Central

Park, Joong-Won

2016-01-01

Background The role of serum alpha-fetoprotein (AFP) levels in the surveillance and diagnosis of hepatocellular carcinoma (HCC) is controversial. The aim of this study was to investigate the value of serially measured serum AFP levels in HCC progression or recurrence after initial treatment. Methods A total of 722 consecutive patients newly diagnosed with HCC and treated at the National Cancer Center, Korea, between January 2004 and December 2009 were enrolled. The AFP ratios between 4–8 weeks post-treatment and those at the time of HCC progression or recurrence were obtained. Multivariate logistic regression analysis was performed to correlate the post-treatment AFP ratios with the presence of HCC progression or recurrence. Results The etiology of HCC was related to chronic hepatitis B virus (HBV) infection in 562 patients (77.8%), chronic hepatitis C virus (HCV) infection in 74 (10.2%), and non-viral cause in 86 (11.9%). There was a significant decrease in serum AFP levels from the baseline to 4 to 8 weeks after treatment (median AFP, 319.6 ng/mL vs. 49.6 ng/mL; p< 0.001). Multivariate analysis showed that an AFP ratio > 1.0 was an independently associated with HCC progression or recurrence. Among the different causes of HCC analyzed, this association was significant only for HCC related to chronic hepatitis B (p< 0.001) and non-viral causes (p<0.05), and limited only to patients who had normal alanine aminotransferase (ALT) levels. Conclusion Serial measurements of serum AFP ratios could be helpful in detecting progression or recurrence in treated patients with HBV-HCC and normal ALT. PMID:27304617

MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation

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

Yasuda, Kazuyo; Hirohashi, Yoshihiko, E-mail: hirohash@sapmed.ac.jp; Kuroda, Takafumi

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as small subpopulation of cancer cells that are endowed with higher tumor-initiating ability. CSCs/CICs are resistant to standard cancer therapies including chemotherapy and radiotherapy, and they are thus thought to be responsible for cancer recurrence and metastasis. Therefore, elucidation of molecular mechanisms of CSCs/CICs is essential to cure cancer. In this study, we analyzed the gene expression profiles of gynecological CSCs/CICs isolated as aldehyde dehydrogenase high (ALDH{sup high}) cells, and found that MAPK13, PTTG1IP, CAPN1 and UBQLN2 were preferentially expressed in CSCs/CICs. MAPK13 is expressed in uterine, ovary, stomach, colon, liver andmore » kidney cancer tissues at higher levels compared with adjacent normal tissues. MAPK13 gene knockdown using siRNA reduced the ALDH{sup high} population and abrogated the tumor-initiating ability. These results indicate that MAPK13 is expressed in gynecological CSCs/CICs and has roles in the maintenance of CSCs/CICs and tumor-initiating ability, and MAPK13 might be a novel molecular target for treatment-resistant CSCs/CICs.« less

Feasibility of Optical Transition Radiation Imaging for Laser-driven Plasma Accelerator Electron-Beam Diagnostics

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

Lumpkin, A. H.; Rule, D. W.; Downer, M. C.

We report the initial considerations of using linearly polarized optical transition radiation (OTR) to characterize the electron beams of laser plasma accelerators (LPAs) such as at the Univ. of Texas at Austin. The two LPAs operate at 100 MeV and 2-GeV, and they currently have estimated normalized emittances at ~ 1-mm mrad regime with beam divergences less than 1/γ and beam sizes to be determined at the micron level. Analytical modeling results indicate the feasibility of using these OTR techniques for the LPA applications.

Effect of varying ventricular function by extrasystolic potentiation on closure of the mitral valve.

NASA Technical Reports Server (NTRS)

Vandenberg, R. A.; Williams, J. C. P.; Sturm, R. E.; Wood , E. H.

1971-01-01

Mitral regurgitant indexes were measured by roentgen videodensitometry in anesthetized dogs without thoracotomy before, during and after extrasystolic potentiation of ventricular contraction while the atria and ventricles were driven in normal temporal sequence simultaneously or in such a way as to induce atrial fibrillation. Small amounts of mitral reflux were observed with simultaneous atrial and ventricular driving and with atrial fibrillation in the control measurements before initiation of extrasystolic potentiation. Reflux became negligible during extrasystolic potentiation and increased beyond control levels after termination of extrasystolic potentiation.

Controlled-release tablet formulation of isoniazid.

PubMed

Jain, N K; Kulkarni, K; Talwar, N

1992-04-01

Guar (GG) and Karaya gums (KG) alone and in combination with hydroxy-propylmethylcellulose (HPMC) were evaluated as release retarding materials to formulate a controlled-release tablet dosage form of isoniazid (1). In vitro release of 1 from tablets followed non-Fickian release profile with rapid initial release. Urinary excretion studies in normal subjects showed steady-state levels of 1 for 13 h. In vitro and in vivo data correlated (r = 0.9794). The studies suggested the potentiality of GG and KG as release retarding materials in formulating controlled-release tablet dosage forms of 1.

Initial Results from the Variable Intensity Sonic Boom Propagation Database

NASA Technical Reports Server (NTRS)

Haering, Edward A., Jr.; Cliatt, Larry J., II; Bunce, Thomas J.; Gabrielson, Thomas B.; Sparrow, Victor W.; Locey, Lance L.

2008-01-01

An extensive sonic boom propagation database with low- to normal-intensity booms (overpressures of 0.08 lbf/sq ft to 2.20 lbf/sq ft) was collected for propagation code validation, and initial results and flight research techniques are presented. Several arrays of microphones were used, including a 10 m tall tower to measure shock wave directionality and the effect of height above ground on acoustic level. A sailplane was employed to measure sonic booms above and within the atmospheric turbulent boundary layer, and the sailplane was positioned to intercept the shock waves between the supersonic airplane and the ground sensors. Sailplane and ground-level sonic boom recordings were used to generate atmospheric turbulence filter functions showing excellent agreement with ground measurements. The sonic boom prediction software PCBoom4 was employed as a preflight planning tool using preflight weather data. The measured data of shock wave directionality, arrival time, and overpressure gave excellent agreement with the PCBoom4-calculated results using the measured aircraft and atmospheric data as inputs. C-weighted acoustic levels generally decreased with increasing height above the ground. A-weighted and perceived levels usually were at a minimum for a height where the elevated microphone pressure rise time history was the straightest, which is a result of incident and ground-reflected shock waves interacting.

Normal sensory and range of motion (ROM) responses during Thoracic Slump Test (ST) in asymptomatic subjects.

PubMed

Joshi, Ketaki C; Eapen, Charu; Kumar, Senthil P

2013-02-01

The purpose of the study was to determine the normal sensory and range of motion (ROM) responses during the movement components of Thoracic Slump Test (Thoracic ST) in asymptomatic subjects. Sixty asymptomatic subjects were included in the study. Thoracic ST was performed in two sequences, proximal initiation, which was proximal to distal and distal initiation, which was distal to proximal. Subjects were randomized into four groups depending on the order of sequences and sides. Outcome measures of sensory responses (intensity, type, and location) and ROM responses were recorded after each sequence. Friedman's test was done to compare between sensory responses of the subjects. Between-component comparison for prevalence of sensory responses within each sequence was done using Kruskal-Wallis test and Wilcoxonsigned ranks test was used for between-component comparisons of intensity of symptoms within each sequence of testing. Independent t test was used to assess the ROM responses. Results show the prevalence of sensory responses, its nature, area and intensity. These sensory and ROM responses may be considered as normal response of Thoracic ST. The intensity of the symptoms of proximal initiation sequence (1.09±1.35 cm) was significant (P<0.05) when compared to distal initiation sequence (0.08±1.26 cm). The change in the ROM was significant (P<0.05) for distal initiation (7.55±4.51 degrees) when compared to proximal initiation (4.96±3.76 degrees). These normal responses may be used as a reference when using the Thoracic ST as an assessment technique.

Normal sensory and range of motion (ROM) responses during Thoracic Slump Test (ST) in asymptomatic subjects

PubMed Central

Joshi, Ketaki C; Eapen, Charu; Kumar, Senthil P

2013-01-01

The purpose of the study was to determine the normal sensory and range of motion (ROM) responses during the movement components of Thoracic Slump Test (Thoracic ST) in asymptomatic subjects. Sixty asymptomatic subjects were included in the study. Thoracic ST was performed in two sequences, proximal initiation, which was proximal to distal and distal initiation, which was distal to proximal. Subjects were randomized into four groups depending on the order of sequences and sides. Outcome measures of sensory responses (intensity, type, and location) and ROM responses were recorded after each sequence. Friedman’s test was done to compare between sensory responses of the subjects. Between-component comparison for prevalence of sensory responses within each sequence was done using Kruskal–Wallis test and Wilcoxonsigned ranks test was used for between-component comparisons of intensity of symptoms within each sequence of testing. Independent t test was used to assess the ROM responses. Results show the prevalence of sensory responses, its nature, area and intensity. These sensory and ROM responses may be considered as normal response of Thoracic ST. The intensity of the symptoms of proximal initiation sequence (1.09±1.35 cm) was significant (P<0.05) when compared to distal initiation sequence (0.08±1.26 cm). The change in the ROM was significant (P<0.05) for distal initiation (7.55±4.51 degrees) when compared to proximal initiation (4.96±3.76 degrees). These normal responses may be used as a reference when using the Thoracic ST as an assessment technique. PMID:24421610

Regulatory Effect of Low-Intensity Optical Radiation on Oxygenation of Blood Irradiated In Vivo and Metabolic Processes

NASA Astrophysics Data System (ADS)

Zalesskaya, G. A.; Laskina, O. V.

2016-03-01

For three series of blood samples, we have studied the effect of therapeutic doses of low-intensity optical radiation (LOR) on oxygenation parameters of blood irradiated in vivo, and also on the levels of some metabolites: lactate, glucose, cholesterol. The quality of blood oxygenation was assessed using three parameters: the partial pressure of oxygen pVO2, the oxygen saturation of hemoglobin SVO2, and the oxygen level in arterial and venous blood, varying under the influence of low-intensity optical radiation due to photodissociation of hemoglobin/ligand complexes. We have established that during photohemotherapy (PHT), including extracorporeal, supravascular, and intravenous blood irradiation, positive changes occur in the oxygenation parameters and the metabolite levels, while after the courses of PHT have been completed, the individual changes in such parameters in individual patients were both positive and negative. The regulatory effect of PHT was apparent in the tendency toward a decrease in high initial values and an increase in low initial values both for the oxygenation parameters and for the metabolites; but at the doses recommended for use, PHT had a regulatory but still not a normalizing effect.

NEURO-GUMORALE SUBSTANCES OF DOG BLOOD DURING ACUTE RADIATION SICKNESS. I. CHANGES IN BLOOD ACETYLCHOLINE AND CHOLINESTERASE SYSTEM (in Russian)

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

Kuznetzova, N.E.

1963-01-01

Experiments carried out on 13 male dogs, 2 to 5 years old and weighing 10 to 20 kg, showed that in the initial stages of chroric radiation sickness the blood content of acetylcholine increased and the cholinesterase decreased. Moreove r, the increase in the acetylcholine level during the first 3 to 4 hrs proceeded at a greater rate than the cholinesterase decrease. Shifts in the enzyme system were more pronounced in dogs with greater resistance. However, during the recovery period acetylcholine and cholinesterase restoration took place at earlier periods in dogs with higher resistance. Not only was the cholinesterase activitymore » restored, but it increased to 1.5 to 2 times the initial level. The level of acetylcholine and cholinesterase was not restored in the blood of dogs during terminal periods. In dogs exposed to subacute doses, 300 r, enzyme normalization took place 29 to 41 days following exposure. Correlation of data on enzyme changes in single and chronic exposures indicated identical trends It was postulated that acetylcholine -cholinesterase participate in compensating reactions of organisms during radiation sickness. (R.V.J.)« less

Hypoglycemia incidence and risk factors assessment in hospitalized neonates.

PubMed

Zhou, Wei; Yu, Jun; Wu, Yiqi; Zhang, Huawei

2015-03-01

To assess the incidence and risk factors of hypoglycemia in hospitalized neonates in China. Blood glucose level in hospitalized neonates was monitored routinely. Also, in high-risk newborns and neonates with abnormal blood glucose levels in initial detection, the blood sugar level was monitored daily until it was back to normal and stable. Hypoglycemia was detected in 113 out of 668 hospitalized neonates, and the incidence of hypoglycemia was 16.9%. The statistical analysis also showed that hypoglycemia always occurred within one week after birth, especially within three days after birth. Neonates with premature birth, low birth weight and perinatal asphyxia were susceptible to hypoglycemia. Active and continuous monitoring of blood glucose level should be performed in the early newborns, especially in high-risk children, and attention should be paid to timely feeding for the early diagnosis and treatment of neonatal hypoglycemia to reduce its impact on the newborns.

A case of probable labetalol induced hyperkalaemia in pre-eclampsia.

PubMed

Thomas, Binny; Abdul Rouf, P V; El Kassem, Wessam; Al Hail, Moza; Stewart, Derek; Tharannum, Asma; Ahmed, Afif; Al Saadi, Muna

2014-12-01

Hyperkalemia can cause altered cardiac electrical conduction resulting in death. We describe a case of a 23-year old pregnant patient who presented with severe epigastric pain and vomiting. She was severely pre- eclamptic and received initial treatment with intravenous labetalol and decision was taken to deliver. She quickly became hyperkalaemic (serum potassium level 6.4 mmol/L) and labetalol was discontinued and intravenous hydralazine commenced. Post-surgery, her potassium levels were normal but due to rapidly rising blood pressure labetalol was recommenced, resulting in elevated potassium levels. Labetolol was discontinued, hydralazine prescribed, and potassium levels normalised. The adverse reaction was classified as 'probably' due to labetolol using the Naranjo Adverse Drug Reaction scale. This is the first reported case of labetolol induced hyperkalaemia in pregnancy, with life threatening consequences and hence all health professionals should be alert to this potential effect.

Influence of the Timing of Antiretroviral Therapy on the Potential for Normalization of Immune Status in Human Immunodeficiency Virus 1–Infected Individuals

PubMed Central

Okulicz, Jason F.; Le, Tuan D.; Agan, Brian K.; Camargo, Jose F.; Landrum, Michael L.; Wright, Edwina; Dolan, Matthew J.; Ganesan, Anuradha; Ferguson, Tomas M.; Smith, Davey M.; Richman, Douglas D.; Little, Susan J.; Clark, Robert A.; He, Weijing; Ahuja, Sunil K.

2014-01-01

IMPORTANCE In individuals with human immunodeficiency virus 1 (HIV-1) infection who are receiving antiretroviral therapy (ART), factors that promote full immune recovery are not well characterized. OBJECTIVE To investigate the influence of the timing of ART relative to HIV-1 infection on normalization of CD4+ T-cell counts, AIDS risk, and immune function. DESIGN, SETTING, AND PARTICIPANTS Participants in the observational US Military HIV Natural History Study with documented estimated dates of seroconversion (EDS) who achieved virologic suppression with ART were evaluated. Markers indicative of immune activation, dysfunction, and responsiveness were determined. Responses to hepatitis B virus (HBV) vaccine, an indicator of in vivo immune function, were also assessed. The timing of ART was indexed to the EDS and/or entry into the cohort. The CD4+ counts in HIV-1–uninfected populations were surveyed. MAIN OUTCOMES AND MEASURES Normalization of CD4+ counts to 900 cells/μL or higher, AIDS development, HBV vaccine response, as well as T-cell activation, dysfunction, and responsiveness. RESULTS The median CD4+ count in HIV-1–uninfected populations was approximately 900 cells/μL. Among 1119 HIV-1–infected participants, CD4+ normalization was achieved in 38.4% vs 28.3% of those initiating ART within 12 months vs after 12 months from the EDS (P = .001). Incrementally higher CD4+ recovery (<500,500–899, and ≥900 cells/μL) was associated with stepwise decreases in AIDS risk and reversion of markers of immune activation, dysfunction, and responsiveness to levels approximating those found in HIV-1–uninfected persons. Participants with CD4+ counts of 500 cells/μL or higher at study entry (adjusted odds ratio [aOR], 2.00; 95% CI, 1.51–2.64; P < .001) or ART initiation (aOR, 4.08; 95% CI, 3.14–5.30; P < .001) had significantly increased CD4+ normalization rates compared with other participants. However, even among individuals with a CD4+ count of 500 cells/μL or higher at both study entry and before ART, the odds of CD4+ normalization were 80% lower in those initiating ART after 12 months from the EDS and study entry (aOR, 0.20; 95% CI, 0.07–0.53; P = 001). Initiation of ART within 12 months of EDS vs later was associated with a significantly lower risk of AIDS (7.8% vs 15.3%; P = .002), reduced T-cell activation (percent CD4+HLA-DR+ effector memory T cells, 12.0% vs 15.6%; P = .03), and increased responsiveness to HBV vaccine (67.9% vs 50.9%; P = .07). CONCLUSIONS AND RELEVANCE Deferral of ART beyond 12 months of the EDS diminishes the likelihood of restoring immunologic health in HIV-1–infected individuals. PMID:25419650

Empirical Research on Ecological Development Level of Resource-based Industries-Base on the data of the Silk Road Economic Belt Core Zone

NASA Astrophysics Data System (ADS)

Wang, Lei; Yan, Min

2017-11-01

Industrial ecology is the epitome of sustainable development in industry level, is one effective gateway to realizing green transformation. On the basis of industrial ecology development, including resource efficiency and environmental efficiency of ecological evaluation index system, this paper evaluates the level of industrial ecology development of resource-based industries in Xinjiang using entropy method. Research shows that the overall ecological development level of resource-based industries has remained at continuous improved trend with slow improvement in resource efficiency, and relative faster improvement in environmental efficiency. With economic development entering into the period of new normal at the end of the “twelfth five year plan”, the resource efficiency of ecological development of resource-based industries demonstrated a downward trend. The overall level of industrial ecology also faced with certain fluctuations, various ecological development level of resource-based industries also presented a downward trend. To promote ecological development of resource-based industries in Xinjiang, countermeasures and suggestions are initiated.

40 CFR 68.52 - Operating procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Initial startup; (2) Normal operations; (3) Temporary operations; (4) Emergency shutdown and operations; (5) Normal shutdown; (6) Startup following a normal or emergency shutdown or a major change that... are updated, if necessary, whenever a major change occurs and prior to startup of the changed process. ...

40 CFR 68.52 - Operating procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Initial startup; (2) Normal operations; (3) Temporary operations; (4) Emergency shutdown and operations; (5) Normal shutdown; (6) Startup following a normal or emergency shutdown or a major change that... are updated, if necessary, whenever a major change occurs and prior to startup of the changed process. ...

40 CFR 68.52 - Operating procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Initial startup; (2) Normal operations; (3) Temporary operations; (4) Emergency shutdown and operations; (5) Normal shutdown; (6) Startup following a normal or emergency shutdown or a major change that... are updated, if necessary, whenever a major change occurs and prior to startup of the changed process. ...

40 CFR 68.52 - Operating procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Initial startup; (2) Normal operations; (3) Temporary operations; (4) Emergency shutdown and operations; (5) Normal shutdown; (6) Startup following a normal or emergency shutdown or a major change that... are updated, if necessary, whenever a major change occurs and prior to startup of the changed process. ...

Initial postmarketing experience with crotalidae polyvalent immune Fab for treatment of rattlesnake envenomation.

PubMed

Ruha, Anne-Michelle; Curry, Steven C; Beuhler, Michael; Katz, Ken; Brooks, Daniel E; Graeme, Kimberlie A; Wallace, Kevin; Gerkin, Richard; Lovecchio, Frank; Wax, Paul; Selden, Brad

2002-06-01

We describe our postmarketing experience with patients receiving Crotalidae polyvalent immune Fab (CroFab; FabAV) antivenom for treatment of rattlesnake envenomation. The charts of 28 patients admitted between March 1 and September 9, 2001, with rattlesnake envenomation and treated with FabAV were reviewed for demographic information, time until antivenom treatment, laboratory findings, evidence of hypersensitivity reaction, length of hospital stay, and readmission to the hospital. All patients had swelling, 20 patients had elevated prothrombin times (>14 seconds), 12 patients had low fibrinogen levels (<170 mg/dL), and 6 patients had thrombocytopenia (platelet count <120,000/mm(3)) on presentation. The total dose of FabAV ranged from 10 to 47 vials per patient. Hypofibrinogenemia was resistant to FabAV in some patients. On follow-up, recurrence of coagulopathy was detected in 3 patients, and recurrence of thrombocytopenia was detected in 1 patient. Two patients demonstrated delayed-onset severe thrombocytopenia. Recurrence or delayed-onset toxicity might have been underestimated because of incomplete follow-up in some patients. No acute hypersensitivity reactions occurred. Two patients reported mild symptoms of possible serum sickness on follow-up. FabAV effectively controlled the effects of envenomation; however, initial control of coagulopathy was difficult to achieve in some cases, and recurrence or delayed-onset hematotoxicity was common. When initially managing hematotoxicity, a trend toward normalization of laboratory values might be a more reasonable end point for FabAV treatment than attainment of normal reference values in nonbleeding patients.

A Case of Vitamin-D-Dependent Rickets Type 1A with Normal 1,25-Dihydroxyvitamin D Caused by Two Novel Mutations of the CYP27B1 Gene.

PubMed

Giannakopoulos, Aris; Efthymiadou, Alexandra; Chrysis, Dionisios

2017-01-01

Vitamin-D-dependent rickets 1A (VDDR-1A) is caused by mutations of the renal CYP27B1 gene and is a rare form of rickets. Herein, we report a 20-month-old toddler who presented with inability to walk and failure to thrive. The clinical, biochemical and radiological findings were consistent with a diagnosis of rickets, specifically of the genetic type due to increased 25-OH vitamin D stores. Our patient was a compound heterozygote with 2 novel mutations: c.242G>A(p.Gly81Glu) and c.1144C>G (p.Pro382Ala) in the CYP27B1 gene. Analysis of both mutations with in silico models predicted a deleterious effect on 25-OH vitamin D 1α-hydroxylase function. Interestingly, the levels of 1,25-(OH)2 vitamin D were within normal limits. Our patient was initiated on 1α-hydroxyvitamin D (alfacalcidol) and supplemental calcium. Monitoring of bone metabolism showed a normalization of all bone metabolism serum indices after 3 months of therapy and, thereafter, only alfacalcidol was given at a maintenance dose. The clinical follow-up showed a dramatic improvement in musculoskeletal activity, and the patient regained acceleration in height and weight appropriate for his age. This rare case report of VDDR-1A with normal levels of 1,25-(OH)2 vitamin D enhances our awareness for this type of rickets in clinical practice. © 2016 S. Karger AG, Basel.

An unusual case of recurrent Guillain-Barré syndrome with normal cerebrospinal fluid protein levels: a case report.

PubMed

Gunatilake, Sonali Sihindi Chapa; Gamlath, Rohitha; Wimalaratna, Harith

2016-09-05

Guillain-Barré syndrome is an acquired polyradiculo-neuropathy, often preceded by an antecedent event. It is a monophasic disease but a recurrence rate of 1-6 % is documented in a subset group of patients. Patients with Guillain-Barré syndrome show cerebrospinal fluid albuminocytologic dissociation. Normal cerebrospinal fluid protein levels during both initial and recurrent episodes of Guillain-Barré syndrome is a rare occurrence and has not been described earlier in the literature. Twenty-five-year-old Sri Lankan female with past history of complete recovery following an acute inflammatory demyelinating polyneuropathy (AIDP) variant of Guillain-Barré syndrome 12 years back presented with acute, ascending symmetrical flaccid quadriparasis extending to bulbar muscles, bilateral VII cranial nerves and respiratory compromise needing mechanical ventilation. Nerve conduction study revealed AIDP variant of Guillain-Barré syndrome. Cerebrospinal fluid analysis done after 2 weeks were normal during both episodes without albuminocytologic dissociation. She was treated with intravenous immunoglobulin resulting in a remarkable recovery. Both episodes had a complete clinical recovery in three and four months' time respectively, rather a faster recovery than usually expected. Recurrence of Guillain-Barré syndrome can occur in a subset of patients with Guillain-Barré syndrome even after many years of asymptomatic period. Normal cerebrospinal fluid profile does not exclude Guillain-Barré syndrome and may occur in subsequent recurrences of Guillain-Barré syndrome arising the need for further studies to identify the pathophysiology and the possibility of a different subtype of Guillain-Barré syndrome.

Evaluation of disease progression in INCL by MR spectroscopy

PubMed Central

Baker, Eva H; Levin, Sondra W; Zhang, Zhongjian; Mukherjee, Anil B

2015-01-01

Objective Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative storage disease caused by palmitoyl-protein thioesterase-1 deficiency, which impairs degradation of palmitoylated proteins (constituents of ceroid) by lysosomal hydrolases. Consequent lysosomal ceroid accumulation leads to neuronal injury. As part of a pilot study to evaluate treatment benefits of cysteamine bitartrate and N-acetylcysteine, we quantitatively measured brain metabolite levels using magnetic resonance spectroscopy (MRS). Methods A subset of two patients from a larger treatment and follow-up study underwent serial quantitative single-voxel MRS examinations of five anatomical sites. Three echo times were acquired in order to estimate metabolite T2. Measured metabolite levels included correction for partial volume of cerebrospinal fluid. Comparison of INCL patients was made to a reference group composed of asymptomatic and minimally symptomatic Niemann-Pick disease type C patients. Results In INCL patients, N-acetylaspartate (NAA) was abnormally low at all locations upon initial measurement, and further declined throughout the follow-up period. In the cerebrum (affected early in the disease course), choline and myo-inositol were initially elevated and fell during the follow-up period, whereas in the cerebellum and brainstem (affected later), choline and myo-inositol were initially normal and rose subsequently. Interpretation Choline and myo-inositol levels in our patients are consistent with patterns of neuroinflammation observed in two INCL mouse models. Low, persistently declining NAA was expected based on the progressive, irreversible nature of the disease. Progression of metabolite levels in INCL has not been previously quantified; therefore the results of this study serve as a reference for quantitative evaluation of future therapeutic interventions. PMID:26339674

Evaluation of disease progression in INCL by MR spectroscopy.

PubMed

Baker, Eva H; Levin, Sondra W; Zhang, Zhongjian; Mukherjee, Anil B

2015-08-01

Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative storage disease caused by palmitoyl-protein thioesterase-1 deficiency, which impairs degradation of palmitoylated proteins (constituents of ceroid) by lysosomal hydrolases. Consequent lysosomal ceroid accumulation leads to neuronal injury. As part of a pilot study to evaluate treatment benefits of cysteamine bitartrate and N-acetylcysteine, we quantitatively measured brain metabolite levels using magnetic resonance spectroscopy (MRS). A subset of two patients from a larger treatment and follow-up study underwent serial quantitative single-voxel MRS examinations of five anatomical sites. Three echo times were acquired in order to estimate metabolite T2. Measured metabolite levels included correction for partial volume of cerebrospinal fluid. Comparison of INCL patients was made to a reference group composed of asymptomatic and minimally symptomatic Niemann-Pick disease type C patients. In INCL patients, N-acetylaspartate (NAA) was abnormally low at all locations upon initial measurement, and further declined throughout the follow-up period. In the cerebrum (affected early in the disease course), choline and myo-inositol were initially elevated and fell during the follow-up period, whereas in the cerebellum and brainstem (affected later), choline and myo-inositol were initially normal and rose subsequently. Choline and myo-inositol levels in our patients are consistent with patterns of neuroinflammation observed in two INCL mouse models. Low, persistently declining NAA was expected based on the progressive, irreversible nature of the disease. Progression of metabolite levels in INCL has not been previously quantified; therefore the results of this study serve as a reference for quantitative evaluation of future therapeutic interventions.

Serum levels of interleukin 6 in schizophrenic patients during treatment augmentation with sarcosine (results of the PULSAR study).

PubMed

Strzelecki, Dominik; Urban-Kowalczyk, Małgorzata; Wysokiński, Adam

2018-03-01

Augmentation of sarcosine, a natural inhibitor of the glycine transporter type I, normalizes glutamatergic neurotransmission, having beneficial impact on primary negative symptoms in schizophrenia and may also influence immune system and interleukin 6 (IL-6) levels. Finding a relationship between initial IL-6 serum concentrations or its changes and severity of symptoms as a result of sarcosine addition to stable antipsychotic treatment. Fifity-eight individuals with schizophrenia with predominantly negative symptoms completed a 6-month randomized, double-blind placebo-controlled prospective study. Patients received 2 g of sarcosine (n = 29) or placebo (n = 30) daily per os. We measured IL-6 levels and severity of symptoms at the beginning, after 6 weeks and 6 months. As main clinical tools, we used Positive and Negative Syndrome Scale (PANSS) and Calgary depression scale for schizophrenia (CDSS). Augmentation with sarcosine had no effect on IL-6 serum levels in all time points. We noted significant improvements in negative symptoms, general psychopathology, and total PANSS score in the sarcosine group. We found correlation of initial serum IL-6 with severity of positive symptoms and negative association between IL-6 levels reduction and positive symptoms reduction. Sarcosine does not significantly affect IL-6 concentrations but IL-6 may be involved in mechanisms related to the presence of positive symptoms. Copyright © 2018 John Wiley & Sons, Ltd.

Single-Photon Emission Computed Tomography Is an Ambiguous Imaging Method on Initial Diagnosis for Acute Encephalopathy.

PubMed

Yamanaka, Gaku; Morishita, Nastumi; Oana, Shingo; Takeshita, Mika; Morichi, Shinichiro; Ishida, Yu; Kashiwagi, Yasuyo; Kawashima, Hisashi

2016-01-01

The distinction between acute encephalopathy (AE) and convulsive disorders with pyrexia may be problematic. We analyzed the clinical and laboratory features in 127 children who were admitted for suspected AE. They were categorized into (1) definite acute encephalopathy group (DAEG; n = 17, abnormal findings on electroencephalography [EEG], magnetic resonance imaging, or single-photon emission computed tomography [SPECT] with prolonged impaired consciousness), (2) probable acute encephalopathy group (PAEG; n = 21, abnormal findings without prolonged impaired consciousness), and (3) nonacute encephalopathy group (NAEG; n = 89). Cerebrospinal fluid interleukin-6 (CSF IL-6), and serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine phosphokinase levels were significantly higher in DAEG compared with NAEG but not PAEG. No significant differences were observed between DAEG and PAEG except for serum creatinine levels. In PAEG, an area of hypoperfusion was observed on SPECT images of nine patients with normal CSF IL-6 levels. AE was suspected in two PAEG patients who exhibited high CSF IL-6 levels and abnormal EEG findings without abnormal SPECT findings. All seven patients with severe neurological sequelae were categorized to DAEG. CSF IL-6 and serum AST, ALT, and creatine kinase levels may be valid predictors of typical AE; prolonged impaired consciousness is an important sign of AE. However, SPECT may not be suitable for initial diagnosis of AE. Georg Thieme Verlag KG Stuttgart · New York.

Population Impact of Drug Interactions with Warfarin: A Real-World Data Approach.

PubMed

Martín-Pérez, Mar; Gaist, David; de Abajo, Francisco J; Rodríguez, Luis A García

2018-03-01

 To investigate the population impact of previously reported interactions between warfarin and other drugs on international normalized ratio (INR) levels.  Using The Health Improvement Network (THIN), a United Kingdom primary care database, a cohort of warfarin users between 2005 and 2013 ( N  = 121,962) was followed until the first qualifying prescription for the potential interacting drugs was evaluated. Sixteen sub-cohorts, one for each study drug, and a control sub-cohort of warfarin were ascertained. Short-term changes in INR levels were assessed by comparing INR values measured before and after initiation of the interacting drug with paired Student's t -test. We also evaluated the proportion of patients with INR values outside the therapeutic range (INR: 2-3).  Miconazole use was associated with the highest mean increase in INR (+3.35), followed by amiodarone (+1.28), fluconazole (+0.79), metronidazole (+0.75) and nystatin (+0.65). After subtracting the natural INR variation observed in the control sub-cohort, supra-therapeutic levels (INR > 3) were found in 53.2% (miconazole), 45.5% (amiodarone), 23.3% (metronidazole), 23.2% (fluconazole) and 17.6% (nystatin) of patients initiating treatment with these drugs. Carbamazepine use was associated with a mean INR decrease of -0.63 and infra-therapeutic levels (INR < 2) were observed in 46.2% of patients initiating carbamazepine. For all other drugs, the change was small to moderate, in absolute INR units (+0.23 to +0.55) and in the proportion of patients with INR levels out of therapeutic range (<16%).  Clinically potentially important interactions were observed in several study drugs. The majority of them, although confirmed, had little impact after adjusting for standard INR variability in the general population of warfarin users. Schattauer GmbH Stuttgart.

The Effect of Ketogenic Diet on Serum Selenium Levels in Patients with Intractable Epilepsy.

PubMed

Arslan, Nur; Kose, Engin; Guzel, Orkide

2017-07-01

The aim of the present study was to evaluate serum selenium levels in children receiving olive oil-based ketogenic diet (KD) for intractable seizures for at least 1 year. Out of 320 patients who were initiated on KD, patients who continued receiving KD for at least 12 months were enrolled. Sixteen patients who had selenium deficiency at the time of starting KD were excluded. Finally, a total of 110 patients (mean age 7.3 ± 4.2 years) were included. Serum selenium levels were measured at baseline and at 3, 6, and 12 months after treatment initiation by using atomic absorption spectroscopy. Selenium deficiency was defined as a serum selenium level <48 μg/L at each visit. Repeated measure ANOVA with post hoc Bonferroni correction was used for data analysis. Mean duration of KD was 15.3 ± 4.3 months. Mean serum selenium levels were significantly lower at 6 and 12 months of KD treatment (66.2 ± 23.3 and 57.2 ± 16.2 μg/L, respectively) compared to pre-treatment levels (79.3 ± 25.7 μg/L) (p = 0.001). On the other hand, selenium levels did not show any significant difference at 3 months of KD treatment (70.0 ± 21.2 μg/L) compared to baseline levels (p = 0.076). A total of 54 patients (49.1%) were diagnosed with selenium deficiency, and oral selenium medication was initiated for these patients. No relevant clinical findings were detected, and echocardiographic findings were normal in all patients. The decline of the serum selenium concentrations after 6 and 12 months of ketogenic diet suggests that patients on this highly prescriptive dietary treatment need close monitoring of this trace element.

