Keratin, luminal epithelial antigen and carcinoembryonic antigen in human urinary bladder carcinomas. An immunohistochemical study.

PubMed

Nathrath, W B; Arnholdt, H; Wilson, P D

1982-01-01

14 urinary bladder carcinomas of all main types were investigated with antisera to "broad spectrum keratin" (aK), "luminal epithelial antigen" (aLEA) and carcinoembryonic antigen (aCEA), using an indirect immunoperoxidase method on formalin fixed paraffin embedded sections. Keratin and LEA were both present in normal transitional epithelium, papilloma and carcinoma in situ whereas CEA was absent. Transitional cell carcinomas reacted with both aK and aLEA whereas CEA was seen only in a few foci. In squamous metaplasia and squamous carcinoma reaction with aK was particularly strong, while LEA was almost lacking and CEA was present in necrotic centres. In adenocarcinomas aK and aLEA reacted equally while aCEA reacted only on the surface.

Medically Unexplained Symptoms

MedlinePlus

WRIISC War Related Illness and Injury Study Center Office of Public Health Department of Veterans Affairs MEDICALLY UNEXPLAINED SYMPTOMS A RESOURCE FOR VETERANS, SERVICE MEMBERS, AND THEIR FAMILIES Medically Unexplained ...

Unexplained somatic symptoms during major depression: prevalence and clinical impact in a national sample of Italian psychiatric outpatients.

PubMed

Perugi, Giulio; Canonico, Pier Luigi; Carbonato, Paolo; Mencacci, Claudio; Muscettola, Giovanni; Pani, Luca; Torta, Riccardo; Vampini, Claudio; Fornaro, Michele; Parazzini, Fabio; Dumitriu, Arina

2011-01-01

The aim of this study was to explore the prevalence and impact of unexplained somatic symptoms during major depression. A total of 560 consecutive outpatients with a major depressive episode according to the DSM-IV (text revision) were evaluated in 30 psychiatric facilities throughout Italy. 'Unexplained' somatic symptoms were evaluated using the 30-item Somatic Symptoms Checklist (SSCL-30). Somatic symptoms were considered explained if they were best accounted for as coming from a concomitant physical illness or side effects. Patients evaluated their own mood symptomatology using the Zung questionnaires for depression and anxiety and the Hypomania Checklist-32. According to the SSCL-30, only 90 subjects (16.1%) had no unexplained somatic symptoms, while 231 (41.3%) had 1-5 unexplained symptoms and 239 (42.7%) had more than 5. Asthenia was the most commonly observed unexplained somatic symptom (53% of patients). Unexplained somatic symptoms were more common in females and among those suffering from major depression and depression not otherwise specified rather than in patients with recurrent major depression and bipolar disorders. No relationship between unexplained somatic symptoms and hypomanic features was observed. The presence of a large number of unexplained somatic symptoms is associated with more severe depression and higher rates of misdiagnosis and inappropriate treatment. Copyright © 2011 S. Karger AG, Basel.

The medically unexplained revisited.

PubMed

Eriksen, Thor Eirik; Kirkengen, Anna Luise; Vetlesen, Arne Johan

2013-08-01

Medicine is facing wide-ranging challenges concerning the so-called medically unexplained disorders. The epidemiology is confusing, different medical specialties claim ownership of their unexplained territory and the unexplained conditions are themselves promoted through a highly complicated and sophisticated use of language. Confronting the outcome, i.e. numerous medical acronyms, we reflect upon principles of systematizing, contextual and social considerations and ways of thinking about these phenomena. Finally we address what we consider to be crucial dimensions concerning the landscape of unexplained "matters"; fatigued being, pain-full being and dys-ordered being, all expressive momentums of an aesthetic of resistance.

The usefulness of carotid sinus massage in different patient groups.