Statistical Mechanical Analysis of Online Learning with Weight Normalization in Single Layer Perceptron

NASA Astrophysics Data System (ADS)

Yoshida, Yuki; Karakida, Ryo; Okada, Masato; Amari, Shun-ichi

2017-04-01

Weight normalization, a newly proposed optimization method for neural networks by Salimans and Kingma (2016), decomposes the weight vector of a neural network into a radial length and a direction vector, and the decomposed parameters follow their steepest descent update. They reported that learning with the weight normalization achieves better converging speed in several tasks including image recognition and reinforcement learning than learning with the conventional parameterization. However, it remains theoretically uncovered how the weight normalization improves the converging speed. In this study, we applied a statistical mechanical technique to analyze on-line learning in single layer linear and nonlinear perceptrons with weight normalization. By deriving order parameters of the learning dynamics, we confirmed quantitatively that weight normalization realizes fast converging speed by automatically tuning the effective learning rate, regardless of the nonlinearity of the neural network. This property is realized when the initial value of the radial length is near the global minimum; therefore, our theory suggests that it is important to choose the initial value of the radial length appropriately when using weight normalization.

Diagnostic utility, safety, and cost-effectiveness of emergency department-initiated early scheduled technetium-99m single photon emission computed tomography imaging followed by expedited outpatient cardiac clinic visits in acute chest pain syndromes.

PubMed

Wong, Raymond C; Sinha, Arvind Kumar; Mahadevan, Malcolm; Yeo, Tiong Cheng

2010-09-01

Conventional emergency department (EMD) approach to triaging acute chest pain syndromes may lead to unnecessary admissions, resulting to in-hospital bed occupancy and increased healthcare costs. We explore the diagnostic utility of early (less than a week) outpatient scheduled single photon emission computed tomography (SPECT) in intermediate-risk chest pain subjects who presented to EMD with non-diagnostic electrocardiogram and negative serum troponin level. Additionally, we intend to study the safety and cost-effectiveness of such a strategy. We conduct a prospective, non-randomized study of 108 subjects who fit the inclusion criteria. After SPECT studies, all subjects were evaluated in the cardiac clinic within 2 weeks of EMD visits. Final diagnosis of coronary artery disease and subsequent disposition to standard medical therapy or follow-on angiography were decided by incorporating pre-test clinical data and SPECT results. Adverse events defined as myocardial infarction and cardiac death was tracked between EMD visit and eventual therapy (either medical therapy or coronary revascularization). Finally, cost-effectiveness was determined based on estimated cost and days of hospitalization saved between standard strategies of ward admission for further evaluation versus the present early outpatient SPECT-based workflow. Among 108 subjects (mean age 58 years, 59% male) included for analysis, 82 (76%) had normal perfusion status. There was no statistical difference in baseline characteristics and prior ischemic heart disease history between groups. In the 26 abnormal perfusion subjects, seven had follow-on coronary angiography in which three were found to have significant stenotic coronary lesions, but only one had intervention performed. There was an unscheduled coronary angiography in the normal perfusion group that yielded normal coronary anatomy. There was no adverse clinical event in both groups. Compared with standard strategy, early outpatient SPECT initiated by EMD physicians followed by cardiac clinic evaluation resulted in 2.9 days of hospitalization or $781.23 saved per patient per EMD visit. EMD-initiated early SPECT studies followed by cardiac clinic evaluation in intermediate-risk acute chest pain syndromes with non-diagnostic ECG and negative serum troponin levels carries excellent diagnostic and therapeutic utility, in addition to being safe and cost-effective.

Hypothyroidism in the elderly: diagnosis and management

PubMed Central

Bensenor, Isabela M; Olmos, Rodrigo D; Lotufo, Paulo A

2012-01-01

Thyroid disorders are highly prevalent, occurring most frequently in aging women. Thyroid-associated symptoms are very similar to symptoms of the aging process; thus, improved methods for diagnosing overt and subclinical hypothyroidism in elderly people are crucial. Thyrotropin measurement is considered to be the main test for detecting hypothyroidism. Combined evaluations of thyroid stimulating hormone (TSH) and free-thyroxine can detect overt hypothyroidism (high TSH with low free-thyroxine levels) and subclinical hypothyroidism (high TSH with normal free-thyroxine levels). It is difficult to confirm the diagnosis of thyroid diseases based only on symptoms, but presence of symptoms could be an indicator of who should be evaluated for thyroid function. The most important reasons to treat overt hypothyroidism are to relieve symptoms and avoid progression to myxedema. Overt hypothyroidism is classically treated using L-thyroxine; elderly patients require a low initial dose that is increased every 4 to 6 weeks until normalization of TSH levels. After stabilization, TSH levels are monitored yearly. There is no doubt about the indication for treatment of overt hypothyroidism, but indications for treatment of subclinical disease are controversial. Although treatment of subclinical hypothyroidism may result in lipid profile improvement, there is no evidence that this improvement is associated with decreased cardiovascular or all-cause mortality in elderly patients. In patients with a high risk of progression from subclinical to overt disease, close monitoring of thyroid function could be the best option. PMID:22573936

Synergy of bone marrow transplantation and curcumin ensue protective effects at early onset of diabetes in mice.

PubMed

Arivazhagan, Arivarasan; Krishna, Soni; Yadav, Shivangi; Shah, Harshit Rajesh; Kumar, Pravir; Ambasta, Rashmi Kumar

2015-07-01

The aim of this study was to investigate the early onset effects of diabetes on pro-angiogenic signaling pathway, total number of bone marrow cells, organs (pancreas and kidney) damage and the reversal effect of diabetes by combinatorial treatment of curcumin and bone marrow transplantation in streptozotocin (STZ) induced diabetic mice. In the present study, Streptozotocin induced diabetic mice were transplanted with bone marrow cells (2 × 10(6) ) followed by the administration of curcumin (80 mg/kg bodyweight). Effect of diabetes on the different organs was studied by H&E, Western blotting and immunofluorescence using vascular endothelial growth factor (VEGF), platelet/endothelial cell adhesion molecule (PECAM), insulin, Caspase-9 and Caspase-3 antibodies. The effect of diabetes results in the reduction of the total cell number and viability of the bone marrow cells, organ degeneration and lower VEGF/PECAM expression. However, transplantation with normal bone marrow cells significantly reduced the blood glucose levels (above normal range) and initiated the organ regeneration via the VEGF/PECAM mediated manner. Curcumin treatment further reduced the blood glucose level (near normal); and accelerated the organ regeneration, enhanced VEGF/PECAM expression and decreased caspase expression level in the organs. Curcumin also had a protective role against the glucotoxicity test performed on the bone marrow cells. This study suggests that bone marrow transplantation and curcumin administration is an effective treatment in reversing the early onset effects of diabetes via the VEGF/PECAM signaling pathway. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Takotsubo cardiomyopathy associated with thyrotoxicosis: a case report and review of the literature.

PubMed

Eliades, Myrto; El-Maouche, Diala; Choudhary, Chitra; Zinsmeister, Bruce; Burman, Kenneth D

2014-02-01

Takotsubo or stress-induced cardiomyopathy is a form of reversible cardiomyopathy commonly associated with emotional or physical stress. Thyrotoxicosis has been identified as a rare cause of Takotsubo cardiomyopathy, with only 12 cases reported in the literature. Here, we report a case of thyroid storm presenting with Takotsubo cardiomyopathy in the setting of Graves' disease. A 71-year-old woman presented with abdominal pain, vomiting, confusion, and history of weight loss. She was initially diagnosed and treated for diabetic ketoacidosis at another hospital and was transferred to our hospital one day after initial presentation because of concern for acute coronary syndrome. A diagnosis of Takotsubo cardiomyopathy was made on the basis of cardiac catheterization. At that time, she was diagnosed and treated for thyroid storm. Follow-up 7 weeks later revealed improvement of her cardiac function and near-normalization of thyroid hormone levels. In this patient, who presented with symptoms of heart failure, acute coronary syndrome was initially considered, but the diagnosis of Takotsubo cardiomyopathy associated with thyroid storm was ultimately made based on cardiac catheterization and laboratory investigation. Thyrotoxicosis is associated with adverse disturbances in the cardiovascular system. Takotsubo cardiomyopathy could be a presenting manifestation of thyroid storm, perhaps related to excess catecholamine levels or sensitivity.

Difference of Self-identity Levels between Strabismus Patients and Normal Controls

PubMed Central

Kim, Youngjun; Kim, Cheron; Kim, Seongjae; Han, Yongseop; Chung, Inyoung; Seo, Seongwook; Park, Jongmoon

2016-01-01

Purpose To evaluate differences in self-identity in patients diagnosed with strabismus, patients who underwent strabismus surgery, and healthy control individuals. Methods Self-identity testing was done during a military service physical examination. There were three subject groups: subjects with strabismus (group 1), subjects who had undergone corrective strabismus surgery (group 2), and subjects free of strabismus (group 3). The self-identity test was comprised of six sub-sections (subjectivity, self-acceptance, future confidence, goal orientation, initiative, and familiarity). Statistical significance of the sub-sections was compared across the three groups. Correlations in age at the time of surgery and across the six sub-sections were investigated in group 2. Results A total of 351 subjects were enrolled in the study; 96 subjects were in group 1, 108 subjects were in group 2, and 147 subjects were in group 3. Significant differences were evident in subjectivity, self-acceptance, initiative and familiarity between groups 1 and 3. No significant differences were found between groups 2 and 3. In group 2, statistical significance was evident between age at surgery and initiative and familiarity (r = −0.333, p < 0.001; r = −0.433, p < 0.001, respectively). Conclusions Self-identity is greater in non-strabismus subjects than strabismus subjects. Correction of strabismus may increase self-identity levels. PMID:27980359

The utilization of a non-invasive fluorescence imaging system to follow clinical dermatological MAL-PDT

NASA Astrophysics Data System (ADS)

Tyrrell, Jessica; Campbell, Sandra; Curnow, Alison

2009-06-01

This study employed a commercially available, non-invasive, fluorescence imaging system (Dyaderm, Biocam, Germany), to measure protoporphyrin IX (PpIX) concentration at several different stages during clinical dermatological methyl aminolevulinate photodynamic therapy (MAL-PDT). We validated the system prior to use to ensure that the PpIX changes witnessed were accurate and not due to environmental or user induced artifacts. The system was then employed to acquire color (morphological) and fluorescent (physiological) images simultaneously during dermatological PDT. Clinical data was collected from a range of licensed dermatological conditions (actinic keratosis, Bowen's disease and superficial basal cell carcinoma) during initial and subsequent PDT treatment cycles. The initial clinical data indicated that each type of licensed lesion considered responded in a similar manner following the application of Metvix (Galderma, U.K.) and the subsequent light irradiation (Aktilite, Galderma, U.K.). Images acquired three hours after Metvix application showed a significant increase in PpIX concentration within the lesion (P < 0.05), whilst PpIX levels in the surrounding normal tissue remained unaltered. After irradiation, the PpIX concentration was significantly decreased and returned to a level similar to the initial concentration originally observed. Lesions that received subsequent treatment cycles accumulated significantly less PpIX (P < 0.05) prior to irradiation.

Case of remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome) showing dermatomyositis-like eruption.

PubMed

Takeda, Kiminobu; Fujita, Jun; Fujii, Toshiki; Tanabe, Hiroshi; Mochizuki, Takashi; Yanagihara, Makoto

2010-01-01

A 73-year-old woman developed linear erythema at the sites of scratching-induced scars on the bilateral thighs 2 weeks before the initial consultation. Subsequently, edematous erythema developed in the upper eyelids, dorsum of the nose and the face, and pitting edema in the dorsum of the bilateral hands and feet. The C-reactive protein (CRP) level was 8.2 mg/dL and erythrocyte sedimentation rate (ESR) 121 mm/h. The antinuclear antibody titer was 1:160, and rheumatoid factor (RF) and anti-Jo-1 antibody were negative. X-ray examination of the bilateral hands showed neither narrowing of the joint spaces nor bone erosion. Ga scintigraphy showed synovitis of the bilateral wrists. A diagnosis of remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE) was made. The erythema disappeared after diclofenac sodium administration. However, because the joint swelling and pitting edema did not improve, p.o. administration of prednisolone (20 mg/day) was initiated. The CRP and ESR levels normalized 2 months after the initiation of administration, and pitting edema disappeared after 3 months. We report this case because linear erythema like that observed in dermatomyositis has not been described as eruptions associated with RS3PE.

Difference of Self-identity Levels between Strabismus Patients and Normal Controls.

PubMed

Kim, Youngjun; Kim, Cheron; Kim, Seongjae; Han, Yongseop; Chung, Inyoung; Seo, Seongwook; Park, Jongmoon; Yoo, Jimyong

2016-12-01

To evaluate differences in self-identity in patients diagnosed with strabismus, patients who underwent strabismus surgery, and healthy control individuals. Self-identity testing was done during a military service physical examination. There were three subject groups: subjects with strabismus (group 1), subjects who had undergone corrective strabismus surgery (group 2), and subjects free of strabismus (group 3). The self-identity test was comprised of six sub-sections (subjectivity, self-acceptance, future confidence, goal orientation, initiative, and familiarity). Statistical significance of the sub-sections was compared across the three groups. Correlations in age at the time of surgery and across the six sub-sections were investigated in group 2. A total of 351 subjects were enrolled in the study; 96 subjects were in group 1, 108 subjects were in group 2, and 147 subjects were in group 3. Significant differences were evident in subjectivity, self-acceptance, initiative and familiarity between groups 1 and 3. No significant differences were found between groups 2 and 3. In group 2, statistical significance was evident between age at surgery and initiative and familiarity (r = -0.333, p < 0.001; r = -0.433, p < 0.001, respectively). Self-identity is greater in non-strabismus subjects than strabismus subjects. Correction of strabismus may increase self-identity levels.

Takotsubo Cardiomyopathy Associated with Thyrotoxicosis: A Case Report and Review of the Literature

PubMed Central

El-Maouche, Diala; Choudhary, Chitra; Zinsmeister, Bruce; Burman, Kenneth D.

2014-01-01

Background: Takotsubo or stress-induced cardiomyopathy is a form of reversible cardiomyopathy commonly associated with emotional or physical stress. Thyrotoxicosis has been identified as a rare cause of Takotsubo cardiomyopathy, with only 12 cases reported in the literature. Here, we report a case of thyroid storm presenting with Takotsubo cardiomyopathy in the setting of Graves' disease. Patient Findings: A 71-year-old woman presented with abdominal pain, vomiting, confusion, and history of weight loss. She was initially diagnosed and treated for diabetic ketoacidosis at another hospital and was transferred to our hospital one day after initial presentation because of concern for acute coronary syndrome. A diagnosis of Takotsubo cardiomyopathy was made on the basis of cardiac catheterization. At that time, she was diagnosed and treated for thyroid storm. Follow-up 7 weeks later revealed improvement of her cardiac function and near-normalization of thyroid hormone levels. Summary: In this patient, who presented with symptoms of heart failure, acute coronary syndrome was initially considered, but the diagnosis of Takotsubo cardiomyopathy associated with thyroid storm was ultimately made based on cardiac catheterization and laboratory investigation. Conclusions: Thyrotoxicosis is associated with adverse disturbances in the cardiovascular system. Takotsubo cardiomyopathy could be a presenting manifestation of thyroid storm, perhaps related to excess catecholamine levels or sensitivity. PMID:23560557

[Differences in anticipatory postural adjustments between self-generated and triggered gait initiation in 20 healthy subjects].

PubMed

Delval, A; Krystkowiak, P; Blatt, J-L; Labyt, E; Destée, A; Derambure, P; Defebvre, L

2005-01-01

Preparation of upper-limb movements differs between self-paced and triggered conditions. This study analyzed the anticipatory postural adjustments (APAs) of gait initiation in normal subjects in 2 conditions: self-generated and triggered by a "beep" sound. We recorded kinematic, spatiotemporal parameters of the first two steps by means of video motion analysis (6 infrared cameras), and kinetic parameters (using a force platform and the optoelectronic system) in 20 normal subjects. Two conditions: 1) self-generated initiation; and 2) initiation triggered by a "beep" sound were studied to evaluate the APA phase, by recording kinetic data (duration of the APAs, trajectory of the center of pressure, speed and trajectory of the center of mass). Kinematic data (first and second step speed, length and duration) were also recorded. First step speed and length were increased in self-paced gait initiation compared to triggered gait initiation in controls. We found no difference between the 2 conditions in terms of second step kinematic data. It was caused by a significant difference between the 2 conditions for the temporal characteristics of anticipatory postural adjustments (APAs) in the initiation of the first step, which was longer when normal subjects performed self-generated gait initiation. The trajectory of center of pressure and center of mass remained the same in the 2 conditions. APAs of gait initiation process are delayed under self-paced condition, although they do not differ qualitatively between reaction time and self-paced condition. Neuphysiological support of self-generated movement could explain these differences.

Neonatal Hyperbilirubinemia in infants with G6PD c.563C > TVariant

PubMed Central

2012-01-01

Background There is a strong correlation between glucose-6-phosphate dehydrogenase (G6PD) deficiency and neonatal hyperbilirubinemia with a rare but potential threat of devastating acute bilirubin encephalopathy. G6PD deficiency was observed in 4–14% of hospitalized icteric neonates in Pakistan. G6PD c.563C > T is the most frequently reported variant in this population. The present study was aimed at evaluating the time to onset of hyperbilirubinemia and the postnatal bilirubin trajectory in infants having G6PD c.563C > T. Methods This was a case–control study conducted at The Aga Khan University, Pakistan during the year 2008. We studied 216 icteric male neonates who were re-admitted for phototherapy during the study period. No selection was exercised. Medical records showed that 32 were G6PD deficient while 184 were G6PD normal. Each infant was studied for birth weight, gestational age, age at the time of presentation, presence of cephalhematoma, sepsis and neurological signs, peak bilirubin level, age at peak bilirubin level, days of hospitalization, whether phototherapy or exchange blood transfusion was initiated, and the outcome. During hospital stay, each baby was tested for complete blood count, reticulocyte count, ABO and Rh blood type, direct antiglobulin test and quantitative G6PD estimation [by kinetic determination of G6PDH]. G6PDgenotype was analyzed in 32 deficient infants through PCR-RFLP analysis and gene sequencing. Results G6PD variants c.563C > T and c.131 C > G were observed in 21 (65%) and three (9%) of the 32 G6PD deficient infants, respectively. DNA of eight (25%) newborns remained uncharacterized. In contrast to G6PD normal neonates, infants with c.563C > T variant had significantly lower enzyme activity (mean ± 1SD; 0.3 ± 0.2 U/gHb vs. 14.0 ± 4.5 U/gHb, p < 0.001) experienced higher peak levels of total serum bilirubin (mean ± 1SD; 16.8 ± 5.4 mg/dl vs. 13.8 ± 4.6 mg/dl, p = 0.008) which peaked earlier after birth (mean ± 1SD 2.9 ± 1.6 vs. 4.3 ± 2.3 days, p = 0.007). No statistically significant difference was observed in mean weight, age at presentation, hemoglobin, reticulocyte count, TSH level, hospital stay or in the frequency of initiation of phototherapy or blood exchange between the two groups. Conclusions We concluded that infants with G6PD c.563C > T variant developed jaundice earlier than infants with normal G6PD enzyme levels. Compared to G6PD normal infants, G6PD c.563C > T carrying infants had significantly low G6PD activity. PMID:22906047

Obesity-programmed mice are rescued by early genetic intervention

PubMed Central

Bumaschny, Viviana F.; Yamashita, Miho; Casas-Cordero, Rodrigo; Otero-Corchón, Verónica; de Souza, Flávio S.J.; Rubinstein, Marcelo; Low, Malcolm J.

2012-01-01

Obesity is a chronic metabolic disorder affecting half a billion people worldwide. Major difficulties in managing obesity are the cessation of continued weight loss in patients after an initial period of responsiveness and rebound to pretreatment weight. It is conceivable that chronic weight gain unrelated to physiological needs induces an allostatic regulatory state that defends a supranormal adipose mass despite its maladaptive consequences. To challenge this hypothesis, we generated a reversible genetic mouse model of early-onset hyperphagia and severe obesity by selectively blocking the expression of the proopiomelanocortin gene (Pomc) in hypothalamic neurons. Eutopic reactivation of central POMC transmission at different stages of overweight progression normalized or greatly reduced food intake in these obesity-programmed mice. Hypothalamic Pomc rescue also attenuated comorbidities such as hyperglycemia, hyperinsulinemia, and hepatic steatosis and normalized locomotor activity. However, effectiveness of treatment to normalize body weight and adiposity declined progressively as the level of obesity at the time of Pomc induction increased. Thus, our study using a novel reversible monogenic obesity model reveals the critical importance of early intervention for the prevention of subsequent allostatic overload that auto-perpetuates obesity. PMID:23093774

Fertility after natural disaster: Hurricane Mitch in Nicaragua

PubMed Central

Davis, Jason

2017-01-01

This investigation evaluates the effect of Hurricane Mitch on women’s reproductive outcomes throughout Nicaragua. This research aim is achieved by analyzing a unique Nicaraguan Living Standards Measurement Study panel dataset that tracks women’s fertility immediately before and at two time points after Hurricane Mitch, combined with satellite-derived municipality-level precipitation data for the 10-day storm period. Results show higher odds of post-disaster fertility in municipalities receiving higher precipitation levels in the immediate post-Hurricane Mitch period. However, fertility normalizes between disaster and non-disaster areas four to six years after the storm. These findings suggest that the disruptive effects of a natural disaster such as Hurricane Mitch can have an initial stimulative effect on fertility but the effect is ephemeral. PMID:28694556

Post-transcriptional regulation in hematopoiesis: RNA binding proteins take control.

PubMed

de Rooij, Laura P M H; Chan, Derek C H; Keyvani Chahi, Ava; Hope, Kristin J

2018-06-13

Normal hematopoiesis is sustained through a carefully orchestrated balance between hematopoietic stem cell (HSC) self-renewal and differentiation. The functional importance of this axis is underscored by the severity of disease phenotypes initiated by abnormal HSC function, including myelodysplastic syndromes and hematopoietic malignancies. Major advances in the understanding of transcriptional regulation of primitive hematopoietic cells have been achieved, however, the post-transcriptional regulatory layer that may impinge on their behavior remains underexplored by comparison. Key players at this level include RNA binding proteins (RBPs), which execute precise and highly coordinated control of gene expression through modulation of RNA properties that include its splicing, polyadenylation, localization, degradation or translation. With the recent identification of RBPs having essential roles in regulating proliferation and cell fate decisions in other systems, there has been an increasing appreciation of the importance of post-transcriptional control at the stem cell level. Here we discuss our current understanding of RBP-driven post-transcriptional regulation in HSC, its implications for normal, perturbed and malignant hematopoiesis, as well as the most recent technological innovations aimed at RBP-RNA network characterization at the systems level. Emerging evidence highlights RBP-driven control as an underappreciated feature of primitive hematopoiesis, the greater understanding of which has important clinical implications.

Study of Burn Scar Extraction Automatically Based on Level Set Method using Remote Sensing Data

PubMed Central

Liu, Yang; Dai, Qin; Liu, JianBo; Liu, ShiBin; Yang, Jin

2014-01-01

Burn scar extraction using remote sensing data is an efficient way to precisely evaluate burn area and measure vegetation recovery. Traditional burn scar extraction methodologies have no well effect on burn scar image with blurred and irregular edges. To address these issues, this paper proposes an automatic method to extract burn scar based on Level Set Method (LSM). This method utilizes the advantages of the different features in remote sensing images, as well as considers the practical needs of extracting the burn scar rapidly and automatically. This approach integrates Change Vector Analysis (CVA), Normalized Difference Vegetation Index (NDVI) and the Normalized Burn Ratio (NBR) to obtain difference image and modifies conventional Level Set Method Chan-Vese (C-V) model with a new initial curve which results from a binary image applying K-means method on fitting errors of two near-infrared band images. Landsat 5 TM and Landsat 8 OLI data sets are used to validate the proposed method. Comparison with conventional C-V model, OSTU algorithm, Fuzzy C-mean (FCM) algorithm are made to show that the proposed approach can extract the outline curve of fire burn scar effectively and exactly. The method has higher extraction accuracy and less algorithm complexity than that of the conventional C-V model. PMID:24503563

Clearance of phenylalanine ammonia-lyase from normal and tumor-bearing mice.

PubMed

Shen, R S; Fritz, R R; Abell, C W

1977-04-01

Yeast phenylalanine ammonia-lyase was administered i.p. to normal and tumor-bearing mice, and its clearance from plasma was studied. Single and multiple weekly injections at dosages of 10,20,50 and 100 units/kg were administered to C57BL female, C57BL X DBA/2F1 male, and A/J female mice. L5178Y murine lymphoblastic leukemia, B16 melanoma, BW10232 adenocarcinoma, and 15091A anaplastic carcinoma were implanted 7 to 11 days prior to enzyme injection in the appropriate host. After a single injection, the average plasma half-lives of phenylalanine ammonia-lyase were 18 to 24 hr in all groups studied. While the other tumors had no effect on the plasma level of phenylalanine ammonia-lyase after a single injection, L5178Y murine lymphoblastic leukemia and 15091A anaplastic carcinoma significantly depressed the maximal level of phenylalanine ammonia-lyase attained in the plasma. After repeated injections of phenylalanine ammonia-lyase, the initial plasma enzyme level was significantly reduced when 20 units/kg were administered, and the clearance of the enzyme from the plasma was greatly accelerated regardless of the amount administered. Furthermore, in tumor-bearing mice, the rate of clearance was significantly more rapid than in the appropriate non-tumor-bearing control.

Clinical use of proton-pump inhibitors but not H2-blockers or antacid/alginates raises the serum levels of amidated gastrin-17, pepsinogen I and pepsinogen II in a random adult population.

PubMed

Agréus, Lars; Storskrubb, Tom; Aro, Pertti; Ronkainen, Jukka; Talley, Nicholas J; Sipponen, Pentti

2009-01-01

Proton-pump inhibitors (PPIs), H(2) receptor antagonists (H(2)RAs) and antacids/alginates reduce intragastric acidity and may thus influence normal gastric physiology. The purpose of this study was to examine the effect of these compounds on serum levels of amidated gastrin-17 (G-17) and pepsinogens (PGI & PGII) in a large, random, adult Swedish population sample with uninfected stomach mucosa. The initial sample subjects (n=1000, mean age 50 years, range 20-80 years) completed a questionnaire on the use of acid inhibitory drugs 1 week and/or 3 months before study entry. All subjects (n=590) with normal gastric mucosa as delineated by serum biomarkers were included. Among them, serum levels of PGI, PGII and G-17 were compared between those who used acid inhibitory drugs and those who did not. The serum levels of G-17 or pepsinogens in the subjects who reported use of H(2)RAs (n=18) or antacid/alginates (n=66) during the previous 3 months did not differ from those in non-users (n=471). However, the median levels of G-17 and pepsinogens were significantly (p<0.001) higher among the PPI users (n=35) than among non-users: the levels were approximately doubled. The ratio of PGI/PGII was, however, similar between PPI users and non-users, or those using antacids/alginates or H(2)RAs. Among subjects using PPIs, the serum levels of pepsinogens correlated positively (p<0.01) with the serum levels of G-17. PPIs but not antacids/alginates or H(2)RAs markedly increase the fasting levels of serum amidated G-17 and pepsinogens among ordinary patients in everyday clinical practice.

Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer.

PubMed

Weickhardt, Andrew J; Rothman, Micol S; Salian-Mehta, Smita; Kiseljak-Vassiliades, Katja; Oton, Ana B; Doebele, Robert C; Wierman, Margaret E; Camidge, D Ross

2012-11-01

The objective of this study was to document the differences in testosterone (T) levels between crizotinib-treated and noncrizotinib-treated patients with metastatic nonsmall cell lung cancer (NSCLC). Testosterone levels were measured in 19 men with metastatic NSCLC who received crizotinib and in 19 men with metastatic NSCLC who did not receive crizotinib. Clinical characteristics of the patients were compared, and additional hormone assays were performed as appropriate. Two patients who began crizotinib and 4 patients who had dose interruptions or who stopped crizotinib therapy had serial hormone measurements, permitting the documentation of dynamic hormone changes on and off crizotinib treatment. Total T levels were low (<241 ng/dL) in 19 of 19 (100%) crizotinib-treated men and in 6 of 19 men (32%) with metastatic NSCLC who did not receive crizotinib (mean T levels, 131 ng/dL and 311 ng/dL, respectively; P = .0002). Only 1 in 5 patients who had anaplastic lymphoma kinase (ALK) gene rearrangements and had not yet received crizotinib had low T. The initiation of crizotinib in 2 patients who had previously normal T levels was associated with a rapid decreases in T and in luteinizing hormone and follicle stimulating hormone levels within 14 to 21 days. Discontinuation of crizotinib led to increases back to normal T levels. Crizotinib therapy caused rapid suppression of T levels in men. The current results indicated that the site of action must include a central (hypothalamic or pituitary) effect, but additional direct testicular effects could not be excluded. Further work is required to assess the correlation between low T levels and crizotinib side effects as well as the exact molecular mechanism and site of drug toxicity. Copyright © 2012 American Cancer Society.

Maternal psychological responses during pregnancy after ultrasonographic detection of structural fetal anomalies: A prospective longitudinal observational study

PubMed Central

Kaasen, Anne; Helbig, Anne; Malt, Ulrik F.; Næs, Tormod; Skari, Hans; Haugen, Guttorm

2017-01-01

In this longitudinal prospective observational study performed at a tertiary perinatal referral centre, we aimed to assess maternal distress in pregnancy in women with ultrasound findings of fetal anomaly and compare this with distress in pregnant women with normal ultrasound findings. Pregnant women with a structural fetal anomaly (n = 48) and normal ultrasound (n = 105) were included. We administered self-report questionnaires (General Health Questionnaire-28, Impact of Event Scale-22 [IES], and Edinburgh Postnatal Depression Scale) a few days following ultrasound detection of a fetal anomaly or a normal ultrasound (T1), 3 weeks post-ultrasound (T2), and at 30 (T3) and 36 weeks gestation (T4). Social dysfunction, health perception, and psychological distress (intrusion, avoidance, arousal, anxiety, and depression) were the main outcome measures. The median gestational age at T1 was 20 and 19 weeks in the group with and without fetal anomaly, respectively. In the fetal anomaly group, all psychological distress scores were highest at T1. In the group with a normal scan, distress scores were stable throughout pregnancy. At all assessments, the fetal anomaly group scored significantly higher (especially on depression-related questions) compared to the normal scan group, except on the IES Intrusion and Arousal subscales at T4, although with large individual differences. In conclusion, women with a known fetal anomaly initially had high stress scores, which gradually decreased, resembling those in women with a normal pregnancy. Psychological stress levels were stable and low during the latter half of gestation in women with a normal pregnancy. PMID:28350879

Oxygen consumption and survival prediction in neonatal rats exposed to prenatal hypervitaminosis A.

PubMed

Newman, L M; Johnson, E M; Cadogan, A S

1983-10-01

Fetal exposure to excess vitamin A results in a highly variable degree of lung pathology and high neonatal mortality in the Long-Evans rat. The present study evaluated O2 consumption in newborn of vitamin A-treated, vehicle-treated, and untreated pregnancies on five consecutive postnatal days beginning with the day of delivery (D0). Pregnant female rats were treated by gavage with 160,000 USP units of retinyl acetate dissolved in 0.5 ml corn oil on days 15 through 19 of gestation. Vehicle and undisturbed controls were run concurrently. All animals delivered spontaneously, and the pups were tattooed and individually tested in a closed system consisting of three chambers submerged within a thermostatically controlled water bath at 33 degrees C. Vitamin A-exposed pups, as a group, have significantly lower QO2 (ml O2 consumed/min/kg body weight) values than controls through postnatal day 2 (p less than 0.05). By days 3 and 4 of age, the mean QO2 values of surviving vitamin A-treated pups were similar to those of controls. A QO2 of 30 or greater on day 0 appears to be critical for early neonatal survival of vitamin A-exposed pups, as 87% of the pups with initial QO2 less than 30 died prior to day 4. Oxygen consumption rates in teratogen-exposed pups exhibiting low QO2 on day 0 rarely reached normal levels. In contrast, the occasional control pup with such low initial levels were well within normal limits (means +/- 1 SD) by the following day.(ABSTRACT TRUNCATED AT 250 WORDS)

Used Nuclear Fuel Loading and Structural Performance Under Normal Conditions of Transport- Demonstration of Approach and Results on Used Fuel Performance Characterization

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

Adkins, Harold; Geelhood, Ken; Koeppel, Brian

2013-09-30

This document addresses Oak Ridge National Laboratory milestone M2FT-13OR0822015 Demonstration of Approach and Results on Used Nuclear Fuel Performance Characterization. This report provides results of the initial demonstration of the modeling capability developed to perform preliminary deterministic evaluations of moderate-to-high burnup used nuclear fuel (UNF) mechanical performance under normal conditions of storage (NCS) and normal conditions of transport (NCT) conditions. This report also provides results from the sensitivity studies that have been performed. Finally, discussion on the long-term goals and objectives of this initiative are provided.

The effects of progesterone selection on psychological symptoms in hormone replacement therapy.

PubMed

Caglayan, Emel Kiyak; Kara, Mustafa; Etiz, Sema; Kumru, Pinar; Aka, Nurettin; Kose, Gultekin

2014-01-01

The aim of this study is to evaluate the effects of hormone replacement therapy using dienogest and medroxyprogesterone acetate on psychological symptoms in perimenopausal and postmenopausal women. A total of 73 patients who sought treatment at the menopause units of the authors' gynecology and obstetrics clinics between of November 2003 and October 2004 complaining of vasomotor symptoms were included in the study prospectively. The cases were divided into two groups: Group I (37 patients) was given 2 mg estradiol valerate and 2 mg dienogest, and Group II (36 patients) was given 2 mg estradiol valerate and 10 mg medroxyprogesterone acetate. The groups' results in months 0 and 6 were compared through the evaluation of vasomotor and psychological symptom levels. No significant difference was found between the groups when the initial levels of vasomotor and psychological symptom subtypes were compared (p = 0.16). It was observed that all the psychological symptoms decreased in the 6th month in the group using dienogest in comparison with the initial situation, and that psychological symptoms increased in the group using medroxyprogesterone acetate in the evaluation performed in the 6th month compared with the initial levels. It was also found out that there was a statistically significant difference between the two groups when compared in terms of these symptoms (p < 0.0001). While the use of dienogest normalizes the general psychological situation and sleep, it was observed that the use of medroxyprogesterone acetate (MPA) worsens the general psychological situation.

MANAGEMENT OF A REEVE'S MUNTJAC ( MUNTIACUS REEVESI) WITH SEIZURES USING LEVETIRACETAM.

PubMed

Blatt, Emily R; Seeley, Kathryn E; Lovett, Mathew C; Junge, Randall E

2017-12-01

This report describes the diagnosis and management of idiopathic epilepsy in a 4-yr-old intact female Reeve's muntjac ( Muntiacus reevesi). The patient was initially witnessed to have isolated paroxysmal events consistent with epileptic seizures (altered consciousness, lateral recumbency, tonic/clonic movement of limbs) lasting less than 3 min with an immediate return to normal consciousness. The seizure frequency increased to >3 seizures within 24 hr and phenobarbital 3 mg/kg orally every 12 hr was started. Because of continued epileptic seizures and low serum phenobarbital levels, the dose was increased until significant elevations of aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were detected. Levetiracetam 40 mg/kg orally every 12 hr was initiated and the phenobarbital was weaned and discontinued. One breakthrough seizure has been witnessed in the 10 mo since starting levetiracetam.

Fast Initialization of Bubble-Memory Systems

NASA Technical Reports Server (NTRS)

Looney, K. T.; Nichols, C. D.; Hayes, P. J.

1986-01-01

Improved scheme several orders of magnitude faster than normal initialization scheme. State-of-the-art commercial bubble-memory device used. Hardware interface designed connects controlling microprocessor to bubblememory circuitry. System software written to exercise various functions of bubble-memory system in comparison made between normal and fast techniques. Future implementations of approach utilize E2PROM (electrically-erasable programable read-only memory) to provide greater system flexibility. Fastinitialization technique applicable to all bubble-memory devices.

Overview of Hypothyroidism in Pregnancy.

PubMed

Kroopnick, Jeffrey M; Kim, Caroline S

2016-11-01

Overt hypothyroidism in pregnancy, defined as an elevated serum thyroid-stimulating hormone (TSH) and reduced serum free thyroxine or a TSH >10 mIU/L, is known to have adverse effects on pregnancy. Subclinical hypothyroidism is typically defined as an elevated TSH and normal FT4 levels. There remains much controversy on the benefit of starting levothyroxine for mothers diagnosed with subclinical hypothyroidism. Recent studies are redefining the normal range for TSH in pregnancy, and the data on whether treatment of subclinical hypothyroidism improves outcomes for the mother and fetus are unclear. One confounding variable is the presence of thyroid peroxidase antibodies, as it may be a surrogate marker for other autoimmune disorders detrimental to pregnancy. If levothyroxine treatment is initiated, the dosing and monitoring strategy is different from nonpregnant individuals. Randomized clinical trials are underway that may better elucidate whether treatment of subclinical hypothyroidism is warranted. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Genetics of Isolated Growth Hormone Deficiency

PubMed Central

2010-01-01

When a child is not following the normal, predicted growth curve, an evaluation for underlying illnesses and central nervous system abnormalities is required, and appropriate consideration should be given to genetic defects causing growth hormone (GH) deficiency (GHD). Because Insulin−like Growth Factor−I (IGF−I) plays a pivotal role, GHD could also be considered as a form of IGF−I deficiency (IGFD). Although IGFD can develop at any level of the GH−releasing hormone (GHRH)−GH−IGF axis, a differentiation should be made between GHD (absent to low GH in circulation) and IGFD (normal to high GH in circulation). The main focus of this review is on the GH gene, the various gene alterations and their possible impact on the pituitary gland. However, although transcription factors regulating the pituitary gland development may cause multiple pituitary hormone deficiency, they may present initially as GHD. Conflict of interest:None declared. PMID:21274339

Magnetic resonance imaging of the normal bovine digit.

PubMed

Raji, A R; Sardari, K; Mirmahmoob, P

2009-08-01

The purpose of this study was defining the normal structures of the digits and hoof in Holstein dairy cattle using Magnetic Resonance Image (MRI). Transverse, Sagital and Dorsoplantar MRI images of three isolated cattle cadaver digits were obtained using Gyroscan T5-NT a magnet of 0.5 Tesla and T1 Weighted sequence. The MRI images were compared to corresponding frozen cross-sections and dissect specimens of the cadaver digits. Relevant anatomical structures were identified and labeled at each level. The MRI images provided anatomical detail of the digits and hoof in Holstein dairy cattle. Transversal images provided excellent depiction of anatomical structures when compared to corresponding frozen cross-sections. The information presented in this paper would serve as an initial reference to the evaluation of MRI images of the digits and hoof in Holstein dairy cattle, that can be used by radiologist, clinicians, surgeon or for research propose in bovine lameness.

An analytical and experimental study of crack extension in center-notched composites

NASA Technical Reports Server (NTRS)

Beuth, Jack L., Jr.; Herakovich, Carl T.

1987-01-01

The normal stress ratio theory for crack extension in anisotropic materials is studied analytically and experimentally. The theory is applied within a microscopic-level analysis of a single center notch of arbitrary orientation in a unidirectional composite material. The bulk of the analytical work of this study applies an elasticity solution for an infinite plate with a center line to obtain critical stress and crack growth direction predictions. An elasticity solution for an infinite plate with a center elliptical flaw is also used to obtain qualitative predictions of the location of crack initiation on the border of a rounded notch tip. The analytical portion of the study includes the formulation of a new crack growth theory that includes local shear stress. Normal stress ratio theory predictions are obtained for notched unidirectional tensile coupons and unidirectional Iosipescu shear specimens. These predictions are subsequently compared to experimental results.

Encephalopathy in an infant with infantile spasms: possible role of valproate toxicity

PubMed Central

Sivathanu, Shobhana; Sampath, Sowmya; Veerasamy, Madhubala; Sunderkumar, Satheeshkumar

2014-01-01

An infant presented with global developmental delay and infantile spasms. EEG was suggestive of hypsarrhythmia. She was started on sodium valproate, clonazepam and adrenocorticotropic hormone injection. After an initial improvement the child developed vomiting, altered sensorium and increase in frequency of seizures suggestive of encephalopathy. Valproate-induced hyperammonaemia or hepatic encephalopathy was considered and the drug was withheld following which there was a dramatic improvement. Paradoxically, the liver function tests and serum ammonia were normal. However, a complete reversal of encephalopathy, on withdrawal of the drug, strongly suggested an adverse drug reaction (ADR) due to valproic acid. Marginal elevation of serum valproic acid prompted us to use the Naranjo ADR probability score to confirm the diagnosis. This case highlights the fact that valproate toxicity can manifest with normal liver function and serum ammonia levels. This is the youngest reported case with this rare form of valproate-induced encephalopathy. PMID:24810446

Sensitivity and Validity of Psychometric Tests for Assessing Driving Impairment: Effects of Sleep Deprivation

PubMed Central

Jongen, Stefan; Perrier, Joy; Vuurman, Eric F.; Ramaekers, Johannes G.; Vermeeren, Annemiek

2015-01-01

Objective To assess drug induced driving impairment, initial screening is needed. However, no consensus has been reached about which initial screening tools have to be used. The present study aims to determine the ability of a battery of psychometric tests to detect performance impairing effects of clinically relevant levels of drowsiness as induced by one night of sleep deprivation. Methods Twenty four healthy volunteers participated in a 2-period crossover study in which the highway driving test was conducted twice: once after normal sleep and once after one night of sleep deprivation. The psychometric tests were conducted on 4 occasions: once after normal sleep (at 11 am) and three times during a single night of sleep deprivation (at 1 am, 5 am, and 11 am). Results On-the-road driving performance was significantly impaired after sleep deprivation, as measured by an increase in Standard Deviation of Lateral Position (SDLP) of 3.1 cm compared to performance after a normal night of sleep. At 5 am, performance in most psychometric tests showed significant impairment. As expected, largest effect sizes were found on performance in the Psychomotor Vigilance Test (PVT). Large effects sizes were also found in the Divided Attention Test (DAT), the Attention Network Test (ANT), and the test for Useful Field of View (UFOV) at 5 and 11 am during sleep deprivation. Effects of sleep deprivation on SDLP correlated significantly with performance changes in the PVT and the DAT, but not with performance changes in the UFOV. Conclusion From the psychometric tests used in this study, the PVT and DAT seem most promising for initial evaluation of drug impairment based on sensitivity and correlations with driving impairment. Further studies are needed to assess the sensitivity and validity of these psychometric tests after benchmark sedative drug use. PMID:25668292

Decrease of premature mothers' stress levels in the intensive care unit.

PubMed

Villamizar-Carvajal, B; Vargas-Porras, C; García-Corzo, J R

2018-04-03

To determine the effectiveness of the 'Creating Opportunities for Parent Empowerment' (COPE) programme in reducing stress levels in mothers of preterm infants in the neonatal intensive care unit (NICU). Clinical trial performed in Colombia, including mothers of infants younger than 34 weeks of gestation, hospitalized, without a history of premature delivery. The mothers with psychiatric illnesses, language disorders, history of use of psychoactive substances and whose newborns had a congenital malformation were excluded. A group intervened with the COPE programme and a control group with the usual institutional management were formed. Block randomization and masking was used for mothers and evaluators. The Parental Stress Scale was applied: NICU; Shapiro Wilk normality test, Wilcoxon test and covariance analysis (ANCOVA) with a significance level of p<.05, 95% CI. 66 mothers were enrolled. The two groups were similar in their demographic characteristics and in the initial stress level score. The control group increased the final stress score in two categories and the intervention group decreased final values in all categories. The initial and final scores of the overall general stress level showed a significant decrease (p<.01), but when comparing with the ANCOVA analysis there was no significant difference (p=.4). The COPE programme reduces the level of maternal stress, strengthening aspects during hospitalization, such as: emotional support, strengthening their role as caregivers and interaction with their babies and the development of a friendly environment in the NICU. Copyright © 2018. Publicado por Elsevier España, S.L.U.

A decreased soluble Klotho level with normal eGFR, FGF23, serum phosphate, and FEP in an ADPKD patient with enlarged kidneys due to multiple cysts.

PubMed

Kanai, Takahiro; Shiizaki, Kazuhiro; Betsui, Hiroyuki; Aoyagi, Jun; Yamagata, Takanori

2018-05-16

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disorder. ADPKD is characterized clinically by the presence of multiple bilateral renal cysts that lead to chronic renal failure. The cysts evolve from renal tubular epithelial cells that express the Klotho gene. Notably, Klotho acts as a co-receptor for fibroblast growth factor 23 (FGF23); in this context, it induces phosphaturia and maintains serum phosphate at a normal level. Many reports have shown that decreases in the soluble Klotho level and increases in the FGF23 level are associated with glomerular filtration rate (GFR) decline, but a recent study observed these changes in patient with normal eGFR. It remains unclear whether the decrease in the Klotho level precedes the increase in FGF23. Here, we present an ADPKD patient with enlarged kidneys due to multiple cysts who had a decreased soluble Klotho level but a normal eGFR and a normal FGF23 level. The patient's serum phosphate level was normal, as was the fractional excretion of phosphate (FEP). This appears to be the first reported case to show a decreased soluble Klotho level plus normal eGFR, FGF23, and FEP. These results suggest that Klotho decreases before FGF23 increases and further suggest that Klotho is not required to maintain normal serum phosphate levels in ADPKD if the FEP and serum phosphate levels are normal.

TSNA levels in machine-generated mainstream cigarette smoke: 35 years of data.

PubMed

Appleton, Scott; Olegario, Raquel M; Lipowicz, Peter J

2013-07-01

This paper characterizes historical and current tobacco specific nitrosamine (TSNA) levels in mainstream (MS) cigarette smoke of US commercial cigarettes. To conduct this analysis, we gathered 35 years of published data of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN) levels in MS cigarette smoke. We also assessed internal data of MS smoke NNK and NNN levels generated from various market monitoring initiatives and from control cigarettes used in a multi-year program for testing cigarette ingredients. In all, we analyzed machine smoking data from 401 cigarette samples representing a wide range of products and design characteristics from multiple manufacturers and market leaders. There was no indication that TSNA levels systematically increased in cigarette MS smoke over the 35-year analysis period. In particular, TSNA levels expressed as either per cigarette or normalized for tar suggest a downward trend in MS smoke over the past 10 years. The apparent downward trend in TSNA levels in MS smoke may reflect industry and agricultural community efforts to reduce levels of TSNAs in tobacco and cigarette smoke. Copyright © 2013 Elsevier Inc. All rights reserved.

Costing the supply chain for delivery of ACT and RDTs in the public sector in Benin and Kenya.

PubMed

Shretta, Rima; Johnson, Brittany; Smith, Lisa; Doumbia, Seydou; de Savigny, Don; Anupindi, Ravi; Yadav, Prashant

2015-02-05

Studies have shown that supply chain costs are a significant proportion of total programme costs. Nevertheless, the costs of delivering specific products are poorly understood and ballpark estimates are often used to inadequately plan for the budgetary implications of supply chain expenses. The purpose of this research was to estimate the country level costs of the public sector supply chain for artemisinin-based combination therapy (ACT) and rapid diagnostic tests (RDTs) from the central to the peripheral levels in Benin and Kenya. A micro-costing approach was used and primary data on the various cost components of the supply chain was collected at the central, intermediate, and facility levels between September and November 2013. Information sources included central warehouse databases, health facility records, transport schedules, and expenditure reports. Data from document reviews and semi-structured interviews were used to identify cost inputs and estimate actual costs. Sampling was purposive to isolate key variables of interest. Survey guides were developed and administered electronically. Data were extracted into Microsoft Excel, and the supply chain cost per unit of ACT and RDT distributed by function and level of system was calculated. In Benin, supply chain costs added USD 0.2011 to the initial acquisition cost of ACT and USD 0.3375 to RDTs (normalized to USD 1). In Kenya, they added USD 0.2443 to the acquisition cost of ACT and USD 0.1895 to RDTs (normalized to USD 1). Total supply chain costs accounted for more than 30% of the initial acquisition cost of the products in some cases and these costs were highly sensitive to product volumes. The major cost drivers were found to be labour, transport, and utilities with health facilities carrying the majority of the cost per unit of product. Accurate cost estimates are needed to ensure adequate resources are available for supply chain activities. Product volumes should be considered when costing supply chain functions rather than dollar value. Further work is needed to develop extrapolative costing models that can be applied at country level without extensive micro-costing exercises. This will allow other countries to generate more accurate estimates in the future.

Normal and pathological serum levels of alpha2-macroglobulins in men and mice.

PubMed Central

Tunstall, A M; Merriman, J M; Milne, I; James, K

1975-01-01

The serum levels of alpha2-macroglobulin have been measured in normal men and mice and in a number of immunopathological conditions. Normal human concentrations are high in youth, reach their minimum in middle age, and gradually increase with old age. In all age groups the mean is higher in the female than in the male. Conversely, in normal mice the alpha2M level is low in youth, maximum in middle age, and shows a slight depression with old age, and the levels are frequently higher in males than in females; there are also strain variations. In human immunopathological conditions, there are some deviations from the normal alpha2M level but these are seen to be changes from the normal distribution of values around the mean, rather than significant elevation or depression of mean values. In some disease states studied there are differences between the sexes in the deviation from normal. "Abnormal" strains of mice had alpha2M levels within the range exhibited by "normal" mice but changes in the levels are seen in mice with various myelomas. Images PMID:47865

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study.

PubMed

Yuan, Hong; Zhang, Lei; Frank, Jonathan E; Inscoe, Christina R; Burk, Laurel M; Hadsell, Mike; Lee, Yueh Z; Lu, Jianping; Chang, Sha; Zhou, Otto

2015-09-01

Microbeam radiation treatment (MRT) using synchrotron radiation has shown great promise in the treatment of brain tumors, with a demonstrated ability to eradicate the tumor while sparing normal tissue in small animal models. With the goal of expediting the advancement of MRT research beyond the limited number of synchrotron facilities in the world, we recently developed a compact laboratory-scale microbeam irradiator using carbon nanotube (CNT) field emission-based X-ray source array technology. The focus of this study is to evaluate the effects of the microbeam radiation generated by this compact irradiator in terms of tumor control and normal tissue damage in a mouse brain tumor model. Mice with U87MG human glioblastoma were treated with sham irradiation, low-dose MRT, high-dose MRT or 10 Gy broad-beam radiation treatment (BRT). The microbeams were 280 μm wide and spaced at 900 μm center-to-center with peak dose at either 48 Gy (low-dose MRT) or 72 Gy (high-dose MRT). Survival studies showed that the mice treated with both MRT protocols had a significantly extended life span compared to the untreated control group (31.4 and 48.5% of life extension for low- and high-dose MRT, respectively) and had similar survival to the BRT group. Immunostaining on MRT mice demonstrated much higher DNA damage and apoptosis level in tumor tissue compared to the normal brain tissue. Apoptosis in normal tissue was significantly lower in the low-dose MRT group compared to that in the BRT group at 48 h postirradiation. Interestingly, there was a significantly higher level of cell proliferation in the MRT-treated normal tissue compared to that in the BRT-treated mice, indicating rapid normal tissue repairing process after MRT. Microbeam radiation exposure on normal brain tissue causes little apoptosis and no macrophage infiltration at 30 days after exposure. This study is the first biological assessment on MRT effects using the compact CNT-based irradiator. It provides an alternative technology that can enable widespread MRT research on mechanistic studies using a preclinical model, as well as further translational research towards clinical applications.

The effects of inpatient hybrid closed-loop therapy initiated within 1 week of type 1 diabetes diagnosis.

PubMed

Buckingham, Bruce A; Beck, Roy W; Ruedy, Katrina J; Cheng, Peiyao; Kollman, Craig; Weinzimer, Stuart A; DiMeglio, Linda A; Bremer, Andrew A; Slover, Robert; Cantwell, Martin

2013-05-01

This article describes our experience with inpatient hybrid closed-loop control (HCLC) initiated shortly after the diagnosis of type 1 diabetes in a randomized trial designed to assess the effectiveness of inpatient HCLC followed by outpatient sensor-augmented pump (SAP) therapy on the preservation of β-cell function. Forty-eight individuals with newly diagnosed type 1 diabetes and positive pancreatic autoantibodies (7.8-37.7 years old) received inpatient HCLC therapy for up to 93 h, initiated within 7 days of diagnosis. On initiation of HCLC, mean glucose concentration was 240±100 mg/dL. During the first day of HCLC, median of the participant's mean glucose concentrations fell rapidly to 146 mg/dL, a level of control that was sustained on Days 2 and 3 (138 mg/dL and 139 mg/dL, respectively). By Day 3, the median percentage of glucose values >250 and <60 mg/dL was <1%. During the first 2 weeks of SAP treatment at home, the median participant mean glucose level was 126 mg/dL (interquartile range, 117, 137 mg/dL), and the median percentage of values between 71 and 180 mg/dL was 85% (interquartile range, 80%, 90%). Inpatient HCLC followed by outpatient SAP therapy can provide a safe and effective means to rapidly reverse glucose toxicity and establish near-normal glycemic control in patients with newly diagnosed type 1 diabetes.

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

Sanders, J.E.; Buckner, C.D.; Leonard, J.M.

One hundred thirty-seven patients had gonadal function evaluated 1-11 years after marrow transplantation. All 15 women less than age 26 and three of nine older than age 26 who were treated with 200 mg/kg cyclophosphamide recovered normal gonadotropin levels and menstruation. Five have had five pregnancies resulting in three live births, one spontaneous abortion, and one elective abortion. Three of 38 women who were prepared with 120 mg/kg cyclophosphamide and 920-1200 rad total-body irradiation had normal gonadotropin levels and menstruation. Two had pregnancies resulting in one spontaneous and one elective abortion. Of 31 men prepared with 200 mg/kg cyclophosphamide, 30more » had normal luteinizing hormone levels, 20 had normal follicle-stimulating hormone levels, and 10 of 15 had spermatogenesis. Four have fathered five normal children. Thirty-six of 41 men prepared with 120 mg/kg cyclophosphamide and 920-1750 rad total-body irradiation had normal luteinizing hormone levels, ten had normal follicle-stimulating hormone levels, and 2 of 32 studied had spermatogenesis. One has fathered two normal children. It was concluded that cyclophosphamide does not prevent return of normal gonadal function in younger women and in most men. Total-body irradiation prevents return of normal gonadal function in the majority of patients.« less

Expression of C-type lectin receptor mRNA in chronic otitis media with cholesteatoma.

PubMed

Kim, Sang Hoon; Han, Seung-Ho; Byun, Jae Yong; Park, Moon Suh; Kim, Young Il; Yeo, Seung Geun

2017-06-01

The levels of expression of various C-type lectin receptors (CLRs) messenger ribo nucleic acids (mRNAs) were significantly higher in cholesteatomas than in normal skin, suggesting that these CLRs may be involved in the pathogenesis of cholesteatoma. Altered expression of pattern recognition receptors may be associated with immune responses in patients with cholesteatoma. This study assessed the levels of expression of CLR mRNAs in normal skin and in cholesteatoma. Cholesteatoma specimens were obtained from 38 patients with acquired cholesteatoma. The levels of expression of various CLR mRNAs were assessed quantitatively using real-time RT-PCR (Reverse transcription polymerase chain reaction) and correlated with age, sex, the presence of bacteria, hearing level, frequency of surgery, and degree of ossicle destruction. The levels of CD206 (cluster of differentiation 206), DEC-205 (Dendritic and epithelial cell-205), MGL (monoacylglycerol lipase), CLEC5A (C-type lectin domain family 5 member A), Dectin-2 (dendrite cell-associated C-type lectin-2), BDCA2 (Blood dendritic cell antigen 2), Mincle, DCIR (dendritic cell immunoreceptor), Dectin-1, MICL (Myeloid inhibitory C type-like lectin), and CLEC12B (C-type lectin domain family 12, member B) mRNAs were significantly higher in cholesteatoma than in control skin samples (p < 0.05). The levels of CLEC5A (C-type lectin domain family 5 member) and Dectin-1 mRNAs were significantly higher in cholesteatomas with ≥2 than ≤1 destroyed ossicles (p < 0.05), and the levels of MGL, Mincle, Dectin-1, and CLEC12B mRNAs were significantly higher in recurrent than initial cholesteatoma specimens (p < 0.05). The level of CLEC5A mRNAs was significantly higher in patients with severe than mild-to-moderate hearing loss (p < 0.05).

37 CFR 1.520 - Ex parte reexamination at the initiative of the Director.

Code of Federal Regulations, 2010 CFR

2010-07-01

... initiative of the Director. 1.520 Section 1.520 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND... Patents Request for Ex Parte Reexamination § 1.520 Ex parte reexamination at the initiative of the.... Normally requests from outside the Office that the Director undertake reexamination on his own initiative...

Thymus and activation-regulated chemokine as a clinical biomarker in atopic dermatitis.

PubMed

Kataoka, Yoko

2014-03-01

Thymus and activation-regulated chemokine (TARC/CCL17) is a member of the T-helper 2 chemokine family. In Japan, serum TARC level has been commercially measured since 2008. After years of experience, we realized that TARC is an extremely useful clinical biomarker for atopic dermatitis (AD) treatment. Usually, physicians conduct a visual examination to determine whether their treatment has been successful; however, the visual examination results may not always be accurate; in such cases, serum TARC levels should be measured to eliminate any ambiguity regarding the treatment outcome. When the waning and waxing of eczema and fluctuations in the serum TARC levels were considered, we frequently found that AD does not follow a natural course but follows non-regulated inflammatory floating caused by insufficient intermittent topical treatment. Serum TARC is a promising biomarker for remission and can be used for accurately monitoring proactive treatment for long-term control. Abnormally high serum TARC levels indicate accelerated pathogenesis of cutaneous inflammation. Rapid normalization and maintaining normal serum TARC levels using appropriate topical treatment is a reasonable strategy for alleviating inflammation without upregulating cytokine expression. Observing serum TARC levels during early intervention for severe infantile AD is worthwhile to determine initial disease activity and evaluate treatment efficacy. Appropriate control of severe early-onset infantile AD is important for improving prognosis of eczema and for preventing food allergies. Additionally, this biomarker is useful for improving patient adherence. Dermatologists will be able to make great progress in treating AD by adopting biomarkers such as TARC for accurately assessing non-visible subclinical disorders. © 2014 Japanese Dermatological Association.

Normal growth and muscle dysfunction in X-linked hypophosphatemic rickets associated with a novel mutation in the PHEX gene.

PubMed

Makras, Polyzois; Hamdy, Neveen A T; Kant, Sarina G; Papapoulos, Socrates E

2008-04-01

X-linked hypophosphatemic rickets (XLH) is characterized by hypophosphatemia and growth retardation. Early diagnosis and treatment improve growth. Our objective was to describe long-term observations of a family with XLH due to a novel mutation of the PHEX gene with unusual clinical features, including normal growth. The mother and her two sons were followed in the same institution for nearly 30 yr. The mother had hypophosphatemia and normal height (Z score, -0.6) without ever receiving any treatment. Her two sons achieved final heights of 183.7 cm (Z score, -0.01) and 182.7 cm (Z score, -0.18), respectively, despite late initiation of treatment with phosphate and low serum phosphate levels. In addition, they had reversible proximal myopathy that took about 7 yr to resolve in one of them. Direct sequencing of the PHEX gene revealed a new splice site mutation in intron 4 of the gene (IVS4+6T-->C) resulting in skipping of exon 4. Three members of a family with XLH due to a novel mutation of the PHEX gene had a normal growth pattern despite late diagnosis and treatment of the two boys and no treatment at all of their mother. The pathophysiological basis of this phenotype-genotype association warrants further investigation.

[Revelation of a polymicrocystic ovary syndrome after one month's treatment by pulsatile GnRH in a patient presenting with functional hypothalamic amenorrhea].

PubMed

Reyss, A C; Merlen, E; Demerle, C; Dewailly, D

2003-12-01

Polycystic ovary syndrome (PCOS) and hypothalamic amenorrhea (HA) are the most frequent causes of endocrine infertility, but their association is an uncommon occurrence. We report the case of a 28-year old woman suffering from infertility and amenorrhea. Her weight was normal (BMI = 19) and she had no hirsutism. She self-reported food restriction and a 10 kg weight loss 5 years ago, concomitant with the onset of amenorrhea. At the initial evaluation, the patient was considered as having HA due to food restriction. At ultrasonography, ovaries were small and multifollicular (right and left area: 2.2 and 2.5 cm(2), respectively; number of cysts 2-9 mm in diameter: 15 and 12, respectively), and no stromal hypertrophy was noted. She has been treated for 1 month by intravenous pulsatile GnRH administration. Although the doses were increased from 5 to 15 microg/pulse every 90 min, no E2 response and no follicular development were observed. Hormonal re-evaluation revealed normal levels of serum LH, FSH and androgens, and a normal LH/FSH ratio. However, a typical aspect of PCO was found at ultrasound (right and left area: 6.5 and 5.5 cm(2), respectively, and more than 15 small cysts arranged peripherally around an increased central stroma in each ovary). The treatment has been then switched to hMG, using the low dose step-up regimen and starting with 75 U/day. In the absence of response after 2 weeks, the dose was increased to 112.5 U/day and a multifollicular reaction occurred, leading to cancellation. In conclusion, we hypothesize that this patient had a "hidden" PCOS when she was hypogonadotrophic and that it developed very rapidly after restitution of a normal gonadotropin level under exogenous GnRH. This occurred despite a low insulin level, showing that hyperinsulinism is not a prerequisite for the development of PCOS in every case.

A Case of 3,4-Dimethoxyamphetamine (3,4-DMA) and 3,4-Methylenedioxymethamphetamine (MDMA) Toxicity with Possible Metabolic Interaction.

PubMed

Darracq, Michael A; Thornton, Stephen L; Minns, Alicia B; Gerona, Roy R

2016-01-01

We present a case of "ecstasy" ingestion revealing 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-dimethoxyamphetamine (3,4-DMA) and absence of cytochrome P450 (CYP)-2D6 MDMA metabolites. A 19-year-old presented following a seizure. Initial vital signs were normal. Laboratories were normal with the exception of sodium 127 mEq/L and urine drugs of abuse screen positive for amphetamines. Twelve hours later, serum sodium was 114 mEq/L and a second seizure occurred. After receiving hypertonic saline (3%), the patient had improvement in mental status and admitted to taking "ecstasy" at a rave prior to her initial presentation. Liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS) of serum and urine revealed MDMA, 3,4-DMA, and the CYP-2B6 MDMA metabolites 3,4-methylendioxyamphetamine (MDA) and 4-hydroxy-3-methoxyamphetamine (HMA). The CYP2D6 metabolites of MDMA, 3,4-dihydromethamphetamine (HHMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), were detected at very low levels. This case highlights the polypharmacy which may exist among users of psychoactive illicit substances and demonstrates that concurrent use of MDMA and 3,4-DMA may predispose patients to severe toxicity. Toxicologists and other healthcare providers should be aware of this potential toxicity.

Educational attainment and hippocampal atrophy in the Alzheimer's disease neuroimaging initiative cohort.

PubMed

Shpanskaya, Katie S; Choudhury, Kingshuk Roy; Hostage, Christopher; Murphy, Kelly R; Petrella, Jeffrey R; Doraiswamy, P Murali

2014-12-01

Subjects with higher cognitive reserve (CR) may be at a lower risk for Alzheimer's disease (AD), but the neural mechanisms underlying this are not known. Hippocampal volume loss is an early event in AD that triggers cognitive decline. Regression analyses of the effects of education on MRI-measured baseline HV in 675 subjects (201 normal, 329 with mild cognitive impairment (MCI), and 146 subjects with mild AD), adjusting for age, gender, APOE ɛ4 status and intracranial volume (ICV). Subjects were derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a large US national biomarker study. The association between higher education and larger HV was significant in AD (P=0.014) but not in cognitively normal or MCI subjects. In AD, HV was about 8% larger in a person with 20 years of education relative to someone with 6 years of education. There was also a trend for the interaction between education and APOE ɛ4 to be significant in AD (P=0.056). A potential protective association between higher education and lower hippocampal atrophy in patients with AD appears consistent with prior epidemiologic data linking higher education levels with lower rates of incident dementia. Longitudinal studies are warranted to confirm these findings. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Hypoglycemic effect of Gymnema sylvestre (retz.,) R.Br leaf in normal and alloxan induced diabetic rats.

PubMed

Sathya, S; Kokilavani, R; Gurusamy, K

2008-10-01

The water extract of Gymnema sylvestre R.Br leaf was tested for hypoglycemic activity in normal and alloxan induced diabetic rats. Grated amount (2ml/kg) of the water extract of Gymnema sylvestre leaf was given to both normal and alloxan induced diabetic rats. A significant reduction of glucose concentration was noticed in normal rats, blood glucose level was significantly reduced in diabetic rats. Protein level is also decreased in diabetic rats. Urea, uric acid and creatinine levels were increased in diabetic condition. After the herbal treatment the levels were altered near to normal level.

The role of rehearsal on the output order of immediate free recall of short and long lists.

PubMed

Grenfell-Essam, Rachel; Ward, Geoff; Tan, Lydia

2013-03-01

Participants tend to initiate immediate free recall (IFR) of short lists of words with the very first word on the list. Three experiments examined whether rehearsal is necessary for this recent finding. In Experiment 1, participants were presented with lists of between 2 and 12 words for IFR at a fast, medium, or slow rate, with and without articulatory suppression (AS). The tendency to initiate output with the first item for short lists (a) did not change greatly when presentation rate was increased from a medium to a fast rate under normal conditions, (b) was reduced but not eliminated by AS, and (c) was maintained at slower rates when rehearsal was allowed but decreased at slower rates when rehearsal was prevented. In Experiment 2, the overt rehearsal methodology was used, and the tendency to initiate output with the first item for short lists was present even in the absence of overt rehearsal. Experiment 3 re-examined IFR under normal encoding conditions and replicated the main findings from the normal encoding conditions of Experiment 1 while using the presentation rates and list lengths of Experiment 2. We argue that rehearsal is not strictly necessary for the tendency to initiate recall with the first item under normal conditions, but rehearsal nevertheless contributes to this effect at slower rates. (c) 2013 APA, all rights reserved.

Cell-extracellular matrix interactions can regulate the switch between growth and differentiation in rat hepatocytes: reciprocal expression of C/EBP alpha and immediate-early growth response transcription factors.