PubMed

Kumar, Narasimhan Pradeep; Thomas, Alan; Mudd, Paul; Morris, Robert O; Masud, Tahir

2003-11-01

to determine the positive yield of carotid sinus massage in different patient groups: unexplained syncope, falls, dizziness and controls. observational study. teaching hospital. we studied consecutive patients over the age of 60 years referred to the 'falls clinic' with a history of unexplained syncope, unexplained falls and unexplained dizziness. We also studied asymptomatic control subjects recruited from a general practice register aged 60 years and over. All patients and control subjects underwent a full clinical assessment (comprehensive history and detailed clinical examination including supine and erect blood pressure measurements) and 12-lead electrocardiography. We performed carotid sinus massage in the supine position for 5 seconds separately on both sides followed by repeating the procedure in the upright positions using a motorised tilt table. Heart rate and blood pressure were recorded using a cardiac monitor and digital plethysmography respectively. The test was considered positive if carotid sinus massage produced asystole with more than a 3 second pause (cardioinhibitory type of carotid sinus syndrome), or a fall in systolic blood pressure of more than 50 mmHg in the absence of significant cardioinhibition (vasodepressor type of carotid sinus syndrome) or where there was evidence of both vasodepressor and cardio-inhibition as above (mixed type). we studied 44 asymptomatic control subjects and 221 symptomatic patients (130 with unexplained syncope, 41 with unexplained falls and 50 with unexplained dizziness). In the overall symptomatic patient group, the positive yield (any type of carotid sinus syndrome) was 17.6% (95% CI = 12.7-22.5). The positive yield in men (26.3% (95% CI = 16.4-36.2)) was twice that in women (13.1% (95% CI = 7.6-18.6)) (P = 0.014). Overall any type of carotid sinus syndrome was present in 22.3% (n = 29) of the syncope group, 17.1% (n = 7) in the unexplained fallers group and 6% (n = 3) in the dizziness group. We also found that no women with unexplained dizziness had a positive carotid sinus massage test. None of the controls demonstrated a positive response. None of the subjects suffered any complications during or after the test. the positive yield of carotid sinus massage in symptomatic patients was 17.6% with the yield in men being twice that in women. None of the asymptomatic control subjects demonstrated a positive response. The yields in unexplained syncope and unexplained falls patients were around 4-fold and 3-fold higher respectively than in unexplained dizziness patients. The positive yield in women with unexplained dizziness (without a definite history of syncope and falls) is zero. Hence, carotid sinus massage in older adults should particularly be targeted at patients with unexplained syncope and unexplained falls.

Unexplained Falls Are Frequent in Patients with Fall-Related Injury Admitted to Orthopaedic Wards: The UFO Study (Unexplained Falls in Older Patients).

PubMed

Chiara, Mussi; Gianluigi, Galizia; Pasquale, Abete; Alessandro, Morrione; Alice, Maraviglia; Gabriele, Noro; Paolo, Cavagnaro; Loredana, Ghirelli; Giovanni, Tava; Franco, Rengo; Giulio, Masotti; Gianfranco, Salvioli; Niccolò, Marchionni; Andrea, Ungar

2013-01-01

To evaluate the incidence of unexplained falls in elderly patients affected by fall-related fractures admitted to orthopaedic wards, we recruited 246 consecutive patients older than 65 (mean age 82 ± 7 years, range 65-101). Falls were defined "accidental" (fall explained by a definite accidental cause), "medical" (fall caused directly by a specific medical disease), "dementia-related" (fall in patients affected by moderate-severe dementia), and "unexplained" (nonaccidental falls, not related to a clear medical or drug-induced cause or with no apparent cause). According to the anamnestic features of the event, older patients had a lower tendency to remember the fall. Patients with accidental fall remember more often the event. Unexplained falls were frequent in both groups of age. Accidental falls were more frequent in younger patients, while dementia-related falls were more common in the older ones. Patients with unexplained falls showed a higher number of depressive symptoms. In a multivariate analysis a higher GDS and syncopal spells were independent predictors of unexplained falls. In conclusion, more than one third of all falls in patients hospitalized in orthopaedic wards were unexplained, particularly in patients with depressive symptoms and syncopal spells. The identification of fall causes must be evaluated in older patients with a fall-related injury.