PubMed Central

Rana, B; Mischoulon, D; Xie, Y; Bucher, N L; Farmer, S R

1994-01-01

Previous investigations have shown that culture of freshly isolated hepatocytes under conventional conditions, i.e., on dried rat tail collagen in the presence of growth factors, facilitates cell growth but also causes an extensive down-regulation of most liver-specific functions. This dedifferentiation process can be prevented if the cells are cultured on a reconstituted basement membrane gel matrix derived from the Englebreth-Holm-Swarm mouse sarcoma tumor (EHS gel). To gain insight into the mechanisms regulating this response to extracellular matrix, we are analyzing the activities of two families of transcription factors, C/EBP and AP-1, which control the transcription of hepatic and growth-responsive genes, respectively. We demonstrate that isolation of hepatocytes from the normal quiescent rat liver by collagenase perfusion activates the immediate-early growth response program, as indicated by increased expression of c-jun, junB, c-fos, and c-myc mRNAs. Adhesion of these activated cells to dried rat tail collagen augments the elevated levels of these mRNAs for the initial 1 to 2 h postplating; junB and c-myc mRNA levels then drop steeply, with junB returning to normal quiescence and the c-myc level remaining slightly elevated during the 3-day culture period. Levels of c-jun mRNA and AP-1 DNA binding activity, however, remain elevated from the outset, while C/EBP alpha mRNA expression is down-regulated, resulting in a decrease in the steady-state levels of the 42- and 30-kDa C/EBP alpha polypeptides and C/EBP alpha DNA binding activity. In contrast, C/EBP beta mRNA production remains at near-normal hepatic levels for 5 to 8 days of culture, although its DNA binding activity decreases severalfold during this time. Adhesion of hepatocytes to the EHS gel for the same period of time dramatically alters this program: it arrests growth and inhibits AP-1 DNA binding activity and the expression of c-jun, junB, and c-myc mRNAs, but, in addition, it restores C/EBP alpha mRNA and protein as well as C/EBP alpha and C/EBP beta DNA binding activities to the abundant levels present in freshly isolated hepatocytes. These changes are not due merely to growth inhibition, because suppression of hepatocyte proliferation on collagen by epidermal growth factor starvation or addition of transforming growth factor beta does not inhibit AP-1 activity or restore C/EBP alpha DNA binding activity to normal hepatic levels. These data suggest that expression of the normal hepatic phenotype requires that hepatocytes exist in a G0 state of growth arrest, facilitated here by adhesion of cells to the EHS gel, in order to express high levels of hepatic transcription factors such as C/EBP alpha. Images PMID:8065319

Tenofovir monotherapy for hepatitis B after 1 year does not produce renal dysfunction, but is associated with hyperparathyroidism not related to vitamin D.

PubMed

Patricio, Jose A; Lopes, Patricia F; Medeiros, Thalia; Mendes, Guilherme F; Silva, Andrea A; Esberard, Eliane B; Lugon, Jocemir R; Almeida, Jorge R

2016-01-01

Viral hepatitis B (VHB) represents a major public health problem. Studies from HIV multidrug patients have associated the use of tenofovir disoproxil fumarate (TDF) with renal dysfunction and phosphate wasting. The aim of this study was to examine the effect of year-long TDF monotherapy on renal function in VHB patients. We evaluated adult patients diagnosed with VHB before treatment initiation (T0), and after 3 and 12 months (T3 and T12) of TDF initiation. Estimated glomerular filtration rate (eGFR) was estimated by serum cystatin C and creatinine. In addition, urinary electrolytes and tubular biomarkers (cystatin C, β2-microglobulin and neutrophil gelatinase-associated lipocalin) were analyzed, as well as parathyroid hormone (PTH) and 25(OH)vitamin D levels. After 1 year, 32 patients completed the study, 22 (68.7%) men and 12 (37.5%) Whites, mean age 44.1±12.0 years. We found that serum electrolytes were similar at baseline and 3 or 12 months after initiation of TDF monotherapy. In addition, urinary fractional excretions of electrolytes as well as proteinuria, albuminuria, urinary β2-microglobulin, and urinary cystatin C showed no significant differences across the treatment timeline. There were also no statistical differences in the eGFR. There was a statistically significant increase in the PTH (Friedman's test, P=0.012), but the 25(OH)vitamin D levels were in the normal range in the beginning and did not change at the follow-up. Moreover, there was no correlation between the initial levels of vitamin D and the corresponding increases in the PTH values. If used as monotherapy in hepatitis B patients for a 12-month period, TDF is not associated with changes in either eGFR or a panel of urinary biomarkers. Serum and urinary electrolytes also remained unchanged. Of note, a significant increase in the PTH was found, although not related to the 25(OH)vitamin D initial status.

Computational Modeling and Analysis of Insulin Induced Eukaryotic Translation Initiation

PubMed Central

Lequieu, Joshua; Chakrabarti, Anirikh; Nayak, Satyaprakash; Varner, Jeffrey D.

2011-01-01

Insulin, the primary hormone regulating the level of glucose in the bloodstream, modulates a variety of cellular and enzymatic processes in normal and diseased cells. Insulin signals are processed by a complex network of biochemical interactions which ultimately induce gene expression programs or other processes such as translation initiation. Surprisingly, despite the wealth of literature on insulin signaling, the relative importance of the components linking insulin with translation initiation remains unclear. We addressed this question by developing and interrogating a family of mathematical models of insulin induced translation initiation. The insulin network was modeled using mass-action kinetics within an ordinary differential equation (ODE) framework. A family of model parameters was estimated, starting from an initial best fit parameter set, using 24 experimental data sets taken from literature. The residual between model simulations and each of the experimental constraints were simultaneously minimized using multiobjective optimization. Interrogation of the model population, using sensitivity and robustness analysis, identified an insulin-dependent switch that controlled translation initiation. Our analysis suggested that without insulin, a balance between the pro-initiation activity of the GTP-binding protein Rheb and anti-initiation activity of PTEN controlled basal initiation. On the other hand, in the presence of insulin a combination of PI3K and Rheb activity controlled inducible initiation, where PI3K was only critical in the presence of insulin. Other well known regulatory mechanisms governing insulin action, for example IRS-1 negative feedback, modulated the relative importance of PI3K and Rheb but did not fundamentally change the signal flow. PMID:22102801

The Initiation of Smooth Pursuit is Delayed in Anisometropic Amblyopia.

PubMed

Raashid, Rana Arham; Liu, Ivy Ziqian; Blakeman, Alan; Goltz, Herbert C; Wong, Agnes M F

2016-04-01

Several behavioral studies have shown that the reaction times of visually guided movements are slower in people with amblyopia, particularly during amblyopic eye viewing. Here, we tested the hypothesis that the initiation of smooth pursuit eye movements, which are responsible for accurately keeping moving objects on the fovea, is delayed in people with anisometropic amblyopia. Eleven participants with anisometropic amblyopia and 14 visually normal observers were asked to track a step-ramp target moving at ±15°/s horizontally as quickly and as accurately as possible. The experiment was conducted under three viewing conditions: amblyopic/nondominant eye, binocular, and fellow/dominant eye viewing. Outcome measures were smooth pursuit latency, open-loop gain, steady state gain, and catch-up saccade frequency. Participants with anisometropic amblyopia initiated smooth pursuit significantly slower during amblyopic eye viewing (206 ± 20 ms) than visually normal observers viewing with their nondominant eye (183 ± 17 ms, P = 0.002). However, mean pursuit latency in the anisometropic amblyopia group during binocular and monocular fellow eye viewing was comparable to the visually normal group. Mean open-loop gain, steady state gain, and catch-up saccade frequency were similar between the two groups, but participants with anisometropic amblyopia exhibited more variable steady state gain (P = 0.045). This study provides evidence of temporally delayed smooth pursuit initiation in anisometropic amblyopia. After initiation, the smooth pursuit velocity profile in anisometropic amblyopia participants is similar to visually normal controls. This finding differs from what has been observed previously in participants with strabismic amblyopia who exhibit reduced smooth pursuit velocity gains with more catch-up saccades.

Proliferative lupus nephritis in the absence of overt systemic lupus erythematosus: A historical study of 12 adult patients.

PubMed

Touzot, Maxime; Terrier, Cécile Saint-Pastou; Faguer, Stanislas; Masson, Ingrid; François, Hélène; Couzi, Lionel; Hummel, Aurélie; Quellard, Nathalie; Touchard, Guy; Jourde-Chiche, Noémie; Goujon, Jean-Michel; Daugas, Eric

2017-12-01

Severe lupus nephritis in the absence of systemic lupus erythematosus (SLE) is a rare condition with an unclear clinical presentation and outcome.We conducted a historical observational study of 12 adult (age >18 years) patients with biopsy-proven severe lupus nephritis or lupus-like nephritis without SLE immunological markers at diagnosis or during follow-up. Excluded were patients with chronic infections with HIV or hepatitis B or C; patients with a bacterial infectious disease; and patients with pure membranous nephropathy. Electron microscopy was retrospectively performed when the material was available. End points were the proportion of patients with a complete response (urine protein to creatinine ratio <0.5 g/day and a normal or near-normal eGFR), partial response (≥50% reduction in proteinuria to subnephrotic levels and a normal or near-normal eGFR), or nonresponse at 12 months or later after the initiation of the treatment.The study included 12 patients (66% female) with a median age of 36.5 years. At diagnosis, median creatinine and proteinuria levels were 1.21 mg/dL (range 0.5-11.6) and 7.5 g/day (1.4-26.7), respectively. Six patients had nephrotic syndrome and acute kidney injury. Renal biopsy examinations revealed class III or class IV A/C lupus nephritis in all cases. Electron microscopy was performed on samples from 5 patients. The results showed mesangial and subendothelial dense deposits consistent with LN in 4 cases, and a retrospective diagnosis of pseudo-amyloid fibrillary glomerulonephritis was made in 1 patient.Patients received immunosuppressive therapy consisting of induction therapy followed by maintenance therapy, similar to treatment for severe lupus nephritis. Remission was recorded in 10 patients at 12 months after the initiation of treatment. One patient reached end-stage renal disease. After a median follow-up of 24 months, 2 patients relapsed.Lupus nephritis in the absence of overt SLE is a nosological entity requiring careful etiological investigation, including systematic electron microscopy examination of renal biopsies to rule out fibrillary glomerulonephritis. In this series, most patients presented with severe glomerulonephritis, which was highly similar to lupus nephritis at presentation and in terms of response to immunosuppressive therapy.

Mortality in a complete 4-year follow up of 85-year-old residents of Leiden, classified by serum level of thyrotropin and thyroxine.

PubMed

Singer, Richard B

2006-01-01

The authors of the source article emphasize the clinical tendency to screen for, detect and treat for thyroid dysfunction in very elderly patients, in which it is a fairly common disorder, often with occult or no symptoms. Published evidence is conflicting on the benefit, if any, of such a program. Accordingly, they devised a prospective, population-based study to determine outcomes, including survival outcome, based on serum levels of thyroid-stimulating hormone (TSH) and thyroxine. A cohort of 558 subjects who had their 85th birthday between September 1997 and September 1999 was enrolled after consent of the subject and screening examination that included serum TSH and thyroxine levels. This represented a 79% sample of all 85-year-old residents of Leiden, the Netherlands. Follow up was complete for survival 4 years to the subject's 89th birthday or prior death, although 70 subjects refused the annual re-examination. Thyroid function, disability, cognitive function and number of chronic diseases were analyzed, in addition to mortality, through Cox regression and other statistical methods. In 67 subjects with abnormally high TSH (>4.8 mIU/ L), the mean annual mortality rate was derived as 64 deaths per 1000 per year. In the 491 subjects with normal TSH or low TSH (<0.3 mIU/L), the mean annual mortality rate was derived at 114 per 1000 per year. Laboratory evidence of hypothyroidism (initially low serum thyroxine) was found in only 37 of the 67 subjects. In the 13% of elderly subjects in Leiden with abnormally high serum TSH levels, the mean annual mortality rate was significantly lower than the mortality rate in the 87% of the elderly patients with normal or low serum TSH. The significance is based on 95% confidence levels of the Poisson distribution. The rate in the group with high TSH levels had 16 deaths in 264 person-years of follow up (FU). The majority with normal or low TSH levels had 193 deaths in 1698 person-years of FU.

A Quick Reference on Respiratory Alkalosis.

PubMed

Johnson, Rebecca A

2017-03-01

Respiratory alkalosis, or primary hypocapnia, occurs when alveolar ventilation exceeds that required to eliminate the carbon dioxide produced by tissues. Concurrent decreases in Paco 2 , increases in pH, and compensatory decreases in blood HCO 3 - levels are associated with respiratory alkalosis. Respiratory alkalosis can be acute or chronic, with metabolic compensation initially consisting of cellular uptake of HCO 3 - and buffering by intracellular phosphates and proteins. Chronic respiratory alkalosis results in longer-lasting decreases in renal reabsorption of HCO 3 - ; the arterial pH can approach near-normal values. Copyright © 2016 Elsevier Inc. All rights reserved.

Initial conditions for dark soliton generation in normal-dispersion fiber lasers.

PubMed

Ge, Y Q; Luo, J L; Li, L; Jin, X X; Tang, D Y; Shen, D Y; Zhang, S M; Zhao, L M

2015-01-01

We report results of numerical simulations on the various initial conditions for dark soliton generation in an all-normal-dispersion fiber laser. All the dark solitons generated are odd dark solitons. Differently from the dark soliton generation in fibers, where an arbitrary dip could evolve into a dark soliton, it is found that the dark soliton can originate only from an initial dip with a certain parameter requirement. A bright pulse with either a hyperbolic secant square, Gaussian, or Lorentz profile can be developed into a dark soliton, provided that the parameters of the initial bright pulse are selected. Dark solitons can be generated in fiber lasers only if there is a phase jump, and this phase jump can be maintained and evolve to π during the pulse evolution.

[Epileptic encephalopathy associated with forced normalization after administration of levetiracetam].

PubMed

Kikuchi, Takahiro; Kato, Mitsuhiro; Takahashi, Nobuya; Nakamura, Kazuyuki; Hayasaka, Kiyoshi

2013-09-01

Here we report a case of a 10-year-old female with unclassified epileptic encephalopathy who showed forced normalization after administration of levetiracetam (LEV). She initially presented with intractable tonic and myoclonic seizures that were observed about 10 times a day along with frequent multifocal sharp and slow wave complexes on electroencephalography (EEG). We were forced to decrease the topiramate dose because of the appearance of nystagmus, and her myoclonic seizures became worse. We added LEV (250 mg/day) and her tonic and myoclonic seizures disappeared one day after initiation of LEV administration. However, she showed hyporesponsiveness and akinesia. The disappearance of paroxysmal discharges on EEG confirmed the diagnosis of forced normalization. Despite continuous administration of LEV, tonic and myoclonic seizures relapsed within a month but her psychotic symptoms resolved simultaneously. To the best of our knowledge, this is the first reported case of forced normalization after LEV administration. It should be noted that LEV may cause forced normalization although it can be started at an adequate dosage.

Analysis of vector wind change with respect to time for Cape Kennedy, Florida: Wind aloft profile change vs. time, phase 1

NASA Technical Reports Server (NTRS)

Adelfang, S. I.

1977-01-01

Wind vector change with respect to time at Cape Kennedy, Florida, is examined according to the theory of multivariate normality. The joint distribution of the four variables represented by the components of the wind vector at an initial time and after a specified elapsed time is hypothesized to be quadravariate normal; the fourteen statistics of this distribution, calculated from fifteen years of twice daily Rawinsonde data are presented by monthly reference periods for each month from 0 to 27 km. The hypotheses that the wind component changes with respect to time is univariate normal, the joint distribution of wind component changes is bivariate normal, and the modulus of vector wind change is Rayleigh, has been tested by comparison with observed distributions. Statistics of the conditional bivariate normal distributions of vector wind at a future time given the vector wind at an initial time are derived. Wind changes over time periods from one to five hours, calculated from Jimsphere data, are presented.

Viewing strategies for simple and chimeric faces: an investigation of perceptual bias in normals and schizophrenic patients using visual scan paths.

PubMed

Phillips, M L; David, A S

1997-11-01

Left hemi-face (LHF) perceptual bias of chimeric faces in normal right-handers is well-documented. We investigated mechanisms underlying this by measuring visual scan paths in right-handed normal controls (n = 9) and schizophrenics (n = 8) for simple, full-face photographs and schematic, happy-sad chimeric faces over 5 s. Normals viewed the left side/ LHF first, more so than the right of all stimuli. Schizophrenics viewed the LHF first more than the right of stimuli for which there was a LHF choice of predominant affect. Neither group demonstrated an overall LHF perceptual bias for the chimeric stimuli. Readjustment of the initial LHF bias in controls was probably a result of increased attention to stimulus detail with scanning, whereas the schizophrenics demonstrated difficulty in redirection of the initial focus of attention. The study highlights the role of visual scan paths as a marker of normal and abnormal attentional processes. Copyright 1997 Academic Press.

Effect of viscosity on food transport and swallow initiation during eating of two-phase food in normal young adults: a pilot study.

PubMed

Matsuo, Koichiro; Kawase, Soichiro; Wakimoto, Nina; Iwatani, Kazuhiro; Masuda, Yuji; Ogasawara, Tadashi

2013-03-01

When eating food containing both liquid and solid phases (two-phase food), the liquid component frequently enters the hypopharynx before swallowing, which may increase the risk of aspiration. We therefore tested whether preswallow bolus transport and swallow initiation would change as the viscosity of two-phase food was increased. Fiberoptic endoscopy was recorded while 18 adult subjects ate 5 g of steamed rice with 3 ml of blue-dye water. Liquid viscosity was set at four levels by adding a thickening agent (0, 1, 2, and 4 wt%, respectively). We measured the timing of the leading edge of the food reaching the base of the epiglottis, as well as the location of the leading edge at swallow initiation. As viscosity increased, the leading edge of the food reached the epiglottis significantly later during chewing and was higher in the pharynx at swallow onset. The time after the leading edge reached the epiglottis did not vary among the viscosities of the two-phase food. This study found that the initial viscosity of two-phase food significantly altered oropharyngeal bolus flow and the timing of swallow initiation. Accordingly, increased two-phase food viscosity may delay food entry into the pharynx and be of use in dysphagic diets.

Heat shock protein-27 protects human bronchial epithelial cells against oxidative stress–mediated apoptosis: possible implication in asthma

PubMed Central

Merendino, Anna M.; Paul, Catherine; Vignola, Antonio M.; Costa, Maria A.; Melis, Mario; Chiappara, Giuseppina; Izzo, V.; Bousquet, J.; Arrigo, André-Patrick

2002-01-01

Inflammation of the human bronchial epithelium, as observed in asthmatics, is characterized by the selective death of the columnar epithelial cells, which desquamate from the basal cells. Tissue repair initiates from basal cells that resist inflammation. Here, we have evaluated the extent of apoptosis as well as the Hsp27 level of expression in epithelial cells from bronchial biopsy samples taken from normal and asthmatic subjects. Hsp27 is a chaperone whose expression protects against oxidative stress. We report that in asthmatic subjects the basal epithelium cells express a high level of Hsp27 but no apoptotic morphology. In contrast, apoptotic columnar cells are devoid of Hsp27 expression. Moreover, we observed a decreased resistance to hydrogen peroxide–induced apoptosis in human bronchial epithelial 16–HBE cells when they were genetically modified to express reduced levels of Hsp27. PMID:12482203

Viewing boxes: a survey in diagnostic radiology departments of Moroccan hospitals.

PubMed

Bentayeb, F; Nfaoiu, K; Basraoui, O; Azevedo, A C P

2010-10-01

This work consists on a survey of the performance of viewing boxes installed in diagnostic radiology departments and included several aspects: checking the illuminance of the diagnostic rooms where the viewing boxes are located as well as the viewing boxes luminance levels and homogeneity. Seven hospitals took part in the survey, being three in the city of Casablanca and four in Rabat. A total of 136 viewing boxes and 18 diagnostic rooms have been checked. It was found that one diagnostic room works under normal conditions and that 80% of the viewing boxes present luminance levels below the international recommendations and the homogeneity is inadequate in 85%. Some simple and cheap initiatives can be performed in these departments to increase luminance and improve homogeneity levels such as cleaning and bulbs replacement. Copyright © 2009 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Crossing the other side of the algorithm: a challenging case of adrenal Cushing's syndrome.

PubMed

Antonio, Imelda Digna Soberano; Sandoval, Mark Anthony Santiago; Lantion-Ang, Frances Lina

2011-12-01

The diagnosis of endogenous Cushing's syndrome and its aetiology involved documenting the hypercotisolism and then determining whether that hypercortisolism is adrenocorticotropic hormone-dependent (ACTH-dependent) or not. Hence, following the algorithm, an undetected ACTH level points to an adrenal Cushing's while a detectable or elevated ACTH level points to either a pituitary or ectopic Cushing's syndrome. The authors present a case of florid adrenal Cushing's syndrome initially presenting with a normal ACTH level, which led to the investigation for an ACTH-secreting tumour. Adding to the confusion, a MRI done showed an intrasellar focus. Knowledge of how ACTH-dependent (versus ACTH-independent) Cushing's syndrome manifests clinically, supported by results of repeat laboratory tests, led to the true diagnosis. This case illustrates that a detectable ACTH does not rule out an adrenal Cushing's syndrome nor does a positive pituitary imaging confirm Cushing's disease.

In vitro measurements of oxygen consumption rates in hTERT-RPE cells exposed to low levels of red light

NASA Astrophysics Data System (ADS)

Wigle, Jeffrey C.; Castellanos, Cherry C.

2016-03-01

Exposure to 2.88 J/cm2 of red light induces an adaptive response against a lethal pulse of 2.0 μm laser radiation in hTERT-RPE cells in vitro, but not in a knockdown mutant for vascular endothelial growth factor c (VEGF-C). The generally accepted initiation sequence for photobiomodulation is that absorption of red light by cytochome c oxidase (CCOX) of the electron transport chain increases the binding affinity of CCOX for O2 vs. nitric oxide (NO). This results in displacement of NO by O2 in the active site of CCOX, thereby increasing cellular respiration and intracellular ATP. We've previously reported that red-light exposure induces a small, but consistently reproducible, increase in NO levels in these cells. But the relative importance of NO and oxidative phosphorylation is unclear because little is known about the relative contributions of NO and ATP to the response. However, if NO dissociation from CCOX actually increases oxidative phosphorylation, one should see a corresponding increase in oxygen consumption. A Seahorse Extracellular Flux Analyzer was used to measure oxygen consumption rates (OCR) in normal and mutant cells as a proxy for oxidative phosphorylation. Both basal respiration and maximum respiration rates in normal cells are significantly higher than in the mutant. The normal cells have a significant amount of "excess capacity," whereas the VEGF-C(KD) have little or none. The OCR in exposed normal cells is lower than in unexposed cells when measured immediately after exposure. The exposures used for these experiments had no effect on the OCR in mutant cells.

Retrospective study of salazosulfapyridine in eight patients with rheumatoid arthritis on hemodialysis.

PubMed

Akiyama, Yuji; Sakurai, Yusei; Kato, Yuji; Furuta, Eiichi; Mimura, Toshihide

2014-03-01

We examined the pharmacokinetics (PK) of salazosulfapyridine (SASP) and its metabolite, sulfapyridine (SP), as well as the influence of hemodialysis (HD), and investigated the utility of consecutive administration of SASP in rheumatoid arthritis patients undergoing HD. The PK of salazosulfapyridine and SP in serum samples from 8 patients was determined using high-performance liquid chromatography. When SASP 500 mg was administered, the area under curve for serum concentration of SASP was similar to that seen with normal subjects in the Phase I study. The maximum serum concentration of SP was significantly higher than that in normal subjects, but was far from the danger level. SASP was not dialyzed, whereas on average 62% of SP was dialyzed. Following 5 consecutive days of administration of SASP, serum levels of SASP and SP on day 5 were rather higher than those on day 1, although both remained within the safe range. SASP administration from four months to three years in seven subjects resulted in four American College of Rheumatology 20 improvement criteria (57.1%), with one developing a rash. If SASP is initiated at a low dosage (≤ 500 mg) and increased up to 1000 mg under careful monitoring, it is safe for HD patients.

Hyperfunctioning thyroid nodules in children and adolescents.

PubMed

de Luca, F; Chaussain, J L; Job, J C

1986-01-01

Eight children and adolescents, seven female and one male, aged 7.1 to 15.0 years, referred over a 12-year period for a solitary mass in an otherwise normal thyroid gland, exhibited a hyperfunctioning nodule on thyroid scintiscan. Tracer uptake in the surrounding thyroid tissue was reduced or completely suppressed, but could be restored after TSH stimulation. Only one patient had mild clinical hyperthyroidism with normal T4 but increased T3 serum levels and blunted TSH responsiveness to TRH. A similar hormonal pattern suggestive of subclinical hyperthyroidism was found in three other subjects who were clinically euthyroid. One patient initially euthyroid progressed to subclinical hyperthyroidism two years later. In the whole group a significant negative relationship was found between serum T3 level and TRH-stimulated TSH peak (r = -0.829, p less than 0.02). All the patients underwent selective surgery after a 3-month to 2-year period of follow-up. Microscopic examination was consistent with adenoma in seven patients, while in one case a well-encapsulated papillary adenocarcinoma was found. Though hyperfunctioning nodules are seldom malignant, their surgical removal must be recommended when they become thyrotoxic, exceed 3 cm or show progressive enlargement.

TSH-induced hyperthyroidism caused by a pituitary tumor.

PubMed

Beck-Peccoz, Paolo; Persani, Luca

2006-09-01

A 45-year-old man presented with frontal headache and visual disturbances to our clinic. For the previous 5 years, he had been receiving treatment for long-lasting mild hyperthyroidism with antithyroid therapy, but therapy had not been carefully followed. During the last 2 years he had also complained of erectile dysfunction and loss of libido. On physical examination, he had a small goiter, normal skin, no Graves' ophthalmopathy, normal BMI, and reduced testis volume and pubic hair. Serum levels of free T3 and T4, serum prolactin, testosterone, serum gonadotropins, insulin-like growth factor 1, adrenocorticotropic hormone, and cortisol were measured. MRI scan, TSH-releasing hormone test, and T3 suppression test were carried out. Levels of pituitary glycoprotein hormone alpha-subunit and sex-hormone-binding protein were also measured. Hyperthyroidism caused by a mixed pituitary adenoma that secretes prolactin and TSH. Trans-sphenoidal resection of the pituitary tumor. After surgery, T3 suppression test failed to completely suppress TSH secretion, which suggested a persistence of residual adenomatous cells. Hyperthyroidism and hypogonadism recurred after 5 years, therefore, treatment with lanreotide was initiated, and resulted in complete resolution of signs and symptoms of the disease.

Thyrotoxicosis presenting as hypogonadism: a case of central hyperthyroidism.

PubMed

Childress, R Dale; Qureshi, M Nauman; Kasparova, Meri; Oktaei, Hooman; Williams-Cleaves, Beverly; Solomon, Solomon S

2004-11-01

Herein, we present a case of central thyrotoxicosis with well-documented serial therapeutic interventions. Thyroid-stimulating hormone (TSH)-secreting pituitary tumors represent a rare cause of hyperthyroidism. It is being diagnosed more frequently with the third-generation TSH assay. Many conditions can produce normal or elevated TSH levels in combination with elevated thyroid hormone levels. The differential diagnosis includes resistance to thyroid hormone (RTH, Refetoff's syndrome), assay interference from anti-T4/T3 and heterophile antibodies, elevated or altered binding proteins, drugs affecting peripheral metabolism, and noncompliance with thyroid replacement therapy. In contrast to RTH, our patient presented had high alpha-subunit-to-TSH molar ratio, failed TSH response to thyrotropin-releasing hormone stimulation, and a large pituitary mass. Normal or high TSH in the presence of elevated T4 or T3 is a fairly common clinical scenario with many etiologic possibilities. This TSH-producing adenoma represents an unusual initial clinical presentation, as hypogonadism appeared before features of thyrotoxicosis were appreciated. This case represents the most modern therapeutic approach to the management of this rare disease. Our patient has done well on octreotide with control of thyrotoxicosis and an additional 30% shrinkage of his tumor mass.

Traction force microscopy of engineered cardiac tissues.

PubMed

Pasqualini, Francesco Silvio; Agarwal, Ashutosh; O'Connor, Blakely Bussie; Liu, Qihan; Sheehy, Sean P; Parker, Kevin Kit

2018-01-01

Cardiac tissue development and pathology have been shown to depend sensitively on microenvironmental mechanical factors, such as extracellular matrix stiffness, in both in vivo and in vitro systems. We present a novel quantitative approach to assess cardiac structure and function by extending the classical traction force microscopy technique to tissue-level preparations. Using this system, we investigated the relationship between contractile proficiency and metabolism in neonate rat ventricular myocytes (NRVM) cultured on gels with stiffness mimicking soft immature (1 kPa), normal healthy (13 kPa), and stiff diseased (90 kPa) cardiac microenvironments. We found that tissues engineered on the softest gels generated the least amount of stress and had the smallest work output. Conversely, cardiomyocytes in tissues engineered on healthy- and disease-mimicking gels generated significantly higher stresses, with the maximal contractile work measured in NRVM engineered on gels of normal stiffness. Interestingly, although tissues on soft gels exhibited poor stress generation and work production, their basal metabolic respiration rate was significantly more elevated than in other groups, suggesting a highly ineffective coupling between energy production and contractile work output. Our novel platform can thus be utilized to quantitatively assess the mechanotransduction pathways that initiate tissue-level structural and functional remodeling in response to substrate stiffness.

Analysis of Mold Friction in a Continuous Casting Using Wavelet Transform

NASA Astrophysics Data System (ADS)

Ma, Yong; Fang, Bohan; Ding, Qiqi; Wang, Fangyin

2018-04-01

Mold friction (MDF) is an important parameter reflecting the lubrication condition between the initial shell and the mold during continuous casting. In this article, based on practical MDF from the slab continuous casting driven by a mechanical vibration device, the characteristics of friction were analyzed by continuous wavelet transform (CWT) and discrete wavelet transform (DWT) in different casting conditions, such as normal casting, level fluctuation, and alarming of the temperature measurement system. The results show that the CWT of friction accurately captures the subtle changes in friction force, such as the periodic characteristic of MDF during normal casting and the disordered feature of MDF during level fluctuation. Most important, the results capture the occurrence of abnormal casting and display the friction frequency characteristics at this abnormal time. In addition, in this article, there are some abnormal casting conditions, and the friction signal is stable until there is a sudden large change when abnormal casting, such as split breakout and submerged entry nozzle breakage, occurs. The DWT has a good ability to capture the friction characteristics for such abnormal situations. In particular, the potential abnormal features of MDF were presented in advance, which provides strong support for identifying abnormal casting and even preventing abnormal casting.

Scram recoveries---C Reactor

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

Constable, D.W.; Pierce, J.R.; Wood, S.A.

1962-04-26

The purpose of this report is to discuss the observations made on two equilibrium scram recovery startups (April 5 and April 16). Normally, the two startups would have little significance but unusual ruptures were experienced in the top near section of the reactor shortly after both startups, which indicates that some similarity could exist between the two. The ruptures were unusual in that the two tubes involved both had multiple ruptures. One tube contained two E{sup 2} ruptures and the other tube contained three overbore metal ruptures. The overbore tube also contained three incipient ruptures (uranium split under the can).more » The initial rise to power on both startups appeared to be normal with the flux peaking on the near side as expected. On the April 16 startup the maximum level reached was 1050 at which time a rupture in overbore tube 3062 caused on increase in pressure resulting in a high trip on the Panellit gauge. A level of 1600 was reached on the April 5 startup which was held for approximately 14 hours at which time the reactor was shut down due to rupture indications on row 29.« less

Computational modeling of the amphibian thyroid axis ...

EPA Pesticide Factsheets

In vitro screening of chemicals for bioactivity together with computational modeling are beginning to replace animal toxicity testing in support of chemical risk assessment. To facilitate this transition, an amphibian thyroid axis model has been developed to describe thyroid homeostasis during Xenopus laevis pro-metamorphosis. The model simulates the dynamic relationships of normal thyroid biology throughout this critical period of amphibian development and includes molecular initiating events (MIEs) for thyroid axis disruption to allow in silico simulations of hormone levels following chemical perturbations. One MIE that has been formally described using the adverse outcome pathway (AOP) framework is thyroperoxidase (TPO) inhibition. The goal of this study was to refine the model parameters and validate model predictions by generating dose-response and time-course biochemical data following exposure to three TPO inhibitors, methimazole, 6-propylthiouracil and 2-mercaptobenzothiazole. Key model variables including gland and blood thyroid hormone (TH) levels were compared to empirical values measured in biological samples at 2, 4, 7 and 10 days following initiation of exposure at Nieuwkoop and Faber (NF) stage 54 (onset of pro-metamorphosis). The secondary objective of these studies was to relate depleted blood TH levels to delayed metamorphosis, the adverse apical outcome. Delayed metamorphosis was evaluated by continuing exposure with a subset of larvae until a

Hypoglycemic effect of Gymnema sylvestre (retz.,) R.Br leaf in normal and alloxan induced diabetic rats

PubMed Central

Sathya, S.; Kokilavani, R.; Gurusamy, K.

2008-01-01

The water extract of Gymnema sylvestre R.Br leaf was tested for hypoglycemic activity in normal and alloxan induced diabetic rats. Grated amount (2ml/kg) of the water extract of Gymnema sylvestre leaf was given to both normal and alloxan induced diabetic rats. A significant reduction of glucose concentration was noticed in normal rats, blood glucose level was significantly reduced in diabetic rats. Protein level is also decreased in diabetic rats. Urea, uric acid and creatinine levels were increased in diabetic condition. After the herbal treatment the levels were altered near to normal level. PMID:22557305

Cerebral Activations Related to Ballistic, Stepwise Interrupted and Gradually Modulated Movements in Parkinson Patients

PubMed Central

Toxopeus, Carolien M.; Maurits, Natasha M.; Valsan, Gopal; Conway, Bernard A.; Leenders, Klaus L.; de Jong, Bauke M.