Altered autonomic nervous system activity in women with unexplained recurrent pregnancy loss.

PubMed

Kataoka, Kumie; Tomiya, Yumi; Sakamoto, Ai; Kamada, Yasuhiko; Hiramatsu, Yuji; Nakatsuka, Mikiya

2015-06-01

Autonomic nervous system activity was studied to evaluate the physical and mental state of women with unexplained recurrent pregnancy loss (RPL). Heart rate variability (HRV) is a measure of beat-to-beat temporal changes in heart rate and provides indirect insight into autonomic nervous system tone and can be used to assess sympathetic and parasympathetic tone. We studied autonomic nervous system activity by measuring HRV in 100 women with unexplained RPL and 61 healthy female volunteers as controls. The degree of mental distress was assessed using the Kessler 6 (K6) scale. The K6 score in women with unexplained RPL was significantly higher than in control women. HRV evaluated on standard deviation of the normal-to-normal interval (SDNN) and total power was significantly lower in women with unexplained RPL compared with control women. These indices were further lower in women with unexplained RPL ≥4. On spectral analysis, high-frequency (HF) power, an index of parasympathetic nervous system activity, was significantly lower in women with unexplained RPL compared with control women, but there was no significant difference in the ratio of low-frequency (LF) power to HF power (LF/HF), an index of sympathetic nervous system activity, between the groups. The physical and mental state of women with unexplained RPL should be evaluated using HRV to offer mental support. Furthermore, study of HRV may elucidate the risk of cardiovascular diseases and the mechanisms underlying unexplained RPL. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Multiplexed detection of tumor markers with multicolor quantum dots based on fluorescence polarization immunoassay.

PubMed

Tian, Jianniao; Zhou, Liujin; Zhao, Yanchun; Wang, Yuan; Peng, Yan; Zhao, Shulin

2012-04-15

A multicolor quantum dot (QD)-based nanosensor for multiplex detection of two tumor markers in a homogeneous format based on fluorescence polarization immunoassay was proposed. QDs520 and QDs620 were labeled alpha-fetoprotein(α-AFP) and carcinoembryonic antigen (CEA), respectively. After separated and purified by ultrafiltration, they were used in fluorescence polarization immunoassay for the simultaneous detection of human serum alpha-fetoprotein and carcinoembryonic antigen. Under the optimal conditions, the multi-analyte immunosensor had a wide linear range (from 0.5 ng mL(-1) to 500 ng mL(-1)) for both two tumor markers and good correlation (0.996 for α-AFP and 0.993 for CEA). The detection limits (LOD) were 0.36 ng mL(-1) for CEA and 0.28 ng mL(-1) for α-AFP (S/N=3). The carcinoembryonic antigen and fetoprotein in clinical serum samples were simultaneously detected. The results from 28 serum samples had a good agreement with enzyme-linked immunosorbent assay (ELISA). The relative standard deviation and the recovery suggested that the precision and the accuracy of this analytical method were satisfactory. This strategy with high sensitivity, good specificity, easy procedures and short analysis time shows great promise for clinical diagnoses and basic discovery. The application of QDs with longer fluorescence lifetime and small fluorescence polarization can be used for the determination of high molecular-weight substances which cannot be analyzed using dye fluorescence polarization immunoassay. Copyright © 2012 Elsevier B.V. All rights reserved.

The assessment of ovulation by a combination of ultrasound and detailed serial hormone profiles in 35 women with long-standing unexplained infertility.

PubMed

Petsos, P; Chandler, C; Oak, M; Ratcliffe, W A; Wood, R; Anderson, D C

1985-06-01

We have examined for the presence of subtle hormonal abnormalities in women with long-standing unexplained infertility. For a full cycle serum LH, FSH, progesterone and oestradiol levels were measured about three times a week, and serial ultrasound scans of the ovaries made until the time of apparent ovulation. The results on 45 cycles in 35 women with unexplained infertility and in three normal volunteers are presented. Normal ovulatory cycles were defined by a length of 26-32 d, and progressive follicular maturation followed by disappearance or abrupt reduction in size of a follicle within 48 h of the recorded LH peak, followed by progressive and sustained rise in serum progesterone levels to more than 25 nmol/l and a luteal phase length of greater than or equal to 13 d. Thirty spontaneous cycles (28 women) were clearly normal while 15 spontaneous cycles (12 women) were abnormal. Abnormalities included luteinization of an unruptured follicle (eight cycles), absence of follicular development (two cycles), poor follicular development (two cycles), persistence of a large ovarian cyst from the preceeding cycle (two cycles) and one aluteal cycle. Six of the abnormal cycles were characterized hormonally by inappropriate elevation of serum LH levels throughout. If this study had been based only on serial ultrasound scans, all results on abnormal cycles might have been misinterpreted. If it had been conducted only with (multiple) progesterone determinations and the level of greater than 25 nmol/l had been taken as indicative of ovulation nine clearly abnormal cycles would have been considered as normal. We conclude that the combination of the hormonal and ultrasound assessment of ovulation increases our confidence for confirmation of normality and reveals various ovulatory disorders which are possibly due to an endocrinological defect or defects.

CEA (Carcinoembryonic Antigen) Test

MedlinePlus

... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Semen Analysis Serotonin Serum Free Light Chains Sex Hormone Binding Globulin ... Transferrin Receptor Stool Culture Stool Elastase Strep ...

CEA blood test

MedlinePlus

Carcinoembryonic antigen blood test ... A blood sample is needed . ... When the needle is inserted to draw blood, some people feel moderate pain. Others feel only a prick or stinging. Afterward, there may be some throbbing or a slight bruise. This ...

Analysis of Wind Tunnel Polar Replicates Using the Modern Design of Experiments

NASA Technical Reports Server (NTRS)

Deloach, Richard; Micol, John R.

2010-01-01

The role of variance in a Modern Design of Experiments analysis of wind tunnel data is reviewed, with distinctions made between explained and unexplained variance. The partitioning of unexplained variance into systematic and random components is illustrated, with examples of the elusive systematic component provided for various types of real-world tests. The importance of detecting and defending against systematic unexplained variance in wind tunnel testing is discussed, and the random and systematic components of unexplained variance are examined for a representative wind tunnel data set acquired in a test in which a missile is used as a test article. The adverse impact of correlated (non-independent) experimental errors is described, and recommendations are offered for replication strategies that facilitate the quantification of random and systematic unexplained variance.

Left Superior Vena Cava Draining Into Left Atrium in Tetralogy of Fallot-Four Cases of a Rare Association.

PubMed

Ramman, Tarun Raina; Dutta, Nilanjan; Chowdhuri, Kuntal Roy; Agrawal, Sunny; Girotra, Sumir; Azad, Sushil; Radhakrishnan, Sitaraman; Iyer, Parvathi Unninayar; Iyer, Krishna Subramony

2018-01-01

Persistent left superior vena cava is a common congenital anomaly of the thoracic venous system. Left superior vena cava draining into left atrium is a malformation of sinus venosus and caval system. The anomaly may be a cause of unexplained hypoxia even in adults. It may give rise to various diagnostic and technical challenges during cardiac catheterization and open-heart surgery. It is often detected serendipitously during diagnostic workup. Isolated left superior vena cava opening into left atrium is very commonly associated with other congenital heart defects. But tetralogy of Fallot is very rarely associated with persistent left superior vena cava which drains into left atrium. We report four such cases who underwent surgical correction successfully.