2012-01-01

Patients with Parkinson’s disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular. PMID:22911738

Monocyte chemoattractant protein-1 and interleukin-8 levels in urine and serum of patents with hemolytic uremic syndrome.

PubMed

van Setten, P A; van Hinsbergh, V W; van den Heuvel, L P; Preyers, F; Dijkman, H B; Assmann, K J; van der Velden, T J; Monnens, L A

1998-06-01

The epidemic form of the hemolytic uremic syndrome (HUS) in children is hallmarked by endothelial cell damage, most predominantly displayed by the glomerular capillaries. The influx of mononuclear (MO) and polymorphonuclear cells (PMNs) into the glomeruli may be an important event in the initiation, prolongation, and progression of glomerular endothelial cell damage in HUS patients. The molecular mechanisms for the recruitment of these leukocytes into the kidney are unclear, but monocyte chemoattractant protein-1 (MCP-1) and IL-8 are suggested to be prime candidates. In this study, we analyzed the presence of both chemokines in 24-h urinary (n = 15) and serum (n = 14) samples of HUS children by specific ELISAs. Furthermore, kidney biopsies of three different HUS children were examined for MO and PMN cell infiltration by histochemical techniques and electron microscopy. Whereas the chemokines MCP-1 and IL-8 were present in only very limited amounts in urine of 17 normal control subjects, serial samples of HUS patients demonstrated significantly elevated levels of both chemokines. HUS children with anuria showed higher initial and maximum chemokine levels than their counterparts without anuria. A strong positive correlation was observed between urinary MCP-1 and IL-8 levels. Whereas initial serum IL-8 levels were significantly increased in HUS children, serum MCP-1 levels were only slightly elevated compared with serum MCP-1 in control children. No correlation was found between urinary and serum chemokine concentrations. Histologic and EM studies of HUS biopsy specimens clearly showed the presence of MOs and to a lesser extent of PMNs in the glomeruli. The present data suggest an important local role for MOs and PMNs in the process of glomerular endothelial-cell damage. The chemokines MCP-1 and IL-8 may possibly be implicated in the pathogenesis of HUS through the recruitment and activation of MOs and PMNs, respectively.

Variations of rat thyroid activity during exposure to high environmental temperature (34 degrees C). Relation between hypothalamic pituitary and thyroid hormone levels.

PubMed

Rousset, B; Cure, M

1975-01-01

Changes in thyroid activity and variations in the hypthalamo-pituitary-thyroid hormone levels were examined in rats exposed to heat (34 degrees C)for3 weeks. Thyroid activity evaluated histologically (epithelium/colloid ratio, nuclear size) by radioiodine exploration (24 hrs 125 I uptake, ratio of mono- to di-125 iodotyrosines - MIT/DIT, ratio of tri- to tetra-125 iodothyronines-T3/T4, and plasma 125I-T4 and assay of plasma T4, evolves in a triphasic manner. 1.a depression phase between day 0 and day 2.5. 2. a rebound of thyroid activity between day 2.5 and day 9.3 a stabilization of thyroid parameters from day 9 to day 24. These results indicate adaptation of thyroid function to heat after 3 weeks. In phase i, plasma TSH )MeKenzie bioassay) fell to undectable levels concurrent with a 50% decrease in hypothalamic TRH (in vitro assay). Plasma TSH peaked on day 4.5, fell on day 9.5 and returned progressively to initial levels. Hypothalamic TRH returned to initial levels after 6.5 days. The rapid and simultaneous decrease in hypothalamic TRH, plasma TSH, plasma T4 and thyroid activity by the 36th hour of heat exposure (34 degrees C) suggests initiation at the hypothalamic level. In the secound phase, the rebound in thyroid activity is presumably due to the peak in circulating TSH in ralation to the marked decrease in plasma T4. The oscillations of phase 2 and the stabilization of all the thyroid parameters in phase 3 may be the reflection of an apparent discrepancy remains between a low plasma T4 and a normal or subnormal plasma TSH. A modification in the "set point" for the control of TSH secretion is discussed.

Lack of utility of telemetry monitoring for identification of cardiac death and life-threatening ventricular dysrhythmias in low-risk patients with chest pain.

PubMed

Hollander, Judd E; Sites, Frank D; Pollack, Charles V; Shofer, Frances S

2004-01-01

Low-risk patients with chest pain are often admitted to monitored beds; however, the use of telemetry beds in this cohort is not evidence based. We tested the hypothesis that monitoring admitted low-risk patients with chest pain for dysrhythmia is low yield (<1% detection of life-threatening dysrhythmias requiring treatment). We conducted a prospective cohort study of emergency department (ED) patients with chest pain with a Goldman risk score of less than 8%, a normal initial creatine kinase-MB level, and a negative initial troponin I level admitted to non-ICU monitored beds. Investigators followed the hospital course daily. The main outcome was cardiovascular death and life-threatening ventricular dysrhythmia during telemetry. Of 3,681 patients with chest pain who presented to the ED, 1,750 patients were admitted to non-ICU monitored beds. Of these, 1,029 patients had a Goldman risk score of less than 8%, a troponin I level of less than 0.3 ng/mL, and a creatine kinase-MB level of less than 5 ng/mL (accounting for 59% of all chest pain telemetry admissions). During hospitalization, there were no patients with sustained ventricular tachycardia/ventricular fibrillation requiring treatment on the telemetry service (0%; 95% confidence interval [CI] 0% to 0.3%). There were 2 deaths: neither was cardiovascular in nature or preventable by monitoring (cardiovascular preventable death rate=0%; 95% CI 0.0% to 0.3%). The routine use of telemetry monitoring for low-risk patients with chest pain is of limited utility. Admission to nonmonitored beds might help alleviate ED crowding without increasing risk of adverse events caused by dysrhythmia in patients with a Goldman risk of less than 8%, an initial troponin I level of less than 0.3 ng/mL, and a creatine kinase-MB level of less than 5 ng/mL.

Determinants of hepatotoxicity after repeated supratherapeutic paracetamol ingestion: systematic review of reported cases.

PubMed

Acheampong, Paul; Thomas, Simon H L

2016-10-01

To evaluate the role of reported daily dose, age and other risk factors, and to assess the value of quantifying serum transaminase activity and paracetamol (acetaminophen) concentration at initial assessment for identifying patients at risk of hepatotoxicity following repeated supratherapeutic paracetamol ingestion (RSPI). Systematic literature review with collation and analysis of individual-level data from reported cases of RSPI associated with liver damage. In 199 cases meeting the selection criteria, severe liver damage (ALT/AST ≥1000 IU l(-1) , liver failure or death) was reported in 186 (93%) cases including 77/78 (99%) children aged ≤6 years. Liver failure occurred in 127 (64%) cases; of these 49 (39%) died. Maximum ingested daily paracetamol doses were above UK recommendations in 143 (72%) patients. US-Australasian thresholds for repeated supratherapeutic ingestions requiring intervention were not met in 71 (36%) cases; of these 35 (49%) developed liver failure and 10 (14%) died. No cases developing liver damage had paracetamol concentration < 20 mg l(-1) and a normal ALT/AST on initial presentation or when RSPI was first suspected, but both of these values were only available for 79 (40%) cases. Severe liver damage is reported after RSPI in adults and children, sometimes involving reported doses below current thresholds for intervention. Paracetamol concentrations <20 mg l(-1) with normal serum ALT/AST activity on initial assessment suggests a low risk of subsequent liver damage. These findings are, however, limited by low patient numbers, publication bias and the accuracy of the histories in reported cases. © 2016 The British Pharmacological Society.

Lupus Anticoagulant-hypoprothrombinemia Syndrome (LAC-HPS) in Children With Systemic Lupus Erythematosus: Report of 3 Cases.

PubMed

Komvilaisak, Patcharee; Wisanuyotin, Suwannee; Jettrisuparb, Arunee; Wiangnon, Surapon

2017-11-01

Lupus anticoagulant, also known as lupus antibody, is generally associated with thrombosis rather than bleeding events. Lupus anticoagulant-hypoprothrombinemia syndrome in children is rather rare but can lead to mild to life-threatening bleeding. Here, we report 3 cases of lupus anticoagulant-hypoprothrombinemia syndrome associated with systemic lupus erythematosus. They initially presented with mucocutaneous bleedings, and subsequently developed other symptoms fulfilling the laboratory criteria for systemic lupus erythematosus. Case 2 and 3 had significant epistaxis and intracerebral hemorrhage responded to systemic corticosteroid along with fresh frozen plasma. Three cases demonstrated acquired hypoprothrombinemia with no correction of mixing studies. Case 1 had low factor X level, which has never been reported previously. In all 3 cases, their coagulogram returned to normal level after corticosteroid treatment.

Hyperparathyroidism Mimicking Metastatic Bone Disease: A Case Report and Review of Literature.

PubMed

Gupta, Monica; Singhal, Lalita; Kumar, Akshay

2018-06-01

Multiple osteolytic lesions are usually associated with metastatic involvement of the bone; however, metabolic bone diseases should also be included in the differential diagnosis. In this study, we describe a case of primary hyperparathyroidism (PHPT) with multiple osteolytic lesions that was diagnosed initially as having metastatic bone involvement. The laboratory results showed hypercalcemia and raised alkaline phosphatase along with fibrosis in the bone marrow biopsy with no increase in tumor markers and normal serum protein electrophoresis. The parathyroid hormone levels were high, which pointed toward a diagnosis of PHPT. Sestamibi scan revealed uptake at the level of the left inferior pole of the thyroid gland, which was suggestive of parathyroid adenoma. The possibility of hyperparathyroidism should be kept in mind when a patient presents with multiple osteolytic lesions and hypercalcemia.

Antihyperglycaemic potential of the water-ethanol extract of Kalanchoe crenata (Crassulaceae).

PubMed

Kamgang, René; Mboumi, Rostand Youmbi; Fondjo, Angèle Foyet; Tagne, Michel Archange Fokam; N'dillé, Gabriel Patrice Roland Mengue; Yonkeu, Jeanne Ngogang

2008-01-01

Kalanchoe crenata is a vegetable widely used in Cameroon and largely efficient in the treatment of diabetes mellitus. The effect of the water-ethanol extract of this plant (WEKC) on blood glucose levels was investigated in fasting normal and diet-induced diabetic rats (MACAPOS 1) after a short- and medium-term treatment. Diabetes was induced by submitting Wistar rats to a hypercaloric sucrose diet over 4 months. Six hours after a single oral administration of WEKC, 135 and 200 mg kg(-1) body weight extracts significantly (P < 0.01) reduced the blood glucose levels both in normal and diabetic rats without real dose-dependent effect. During the medium-term treatment, 200 mg kg(-1) WEKC administered daily for 4 weeks significantly reduced blood glucose levels within week 1 (P < 0.05), with a maximum effect at week 4 (-52%, P < 0.01), while maintaining glycaemia within the normal range. All the WEKC-treated diabetic rats exhibited significant (P < 0.01) increase in insulin sensitivity index (K (ITT)) compared with the initial time and to the untreated diabetic animals. Animals treated for 4 weeks exhibited a slight resistance in body-weight gain and decrease in food and water intake. The WEKC activities on all parameters assessed were comparable with the glibenclamide effects. Qualitative phytochemical screening revealed that K. crenata contains terpenoids, tannins, polysaccharids, saponins, flavonoids and alkaloids. The data suggest that K. crenata might contain important chemical components that could induce significant improvement in glucose clearance and/or uptake and resistance to body-weight gain and insulin sensitivity, and could be a potent alternative or complementary therapeutic substance in the control of type 2 diabetes and other insulin-resistant conditions.

Combined Therapy with Renin-Angiotensin System and Calcium Channel Blockers in Type 2 Diabetic Hypertensive Patients with Proteinuria: Effects on Soluble TWEAK, PTX3, and Flow-Mediated Dilation

PubMed Central

Yilmaz, Mahmut Ilker; Carrero, Juan Jesús; Martín-Ventura, Jose Luis; Sonmez, Alper; Saglam, Mutlu; Celik, Turgay; Yaman, Halil; Yenicesu, Mujdat; Eyileten, Tayfun; Moreno, Juan Antonio; Egido, Jesús

2010-01-01

Background and objectives: Soluble TNF-like weak inducer of apoptosis (sTWEAK) and long pentraxin-3 (PTX3) concentrations have been associated with endothelial function in patients with chronic kidney disease (CKD). This study tested the hypothesis that the improvement in endothelial function after initiation of angiotensin II receptor blocker (valsartan), calcium channel blocker (amlodipine) therapy, or a combination of both is directly linked to the normalization of sTWEAK and PTX3. Design, setting, participants, & measurements: One-hundred-eight diabetic CKD stage I patients with hypertension (56% men, 46.7 ± 5.3 years) were allocated to a 12-week intervention with amlodipine (10 mg/d), valsartan (160 mg/d), or their combination. Plasma levels of sTWEAK, PTX3, and flow-mediated dilation (FMD) were studied during the interventions. Results: All treatment strategies effectively increased FMD and reduced proteinuria, confirming a more prone reduction with the combined therapy. These improvements were followed by significant PTX3 reductions. Valsartan alone and in combination with amlodipine achieved significant incremental raises in sTWEAK plasma levels. More importantly, the changes observed in sTWEAK (β = 0.25, P = 0.006) or PTX3 (β = −0.24, P = 0.007) plasma levels were independently associated with the improvement in ultrasonographically measured FMD. Conclusions: This study shows that treatment with antihypertensive drugs improves FMD and normalizes proteinuria, PTX3, and sTWEAK in diabetic CKD stage I patients with hypertension. The improvement in FMD was independently associated with PTX3 and sTWEAK normalization. Two surrogate biomarkers of endothelial function are therefore identified with potential as therapeutic targets. The study was registered in clinicaltrials.gov as NCT00921570. PMID:20430947

Neuroimmune regulation of neurophysiology in the cerebellum.

PubMed

Gruol, Donna L

2013-06-01

Recent studies have established the existence of an innate immune system in the central nervous system (CNS) and implicated a critical role for this system in both normal and pathological processes. Astrocytes and microglia, normal components of the CNS, are the primary cell types that comprise the innate immune system of the CNS. Basic to their role during normal and adverse conditions is the production of neuroimmune factors such as cytokines and chemokines, which are signaling molecules that initiate or coordinate downstream cellular actions. During adverse conditions, cytokines and chemokines function in defensive and repair. However, if expression of these factors becomes dysregulated, abnormal CNS function can result. Both neurons and glial cells of the CNS express receptors for cytokines and chemokines, but the biological consequence of receptor activation has yet to be fully resolved. Our studies show that neuroadaptive changes are produced in primary cultures of rat cerebellar cells chronically treated with the cytokine interleukin-6 (IL-6) and in the cerebellum of transgenic mice that chronically express elevated levels of IL-6 in the CNS. In the cerebellum in culture and in vivo, the neuroadaptive changes included alterations in the level of expression of proteins involved in gene expression, signal transduction, and synaptic transmission. Associated with these changes were alterations in neuronal function. A comparison of results from the cultured cerebellar cells and cerebellum of the transgenic mice indicated that the effects of IL-6 can vary across neuronal types. However, alterations in mechanisms involved in Ca(2+) homeostasis were observed in all cell types studied. These results indicate that modifications in cerebellar function are likely to occur in disorders associated with elevated levels of IL-6 in the cerebellum.

[Predictive value of pre-treatment hypoalbuminemia in prognosis of resected colorectal cancer].

PubMed

Borda, Fernando; Borda, Ana; Jiménez, Javier; Zozaya, José Manuel; Prieto, Carlos; Gómez, Marta; Urman, Jesús; Ibáñez, Berta

2014-05-01

Albuminemia is part of the antitumoral systemic inflammatory response. We therefore analyzed its possible value in establishing the preoperative prognosis of colorectal carcinoma (CRC). We conducted a retrospective, observational study of a series of consecutive patients who underwent CRC resection. Univariate and multivariate analyses of survival curves were performed in patients with and without pre-treatment hypoalbuminemia (<3.5g/dl), both in the overall group of patients and in the subgroup of those with pTNM stage ii tumors. In addition, we compared the 5-year tumor-related mortality in patients with and without hypoalbuminemia. A total of 207 patients were reviewed (median follow-up: 81 months). In the overall multivariate analysis, survival curves were better in patients with normal albumin levels than in those with hypoalbuminemia (HR=2.82; CI 95%=[1.54-5.19]; P=.001). This better prognostic value of normal albumin levels was also significant in pTNM stage ii tumors: (HR=3.76; CI 95%=[1.40-10.08]; P=.009). The 5-year mortality index was lower in patients with normal albumin levels: overall series=18.8% vs 42.9% (OR=3.24; CI 95%=[1.48-7.12]; p=0.001); pTNM stage ii=13.3% vs 44.4% (OR=5.2; CI 95%=[1.36-20.34]; P=0.004). Pre-treatment hypoalbuminemia (<3.5g/dl) was independently related to shorter survival after tumor resection, both in the overall series of patients and in pTNM stage ii CRC. If these results are confirmed, hypoalbuminemia would be a simple and significant marker of poor prognosis, available at the initial diagnosis. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

Creatine phosphokinase levels in children with severe developmental disturbances.

PubMed

Cohen, D J; Johnson, W; Caparulo, B K; Young, J G

1976-06-01

Serum creatine phosphokinase (CPK) levels were studied in individuals: 40 psychotic children suffering from childhood autism, atypical personality development, and childhood schizophrenia; five children with childhood aphasia; 22 children with severe personality disorders; 29 normal children and normal siblings of psychotic children; and 14 normal parents of psychotic children. Creatine phosphokinase levels from the entire population of adults and children were normally disturbed, and the mean CPK levels for the eight diagnostic groups were within normal limits. Those 22 children with personality disorders had significantly higher CPK levels than the other diagnostic groups. This relatively higher level of CPK may be related to vulnerability to later development of schizophrenic spectrum disorders. There was no apparent relationship between CPK levels and motor activity, nor was there any change in the level of CPK during a trial of psychoactive medication. Creatine phosphokinase levels remained relatively stable on test-retest determination.

Prognostic factors in pemphigus vulgaris and pemphigus foliaceus.

PubMed

Saha, M; Bhogal, B; Black, M M; Cooper, D; Vaughan, R W; Groves, R W

2014-01-01

Pemphigus typically has a chronic course, although there is great variability in disease duration (DD) and time taken to disease remission (DR) between individuals with the disease. The reasons for this are unclear. To explore the prognostic influence of epidemiological, clinical, immunological and genetic factors on disease course and remission in pemphigus vulgaris (PV) and pemphigus foliaceus (PF). This was a retrospective study of patients with PV and PF, recruited from a single UK centre. Direct and indirect immunofluorescence and enzyme-linked immunosorbent assay studies for antidesmoglein (Dsg) antibodies were used to assess immunological factors. Polymerase chain reaction with sequence specific primers (PCR-SSP) was used to assess the Class II human leukocyte antigen status of patients. Prognostic endpoints investigated were time to initial first DR and total DD. Ninety-five patients were recruited (79 PV and 16 PF). Patients of Indo-Asian origin were significantly associated with longer DD than White-British patients (P = 0.029). In addition, younger age at onset was associated with a worse prognosis in terms of DD: the mean age at presentation of patients with DD of < 5 years was 49 years (SEM = 3.4) compared with 40 years (SEM = 1.9) in those with DD > 5 years (P = 0.039). A higher initial intercellular antibody titre on normal human skin substrate was associated with a greater time to initial DR (P = 0.007) and high anti-Dsg 3 levels at baseline were associated with a longer total DD (P = 0.03). Ethnic group, age at presentation, initial intercellular antibody titre and initial Dsg 3 antibody levels all had a significant impact on prognosis of pemphigus. © 2013 British Association of Dermatologists.

Critical role of canonical transient receptor potential channel 7 in initiation of seizures.

PubMed

Phelan, Kevin D; Shwe, U Thaung; Abramowitz, Joel; Birnbaumer, Lutz; Zheng, Fang

2014-08-05

Status epilepticus (SE) is a life-threatening disease that has been recognized since antiquity but still causes over 50,000 deaths annually in the United States. The prevailing view on the pathophysiology of SE is that it is sustained by a loss of normal inhibitory mechanisms of neuronal activity. However, the early process leading to the initiation of SE is not well understood. Here, we show that, as seen in electroencephalograms, SE induced by the muscarinic agonist pilocarpine in mice is preceded by a specific increase in the gamma wave, and genetic ablation of canonical transient receptor potential channel (TRPC) 7 significantly reduces this pilocarpine-induced increase of gamma wave activity, preventing the occurrence of SE. At the cellular level, TRPC7 plays a critical role in the generation of spontaneous epileptiform burst firing in cornu ammonis (CA) 3 pyramidal neurons in brain slices. At the synaptic level, TRPC7 plays a significant role in the long-term potentiation at the CA3 recurrent collateral synapses and Schaffer collateral-CA1 synapses, but not at the mossy fiber-CA3 synapses. Taken together, our data suggest that epileptiform burst firing generated in the CA3 region by activity-dependent enhancement of recurrent collateral synapses may be an early event in the initiation process of SE and that TRPC7 plays a critical role in this cellular event. Our findings reveal that TRPC7 is intimately involved in the initiation of seizures both in vitro and in vivo. To our knowledge, this contribution to initiation of seizures is the first identified functional role for the TRPC7 ion channel.

Clinical case report: a rare cause of acute kidney failure - tissue is the issue.

PubMed

Heggermont, Ward A; Verhoef, Gregor; Evenepoel, Pieter; Sprangers, Ben; Lerut, Evelyn; Tousseyn, Thomas; Claes, Kathleen

2017-06-01

A patient was admitted to the medical emergency department by his family physician. His complaints were weakness and fatigue for more than one week. Four days before admission, he went to his general practitioner for these complaints and also for painful elbows. His physician prescribed diclofenac and esomeprazole. Upon presentation, he had high systolic/diastolic blood pressure (>180/>90 mm Hg, measured repeatedly), and otherwise normal parameters. He had gained 6.5 kg in body weight. Clinical examination was normal, except for very mild bilateral malleolar edema. Routine blood tests showed a strongly elevated serum creatinine, hyperkalemia, and elevated lactate dehydrogenase. Haptoglobin levels were normal. Urinalysis showed a normal sediment, urine and blood cultures remained sterile. Ophthalmoscopy was completely normal, as was a routine chest X-ray. Renal ultrasound demonstrated kidneys with a diameter of 13 cm. Due to uncontrollable hypertension, our patient was hospitalized at the intensive care department where intravenous nifedipine was started, with good instantaneous control of blood pressure. Because of increasing potassium levels acute hemodialysis was started within 24 h after admission. Differential diagnosis consisted of diclofenac- or esomeprazole-induced interstitial nephritis or rapidly progressive glomerulonephritis. A renal biopsy was performed within 72 h after admission. The kidney biopsy showed an overwhelming inflammatory cell infiltrate consisting of a monoclonal lymphocytic cell population. However, the numerous mitotic figures, polyploidy, and prominent nucleoli present, were indicative of a lymphoma. Additional stainings confirmed a non-Hodgkin diffuse large-cell B-cell lymphoma. Treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, and prednisolone) was initiated with very good clinical and biochemical response, yet only mild recovery of kidney function. Occasionally the kidney is involved as an extranodal non-Hodgkin lymphoma (NHL) localization. However, a primary presentation of acute kidney failure due to lymphoma localization is extremely rare. Our case demonstrates that early renal biopsy is indispensable for fast and adequate diagnosis and treatment.

Respiratory response of grass carp Ctenopharyngodon idellus to dissolved oxygen changes at three acclimation temperatures.

PubMed

Zhao, Zhigang; Dong, Shuanglin; Xu, Qiyou

2018-02-01

Respiratory parameters of grass carp were studied during dissolved oxygen (DO) changes from normal DO to hypoxia, then return to normal DO at 15, 25, and 30 °C acclimation, respectively. The results showed that with increases of acclimation temperature at normoxia the respiratory frequency (f R ), oxygen consumption rate (VO 2 ), respiratory stroke volume (V S.R ), gill ventilation (V G ), and V G /VO 2 of grass carp increased significantly, but the oxygen extraction efficiency (EO 2 ) of fish decreased significantly (P < 0.05). With declines of DO levels, the f R , V S.R , V G , and V G /VO 2 of fish increased significantly at different acclimation temperatures (P < 0.05). A slight increase was found in VO 2 , and the EO 2 of fish remained almost constant above DO levels of 3.09, 2.91, and 2.54 mg l -1 at 15, 25, and 30 °C, while the VO 2 and EO 2 began to decrease significantly with further reductions in DO levels (P < 0.05). After 0.5 h of recovery to normoxia from hypoxia at three acclimation, the f R , V S.R , V G , and V G /VO 2 of the fish decreased sharply; meanwhile, the VO 2 and EO 2 increased sharply (P < 0.05). The respiratory parameters of fish gradually approached initial values with prolonged recovery time to normoxia, and reached their initial values in 2.5 h at 25 and 30 °C acclimation. The critical oxygen concentrations (C c ) of fish for VO 2 were 2.42 mg l -1 at 15 °C, 2.02 mg l -1 at 25 °C, and 1.84 mg l -1 at 30 °C, respectively. The results suggest that grass carp are highly adapted to varied DO and short-term hypoxia environments.

Tissue absence initiates regeneration through follistatin-mediated inhibition of activin signaling.

PubMed

Gaviño, Michael A; Wenemoser, Danielle; Wang, Irving E; Reddien, Peter W

2013-09-10

Regeneration is widespread, but mechanisms that activate regeneration remain mysterious. Planarians are capable of whole-body regeneration and mount distinct molecular responses to wounds that result in tissue absence and those that do not. A major question is how these distinct responses are activated. We describe a follistatin homolog (Smed-follistatin) required for planarian regeneration. Smed-follistatin inhibition blocks responses to tissue absence but does not prevent normal tissue turnover. Two activin homologs (Smed-activin-1 and Smed-activin-2) are required for the Smed-follistatin phenotype. Finally, Smed-follistatin is wound-induced and expressed at higher levels following injuries that cause tissue absence. These data suggest that Smed-follistatin inhibits Smed-Activin proteins to trigger regeneration specifically following injuries involving tissue absence and identify a mechanism critical for regeneration initiation, a process important across the animal kingdom. DOI:http://dx.doi.org/10.7554/eLife.00247.001.

Analytical scalings of the linear Richtmyer-Meshkov instability

NASA Astrophysics Data System (ADS)

Cobos, Francisco; Wouchuk, Juan Gustavo

2017-11-01

In the linear Richtmyer-Meshkov instability (RMI), hydrodynamic perturbations are generated behind the transmitted and reflected rippled fronts. The contact surface reaches an asymptotic normal velocity and two different tangential velocities at each side, which are always different for moderate to strong levels of compression, depending on the amount of vorticity generated by the corrugated shocks. We show analytical scaling laws for the ripple velocity (δvi∞)in different physical limits and approximate formulas are provided, valid for arbitrary initial pre-shock parameters. An asymptotic growth for the contact surface ripple of the form ψi(t) ψ∞ + δ vi∞t is obtained. The quantity ψ∞ is in general different from the initial post-shock ripple amplitude, in agreement with the early finding of. Comparison to simulations and experimental work is shown. F.C. acknowledges support from UCLM for a predoctoral fellowship. This work has received support from MINECO, JCCM, and UCLM (Spain).

Can Nor'wester events initiate stratospheric moistening?

NASA Astrophysics Data System (ADS)

Ganguly, Nandita D.; Chakraborty, Rohit; Maitra, Animesh

2017-11-01

The possibility of stratospheric moistening being initiated by deep convective Nor'wester events has been investigated over a period of three years spanning from 2013 to 2015 at a tropical location Kolkata, in India using radiosonde and satellite data. The back trajectories, instability indices, outgoing long wave radiation (OLR), convective available potential energy (CAPE), geopotential height maps, vertical pressure velocity, specific humidity, wind vectors and precipitable water vapour (PWV) have been examined to assess the convective activity prevailing over the atmosphere during these events. Increase in specific humidity, wind velocity at various levels of the lower atmosphere and CAPE values indicate an upwelling of moist air from the troposphere to lower stratosphere during Nor'westers. Decrease in OLR and large differences in the values of instability indices, relative humidity and precipitable water vapour during Nor'westers compared to normal convection also signify high intensity of convection and hence the possibility of higher stratospheric moistening during Nor'wester events.

Placental lactogen secretion during prolonged-pregnancy in the rat: the ovary plays a pivotal role in the control of placental function.

PubMed

Shiota, K; Furuyama, N; Takahashi, M

1991-10-01

The serum of rats at mid-pregnancy contains at least 2 distinct placental lactogen (PL)-like substances tentatively termed placental lactogen-alpha (PL-alpha) and placental lactogen-beta (PL-beta) (Endocrinol Japon 38: 533-540, 1991). We have investigated the secretory patterns of three placental lactogens (PL-alpha, PL-beta and placental lactogen-II) during normal pregnancy and in two prolonged-pregnancy models. Pregnancy was prolonged by the introduction of new corpora lutea by inducing ovulation on day 15 of pregnancy by successive treatments with PMSG (30 IU/rat, sc on day 12) and hCG (10 IU/rat, iv on day 14), and in the second model by progesterone implants on day 15 of pregnancy. During normal pregnancy, each of the 3 PLs exhibited only one secretory peak in the serum; PL-alpha and PL-beta on day 12 and placental lactogen II (PL-II) on day 20. Interestingly, in the rats with new sets of corpora lutea, serum PL-alpha and PL-beta levels began to increase again on day 18 and showed peaks on day 20 for PL-alpha and on day 22 for PL-beta. In this model, the initiation of PL-II secretion was not affected, but high levels were maintained until day 26, when parturition occurred. In rats receiving either PMSG or hCG, the secretory patterns of the PLs were similar to as those during normal pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of Gated Audiovisual Speech Identification in Elderly Hearing Aid Users and Elderly Normal-Hearing Individuals

PubMed Central

Lidestam, Björn; Rönnberg, Jerker

2016-01-01

The present study compared elderly hearing aid (EHA) users (n = 20) with elderly normal-hearing (ENH) listeners (n = 20) in terms of isolation points (IPs, the shortest time required for correct identification of a speech stimulus) and accuracy of audiovisual gated speech stimuli (consonants, words, and final words in highly and less predictable sentences) presented in silence. In addition, we compared the IPs of audiovisual speech stimuli from the present study with auditory ones extracted from a previous study, to determine the impact of the addition of visual cues. Both participant groups achieved ceiling levels in terms of accuracy in the audiovisual identification of gated speech stimuli; however, the EHA group needed longer IPs for the audiovisual identification of consonants and words. The benefit of adding visual cues to auditory speech stimuli was more evident in the EHA group, as audiovisual presentation significantly shortened the IPs for consonants, words, and final words in less predictable sentences; in the ENH group, audiovisual presentation only shortened the IPs for consonants and words. In conclusion, although the audiovisual benefit was greater for EHA group, this group had inferior performance compared with the ENH group in terms of IPs when supportive semantic context was lacking. Consequently, EHA users needed the initial part of the audiovisual speech signal to be longer than did their counterparts with normal hearing to reach the same level of accuracy in the absence of a semantic context. PMID:27317667

Executive functions in adolescents with binge-eating disorder and obesity.

PubMed

Kittel, Rebekka; Schmidt, Ricarda; Hilbert, Anja

2017-08-01

Binge-eating disorder (BED) in adults is associated with alterations in executive functions (EF) and obesity. Much less is known about these relationships in adolescents, including whether poor EF are associated with eating disorder psychopathology and/or elevated body mass index. This study examined EF in response to neutral stimuli in youth with BED. Adolescents with BED and obesity (n = 22), individually matched adolescents with obesity (n = 22), and normal weight (n = 22) completed neuropsychological tests targeting inhibition (Color-Word Interference Test), sustained attention (D2 Concentration Endurance Test), cognitive flexibility (Comprehensive Trail Making Test), and decision-making (Iowa Gambling Task). Adolescents with BED and obesity displayed significantly poorer inhibitory control compared to normal-weight adolescents. This effect persisted after controlling for the level of secondary education. However, initial differences between adolescents with obesity and normal-weight controls regarding inhibitory control and sustained attention vanished after controlling for education. The three groups did not differ regarding cognitive flexibility and decision-making. Moreover, adolescents with BED and obesity did not perform worse than adolescents with obesity on any of the neuropsychological tests. Overall, our results indicate that adolescent BED is associated with only a few alterations in general EF, specifically inhibitory control, and underline BED and educational level as confounding factors in neuropsychological research on obesity. To further delineate EF profiles of adolescents with BED, future research should focus on EF in response to disorder-related stimuli and experimental settings with high ecological validity. © 2017 Wiley Periodicals, Inc.

Postnatal high-protein diet improves learning and memory in premature rats via activation of mTOR signaling.