Prolactinoma presenting as chronic anaemia with osteoporosis: a case report

PubMed Central

2010-01-01

Introduction Unexplained anaemia is a rare mode of presentation for prolactinoma. We describe a case of a man, with chronic anaemia ascribed to old age. Six years later, he was evaluated and diagnosed with a prolactinoma and resultant osteoporosis. Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction. Case presentation We describe the case of a 70-year-old Caucasian man who presented with mild anaemia and tiredness. His anaemia was investigated and ascribed to senescence. Endocrine causes were not considered or tested for. Six years later, he was again referred. Reassessment and direct questioning revealed long-standing sexual dysfunction. It was also discovered that our patient had fractured his radius twice, with minor trauma, during the preceding year. His serum prolactin was massively increased and a magnetic resonance imaging (MRI) scan of the head demonstrated a pituitary mass consistent with a prolactinoma. Dual X-ray absorptiometry revealed osteoporosis. Treatment of the prolactinoma led to a reduction in his serum prolactin with a rise in his haemoglobin to normal levels. This suggested that the prolactinoma was present during the initial presentation and was the cause of his anaemia. Conclusion This case highlights the importance of fully evaluating and investigating unexplained anaemia in older people and that endocrine causes should be considered. Osteoporosis also requires evaluation with secondary causes considered. PMID:20205855

Relapsed prostate cancer with neuroendocrine differentiation and high serum levels of carcinoembryonic antigen without elevation of prostrate-specific antigen: a case report.

PubMed

Kinebuchi, Yoshiaki; Noguchi, Wataru; Irie, Kyoko; Nakayama, Tsuyoshi; Kato, Haruaki; Nishizawa, Osamu

2007-02-01

A 62-year-old man had been treated with combined androgen blockade due to cT2bN1M0 prostate cancer, and his serum prostate-specific antigen (PSA) levels decreased and remained under the level of 0.5 ng/mL during therapy. Approximately 40 months after the initial therapy, difficulty on urination and constipation developed gradually, and serum carcinoembryonic antigen (CEA) and pro-gastrin-releasing peptide (ProGRP) levels were high at this point. He underwent transrectal and transurethral biopsy of the prostate, which revealed adenocarcinoma positive for CEA and chromogranin A. He received palliative pelvic irradiation, and oral estramustine phosphate and etoposide combined therapy. Tumor markers decreased and clinical symptoms improved for several months. The patient died of encephalopathy of unknown etiology approximately 11 months after the relapse.

Carcinoembryonic antigen induces signal transduction in Kupffer cells.

PubMed

Gangopadhyay, A; Lazure, D A; Thomas, P

1997-09-16

Carcinoembryonic antigen (CEA), an intercellular adhesion molecule and a mediator of hepatic metastasis, is processed by an 80 kDa receptor on murine and human Kupffer cells in the liver. Activation of rat Kupffer cells in vitro by CEA via the 80 kDa receptor produced cytokines IL-1alpha and TNF-alpha which involved tyrosine phosphorylation. The peak response of TNF-alpha was 5.6 times greater than the corresponding IL-1alpha response and was associated with enhanced tyrosine phosphorylation of 108 and 125 kDa proteins. Lipopolysaccharide (LPS) treatment, on the other hand, phosphorylated two major proteins with MW of 93 and 119 kDa associated with the loss of phosphorylation from a 125 kDa protein. Results demonstrate that CEA-induced IL-1alpha and TNF-alpha production involves tyrosine phosphorylation and the signaling in CEA treated cells is different than that seen with LPS stimulation.

Doxorubicin-anti-carcinoembryonic antigen immunoconjugate activity in vitro.

PubMed

Richardson, V J; Ford, C H; Tsaltas, G; Gallant, M E

1989-04-01

An in vitro model consisting of a series of 11 human cancer cell lines with varying density of expression of membrane carcinoembryonic antigen (CEA) has been used to evaluate conjugates of doxorubicin (Adriamycin) covalently linked by a carbodiimide method to goat polyclonal antibodies and mouse monoclonal antibodies to CEA. Conjugates were produced which retained both antigen binding and drug cytotoxicity. IC50 values were determined for free drug, free drug mixed with unconjugated antibodies and for the immunoconjugates. Cell lines that were very sensitive to free drug (IC50 less than 100 ng/ml) were also found to be highly sensitive to conjugated drug and similarly cell lines resistant to drug (IC50 greater than 1,000 ng/ml) were also resistant to conjugated drug. Although there was no correlation between CEA expression and conjugates efficacy, competitive inhibition studies using autologous antibody to block conjugate binding to cells indicated immunoconjugates specificity for the CEA target.