PubMed

Su, Zhi-Wen; Liao, Jia-Yi; Zhang, Hui; Zhang, Tao; Wu, Fan; Tian, Xiao-Hua; Zhang, Fei-Tong; Sun, Wei-Wen; Cui, Qi-Liang

2015-06-22

The present study investigated whether a high-protein diet affects spatial learning and memory in premature rats via modulation of mammalian target of rapamycin (mTOR) signaling. Pre- and full-term Sprague-Dawley pups were fed a normal (18% protein) or high-protein (30% protein) diet (HPD) for 6 or 8 weeks after weaning. Spatial learning and memory were tested in the Morris water maze at week 6 and 8. The activation of mTOR signaling pathway components was evaluated by western blotting. Spatial memory performance of premature rats consuming a normal and HPD was lower than that of full-term rats on the same diet at 6 weeks, and was associated with lower levels of ribosomal protein S6 kinase p70 subtype (p70S6K) and initiation factor 4E-binding protein 1 (4EBP1) phosphorylation in the hippocampus. Spatial memory was improved in 8-week-old premature rats on an HPD as compared to those on a normal diet. Premature rats on an HPD had p70S6K and 4EBP1 phosphorylation levels in the hippocampus that were comparable to those of full-term rats on an HPD. Long-term consumption of a protein-rich diet can restore the impairment in learning and memory in pre-term rats via upregulation of mTOR/p70S6K signaling. Copyright © 2015 Elsevier B.V. All rights reserved.

Oxygenation in cervical cancer and normal uterine cervix assessed using blood oxygenation level-dependent (BOLD) MRI at 3T.

PubMed

Hallac, Rami R; Ding, Yao; Yuan, Qing; McColl, Roderick W; Lea, Jayanthi; Sims, Robert D; Weatherall, Paul T; Mason, Ralph P

2012-12-01

Hypoxia is reported to be a biomarker for poor prognosis in cervical cancer. However, a practical noninvasive method is needed for the routine clinical evaluation of tumor hypoxia. This study examined the potential use of blood oxygenation level-dependent (BOLD) contrast MRI as a noninvasive technique to assess tumor vascular oxygenation at 3T. Following Institutional Review Board-approved informed consent and in compliance with the Health Insurance Portability and Accountability Act, successful results were achieved in nine patients with locally advanced cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) stage IIA to IVA] and three normal volunteers. In the first four patients, dynamic T₂*-weighted MRI was performed in the transaxial plane using a multi-shot echo planar imaging sequence whilst patients breathed room air followed by oxygen (15 dm³/min). Later, a multi-echo gradient echo examination was added to provide quantitative R₂* measurements. The baseline T₂*-weighted signal intensity was quite stable, but increased to various extents in tumors on initiation of oxygen breathing. The signal in normal uterus increased significantly, whereas that in the iliacus muscle did not change. R₂* responded significantly in healthy uterus, cervix and eight cervical tumors. This preliminary study demonstrates that BOLD MRI of cervical cancer at 3T is feasible. However, more patients must be evaluated and followed clinically before any prognostic value can be determined. Copyright © 2012 John Wiley & Sons, Ltd.

Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets

PubMed Central

Pensieroso, Simone; Tolazzi, Monica; Chiappetta, Stefania; Nozza, Silvia; Lazzarin, Adriano; Tambussi, Giuseppe; Scarlatti, Gabriella

2015-01-01

Introduction During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART). Materials and Methods To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation. Results Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups. Conclusions In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI. PMID:26474181

Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets.

PubMed

Pogliaghi, Manuela; Ripa, Marco; Pensieroso, Simone; Tolazzi, Monica; Chiappetta, Stefania; Nozza, Silvia; Lazzarin, Adriano; Tambussi, Giuseppe; Scarlatti, Gabriella

2015-01-01

During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART). To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation. Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups. In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI.

Testicular function during puberty and young adulthood in patients with Klinefelter's syndrome with and without spermatozoa in seminal fluid.

PubMed

Rohayem, J; Nieschlag, E; Zitzmann, M; Kliesch, S

2016-11-01

Patients with Klinefelter's syndrome experience progressive testicular degeneration resulting in impaired endocrine function and azoospermia. What proportion of adolescents develop testosterone deficiency during puberty and how many have spermatozoa in their semen is unclear to date. We aimed to investigate testicular function during puberty and young adulthood in patients with Klinefelter's syndrome and to assess testosterone effects in target tissues. The clinical data of 281 patients with non-mosaic Klinefelter's syndrome aged 10-25 years without previous testosterone replacement were reviewed. In late pubertal adolescents, semen analyses were evaluated, and testicular volumes, hormone and haemoglobin (Hb) levels, the number of CAG repeats and final height data were compared to those of 233 age-matched controls with pubertal gynaecomastia. Spontaneous pubertal virilisation to Tanner stages IV-V occurred. Serum T levels ≥10 nmol/L were reached in 62% of patients with Klinefelter's syndrome and in 85% of controls at ages 15-25 (T KFS : 12.2 ± 5.4 vs. T C : 16.6 ± 7.2 nmol/L). LH KFS levels were elevated >10 U/L in 84%, and normal in all controls (LH KFS : 18.6 ± 12.2 vs. LH C : 3.5 ± 1.6 U/L). In nine of 130 (7%) adolescents with Klinefelter's syndrome, spermatozoa (oligozoospermia) were found in semen; all had T levels >7 nmol/L and eight of nine had LH levels ≤18 U/L, while their hormone levels, number of CAG repeats and testicular volumes were not different from those of adolescents with azoospermia. Controls had normal sperm concentrations in 73% (46/63). Semen volumes KFS were normal in 55% vs. 78% in controls; Hb KFS was normal in 89% (Hb C : 97%). Mean final height KFS was 185 ± 8 cm vs. 181 ± 7 cm in controls. Hypergonadotropic hypogonadism develops during early puberty in adolescents with Klinefelter's syndrome and remains compensated in over 60% during ages 15-25, with sufficient testosterone secretion for spontaneous accomplishment of pubertal development. Spermatozoa in semen are rare and associated with T levels >7 nmol/L. Parameters reflecting androgen deficiency in target tissues may help to optimise timing of testosterone substitution, which should preferably not be initiated before fertility status has been clarified. © 2016 American Society of Andrology and European Academy of Andrology.

Insulin-like growth factor-1 and growth hormone (GH) levels in canine cerebrospinal fluid are unaffected by GH or GH secretagogue (MK-0677) administration.

PubMed

Prahalada, S; Block, G; Handt, L; DeBurlet, G; Cahill, M; Hoe, C M; van Zwieten, M J

1999-01-01

Elevation in circulating GH levels results in a dose-related increase in serum insulin-like growth factor-1 (IGF-1) levels in dogs. However, it is not known whether elevations in systemic IGF-1 and GH levels contribute to the cerebrospinal fluid (CSF) levels of these hormones. Therefore, a study was designed in dogs to determine if elevated circulating GH levels was a result of a GH secretagogue (MK-0677) or if exogenous GH administration resulted in increased IGF-1 and GH levels in the CSF of dogs. A total of 12 normal, young adult male dogs were randomized to three treatment groups (4 dogs/group) based on body weight. There were 4 vehicle control dogs. A group of 4 dogs were dosed orally with MK-0677 (5 mg/kg/day) dissolved in deionized water. A third group of 4 dogs received subcutaneous injections of porcine GH (pGH) at a dose of 0.1 IU/kg/day. From all dogs, blood and CSF samples were collected prior to the initiation of treatment and on days 7 and 15 of treatment. All samples were assayed using a validated radioimmunoassay. Administration of MK-0677 or pGH resulted in a statistically significant (P < or = 0.05) increased body weight gain and increased serum IGF-1 and GH levels. In contrast, administration of MK-0677 resulted in no significant (P > 0.05) increase in CSF IGF-1 or GH levels on days 7 or 15 of the study. The CSF IGF-1 values ranged from 1.2 to 2.0 ng/ml with minimal variation among three separate samples taken during the course of the study from each dog. Similarly, the CSF GH levels were very low (< 0.98 ng/ml to 2.4 ng/ml) in all dogs irrespective of treatment group. This study has demonstrated that there is no correlation between the circulating levels of IGF-1 or GH and the levels of these hormones in the CSF of normal dogs. An approximately 100-fold difference between serum and CSF IGF-1 levels in vehicle control dogs suggest that there is a blood-brain barrier for the circulating IGF-1. Similarly, failure to see an elevation in CSF GH levels despite increases in serum GH levels shows that there is a blood-brain barrier for GH in normal dogs. These results suggest that the likely source of GH and IGF-1 in the CSF of dogs is from the CNS.

Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance.

PubMed Central

Dollins, A B; Zhdanova, I V; Wurtman, R J; Lynch, H J; Deng, M H

1994-01-01

We examined effects of very low doses of melatonin (0.1-10 mg, orally) or placebo, administered at 1145 h, on sleep latency and duration, mood, performance, oral temperature, and changes in serum melatonin levels in 20 healthy male volunteers. A repeated-measure double-blind Latin square design was used. Subjects completed a battery of tests designed to assess mood and performance between 0930 and 1730 h. The sedative-like effects of melatonin were assessed by a simple sleep test: at 1330 h subjects were asked to hold a positive pressure switch in each hand and to relax with eyes closed while reclining in a quiet darkened room. Latency and duration of switch release, indicators of sleep, were measured. Areas under the time-melatonin concentration curve varied in proportion to the different melatonin doses ingested, and the 0.1- and 0.3-mg doses generated peak serum melatonin levels that were within the normal range of nocturnal melatonin levels in untreated people. All melatonin doses tested significantly increased sleep duration, as well as self-reported sleepiness and fatigue, relative to placebo. Moreover, all of the doses significantly decreased sleep-onset latency, oral temperature, and the number of correct responses on the Wilkinson auditory vigilance task. These data indicate that orally administered melatonin can be a highly potent hypnotic agent; they also suggest that the physiological increase in serum melatonin levels, which occurs around 2100 h daily, may constitute a signal initiating normal sleep onset. PMID:8127888

Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance.

PubMed

Dollins, A B; Zhdanova, I V; Wurtman, R J; Lynch, H J; Deng, M H

1994-03-01

We examined effects of very low doses of melatonin (0.1-10 mg, orally) or placebo, administered at 1145 h, on sleep latency and duration, mood, performance, oral temperature, and changes in serum melatonin levels in 20 healthy male volunteers. A repeated-measure double-blind Latin square design was used. Subjects completed a battery of tests designed to assess mood and performance between 0930 and 1730 h. The sedative-like effects of melatonin were assessed by a simple sleep test: at 1330 h subjects were asked to hold a positive pressure switch in each hand and to relax with eyes closed while reclining in a quiet darkened room. Latency and duration of switch release, indicators of sleep, were measured. Areas under the time-melatonin concentration curve varied in proportion to the different melatonin doses ingested, and the 0.1- and 0.3-mg doses generated peak serum melatonin levels that were within the normal range of nocturnal melatonin levels in untreated people. All melatonin doses tested significantly increased sleep duration, as well as self-reported sleepiness and fatigue, relative to placebo. Moreover, all of the doses significantly decreased sleep-onset latency, oral temperature, and the number of correct responses on the Wilkinson auditory vigilance task. These data indicate that orally administered melatonin can be a highly potent hypnotic agent; they also suggest that the physiological increase in serum melatonin levels, which occurs around 2100 h daily, may constitute a signal initiating normal sleep onset.

Time-dependent effects of intermittent hydrostatic pressure on articular chondrocyte type II collagen and aggrecan mRNA expression.

PubMed

Smith, R L; Lin, J; Trindade, M C; Shida, J; Kajiyama, G; Vu, T; Hoffman, A R; van der Meulen, M C; Goodman, S B; Schurman, D J; Carter, D R

2000-01-01

The normal loading of joints during daily activities causes the articular cartilage to be exposed to high levels of intermittent hydrostatic pressure. This study quantified effects of intermittent hydrostatic pressure on expression of mRNA for important extracellular matrix constituents. Normal adult bovine articular chondrocytes were isolated and tested in primary culture, either as high-density monolayers or formed aggregates. Loaded cells were exposed to 10 MPa of intermittent hydrostatic pressure at a frequency of 1 Hz for periods of 2, 4, 8, 12, and 24 hrs. Other cells were intermittently loaded for a period of 4 hrs per day for 4 days. Semiquantitative reverse transcription polymerase chain reaction assays were used to assess mRNA signal levels for collagen types II and I and aggrecan. The results showed that type II collagen mRNA signal levels exhibited a biphasic pattern, with an initial increase of approximately five-fold at 4 and 8 hrs that subsequently decreased by 24 hrs. In contrast, aggrecan mRNA signal increased progressively up to three-fold throughout the loading period. Changing the loading profile to 4 hrs per day for 4 days increased the mRNA signal levels for type II collagen nine-fold and for aggrecan twenty-fold when compared to unloaded cultures. These data suggest that specific mechanical loading protocols may be required to optimally promote repair and regeneration of diseased joints.

Synergistic effects of colchicine combined with atorvastatin in rats with hyperlipidemia.

PubMed

Huang, Congwu; Cen, Chuan; Wang, ChengXu; Zhan, Haiyong; Ding, Xin

2014-04-17

Inflammation and endothelial dysfunction is implicated in the atherosclerosis initiation and progression in the setting of hyperlipidemia. Colchicine is a potent anti-inflammatory agent and whether colchicine combined with atorvastatin has synergistic effects on inflammation amelioration and endothelial function improvement is unknown. Hyperlipidemic rat model was produced by high-fat and high-cholesterol diet for 6 weeks. Rats with normal diet were served as shame group. In hyperlipidemic group, normal saline, atorvastatin (10 mg/kg body weight/day), colchicines (0.5 mg/kg body weight/day), or atorvastatin combined with colchicines (same dosages) were prescribed for 2 weeks. Serum levels of lipid profile, C-reactive protein (CRP), liver enzyme, lipoprotein associated phospholipase A2 (Lp-PLA2) and nitric oxide (NO) production were serially assessed. Before the beginning of the study, all laboratory variables were comparable among each group. After 6 weeks of hyperlipidemic model production, serum levels of cholesterols, CRP and Lp-PLA2 were significantly increased when compared to sham group, whereas NO production was reduced. With 2 weeks of colchicine therapy, serum levels of CRP and Lp-PLA2 were decreased and NO production was enhanced in the colchicine group in a lipid-lowering independent manner. Added colchicine into atorvastatin therapy further improved NO production and decreased CRP and Lp-PLA2 levels, indicating a potential synergism of colchicine and atorvastatin. Colchicine combined with atorvastatin may have stronger protective effects on improving endothelial function and ameliorating inflammation in rats with hyperlipidemia.

Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance

NASA Technical Reports Server (NTRS)

Dollins, A. B.; Zhdanova, I. V.; Wurtman, R. J.; Lynch, H. J.; Deng, M. H.

1994-01-01

We examined effects of very low doses of melatonin (0.1-10 mg, orally) or placebo, administered at 1145 h, on sleep latency and duration, mood, performance, oral temperature, and changes in serum melatonin levels in 20 healthy male volunteers. A repeated-measure double-blind Latin square design was used. Subjects completed a battery of tests designed to assess mood and performance between 0930 and 1730 h. The sedative-like effects of melatonin were assessed by a simple sleep test: at 1330 h subjects were asked to hold a positive pressure switch in each hand and to relax with eyes closed while reclining in a quiet darkened room. Latency and duration of switch release, indicators of sleep, were measured. Areas under the time-melatonin concentration curve varied in proportion to the different melatonin doses ingested, and the 0.1- and 0.3-mg doses generated peak serum melatonin levels that were within the normal range of nocturnal melatonin levels in untreated people. All melatonin doses tested significantly increased sleep duration, as well as self-reported sleepiness and fatigue, relative to placebo. Moreover, all of the doses significantly decreased sleep-onset latency, oral temperature, and the number of correct responses on the Wilkinson auditory vigilance task. These data indicate that orally administered melatonin can be a highly potent hypnotic agent; they also suggest that the physiological increase in serum melatonin levels, which occurs around 2100 h daily, may constitute a signal initiating normal sleep onset.

Skeletal muscle calcineurin: influence of phenotype adaptation and atrophy

NASA Technical Reports Server (NTRS)

Spangenburg, E. E.; Williams, J. H.; Roy, R. R.; Talmadge, R. J.; Spangenberg, E. E. (Principal Investigator)

2001-01-01

Calcineurin (CaN) has been implicated as a signaling molecule that can transduce physiological stimuli (e.g., contractile activity) into molecular signals that initiate slow-fiber phenotypic gene expression and muscle growth. To determine the influence of muscle phenotype and atrophy on CaN levels in muscle, the levels of soluble CaN in rat muscles of varying phenotype, as assessed by myosin heavy chain (MHC)-isoform proportions, were determined by Western blotting. CaN levels were significantly greater in the plantaris muscle containing predominantly fast (IIx and IIb) MHC isoforms, compared with the soleus (predominantly type I MHC) or vastus intermedius (VI, contains all 4 adult MHC isoforms). Three months after a complete spinal cord transection (ST), the CaN levels in the VI muscle were significantly reduced, despite a significant increase in fast MHC isoforms. Surprisingly, the levels of CaN in the VI were highly correlated with muscle mass but not MHC isoform proportions in ST and control rats. These data demonstrate that CaN levels in skeletal muscle are highly correlated to muscle mass and that the normal relationship with phenotype is lost after ST.

Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue.

PubMed

Holsti, Mari; Wanhainen, Anders; Lundin, Christina; Björck, Martin; Tegler, Gustaf; Svensson, Johan; Sund, Malin

2018-04-12

Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta ≤ 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA ≥ 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Brain MRS glutamine as a biomarker to guide therapy of hyperammonemic coma.

PubMed

O'Donnell-Luria, Anne H; Lin, Alexander P; Merugumala, Sai K; Rohr, Frances; Waisbren, Susan E; Lynch, Rebecca; Tchekmedyian, Vatche; Goldberg, Aaron D; Bellinger, Andrew; McFaline-Figueroa, J Ricardo; Simon, Tracey; Gershanik, Esteban F; Levy, Bruce D; Cohen, David E; Samuels, Martin A; Berry, Gerard T; Frank, Natasha Y

2017-05-01

Acute idiopathic hyperammonemia in an adult patient is a life-threatening condition often resulting in a rapid progression to irreversible cerebral edema and death. While ammonia-scavenging therapies lower blood ammonia levels, in comparison, clearance of waste nitrogen from the brain may be delayed. Therefore, we used magnetic resonance spectroscopy (MRS) to monitor cerebral glutamine levels, the major reservoir of ammonia, in a gastric bypass patient with hyperammonemic coma undergoing therapy with N-carbamoyl glutamate and the ammonia-scavenging agents, sodium phenylacetate and sodium benzoate. Improvement in mental status mirrored brain glutamine levels, as coma persisted for 48h after plasma ammonia normalized. We hypothesize that the slower clearance for brain glutamine levels accounts for the delay in improvement following initiation of treatment in cases of chronic hyperammonemia. We propose MRS to monitor brain glutamine as a noninvasive approach to be utilized for diagnostic and therapeutic monitoring purposes in adult patients presenting with idiopathic hyperammonemia. Copyright © 2017 Elsevier Inc. All rights reserved.

Small Changes in the Regulation of One Arabidopsis Profilin Isovariant, PRF1, Alter Seedling Development

PubMed Central

McKinney, Elizabeth Cohen; Kandasamy, Muthugapatti K.; Meagher, Richard B.

2001-01-01

Profilin (PRF) is a low-molecular-weight actin binding protein encoded by a diverse gene family in plants. Arabidopsis PRF1 transcripts are moderately well expressed in all vegetative organs. A regulatory mutant in PRF1, prf1-1, was isolated from a library of T-DNA insertions. The insertion disrupted the promoter region of PRF1 100 bp upstream from the transcriptional start site. Although steady state levels of PRF1 transcripts appeared normal in mature prf1-1 plants, the levels in young seedlings were only one-half those observed in wild type. Reactions with a PRF1 isovariant–specific monoclonal antiserum and general anti-profilin antisera demonstrated that PRF1 protein levels also were one-half those found in wild-type seedlings, although total profilin levels were unaffected. Mutant seedlings no longer could downregulate PRF1 levels in the light, as did wild type. Consistent with their molecular phenotypes, young mutant seedlings displayed several morphological phenotypes but developed into apparently normal adult plants. Their initial germination rate and development were slow, and they produced excessive numbers of root hairs. Mutant seedlings had abnormally raised cotyledons, elongated hypocotyls, and elongated cells in the hypocotyl, typical of phenotypes associated with some defects in light and circadian responses. A wild-type PRF1 transgene fully complements the hypocotyl phenotypes in the prf1-1 mutant. The ability of profilin to regulate actin polymerization and participate directly in signal transduction pathways is discussed in light of the prf1-1 phenotypes. PMID:11340190

Effect of magnesium on arrhythmia incidence in patients undergoing coronary artery bypass grafting.

PubMed

Mohammadzadeh, Alireza; Towfighi, Farshad; Jafari, Naser

2018-06-01

Cardiac arrhythmia after coronary artery bypass grafting (CABG) surgery is a common complication of cardiac surgery. The effect of serum magnesium, hypomagnesaemia treatment and prophylactic administration of magnesium in the development and prevention of arrhythmias is controversial and there are many different ideas. This study evaluates the therapeutic effects of magnesium in cardiac arrhythmia after CABG surgery. The clinical trial enrolled 250 patients who underwent CABG. Based on the initial serum levels of magnesium, patients were divided into two groups: hypomagnesium and normomagnesium. Based on bioethics committee requirements, patients in the hypo-magnesium group received magnesium treatments until they attained normal magnesium blood levels. Both groups underwent CABG with normal blood levels of magnesium. After surgery, each group was randomly divided into two subgroups: one subgroup received a bolus dose of magnesium sulphate (30 mg/kg in 5 min) and the other subgroup received a placebo. Subgroups were under observation in the intensive care unit for 3 days and arrhythmias were recorded. Data from all four subgroups were analysed statistically and interpreted. The results of this study showed that the occurrence of arrhythmia was not significantly different among subgroups (P > 0.05). There was no significant relationship between blood levels of magnesium and arrhythmia during the 3 days post-surgery (P > 0.05). The results of this study showed that magnesium sulphate administration did not significantly improve the incidence of arrhythmias in hypo- and normo-magnesium patients after CABG. There was no significant correlation between post-operative serum levels of magnesium and arrhythmia during 3 days. © 2017 Royal Australasian College of Surgeons.

Defibrillation depends on conductivity fluctuations and the degree of disorganization in reentry patterns.

PubMed

Plank, Gernot; Leon, L Joshua; Kimber, Shane; Vigmond, Edward J

2005-02-01

Defibrillation depends on conductivity and disorganization. Cardiac fibrillation is the deterioration of the heart's normally well-organized activity into one or more meandering spiral waves, which subsequently break up into many meandering wave fronts. Delivery of an electric shock (defibrillation) is the only effective way of restoring the normal rhythm. This study focuses on examining whether higher degrees of disorganization requires higher shock strengths to defibrillate and whether microscopic conductivity fluctuations favor shock success. We developed a three-dimensional computer bidomain model of a block of cardiac tissue with straight fibers immersed in a conductive bath. The membrane behavior was described by the Courtemanche human atrial action potential model incorporating electroporation and an acetylcholine- (ACh) dependent potassium current. Intracellular conductivities were varied stochastically around nominal values with variations of up to 50%. A single rotor reentry was initiated and, by adjusting the spatial ACh variation, the level of organization could be controlled. The single rotor could be stabilized or spiral wave breakup could be provoked leading to fibrillatory-like activity. For each level of organization, multiple shock timings and strengths were applied to compute the probability of shock success as a function of shock strength. Our results suggest that the level of the small-scale conductivity fluctuations is a very important factor in defibrillation. A higher variation significantly lowers the required shock strength. Further, we demonstrated that success also heavily depends on the level of organization of the fibrillatory episode. In general, higher levels of disorganization require higher shock strengths to defibrillate.

Liver alpha-amylase gene expression as an early obesity biomarker.

PubMed

Mojbafan, Marzieh; Afsartala, Zohreh; Amoli, Mahsa M; Mahmoudi, Mahdi; Yaghmaei, Parichehreh; Larijani, Bagher; Ebrahim-Habibi, Azadeh

2017-04-01

Obesity is a major health problem worldwide, for which preventive and therapeutic means are still needed. Alpha-amylase is a digestive enzyme whose inhibition has been targeted as a potential anti-obesity strategy. However, alpha-amylase gene expression has not been particularly attended to, and in contrast with pancreatic and salivary amylases, fewer studies have focused on liver alpha-amylase. The present study aimed at investigating the expression of alpha-amylase gene in obese and normal mice at RNA and protein level as well as acarbose effect on this gene expression in hepatocyte cell culture. Control and case groups were fed by normal mouse pellet and high-fat diet respectively, during 8 weeks. After this period, serum biochemical parameters including glucose, cholesterol, triglycerides, AST, ALT and alpha-amylase were assayed. Liver alpha-amylase gene was analyzed by real time PCR, and liver enzyme was assayed with Bernfeld and ELISA methods Hepatocyte cell culture derived from both group were also treated by acarbose and alpha-amylase activity and gene expression was analyzed by above mentioned methods. All biochemical factors showed an increase in obese mice, but the increase in ALT and AST were not statistically significant. Alpha-amylase levels were also increased in obese mice, both at RNA and protein level, while a decrease was seen in obese mice derived hepatocytes after acarbose treatment. Elevated liver alpha-amylase levels may be indicative of initial stages of obesity and the use of acarbose could be considered as a treatment of obesity which could be potentially effective at multiple levels. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Renilla luciferase-based quantitation of Potato virus A infection initiated with Agrobacterium infiltration of N. benthamiana leaves.

PubMed

Eskelin, K; Suntio, T; Hyvärinen, S; Hafren, A; Mäkinen, K

2010-03-01

A quantitation method based on the sensitive detection of Renilla luciferase (Rluc) activity was developed and optimized for Potato virus A (PVA; genus Potyviridae) gene expression. This system is based on infections initiated by Agrobacterium infiltration and subsequent detection of the translation of PVA::Rluc RNA, which is enhanced by viral replication, first within the cells infected initially and later by translation and replication within new cells after spread of the virus. Firefly luciferase (Fluc) was used as an internal control to normalize the Rluc activity. An approximately 10-fold difference in the Rluc/Fluc activity ratio between a movement-deficient and a replication-deficient mutant was observed starting from 48h post Agrobacterium infiltration (h.p.i.). The Rluc activity derived from wild type (wt) PVA increased significantly between 48 and 72h.p.i. and the Rluc/Fluc activity deviated clearly from that of the mutant viruses. Quantitation of the Rluc and Fluc mRNAs by semi-quantitative RT-PCR indicated that increases and decreases in the Renillareniformis luciferase (rluc) mRNA levels coincided with changes in Rluc activity. However, a subtle increase in the mRNA level led to pronounced changes in Rluc activity. PVA CP accumulation was quantitated by enzyme-linked immunosorbent assay. The increase in Rluc activity correlated closely with virus accumulation. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Dispersion relations of elastic waves in one-dimensional piezoelectric/piezomagnetic phononic crystal with initial stresses.

PubMed

Guo, Xiao; Wei, Peijun

2016-03-01

The dispersion relations of elastic waves in a one-dimensional phononic crystal formed by periodically repeating of a pre-stressed piezoelectric slab and a pre-stressed piezomagnetic slab are studied in this paper. The influences of initial stress on the dispersive relation are considered based on the incremental stress theory. First, the incremental stress theory of elastic solid is extended to the magneto-electro-elasto solid. The governing equations, constitutive equations, and boundary conditions of the incremental stresses in a magneto-electro-elasto solid are derived with consideration of the existence of initial stresses. Then, the transfer matrices of a pre-stressed piezoelectric slab and a pre-stressed piezomagnetic slab are formulated, respectively. The total transfer matrix of a single cell in the phononic crystal is obtained by the multiplication of two transfer matrixes related with two adjacent slabs. Furthermore, the Bloch theorem is used to obtain the dispersive equations of in-plane and anti-plane Bloch waves. The dispersive equations are solved numerically and the numerical results are shown graphically. The oblique propagation and the normal propagation situations are both considered. In the case of normal propagation of elastic waves, the analytical expressions of the dispersion equation are derived and compared with other literatures. The influences of initial stresses, including the normal initial stresses and shear initial stresses, on the dispersive relations are both discussed based on the numerical results. Copyright © 2015 Elsevier B.V. All rights reserved.

Spatio-temporal dynamics and laterality effects of face inversion, feature presence and configuration, and face outline

PubMed Central

Marinkovic, Ksenija; Courtney, Maureen G.; Witzel, Thomas; Dale, Anders M.; Halgren, Eric

2014-01-01

Although a crucial role of the fusiform gyrus (FG) in face processing has been demonstrated with a variety of methods, converging evidence suggests that face processing involves an interactive and overlapping processing cascade in distributed brain areas. Here we examine the spatio-temporal stages and their functional tuning to face inversion, presence and configuration of inner features, and face contour in healthy subjects during passive viewing. Anatomically-constrained magnetoencephalography (aMEG) combines high-density whole-head MEG recordings and distributed source modeling with high-resolution structural MRI. Each person's reconstructed cortical surface served to constrain noise-normalized minimum norm inverse source estimates. The earliest activity was estimated to the occipital cortex at ~100 ms after stimulus onset and was sensitive to an initial coarse level visual analysis. Activity in the right-lateralized ventral temporal area (inclusive of the FG) peaked at ~160 ms and was largest to inverted faces. Images containing facial features in the veridical and rearranged configuration irrespective of the facial outline elicited intermediate level activity. The M160 stage may provide structural representations necessary for downstream distributed areas to process identity and emotional expression. However, inverted faces additionally engaged the left ventral temporal area at ~180 ms and were uniquely subserved by bilateral processing. This observation is consistent with the dual route model and spared processing of inverted faces in prosopagnosia. The subsequent deflection, peaking at ~240 ms in the anterior temporal areas bilaterally, was largest to normal, upright faces. It may reflect initial engagement of the distributed network subserving individuation and familiarity. These results support dynamic models suggesting that processing of unfamiliar faces in the absence of a cognitive task is subserved by a distributed and interactive neural circuit. PMID:25426044

Decreased expression of 14-3-3 σ, an early event of malignant transformation of respiratory epithelium, also facilitates progression of squamous cell lung cancer

PubMed Central

Sun, Nan; Wu, Yongkai; Huang, Bo; Liu, Qian; Dong, Yinan; Ding, Jianqiao; Liu, Yongyu

2015-01-01

Background It has been shown that 14-3-3 σ serves as a tumor suppressor gene, and is downregulated in various tumor tissues. However, the role of 14-3-3 σ during the initiation and progression of lung squamous cell carcinoma (SqCC) is not well understood. Methods The expression status of 14-3-3 σ in archival tissue samples from 40 lung SqCC patients (36 with normal bronchia, 19 squamous metaplasia, and 17 dysplasia/carcinoma in situ, in their tissue samples) was examined by immunohistochemical analysis. The proliferation rate and tumor formation ability of the H520 cell transfected with 14-3-3 σ was tested with methyl thiazolyl tetrazolium assay and nude mice subcutaneous injection, respectively. Results In the normal bronchial epithelia, 14-3-3 σ was highly expressed, whereas it was significantly decreased in precancerous and cancerous tissues. Compared with matched invasive cancer tissues, the expression level of 14-3-3 σ in squamous metaplasia was significantly higher (P = 0.049), while that in dysplasia/carcinoma in situ showed no significant changes (P = 0.135). Statistical analysis showed that the expression level of 14-3-3 σ in tumor tissue was associated with the differentiation grade of the tumor (P = 0.001) and the prognosis of the patient (P = 0.003). The overexpression of 14-3-3 σ significantly suppressed the proliferation of H520 cells in vitro and in vivo. Conclusion The inactivation of 14-3-3 σ may be a very early event in tumorigenesis and could facilitate the initiation and progression of lung SqCC in a sustainable way. PMID:26557909

Controlled treatment of primary hypertension with propranolol and spironolactone. A crossover study with special reference to initial plasma renin activity.

PubMed

Karlberg, B E; Kågedal, B; Tegler, L; Tolagen, K; Bergman, B

1976-03-31

Twenty-seven patients with hypertension were randomly allocated to a 10 month crossover study. Treatment consisted of spironolactone (200 mg/day for 2 months), propranolol (320 mg/day for 2 months) and combined administration of both drugs at half the dosage. Between treatment periods placebo was given for 2 months. Fourteen patients were previously untreated. The average pretreatment blood pressure for the entire group was 188/114 +/- 16/7(mean +/- standard deviation) mm Hg supine and 188/118 +/- 20/9 mm Hg standing. Both spironolactone and propranolol reduced blood pressure significantly in both the supine and standing positions. Upright plasma renin activity was determined by radioimmunoassay of angiotensin I. The average initial level was 1.9 +/- 1.2 (range 0.4 to 5.0) ng/ml/hr. There was a close correlation between plasma renin activity and the effects of the drugs: With increasing renin level the response to propranolol was better whereas the opposite was true for spironolactone. The combination of spironolactone and propranolol decreased the blood pressure still further in the supine and standing positions, irrespective of initial plasma renin activity. All patients achieved a normal supine pressure. Blood pressure and plasma renin activity returned toward pretreatment values during placebo administration. It is concluded that pretreatment levels of plasma renin activity can predict the antihypertensive response to propranolol and spironolactone. The combination of the two drugs, which have different modes of action, will effectively reduce blood pressure in hypertension. The results support the concept that the renin-angiotensin-aldo-sterone system may be involved in primary hypertension.

Effect of Volume of Fluid Resuscitation on Metabolic Normalization in Children Presenting in Diabetic Ketoacidosis: A Randomized Controlled Trial.

PubMed

Bakes, Katherine; Haukoos, Jason S; Deakyne, Sara J; Hopkins, Emily; Easter, Josh; McFann, Kim; Brent, Alison; Rewers, Arleta

2016-04-01

The optimal rate of fluid administration in pediatric diabetic ketoacidosis (DKA) is unknown. Our aim was to determine whether the volume of fluid administration in children with DKA influences the rate of metabolic normalization. We performed a randomized controlled trial conducted in a tertiary pediatric emergency department from December 2007 until June 2010. The primary outcome was time to metabolic normalization; secondary outcomes were time to bicarbonate normalization, pH normalization, overall length of hospital treatment, and adverse outcomes. Children between 0 and 18 years of age were eligible if they had type 1 diabetes mellitus and DKA. Patients were randomized to receive intravenous (IV) fluid at low volume (10 mL/kg bolus + 1.25 × maintenance rate) or high volume (20 mL/kg bolus + 1.5 × maintenance rate) (n = 25 in each). After adjusting for initial differences in bicarbonate levels, time to metabolic normalization was significantly faster in the higher-volume infusion group compared to the low-volume infusion group (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.0-3.9; p = 0.04). Higher-volume IV fluid infusion appeared to hasten, to a greater extent, normalization of pH (HR = 2.5; 95% CI 1.2-5.0; p = 0.01) than normalization of serum bicarbonate (HR = 1.2; 95% CI 0.6-2.3; p = 0.6). The length of hospital treatment HR (0.8; 95% CI 0.4-1.5; p = 0.5) and time to discharge HR (0.8; 95% CI 0.4-1.5; p = 0.5) did not differ between treatment groups. Higher-volume fluid infusion in the treatment of pediatric DKA patients significantly shortened metabolic normalization time, but did not change overall length of hospital treatment. ClinicalTrials.gov ID NCT01701557. Copyright © 2016 Elsevier Inc. All rights reserved.

The Initiation of Smooth Pursuit is Delayed in Anisometropic Amblyopia

PubMed Central

Raashid, Rana Arham; Liu, Ivy Ziqian; Blakeman, Alan; Goltz, Herbert C.; Wong, Agnes M. F.

2016-01-01

Purpose Several behavioral studies have shown that the reaction times of visually guided movements are slower in people with amblyopia, particularly during amblyopic eye viewing. Here, we tested the hypothesis that the initiation of smooth pursuit eye movements, which are responsible for accurately keeping moving objects on the fovea, is delayed in people with anisometropic amblyopia. Methods Eleven participants with anisometropic amblyopia and 14 visually normal observers were asked to track a step-ramp target moving at ±15°/s horizontally as quickly and as accurately as possible. The experiment was conducted under three viewing conditions: amblyopic/nondominant eye, binocular, and fellow/dominant eye viewing. Outcome measures were smooth pursuit latency, open-loop gain, steady state gain, and catch-up saccade frequency. Results Participants with anisometropic amblyopia initiated smooth pursuit significantly slower during amblyopic eye viewing (206 ± 20 ms) than visually normal observers viewing with their nondominant eye (183 ± 17 ms, P = 0.002). However, mean pursuit latency in the anisometropic amblyopia group during binocular and monocular fellow eye viewing was comparable to the visually normal group. Mean open-loop gain, steady state gain, and catch-up saccade frequency were similar between the two groups, but participants with anisometropic amblyopia exhibited more variable steady state gain (P = 0.045). Conclusions This study provides evidence of temporally delayed smooth pursuit initiation in anisometropic amblyopia. After initiation, the smooth pursuit velocity profile in anisometropic amblyopia participants is similar to visually normal controls. This finding differs from what has been observed previously in participants with strabismic amblyopia who exhibit reduced smooth pursuit velocity gains with more catch-up saccades. PMID:27070109

An Evaluation of Deficits in Semantic Cuing, Proactive and Retroactive Interference as Early Features of Alzheimer’s disease

PubMed Central

Crocco, Elizabeth; Curiel, Rosie E.; Acevedo, Amarilis; Czaja, Sara J.; Loewenstein, David A.

2015-01-01

OBJECTIVE To determine the degree to which susceptibility to different types of semantic interference may reflect the earliest manifestations of early Alzheimer disease (AD) beyond the effects of global memory impairment. METHODS Normal elderly (NE) subjects (n= 47), subjects with amnestic mild cognitive impairment (aMCI: n=34) and 40 subjects with probable AD were evaluated using a unique cued recall paradigm that allowed for an evaluation of both proactive and retroactive interference effects while controlling for global memory impairment (LASSI-L procedure). RESULTS Controlling for overall memory impairment, aMCI subjects had much greater proactive and retroactive interference effects than NE subjects. LASSI-L indices of learning using cued recall evidenced high levels of sensitivity and specificity with an overall correct classification rate of 90%. These provided better discrimination than traditional neuropsychological measures of memory function. CONCLUSION The LASSI-L paradigm is unique and unlike other assessments of memory in that items presented for cued recall are explicitly presented, and semantic interference and cuing effects can be assessed while controlling for initial level of memory impairment. This represents a powerful procedure allowing the participant to serve as his or her own control. The high levels of discrimination between subjects with aMCI and normal cognition that exceeded traditional neuropsychological measures makes the LASSI-L worthy of further research in the detection of early AD. PMID:23768680

Correction of glucocerebrosidase deficiency after retroviral-mediated gene transfer into hematopoietic progenitor cells from patients with Gaucher disease

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

Fink, J.K.; Correll, P.H.; Perry, L.K.

1990-03-01

Retroviral gene transfer has been used successfully to correct the glucocerebrosidase (GCase) deficiency in primary hematopoietic cells from patients with Gaucher disease. For this model of somatic gene therapy, the authors developed a high-titer, amphotropic retroviral vector designated NTG in which the human GCase gene was driven by the mutant polyoma virus enhancer/herpesvirus thymidine kinase gene (tk) promoter (Py{sup +}/Htk). NTG normalized GCase activity in transduced Gaucher fibroblasts and efficiently infected human monocytic and erythroleukemic cell lines. RNA blot-hybridization (Northern blot) analysis of these hemaptopoietic cell lines showed unexpectedly high-level expression from the Moloney murine leukemia virus long terminal repeatmore » (Mo-MLV LTR) and levels of Py{sup +}/Htk enhancer/promoter-initiated human GCase RNA that approximated endogenous GCase RNA levels. Furthermore, NTG efficiently infected human hematopoietic progenitor cells. Detection of the provirus in approximately one-third of NTG-infected progenitor colonies that had not been selected in G418-containing medium indicates that relative resistance to G418 underestimated the actual gene transfer efficiency. Northern blot analysis of NTG-infected, progenitor-derived cells showed expression from both the Mo-MLV LTR and the Py{sup +}/Htk enhancer/promoter. NTG-transduced hematopoietic progenitor cells from patients with Gaucher disease generated progeny in which GCase activity has been normalized.« less

[Autoimmune insulitis in patients with type 2 diabetes mellitus A randomized clinical trial in hospitalized patients].

PubMed

Martinka, Emil; Rončáková, Mariana; Mišániková, Michaela; Davani, Arash

It is not always easy to classify diabetes (DM) diagnosed in adults, with a significant group of patients initially classified and treated for type 2 diabetes mellitus (DM2T) presenting signs indicating the presence of autoimmune insulitis (AI), which is characteristic of type 1 diabetes mellitus (DM1T), or latent autoimmune diabetes mellitus in adults (LADA). Identify the proportion of patients entered with DM2T who present AI signs, and the number of patients of that proportion, who at the same time present low insulin secretion, and what clinical and laboratory manifestations could be used to differentiate between these patients.Cohort and methods: A randomized clinical trial with a pre-determined set of assessed parameters for n = 625 patients, who were hospitalized during the first 6 months of 2016 at the National Endocrinology and Diabetology Institute (NEDU), Lubochna. Apart from the standard parameters, C-peptide (CP) and autoantibodies to glutamic acid decarboxylase (GADA) were examined for each patient. GADA positive (GADA+) patients were compared to GADA negative (GADA-) patients in the following parameters: gender, age, age at the time of dia-gnosing DM, duration of DM, HbA1c, incidence of hypoglycemia, lipidogram, fasting C-peptide levels, BMI, waist circumference, incidence of hypoglycemias, presence of microvascular and macrovascular complications, treatment of dia-betes and incidence of other endocrinopathies. GADA+ with low CP were subsequently compared to GADA+ patients with normal CP. Of 625 patients originally classified and treated as DM2T, 13 % were GADA+. 31 % of them had low CP (< 0.2 nmol/l) and 28 % had CP levels within the intermediary range (0.2-0.4 nmol/l). Females made up a larger proportion of GADA+ patients, with a lower BMI, smaller waist circumference, lower CP, higher HDL cholesterol levels, a greater incidence of hypoglycemias and lower total daily dose of insulin. GADA+ patients with low CP differed from GADA+ patients with normal CP in higher HDL cholesterol levels, lower triglyceride levels and earlier need of insulin thera-py. The testing for GADA and CP levels with regard to the other relevant characteristics led to re-classification, or more precisely adding of DM1T/LADA (as the main, or parallel cause of DM) for 2.9 % of all the patients included and a clinically significant proportion of AI could be assumed in 6.1 % of the patients. The results of our study show that the pathogenesis of DM in patients initially diagnosed and registered with DM2T and with concurrent presence of GADA includes mechanisms characteristic of both DM2T (insulin resistance) and DM1T (autoimmune insulitis) acting in parallel, with different intensity, in differing proportions and time sequence as a fluid continuum, which also accounts for the differences between individual patients. The characteristics highlighting the presence and role of AI based on our results include high titre of GADA+, low CP levels, early need of insulin therapy, presence of thyroid disorder, higher HDL cholesterol levels and lower triglyceride levels. The characteristics highlighting the dominance of mechanisms characteristic of DM2T (insulin resistance) included higher BMI and waist circumference values, normal CP levels, low HDL cholesterol levels, higher triglyceride levels, higher blood pressure and borderline titre of GADA. autoimmune diabetes mellitus - C-peptide - GADA - HDL-cholesterol - classification.

Online monitoring of oil film using electrical capacitance tomography and level set method.

PubMed

Xue, Q; Sun, B Y; Cui, Z Q; Ma, M; Wang, H X

2015-08-01

In the application of oil-air lubrication system, electrical capacitance tomography (ECT) provides a promising way for monitoring oil film in the pipelines by reconstructing cross sectional oil distributions in real time. While in the case of small diameter pipe and thin oil film, the thickness of the oil film is hard to be observed visually since the interface of oil and air is not obvious in the reconstructed images. And the existence of artifacts in the reconstructions has seriously influenced the effectiveness of image segmentation techniques such as level set method. Besides, level set method is also unavailable for online monitoring due to its low computation speed. To address these problems, a modified level set method is developed: a distance regularized level set evolution formulation is extended to image two-phase flow online using an ECT system, a narrowband image filter is defined to eliminate the influence of artifacts, and considering the continuity of the oil distribution variation, the detected oil-air interface of a former image can be used as the initial contour for the detection of the subsequent frame; thus, the propagation from the initial contour to the boundary can be greatly accelerated, making it possible for real time tracking. To testify the feasibility of the proposed method, an oil-air lubrication facility with 4 mm inner diameter pipe is measured in normal operation using an 8-electrode ECT system. Both simulation and experiment results indicate that the modified level set method is capable of visualizing the oil-air interface accurately online.

Online monitoring of oil film using electrical capacitance tomography and level set method

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

Xue, Q., E-mail: xueqian@tju.edu.cn; Ma, M.; Sun, B. Y.

2015-08-15

In the application of oil-air lubrication system, electrical capacitance tomography (ECT) provides a promising way for monitoring oil film in the pipelines by reconstructing cross sectional oil distributions in real time. While in the case of small diameter pipe and thin oil film, the thickness of the oil film is hard to be observed visually since the interface of oil and air is not obvious in the reconstructed images. And the existence of artifacts in the reconstructions has seriously influenced the effectiveness of image segmentation techniques such as level set method. Besides, level set method is also unavailable for onlinemore » monitoring due to its low computation speed. To address these problems, a modified level set method is developed: a distance regularized level set evolution formulation is extended to image two-phase flow online using an ECT system, a narrowband image filter is defined to eliminate the influence of artifacts, and considering the continuity of the oil distribution variation, the detected oil-air interface of a former image can be used as the initial contour for the detection of the subsequent frame; thus, the propagation from the initial contour to the boundary can be greatly accelerated, making it possible for real time tracking. To testify the feasibility of the proposed method, an oil-air lubrication facility with 4 mm inner diameter pipe is measured in normal operation using an 8-electrode ECT system. Both simulation and experiment results indicate that the modified level set method is capable of visualizing the oil-air interface accurately online.« less

Early Menarche and Gestational Diabetes Mellitus at First Live Birth.

PubMed

Shen, Yun; Hu, Hui; D Taylor, Brandie; Kan, Haidong; Xu, Xiaohui

2017-03-01

To examine the association between early menarche and gestational diabetes mellitus (GDM). Data from the National Health and Nutrition Examination Survey 2007-2012 were used to investigate the association between age at menarche and the risk of GDM at first birth among 5914 women. A growth mixture model was used to detect distinctive menarche onset patterns based on self-reported age at menarche. Logistic regression models were then used to examine the associations between menarche initiation patterns and GDM after adjusting for sociodemographic factors, family history of diabetes mellitus, lifetime greatest Body Mass Index, smoking status, and physical activity level. Among the 5914 first-time mothers, 3.4 % had self-reported GDM. We detected three groups with heterogeneous menarche onset patterns, the Early, Normal, and Late Menarche Groups. The regression model shows that compared to the Normal Menarche Group, the Early Menarche Group had 1.75 (95 % CI 1.10, 2.79) times the odds of having GDM. No statistically significant difference was observed between the Normal and the Late Menarche Group. This study suggests that early menarche may be a risk factor of GDM. Future studies are warranted to examine and confirm this finding.

The use of a tactile interface to convey position and motion perceptions

NASA Technical Reports Server (NTRS)

Rupert, A. H.; Guedry, F. E.; Reschke, M. F.

1994-01-01

Under normal terrestrial conditions, perception of position and motion is determined by central nervous system integration of concordant and redundant information from multiple sensory channels (somatosensory, vestibular, visual), which collectively yield vertical perceptions. In the acceleration environment experienced by the pilots, the somatosensory and vestibular sensors frequently present false information concerning the direction of gravity. When presented with conflicting sensory information, it is normal for pilots to experience episodes of disorientation. We have developed a tactile interface that obtains vertical roll and pitch information from a gyro-stabilized attitude indicator and maps this information in a one-to-one correspondence onto the torso of the body using a matrix of vibrotactors. This enables the pilot to continuously maintain an awareness of aircraft attitude without reference to visual cues, utilizing a sensory channel that normally operates at the subconscious level. Although initially developed to improve pilot spatial awareness, this device has obvious applications to 1) simulation and training, 2) nonvisual tracking of targets, which can reduce the need for pilots to make head movements in the high-G environment of aerial combat, and 3) orientation in environments with minimal somatosensory cues (e.g., underwater) or gravitational cues (e.g., space).

Mitochondrial function in diaphragm of emphysematous hamsters after treatment with nandrolone.

PubMed

Wijnhoven, Hanneke J H; Ennen, Leo; Rodenburg, Richard J T; Dekhuijzen, P N Richard

2006-01-01

Respiratory failure in patients with COPD may be caused by insufficient force production or insufficient endurance capacity of the respiratory muscles. Anabolic steroids may improve respiratory muscle function in COPD. The effect of anabolic steroids on mitochondrial function in the diaphragm in emphysema is unknown. In an emphysematous male hamster model, we investigated whether administration of the anabolic steroid nandrolone decanoate (ND) altered the activity of mitochondrial respiratory chain complexes in the diaphragm. The bodyweight of hamsters treated with ND was decreased after treatment compared with initial values, and serum testosterone levels were significantly lower in hamsters treated with ND than in control hamsters. No difference in the activity of mitochondrial respiratory chain complexes in the diaphragm between normal and emphysematous hamsters was observed. Treatment with ND did not change the activity of mitochondrial respiratory chain complexes in the diaphragm of both normal and emphysematous hamsters. In emphysematous hamsters, administration of ND decreased the activity of succinate:cytochrome c oxidoreductase compared with ND treatment in normal hamsters. We conclude that anabolic steroids have negative effects on the activity of succinate:cytochrome c oxidoreductase and anabolic status in this emphysematous hamster model.

Mitochondrial function in diaphragm of emphysematous hamsters after treatment with nandrolone

PubMed Central

Wijnhoven, Hanneke JH; Ennen, Leo; Rodenburg, Richard JT; Dekhuijzen, PN Richard

2006-01-01

Respiratory failure in patients with COPD may be caused by insufficient force production or insufficient endurance capacity of the respiratory muscles. Anabolic steroids may improve respiratory muscle function in COPD. The effect of anabolic steroids on mitochondrial function in the diaphragm in emphysema is unknown. In an emphysematous male hamster model, we investigated whether administration of the anabolic steroid nandrolone decanoate (ND) altered the activity of mitochondrial respiratory chain complexes in the diaphragm. The bodyweight of hamsters treated with ND was decreased after treatment compared with initial values, and serum testosterone levels were significantly lower in hamsters treated with ND than in control hamsters. No difference in the activity of mitochondrial respiratory chain complexes in the diaphragm between normal and emphysematous hamsters was observed. Treatment with ND did not change the activity of mitochondrial respiratory chain complexes in the diaphragm of both normal and emphysematous hamsters. In emphysematous hamsters, administration of ND decreased the activity of succinate:cytochrome c oxidoreductase compared with ND treatment in normal hamsters. We conclude that anabolic steroids have negative effects on the activity of succinate:cytochrome c oxidoreductase and anabolic status in this emphysematous hamster model. PMID:18046906

[An unexpected stage of alkalosis in the dynamics of the early posthemorrhagic period].

PubMed

Beliaev, A V

2000-01-01

A study was made on acid-base metabolism in early posthemorrhagic period as exemplified by examination of patients presenting with gastrointestinal hemorrhage. It has been ascertained that hemorrhage is accompanied by a mixed variant of the acid-base state (ABS) deviation, namely metabolic lactate-acidosis and respiratory alkalosis. In the time-related course of posthemorrhagic period such deviations persist in patients with lethal outcome; with the disease running a favourable course the above deviations are found to return to normal quite soon. The development of complications leads to staging in ABC, its stages being as follows: stage I--the initial stage, stage II--persisting metabolic acidosis and respiratory alkalosis, stage III--alkalosis, stage IV--normalization, with stage III of ABS being encouraged by hypocapnia caused by function disorders of the lungs in early posthemorrhagic period, normalization of cell metabolism, increase in the rate of urination as a reflection of the third earlier identified stage of water metabolism, with the H+ excretion in the urine at the previous level. The identified ABS stage III threatens coming trouble, being accompanied by metabolic deviations together with a risk of function disorder of the myocardium.

Preoperative normal level of parathyroid hormone signifies an early and mild form of primary hyperparathyroidism.

PubMed

Bergenfelz, Anders; Lindblom, Pia; Lindergård, Birger; Valdemarsson, Stig; Westerdahl, Johan

2003-04-01

Contemporary patients are often diagnosed with mild or intermittent hypercalcemia. In addition, most studies demonstrate patients with parathyroid (PTH) levels in the upper normal range. The aim of the present investigation was to define subgroups of patients with mild primary hyperparathyroidism (pHPT), which could be of importance in the decision for or against surgical treatment. Two-hundred and eleven patients, operated for pHPT were investigated with biochemical variables known to reflect PTH activity, renal function, and bone mineral content. The preoperative diagnosis of pHPT was based on the presence of hypercalcemia combined with an inappropriate serum concentration of PTH. The mean age of the patients was 64 +/- 14 years and the mean serum level of calcium was 2.78 +/- 0.19 mmol/L. One hundred and sixty-two patients (77%) had raised levels of calcium and PTH the day before surgery (overt pHPT), 25 patients (12%) had a normal level of calcium and a raised PTH level (normal calcium group), and 20 patients (9%) had a raised level of calcium and a normal level of PTH (normal PTH group). In four patients the level of calcium and PTH was normal. Between-group analysis demonstrated no major difference in symptom and signs of pHPT. Except for lower adenoma weight, patients in the normal calcium group did not essentially differ from the patients in the overt pHPT group. However, patients in the normal PTH group were a decade younger, and had better renal function, lower bone turnover, and a preserved bone density compared with patients in the overt pHPT group. In conclusion, the data from the present investigation show that pHPT patients with a preoperative normal PTH level have an early and mild form of the disease. Furthermore, the serum calcium concentration does not reflect disease severity in pHPT.

Ku Protein Levels, Localization and Association to Replication Origins in Different Stages of Breast Tumor Progression

PubMed Central

Abdelbaqi, Khalil; Di Paola, Domenic; Rampakakis, Emmanouil; Zannis-Hadjopoulos, Maria

2013-01-01

Human origins of DNA replication are specific sequences within the genome whereby DNA replication is initiated. A select group of proteins, known as the pre-replication (pre-RC) complex, in whose formation the Ku protein (Ku70/Ku86) was shown to play a role, bind to replication origins to initiate DNA replication. In this study, we have examined the involvement of Ku in breast tumorigenesis and tumor progression and found that the Ku protein expression levels in human breast metastatic (MCF10AC1a) cells were higher in the chromatin fraction compared to hyperplastic (MCF10AT) and normal (MCF10A) human breast cells, but remained constant in both the nuclear and cytoplasmic fractions. In contrast, in human intestinal cells, the Ku expression level was relatively constant for all cell fractions. Nascent DNA abundance and chromatin association of Ku70/86 revealed that the c-myc origin activity in MCF10AC1a is 2.5 to 5-fold higher than in MCF10AT and MCF10A, respectively, and Ku was bound to the c-myc origin more abundantly in MCF10AC1a, by approximately 1.5 to 4.2-fold higher than in MCF10AT and MCF10A, respectively. In contrast, similar nascent DNA abundance and chromatin association was found for all cell lines for the lamin B2 origin, associated with the constitutively active housekeeping lamin B2 gene. Electrophoretic mobility shift assays (EMSAs) performed on the nuclear extracts (NEs) of the three cell types revealed the presence of protein-DNA replication complexes on both the c-myc and lamin B2 origins, but an increase in binding activity was observed from normal, to transformed, to cancer cells for the c-myc origin, whereas no such difference was seen for the lamin B2 origin. Overall, the results suggest that increased Ku chromatin association, beyond wild type levels, alters cellular processes, which have been implicated in tumorigenesis. PMID:23781282

Elevated blood lipids are uncommon in patients with post-polio syndrome--a cross sectional study.

PubMed

Melin, Eva; Kahan, Thomas; Borg, Kristian

2015-04-29

The post-polio syndrome occurs in people who previously have had poliomyelitis. After the initial recovery, new or increasing neurologic symptoms occur. Inflammation and dyslipidaemia may play an important role in the development of atherosclerotic complications, for example myocardial infarction and angina pectoris. Previous studies on cardiovascular risk factors in the post-polio syndrome have found a higher prevalence of hypertension, ischemic heart disease, hyperlipidaemia, and stroke in these patients. The present study was undertaken in order to evaluate whether post-polio patients have elevated lipid values, and if blood lipid abnormalities could be correlated to signs of inflammation. Cross-sectional study of 89 consecutive post-polio patients, (53 women, mean age 65 years) from the Post-Polio Outpatient Clinic, Danderyd University Hospital, Stockholm, Sweden. The lipid profiles of post-polio patients were compared to age and sex matched reference values from two earlier studies. Statistical analyses were performed by the Student's t-test, and linear regression analyses were assessed by Pearson's correlation coefficient. Mean total cholesterol levels (5.7 mmol/L) were low or normal in post-polio patients, whereas low density lipoprotein levels (3.6 mmol/L) were normal, and high density lipoprotein (1.5 mmol/L) and triglycerides (1.4 mmol/L) lower than reference values. The prevalence of diabetes (7%), hypertension (38%), concomitant cardiovascular disease, (including angina pectoris, myocardial infarction, heart failure, atrial fibrillation and stroke) (7%), and calculated 10 year risk of coronary heart disease according to Framingham risk score algorithm (8%) was not increased in post-polio patients. Compared to reference populations, post-polio patients in Sweden appear to have low or normal total cholesterol and low density lipoprotein levels, whereas high density lipoprotein and triglyceride levels are low. Hence, a possible persisting inflammatory process in post-polio syndrome does not seem to be associated with increased lipids and an increased risk for coronary heart disease events.

Normal Language Skills and Normal Intelligence in a Child with de Lange Syndrome.

ERIC Educational Resources Information Center

Cameron, Thomas H.; Kelly, Desmond P.

1988-01-01

The subject of this case report is a two-year, seven-month-old girl with de Lange syndrome, normal intelligence, and age-appropriate language skills. She demonstrated initial delays in gross motor skills and in receptive and expressive language but responded well to intensive speech and language intervention, as well as to physical therapy.…

Ovipositional response elicited by normal, irradiated, F$sub 1$ male progeny, or castrated male Trichoplusia ni (Lepidoptera: Noctuidae)

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

Karpenko, C.P.; North, D.T.

1973-11-01

The ovipositional response of untreated Trichoplusia ni (Hubner) females that had mated to unirradiated, irradiated, F/sub 1/ male progeny from irradiated males, or castrated males was studied. Females that mated with irradiated males or F/sub 1/ sons of irradiated males oviposited fewer eggs than females that mated with control males, when all females had received a normal quantity of eupyrene and apyrene sperm. Irradiated males and F/sub 1/ sons of irradiated males that transferred an apparently normal sperm complement elicited significantly better oviposition from untreated females than did treated males that transferred mostly apyrene sperm, apyrene sperm only, or nomore » sperm. Males in the latter categories elicited a better ovipositional response from the untreated females than was observed in virgin females. Normal eupyrene sperm and possibly at least 1 accessory fiuid are required to initiate a completely normal ovipositional response in cabbage looper females. The accessory secretion triggers a significant increase in oviposition, but the greatest increase occurs when males contribute normal amounts of eupyrene sperm. The initiation of oviposition and female receptivity may be closely related in this species. (auth)« less

Investigating cellular network heterogeneity and modularity in cancer: a network entropy and unbalanced motif approach.

PubMed

Cheng, Feixiong; Liu, Chuang; Shen, Bairong; Zhao, Zhongming

2016-08-26

Cancer is increasingly recognized as a cellular system phenomenon that is attributed to the accumulation of genetic or epigenetic alterations leading to the perturbation of the molecular network architecture. Elucidation of network properties that can characterize tumor initiation and progression, or pinpoint the molecular targets related to the drug sensitivity or resistance, is therefore of critical importance for providing systems-level insights into tumorigenesis and clinical outcome in the molecularly targeted cancer therapy. In this study, we developed a network-based framework to quantitatively examine cellular network heterogeneity and modularity in cancer. Specifically, we constructed gene co-expressed protein interaction networks derived from large-scale RNA-Seq data across 8 cancer types generated in The Cancer Genome Atlas (TCGA) project. We performed gene network entropy and balanced versus unbalanced motif analysis to investigate cellular network heterogeneity and modularity in tumor versus normal tissues, different stages of progression, and drug resistant versus sensitive cancer cell lines. We found that tumorigenesis could be characterized by a significant increase of gene network entropy in all of the 8 cancer types. The ratio of the balanced motifs in normal tissues is higher than that of tumors, while the ratio of unbalanced motifs in tumors is higher than that of normal tissues in all of the 8 cancer types. Furthermore, we showed that network entropy could be used to characterize tumor progression and anticancer drug responses. For example, we found that kinase inhibitor resistant cancer cell lines had higher entropy compared to that of sensitive cell lines using the integrative analysis of microarray gene expression and drug pharmacological data collected from the Genomics of Drug Sensitivity in Cancer database. In addition, we provided potential network-level evidence that smoking might increase cancer cellular network heterogeneity and further contribute to tyrosine kinase inhibitor (e.g., gefitinib) resistance. In summary, we demonstrated that network properties such as network entropy and unbalanced motifs associated with tumor initiation, progression, and anticancer drug responses, suggesting new potential network-based prognostic and predictive measure in cancer.

Neurogranin as a predictor of memory and executive function decline in MCI patients.

PubMed

Headley, Alison; De Leon-Benedetti, Andres; Dong, Chuanhui; Levin, Bonnie; Loewenstein, David; Camargo, Christian; Rundek, Tatjana; Zetterberg, Henrik; Blennow, Kaj; Wright, Clinton B; Sun, Xiaoyan

2018-03-06

To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD). Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included. High levels of CSF Ng were associated with poor baseline memory scores (β = -0.21, p < 0.0001). CSF Ng predicted both memory and executive function decline over time (β = -0.0313, p = 0.0068 and β = -0.0346, p = 0.0169, respectively) independently of age, sex, education, and APOE ε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ 42 ) were controlled for in these analyses. High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ 42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD. © 2018 American Academy of Neurology.

Efficacy, safety, and pharmacokinetics of sustained-release lanreotide (lanreotide Autogel) in Japanese patients with acromegaly or pituitary gigantism.

PubMed

Shimatsu, Akira; Teramoto, Akira; Hizuka, Naomi; Kitai, Kazuo; Ramis, Joaquim; Chihara, Kazuo

2013-01-01

The somatostatin analog lanreotide Autogel has proven to be efficacious for treating acromegaly in international studies and in clinical practices around the world. However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism. In an open-label, parallel-group, dose-response study, 32 patients (29 with acromegaly, 3 with pituitary gigantism) received 5 injections of 60, 90, or 120 mg of lanreotide Autogel over 24 weeks. Four weeks after the first injection, 41% of patients achieved serum GH level of <2.5 ng/mL and insulin-like growth factor-I (IGF-I) level was normalized in 31%. Values at Week 24 were 53% for GH and 44% for IGF-I. Dose-dependent decreases in serum GH and IGF-I levels were observed with dose-related changes in pharmacokinetic parameters. In an open-label, long-term study, 32 patients (30 with acromegaly, 2 with pituitary gigantism) received lanreotide Autogel once every 4 weeks for a total of 13 injections. Dosing was initiated with 90 mg and adjusted according to clinical responses at Weeks 16 and/or 32. At Week 52, 47% of patients had serum GH levels of <2.5 ng/mL and 53% had normalized IGF-I level. In both studies, acromegaly symptoms improved and treatment was generally well tolerated although gastrointestinal symptoms and injection site induration were reported. In conclusion, lanreotide Autogel provided early and sustained control of elevated GH and IGF-I levels, improved acromegaly symptoms, and was well tolerated in Japanese patients with acromegaly or pituitary gigantism.

Initiation of Swarming Motility by Proteus mirabilis Occurs in Response to Specific Cues Present in Urine and Requires Excess l-Glutamine

PubMed Central

Armbruster, Chelsie E.; Hodges, Steven A.

2013-01-01

Proteus mirabilis, a leading cause of catheter-associated urinary tract infection (CaUTI), differentiates into swarm cells that migrate across catheter surfaces and medium solidified with 1.5% agar. While many genes and nutrient requirements involved in the swarming process have been identified, few studies have addressed the signals that promote initiation of swarming following initial contact with a surface. In this study, we show that P. mirabilis CaUTI isolates initiate swarming in response to specific nutrients and environmental cues. Thirty-three compounds, including amino acids, polyamines, fatty acids, and tricarboxylic acid (TCA) cycle intermediates, were tested for the ability to promote swarming when added to normally nonpermissive media. l-Arginine, l-glutamine, dl-histidine, malate, and dl-ornithine promoted swarming on several types of media without enhancing swimming motility or growth rate. Testing of isogenic mutants revealed that swarming in response to the cues required putrescine biosynthesis and pathways involved in amino acid metabolism. Furthermore, excess glutamine was found to be a strict requirement for swarming on normal swarm agar in addition to being a swarming cue under normally nonpermissive conditions. We thus conclude that initiation of swarming occurs in response to specific cues and that manipulating concentrations of key nutrient cues can signal whether or not a particular environment is permissive for swarming. PMID:23316040

Cytoskeletal role in the transition from compensated to decompensated hypertrophy during adult canine left ventricular pressure overloading

NASA Technical Reports Server (NTRS)

Tagawa, H.; Koide, M.; Sato, H.; Zile, M. R.; Carabello, B. A.; Cooper, G. 4th

1998-01-01

Increased microtubule density causes cardiocyte contractile dysfunction in right ventricular (RV) pressure-overload hypertrophy, and these linked phenotypic and contractile abnormalities persist and progress during the transition to failure. Although more severe in cells from failing than hypertrophied RVs, the mechanical defects are normalized in each case by microtubule depolymerization. To define the role of increased microtubule density in left ventricular (LV) pressure-overload hypertrophy and failure, in a given LV we examined ventricular mechanics, sarcomere mechanics, and free tubulin and microtubule levels in control dogs and in dogs with aortic stenosis both with LV hypertrophy alone and with initially compensated hypertrophy that had progressed to LV muscle failure. In comparing initial values with those at study 8 weeks later, dogs with hypertrophy alone had a very substantial increase in LV mass but preservation of a normal ejection fraction and mean systolic wall stress. Dogs with hypertrophy and associated failure had a substantial but lesser increase in LV mass and a reduction in ejection fraction, as well as a marked increase in mean systolic wall stress. Cardiocyte contractile function was equivalent, and unaffected by microtubule depolymerization, in cells from control LVs and those with compensated hypertrophy. In contrast, cardiocyte contractile function in cells from failing LVs was quite depressed but was normalized by microtubule depolymerization. Microtubules were increased only in failing LVs. These contractile and cytoskeletal changes, when assayed longitudinally in a given dog by biopsy, appeared in failing ventricles only when wall stress began to increase and function began to decrease. Thus, the microtubule-based cardiocyte contractile dysfunction characteristic of pressure-hypertrophied myocardium, originally described in the RV, obtains equally in the LV but is shown here to have a specific association with increased wall stress.

Knowledge Representation for Decision Making Agents

DTIC Science & Technology

2013-07-15

knowledge map. This knowledge map is a dictionary data structure called tmap in the code. It represents a network of locations with a number [0,1...fillRandom(): Informed initial tmap distribution (randomly generated per node) with belief one. • initialBelief = 3 uses fillCenter(): normal...triggered on AllMyFMsHaveBeenInitialized. 2. Executes main.py • Initializes knowledge map labeled tmap . • Calls initialize search() – resets distanceTot and

Weight changes and their associations with demographic and clinical characteristics in risperidone maintenance treatment for schizophrenia.

PubMed

Xiang, Y-T; Wang, C-Y; Ungvari, G S; Kreyenbuhl, J A; Chiu, H F K; Lai, K Y C; Lee, E H M; Bo, Q-J; Dixon, L B

2011-06-01

This study aimed to characterize weight changes in schizophrenia patients taking risperidone as part of a randomized, controlled, open-label clinical trial. A total of 374 patients with schizophrenia who had been clinically stabilized following an acute episode were randomly assigned to a 'no-dose-reduction' group (initial optimal therapeutic doses continued throughout the study), a '4-week group' (initial optimal therapeutic doses continued for 4 weeks followed by a half dose reduction that was maintained until the end of the study) or a '26-week group' (initial optimal therapeutic doses continued for 26 weeks followed by a half dose reduction until the end of the study). Participants were assessed monthly using standardized assessment instruments during the first 6 months, and then every 2 months until the last recruited patient completed the 1-year follow-up. Weight gain was defined as gaining at least 7% of initial body weight, weight loss as losing at least 7% of initial body weight. A BMI <18.5 kg m⁻² was defined as underweight, 18.5-24.9 kg m⁻² as normal range, and ≥ 25 kg m⁻² as overweight or obese. At the end of follow-up, of the patients who started within the underweight range (n=22), 77.3% gained weight, whereas 4.5% lost weight. The corresponding figures were 39.6% and 4.8% in patients who started at normal weight (n=273), respectively, and 17.7% and 17.7% in patients who started at overweight (n=79), respectively. At the same time, 59.1% of the patients who started at underweight range went into the normal weight and 13.6% into the overweight/obese range, respectively, while 24.5% of those who started at normal weight went into the overweight/obese range, and 1.1% into underweight range, respectively; 20.3% of those who started at overweight range went into normal weight at the end of the follow-up. Multiple logistic regression analyses revealed that being underweight or normal weight at study entry predicted weight gain compared to being overweight, whereas being overweight at entry was associated with a higher likelihood of weight loss compared to being normal weight. No correlation was found between weight change and dose reduction. Weight change is a common, long-term, but heterogeneous side effect in risperidone maintenance treatment for stable schizophrenia patients. Special attention should be paid to fluctuations in weight that may occur throughout the course of treatment with risperidone. © Georg Thieme Verlag KG Stuttgart · New York.

Androgen deprivation decreases prostate specific antigen in the absence of tumor: implications for interpretation of PSA results.

PubMed

Wenisch, Judith M; Mayr, Florian B; Spiel, Alexander O; Radicioni, Milko; Jilma, Bernd; Jilma-Stohlawetz, Petra

2014-03-01

Prostate-specific antigen (PSA) is used as an outcome measure for relapsed disease in prostate cancer. Nonetheless, there are considerable concerns about its indiscriminate use as a surrogate endpoint for cell growth or survival. We hypothesized that treatment with a luteinizing hormone releasing hormone (LHRH) analog would decrease PSA levels even in the absence of malignant disease. We determined testosterone and PSA levels in 30 healthy volunteers after a single intramuscular injection of a LHRH depot formulation. Testosterone and PSA levels were quantified by radioimmunoassay and electrochemi-luminescence immunoassay, respectively. After an initial flare-up during the first 3 days testosterone decreased reaching castration levels in 18 of the 30 young men (60%). After the nadir on day 28, testosterone levels increased to normal again. Changes in PSA paralleled those of testosterone. Castration reduced PSA levels by 29% (95% CI 19%-39%) compared to baseline (p<0.0001). LHRH superagonists decrease PSA levels by testosterone deprivation. Conferring these findings to tumor patients, decreases in PSA after treatment with LHRH analogs might not only reflect disease regression but also a direct testosterone mediated effect on PSA. Thus, PSA levels should be cautiously interpreted when patients receive hormonal therapy.

30 CFR 47.2 - Operators and chemicals covered; initial miner training.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Operators and chemicals covered; initial miner... Training § 47.2 Operators and chemicals covered; initial miner training. (a) This part applies to any operator producing or using a hazardous chemical to which a miner can be exposed under normal conditions of...

30 CFR 47.2 - Operators and chemicals covered; initial miner training.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Operators and chemicals covered; initial miner... Training § 47.2 Operators and chemicals covered; initial miner training. (a) This part applies to any operator producing or using a hazardous chemical to which a miner can be exposed under normal conditions of...

30 CFR 47.2 - Operators and chemicals covered; initial miner training.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Operators and chemicals covered; initial miner... Training § 47.2 Operators and chemicals covered; initial miner training. (a) This part applies to any operator producing or using a hazardous chemical to which a miner can be exposed under normal conditions of...

30 CFR 47.2 - Operators and chemicals covered; initial miner training.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Operators and chemicals covered; initial miner... Training § 47.2 Operators and chemicals covered; initial miner training. (a) This part applies to any operator producing or using a hazardous chemical to which a miner can be exposed under normal conditions of...

30 CFR 47.2 - Operators and chemicals covered; initial miner training.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Operators and chemicals covered; initial miner... Training § 47.2 Operators and chemicals covered; initial miner training. (a) This part applies to any operator producing or using a hazardous chemical to which a miner can be exposed under normal conditions of...

14 CFR 121.419 - Pilots and flight engineers: Initial, transition, and upgrade ground training.

Code of Federal Regulations, 2012 CFR

2012-01-01

...; (ix) Flight planning; (x) Each normal and emergency procedure; and (xi) The approved Airplane Flight... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Pilots and flight engineers: Initial... Program § 121.419 Pilots and flight engineers: Initial, transition, and upgrade ground training. (a...

14 CFR 121.419 - Pilots and flight engineers: Initial, transition, and upgrade ground training.

Code of Federal Regulations, 2011 CFR

2011-01-01

...; (ix) Flight planning; (x) Each normal and emergency procedure; and (xi) The approved Airplane Flight... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Pilots and flight engineers: Initial... Program § 121.419 Pilots and flight engineers: Initial, transition, and upgrade ground training. (a...

14 CFR 121.419 - Pilots and flight engineers: Initial, transition, and upgrade ground training.

Code of Federal Regulations, 2014 CFR

2014-01-01

...; (ix) Flight planning; (x) Each normal and emergency procedure; and (xi) The approved Airplane Flight... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Pilots and flight engineers: Initial... Program § 121.419 Pilots and flight engineers: Initial, transition, and upgrade ground training. Link to...

14 CFR 121.419 - Pilots and flight engineers: Initial, transition, and upgrade ground training.

Code of Federal Regulations, 2010 CFR

2010-01-01

...; (ix) Flight planning; (x) Each normal and emergency procedure; and (xi) The approved Airplane Flight... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Pilots and flight engineers: Initial... Program § 121.419 Pilots and flight engineers: Initial, transition, and upgrade ground training. (a...

14 CFR 121.419 - Pilots and flight engineers: Initial, transition, and upgrade ground training.

Code of Federal Regulations, 2013 CFR

2013-01-01

...; (ix) Flight planning; (x) Each normal and emergency procedure; and (xi) The approved Airplane Flight... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Pilots and flight engineers: Initial... Program § 121.419 Pilots and flight engineers: Initial, transition, and upgrade ground training. (a...

Normal and cancer mammary stem cells evade interferon-induced constraint through the miR-199a-LCOR Axis

PubMed Central

Celià-Terrassa, Toni; Liu, Daniel; Choudhury, Abrar; Hang, Xiang; Wei, Yong; Zamalloa, Jose; Alfaro-Aco, Raymundo; Chakrabarti, Rumela; Jiang, Yi-Zhou; Koh, Bong Ihn; Smith, Heath; DeCoste, Christina; Li, Jun-Jing; Shao, Zhi-Ming; Kang, Yibin

2017-01-01

Tumor-initiating cells (TICs), or cancer stem cells (CSC), possess stem cell-like properties observed in normal adult tissue stem cells. Normal and cancerous stem cells may therefore share regulatory mechanisms for maintaining self-renewing capacity and resisting differentiation elicited by cell-intrinsic or microenvironmental cues. Here, we show that miR-199a promotes stem cell properties in mammary stem cells (MaSCs) and breast CSCs by directly repressing nuclear receptor corepressor LCOR, which primes interferon (IFN) responses. Elevated miR-199a expression in stem cell-enriched populations protects normal and malignant stem-like cells from differentiation and senescence induced by IFNs that are produced by epithelial and immune cells in the mammary gland. Importantly, the miR-199a-LCOR-IFN axis is activated in poorly differentiated ER− breast tumors, functionally promotes tumor initiation and metastasis, and is associated with poor clinical outcome. Our study therefore reveals a common mechanism shared by normal and malignant stem cells to protect them from suppressive immune cytokine signaling. PMID:28530657

What`s normal?: Body condition in Great Lakes herring gulls

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

Hebert, C.E.; Shutt, J.L.

1994-12-31

The Canadian Wildlife Service`s herring gull (Larus argentatus) surveillance program has demonstrated the usefulness of this species as a monitor of spatial and temporal trends in contaminant levels. However, the effects of environmental contaminants on gulls are difficult to distinguish from the effects of other anthropogenic stressors such as the introduction of exotic species, overfishing and habitat loss. To understand the relative importance of these factors in regulating the success of individual gulls and, hence, gull populations, the authors must first have a better understanding of what constitutes a ``normal`` bird. Improving the ability to differentiate between normal and abnormalmore » birds is crucial in any health assessment of Great Lakes gulls. Body condition has been shown to be an important measure of a bird`s ability to provide energy for egg production, migration etc. Numerous approaches have been used to assess condition, most of which required that the bird be sacrificed. In this study, the authors describe a nonlethal technique to quantify body condition in herring gulls. Multivariate statistics are used to quantify body size, relate body size to total mass and from that, determine relative body condition. Initially, body condition is assessed in gulls from a reference colony where reproductive success is normal and anthropogenic influences are limited. This reference population is then used as a baseline against which other gull populations are compared.« less

False-normal vitamin B12 results in a patient with pernicious anaemia.

PubMed

Wainwright, P; Narayanan, S; Cook, P

2015-12-01

Pernicious anaemia is a common autoimmune disorder with a prevalence of approximately 4% amongst Europeans. If untreated, it can result in permanent neurological disability or death. Central to the diagnosis is establishing the presence of vitamin B12 deficiency. Concern has been raised recently regarding false-normal results obtained with competitive-binding vitamin B12 assays performed on automated biochemistry platforms in patients with pernicious anaemia due to the presence of interfering anti-intrinsic factor antibodies in the patient sample. We report a case in which diagnosis of pernicious anaemia was delayed due to false-normal vitamin B12 results. Questioning the results in light of high pre-test probability, and knowledge of the role of functional markers of vitamin B12 deficiency enabled the correct diagnosis to be made so that effective treatment could be initiated. It is crucial that those who frequently request vitamin B12 are aware of the potential problems with the available assays and how these problems can be addressed. We suggest that all patients with normal vitamin B12 levels where there is a high clinical suspicion for deficiency such as a macrocytic anaemia, neurological symptoms or megaloblastic bone marrow should have a functional assay of vitamin B12 (plasma homocysteine or methylmalonic acid) checked to further investigate for vitamin B12 deficiency. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Blood glucose may condition factor VII levels in diabetic and normal subjects.

PubMed

Ceriello, A; Giugliano, D; Quatraro, A; Dello Russo, P; Torella, R

1988-12-01

Increased factor VII levels have been reported in Type 1 (insulin-dependent) diabetic subjects. A direct correlation between fasting plasma glucose and factor VII level was found to exist in both diabetic and normal subjects. Induced-hyperglycaemia was able to increase factor VII levels in both diabetic patients and normal control subjects while, when euglycaemia was achieved in diabetic patients, factor VII values returned to normal range. This study shows that the level of factor VII may be directly conditioned by circulating blood glucose and, therefore, stresses the role of hyperglycaemia in conditioning coagulation abnormalities in diabetes mellitus.

Regulatory Mechanisms That Prevent Re-initiation of DNA Replication Can Be Locally Modulated at Origins by Nearby Sequence Elements

PubMed Central

Richardson, Christopher D.; Li, Joachim J.

2014-01-01

Eukaryotic cells must inhibit re-initiation of DNA replication at each of the thousands of origins in their genome because re-initiation can generate genomic alterations with extraordinary frequency. To minimize the probability of re-initiation from so many origins, cells use a battery of regulatory mechanisms that reduce the activity of replication initiation proteins. Given the global nature of these mechanisms, it has been presumed that all origins are inhibited identically. However, origins re-initiate with diverse efficiencies when these mechanisms are disabled, and this diversity cannot be explained by differences in the efficiency or timing of origin initiation during normal S phase replication. This observation raises the possibility of an additional layer of replication control that can differentially regulate re-initiation at distinct origins. We have identified novel genetic elements that are necessary for preferential re-initiation of two origins and sufficient to confer preferential re-initiation on heterologous origins when the control of re-initiation is partially deregulated. The elements do not enhance the S phase timing or efficiency of adjacent origins and thus are specifically acting as re-initiation promoters (RIPs). We have mapped the two RIPs to ∼60 bp AT rich sequences that act in a distance- and sequence-dependent manner. During the induction of re-replication, Mcm2-7 reassociates both with origins that preferentially re-initiate and origins that do not, suggesting that the RIP elements can overcome a block to re-initiation imposed after Mcm2-7 associates with origins. Our findings identify a local level of control in the block to re-initiation. This local control creates a complex genomic landscape of re-replication potential that is revealed when global mechanisms preventing re-replication are compromised. Hence, if re-replication does contribute to genomic alterations, as has been speculated for cancer cells, some regions of the genome may be more susceptible to these alterations than others. PMID:24945837

Effect of root canal obturation with calcium silicate materials on pH change in simulated root resorption defects.

PubMed

Aggarwal, Vivek; Singla, Mamta; Miglani, Sanjay; Sharma, Ritu

2018-01-01

This study evaluated the effect of 3 commercially available calcium silicate materials (CSMs) on pH changes in simulated root resorption defects. Simulated root resorption defects were prepared on the facial root surface of 40 mandibular premolars. The depth of each defect was individually calculated to standardize the remaining dentin thickness to 1 mm. Prepared canals were obturated with the 3 CSMs. Ten specimens were kept as controls, filled with unbuffered normal saline. The pH measurements were taken at 1 hour, 6 hours, 1 day, 1 week, 2 weeks, 3 weeks, 1 month, and 2 months. All CSM groups exhibited an initial alkaline pH of 9.0-9.7. The pH decreased to 8.0-8.5 after 2 months of storage. There were no significant differences between pH measurements at other time intervals. The CSM groups exhibited higher pH levels than the control group. The results showed that intracanal placement of the CSMs maintained initial pH levels of 9.0-9.7 inside the simulated resorption defects; these measurements gradually decreased to 8.0-8.5 over the span of 2 months.

Stolon regression

PubMed Central

Cherry Vogt, Kimberly S

2008-01-01

Many colonial organisms encrust surfaces with feeding and reproductive polyps connected by vascular stolons. Such colonies often show a dichotomy between runner-like forms, with widely spaced polyps and long stolon connections, and sheet-like forms, with closely spaced polyps and short stolon connections. Generative processes, such as rates of polyp initiation relative to rates of stolon elongation, are typically thought to underlie this dichotomy. Regressive processes, such as tissue regression and cell death, may also be relevant. In this context, we have recently characterized the process of stolon regression in a colonial cnidarian, Podocoryna carnea. Stolon regression occurs naturally in these colonies. To characterize this process in detail, high levels of stolon regression were induced in experimental colonies by treatment with reactive oxygen and reactive nitrogen species (ROS and RNS). Either treatment results in stolon regression and is accompanied by high levels of endogenous ROS and RNS as well as morphological indications of cell death in the regressing stolon. The initiating step in regression appears to be a perturbation of normal colony-wide gastrovascular flow. This suggests more general connections between stolon regression and a wide variety of environmental effects. Here we summarize our results and further discuss such connections. PMID:19704785

Health outcomes following liver function testing in primary care: a retrospective cohort study.

PubMed

McLernon, David J; Donnan, Peter T; Ryder, Stephen; Roderick, Paul; Sullivan, Frank M; Rosenberg, William; Dillon, John F

2009-08-01

patients who present with abnormal liver function tests (LFTs) in primary care and no obvious symptoms can be difficult to manage. The objective is to follow-up a cohort of liver function tested patients to determine their outcome. This population-based retrospective cohort study was conducted in Tayside, Scotland, from 1989 to 2003. Subjects were patients with no clinically obvious liver disease at initial liver function testing in primary care. Main outcomes were diagnosed liver disease and mortality. Record linkage of databases ascertained risk factors and outcomes. Measures of performance were calculated and Weibull regression analysis from initial LFT date was performed on all outcomes by level of abnormality. In total, 95 977 patients had 364 194 incident initial LFTs, with median follow-up 3.7 years. A total of 21.7% had at least one abnormal LFT and 1108 (1.15%) developed liver disease. Elevated transaminase was strongly associated with diagnosed liver disease, hazard ratio (HR) = 4.23 (95% confidence interval 3.55, 5.04) for mild levels and HR = 12.67 (95% CI 9.74, 16.47) for severe levels versus normal. For gamma-glutamyl transferase, these hazards were 2.54 (95% CI 2.17, 2.96) and 13.44 (95% CI 10.71, 16.87), respectively. Low albumin was strongly associated with all-cause mortality, HR = 2.65 (95% CI 2.47, 2.85) for mild levels and HR = 4.99 (95% CI 4.26, 5.84) for severe levels. Sensitivity for predicting events over 5 years was low and specificity high. All LFTs were predictive markers for liver disease as well as general ill health, although sensitivity was poor. Most patients with abnormal LFTs had no later formal diagnosis of liver disease within the study period. The time taken to develop liver disease in these patients provides opportunity to intervene.

Ultrasound mediated transdermal insulin delivery in pigs using a lightweight transducer.

PubMed

Park, E J; Werner, Jacob; Smith, Nadine Barrie

2007-07-01

In previous studies, ultrasound mediated transdermal drug delivery has shown a promising potential as a method for noninvasive drug administration. For prospective future human application, this study was designed to determine the feasibility of lightweight cymbal transducer array as a practical device for noninvasive transdermal insulin delivery in large pigs. Six Yorkshire pigs (100-140 lbs) were divided into two groups. As the control (n = 3), the first group did not receive any ultrasound exposure with the insulin. The second group (n = 3) was treated with ultrasound and insulin at 20 kHz with an I(sptp) = 100 mW/cm(2) at a 20% duty cycle for 60 min. With the pigs in lateral recumbency after anesthesia, the ultrasound transducer with insulin was placed on the axillary area of the pig. At the beginning and every 15 min up to 90 min, the blood glucose level was determined using a glucose monitoring system. To compare the results of individual animals, the change of blood glucose level was normalized to each animal's initial glucose value at the start of the experiment. Although each animal had a different initial glucose level, the mean and standard error for the six animals was 146 +/- 13 mg/dl. For the control group, the blood glucose level increased to 31 +/- 21 mg/dl compared to the initial baseline over the 90 min experiment. However for the ultrasound with insulin treated group, the glucose level decreased to -72 +/- 5 mg/dl at 60 min (p < 0.05) and continued to decrease to -91 +/- 23 mg/dl in 90 min (p < 0.05). The results indicate the feasibility of ultrasound mediated transdermal insulin delivery using the cymbal transducer array in animal with a similar size and weight to a human. Based on these result, the cymbal array has potential as a practical ultrasound system for noninvasive transdermal insulin delivery for diabetes management.

Initial CSF total tau correlates with 1-year outcome in patients with traumatic brain injury.

PubMed

Ost, M; Nylén, K; Csajbok, L; Ohrfelt, A Olsson; Tullberg, M; Wikkelsö, C; Nellgård, P; Rosengren, L; Blennow, K; Nellgård, B

2006-11-14

We investigated if tau, microtubular binding protein, in serum and ventricular CSF (vCSF) in patients with severe traumatic brain injury (TBI) during the initial posttraumatic days correlated to 1-year outcome. Patients with severe TBI (n = 39, Glasgow Coma Scale score 2,126 pg/mL on days 2 to 3 discriminated between dead and alive (sensitivity of 100% and a specificity of 81%). A vCSF total tau level of >702 pg/mL on days 2 to 3 discriminated between bad (GOSE 1 to 4) and good (GOSE 5 to 8) outcome (sensitivity of 83% and a specificity of 69%). Patients with GOSE 1 (dead) had higher vCSF total tau levels on days 2 to 3 (p < 0.001) vs both surviving patients (GOSE 2 to 8) and those with NPH. Total tau was not detected in serum throughout the study. The increase in ventricular CSF (vCSF) total tau probably reflects axonal damage, known to be a central pathologic mechanism in traumatic brain injury (TBI). These results suggest that vCSF total tau may be an important early biochemical neuromarker for predicting long-term outcome in patients with a severe TBI.

Determining the diagnostic value of endogenous carbon monoxide in chronic obstructive pulmonary disease exacerbations.

PubMed

Dogan, Nurettin Özgür; Corbacioglu, Seref Kerem; Bildik, Fikret; Kilicaslan, Isa; Günaydin, Gül Pamukcu; Cevik, Yunsur; Ülker, Volkan; Hakoglu, Onur; Gökcen, Emre

2014-09-01

To determine whether endogenous carbon monoxide levels in exacerbations of Chronic Obstructive Pulmonary Disease patients were higher compared to healthy individuals and to investigate alteration of carbon monoxide levels across the three different severity stages of Global Initiative for Chronic Obstructive Lung Disease criteria related to Chronic Obstructive Pulmonary Disease exacerbations. The prospective study was conducted from January to March 2011 at two medical institutions in Ankara, Turkey, and comprised patients of acute Chronic Obstructive Pulmonary Disease exacerbations. The severity of the exacerbations was based on the Global Initiative for Chronic Obstructive Lung Disease criteria. Patients with active tobacco smoking, suspicious carbon monoxide poisoning and uncertain diagnosis were excluded. healthy control subjects who did not have any comorbid diseases and smoking habitus were also enrolled to compare the differences between carboxyhaemoglobin levels A two-tailed Mann-Whitney U test with Bonferroni correction was done following a Kruskal-Wallis test for statistical purposes. There were 90 patients and 81 controls in the study. Carboxyhaemoglobin levels were higher in the patients than the controls (p < 0.001). As for the three severity stages, Group 1 had a median carboxyhaemoglobin of 1.6 (0.95- 2.00). The corresponding levels in Group 2 (1.8 [1.38-2.20]) and Group 3 (1.9 [1.5-3.0]) were higher than the controls (p < 0.001 and p < 0.005 respectively). No statistically significant difference between Group 1 and the controls (1.30 [1.10-1.55]) was observed (p < 0.434). Carboxyhaemoglobin levels were significantly higher in exacerbations compared with the normal population. Also, in more serious exacerbations, carboxyhaemoglobin levels were significantly increased compared with healthy individuals and mild exacerbations.

Cervical Fracture With Transient Tetraplegia in a Youth Football Player: Case Report and Review of the Literature

PubMed Central

Molinari, Robert; Molinari, William J

2010-01-01

Background/Objective: Serious cervical spinal injuries in organized youth football are rare. Cervical fracture with neurologic injury is rarely reported in organized youth football players with no pre-existing risk fractures for transient tetraplegia. Methods: Case report and literature review. Results: After being improperly tackled by an opponent of significantly larger body size, a player sustained a C7 posterior cervical fracture with transient tetraplegia. He was immobilized in a cervical collar and sent to a level 1 trauma center for evaluation. Initial examination showed bilateral paresthesia of the limbs with normal motor function (ASIA D). Initial radiographs of the cervical spine showed a displaced extension-compression fracture of the C7 spinous process. Magnetic resonance imaging of the cervical spine showed edema in the spinal cord in the region of the injury along with significant posterior injury. Imaging studies showed normal volumetric measurements of the spinal canal and no pre-existing risk factors for spinal stenosis or spinal cord injury. Radiographs showed that cervical fracture was healed at 9-month follow-up examination. At 1-year follow-up, the patient was asymptomatic. Radiographs showed healed fracture with no residual instability and full range of cervical spine motion on flexion–extension views. Conclusions: This case underscores the potential for serious cervical spinal injuries in organized youth sports when players are physically overmatched, and improper tackling technique is used. PMID:20486536

Differential regulation of spo0A transcription in Bacillus subtilis: glucose represses promoter switching at the initiation of sporulation.

PubMed

Chibazakura, T; Kawamura, F; Takahashi, H

1991-04-01

We have shown by S1 nuclease mapping with in vivo transcripts that the differential expression of a sporulation-regulatory gene, spo0A, is regulated by switching of two discrete promoters during the initiation of sporulation in Bacillus subtilis; vegetative mRNA was transcribed from an upstream promoter (Pv, vegetative promoter), and sporulation-specific mRNA was transcribed from the other promoter (Ps, sporulation-specific promoter) about 150 bp downstream of the Pv promoter. Transcription from the Pv promoter was at a low level and shut off at T0.5. On the other hand, transcription from the Ps promoter was strongly induced at T0.5 and increased until T2.5. In the presence of 2% glucose, Pv-directed transcription was not shut off and was observed even at T1.5, whereas the induction of Ps-directed transcription was completely repressed. A mutant in which the spo0A gene was transcribed only from the Ps promoter could sporulate normally in the presence of 0.1% glucose but could not sporulate at all in the presence of 2% glucose. In a catabolite-resistant sporulation mutant carrying crsA47 (sigA47), a mutation within the gene encoding sigma A, normal promoter switching from Pv to Ps was observed in the presence of 2% glucose.

Empirical analysis on the runners' velocity distribution in city marathons

NASA Astrophysics Data System (ADS)

Lin, Zhenquan; Meng, Fan

2018-01-01

In recent decades, much researches have been performed on human temporal activity and mobility patterns, while few investigations have been made to examine the features of the velocity distributions of human mobility patterns. In this paper, we investigated empirically the velocity distributions of finishers in New York City marathon, American Chicago marathon, Berlin marathon and London marathon. By statistical analyses on the datasets of the finish time records, we captured some statistical features of human behaviors in marathons: (1) The velocity distributions of all finishers and of partial finishers in the fastest age group both follow log-normal distribution; (2) In the New York City marathon, the velocity distribution of all male runners in eight 5-kilometer internal timing courses undergoes two transitions: from log-normal distribution at the initial stage (several initial courses) to the Gaussian distribution at the middle stage (several middle courses), and to log-normal distribution at the last stage (several last courses); (3) The intensity of the competition, which is described by the root-mean-square value of the rank changes of all runners, goes weaker from initial stage to the middle stage corresponding to the transition of the velocity distribution from log-normal distribution to Gaussian distribution, and when the competition gets stronger in the last course of the middle stage, there will come a transition from Gaussian distribution to log-normal one at last stage. This study may enrich the researches on human mobility patterns and attract attentions on the velocity features of human mobility.

Influence of surface-normal ground acceleration on the initiation of the Jih-Feng-Erh-Shan landslide during the 1999 Chi-Chi, Taiwan, earthquake

USGS Publications Warehouse

Huang, C.-C.; Lee, Y.-H.; Liu, Huaibao P.; Keefer, D.K.; Jibson, R.W.

2001-01-01

The 1999 Chi-Chi, Taiwan, earthquake triggered numerous landslides throughout a large area in the Central Range, to the east, southeast, and south of the fault rupture. Among them are two large rock avalanches, at Tsaoling and at Jih-Feng-Erh-Shan. At Jih-Feng-Erh-Shan, the entire thickness (30-50 m) of the Miocene Changhukeng Shale over an area of 1 km2 slid down its bedding plane for a distance of about 1 km. Initial movement of the landslide was nearly purely translational. We investigate the effect of surface-normal acceleration on the initiation of the Jih-Feng-Erh-Shan landslide using a block slide model. We show that this acceleration, currently not considered by dynamic slope-stability analysis methods, significantly influences the initiation of the landslide.

Computational modes and the Machenauer N.L.N.M.I. of the GLAS 4th order model. [NonLinear Normal Mode Initialization in numerical weather forecasting

NASA Technical Reports Server (NTRS)

Navon, I. M.; Bloom, S.; Takacs, L. L.

1985-01-01

An attempt was made to use the GLAS global 4th order shallow water equations to perform a Machenhauer nonlinear normal mode initialization (NLNMI) for the external vertical mode. A new algorithm was defined for identifying and filtering out computational modes which affect the convergence of the Machenhauer iterative procedure. The computational modes and zonal waves were linearly initialized and gravitational modes were nonlinearly initialized. The Machenhauer NLNMI was insensitive to the absence of high zonal wave numbers. The effects of the Machenhauer scheme were evaluated by performing 24 hr integrations with nondissipative and dissipative explicit time integration models. The NLNMI was found to be inferior to the Rasch (1984) pseudo-secant technique for obtaining convergence when the time scales of nonlinear forcing were much smaller than the time scales expected from the natural frequency of the mode.

Levels-Of-Processing Effect on Word Recognition in Schizophrenia

PubMed Central

Ragland, J. Daniel; Moelter, Stephen T.; McGrath, Claire; Hill, S. Kristian; Gur, Raquel E.; Bilker, Warren B.; Siegel, Steven J.; Gur, Ruben C.

2015-01-01

Background Individuals with schizophrenia have difficulty organizing words semantically to facilitate encoding. This is commonly attributed to organizational rather than semantic processing limitations. By requiring participants to classify and encode words on either a shallow (e.g., uppercase/lowercase) or deep level (e.g., concrete/abstract), the levels-of-processing paradigm eliminates the need to generate organizational strategies. Methods This paradigm was administered to 30 patients with schizophrenia and 30 healthy comparison subjects to test whether providing a strategy would improve patient performance. Results Word classification during shallow and deep encoding was slower and less accurate in patients. Patients also responded slowly during recognition testing and maintained a more conservative response bias following deep encoding; however, both groups showed a robust levels-of-processing effect on recognition accuracy, with unimpaired patient performance following both shallow and deep encoding. Conclusions This normal levels-of-processing effect in the patient sample suggests that semantic processing is sufficiently intact for patients to benefit from organizational cues. Memory remediation efforts may therefore be most successful if they focus on teaching patients to form organizational strategies during initial encoding. PMID:14643082

Levels-of-processing effect on word recognition in schizophrenia.

PubMed

Ragland, J Daniel; Moelter, Stephen T; McGrath, Claire; Hill, S Kristian; Gur, Raquel E; Bilker, Warren B; Siegel, Steven J; Gur, Ruben C

2003-12-01

Individuals with schizophrenia have difficulty organizing words semantically to facilitate encoding. This is commonly attributed to organizational rather than semantic processing limitations. By requiring participants to classify and encode words on either a shallow (e.g., uppercase/lowercase) or deep level (e.g., concrete/abstract), the levels-of-processing paradigm eliminates the need to generate organizational strategies. This paradigm was administered to 30 patients with schizophrenia and 30 healthy comparison subjects to test whether providing a strategy would improve patient performance. Word classification during shallow and deep encoding was slower and less accurate in patients. Patients also responded slowly during recognition testing and maintained a more conservative response bias following deep encoding; however, both groups showed a robust levels-of-processing effect on recognition accuracy, with unimpaired patient performance following both shallow and deep encoding. This normal levels-of-processing effect in the patient sample suggests that semantic processing is sufficiently intact for patients to benefit from organizational cues. Memory remediation efforts may therefore be most successful if they focus on teaching patients to form organizational strategies during initial encoding.

Recommended de minimis radiation dose rates for Canada. Report No. INFO-0355

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

Not Available

1990-01-01

A de minimis dose or dose rate as used in this report represents a level of risk which is generally accepted as being of no significance to an individual, or in the case of a population, of no significance to society. The report describes the risk of biological effects from radiation; radiation from natural and man-made sources; normal incidences of cancer and genetic defects; initiatives by other agencies in the U.S., the U.K. and internationally; the importance of collective dose and dose rate; assigning values to the de minimis dose rates; and application of the de minimis dose rates.

Effects of Severe Bothersome Tinnitus on Cognitive Function Measured with Standardized Tests

PubMed Central

Pierce, Katherine J.; Kallogjeri, Dorina; Piccirillo, Jay F.; Garcia, Keith S.; Nicklaus, Joyce E.; Burton, Harold

2012-01-01

Neurocognitive tests compared abilities in people with bothersome tinnitus against an age, gender, and education matched normative population. Participants between 18 and 60 years had subjective, unilateral or bilateral, non-pulsatile tinnitus for >6 months, and a Tinnitus Handicap Inventory score of ≥38. Results from a first testing session showed deficits in learning, learning rates, immediate recall of heard words, and use of a serial order encoding strategy. Initial reliance on serial order encoding and later, increased intrusion of incorrect words towards normal levels might indicate a less demanding strategy to compensate for weakness in associative memory for semantic categories. PMID:22168528

[National screening for phenylketonuria, congenital hypothyroidism and congenital adrenal hyperplasia].

PubMed

Osório, R V; Vilarinho, L; Soares, J P

1992-03-01

In Portugal the screening for phenylketonuria (PKU) and congenital hypothyroidism (CH) was begun towards the end of 1979, and by 1990 59 cases of PKU and 227 cases of CH had been detected. The early initiation of treatment and the observed mental and motor development, point towards a normal development in these children. A trial screen for congenital adrenal hyperplasia was carried out in 100.000 newborns, from which it was concluded that, under the present conditions, screening at a national level is not justified. A similar study is currently being undertaken for biotinidase deficiency and cystic fibrosis. The results ares discussed, as are the cost/benefits evaluations.