Etiology of Syncope and Unexplained Falls in Elderly Adults with Dementia: Syncope and Dementia (SYD) Study.

PubMed

Ungar, Andrea; Mussi, Chiara; Ceccofiglio, Alice; Bellelli, Giuseppe; Nicosia, Franco; Bo, Mario; Riccio, Daniela; Martone, Anna Maria; Guadagno, Livia; Noro, Gabriele; Ghidoni, Giulia; Rafanelli, Martina; Marchionni, Niccolò; Abete, Pasquale

2016-08-01

To investigate the etiology of transient loss of consciousness (T-LOC) suspected to be syncope and unexplained falls in elderly adults with dementia. Prospective, observational, multicenter study. Acute care wards, syncope units or centers for the diagnosis of dementia. Individuals aged 65 and older with a diagnosis of dementia and one or more episodes of T-LOC of a suspected syncopal nature or unexplained falls during the previous 3 months were enrolled. The causes of T-LOC suspected to be syncope and unexplained falls were evaluated using a simplified protocol based on European Society of Cardiology guidelines. Of 357 individuals enrolled, 181 (50.7%) had been referred for T-LOC suspected to be syncope, 166 (46.5%) for unexplained falls, and 10 (2.8%) for both. An initially suspected diagnosis of syncope was confirmed in 158 (87.3%), and syncope was identified as the cause of the event in 75 (45.2%) of those referred for unexplained falls. Orthostatic hypotension was the cause of the event in 117 of 242 (48.3%) participants with a final diagnosis of syncope. The simplified syncope diagnostic protocol can be used in elderly people with dementia referred for suspected syncope or unexplained falls. Unexplained falls may mask a diagnosis of syncope or pseudosyncope in almost 50% of cases. Given the high prevalence of orthostatic syncope in participants (~50%), a systematic reappraisal of drugs potentially responsible for orthostatic hypotension is warranted. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Quantifying and Projecting Relative Sea-Level Rise At The Regional Scale: The Bangladesh Sea-Level Project (BanD-AID)

NASA Astrophysics Data System (ADS)

Shum, C. K.; Kuo, C. Y.; Guo, J.; Shang, K.; Tseng, K. H.; Wan, J.; Calmant, S.; Ballu, V.; Valty, P.; Kusche, J.; Hossain, F.; Khan, Z. H.; Rietbroek, R.; Uebbing, B.

2014-12-01

The potential for accelerated sea-level rise under anthropogenic warming is a significant societal problem, in particular in world's coastal deltaic regions where about half of the world's population resides. Quantifying geophysical sources of sea-level rise with the goal of improved projection at local scales remains a complex and challenging interdisciplinary research problem. These processes include ice-sheet/glacier ablations, steric sea-level, solid Earth uplift or subsidence due to GIA, tectonics, sediment loading or anthropogenic causes, hydrologic imbalance, and human processes including water retention in reservoirs and aquifer extraction. The 2013 IPCC AR5 concluded that the observed and explained geophysical causes of global geocentric sea-level rise, 1993-2010, is closer towards closure. However, the discrepancy reveals that circa 1.3→37.5% of the observed sea-level rise remains unexplained. This relatively large discrepancy is primarily attributable to the wide range of estimates of respective contributions of Greenland and Antarctic ice-sheets and mountain/peripheral glaciers to sea-level rise. Understanding and quantifying the natural and anthropogenic processes governing solid Earth (land, islands and sea-floor) uplift or subsidence at the regional and local scales remain elusive to enable addressing coastal vulnerability due to relative sea-level rise hazards, such as the Bangladesh Delta. This study focuses on addressing coastal vulnerability of Bangladesh, a Belmont Forum/IGFA project, BanD-AID (http://Belmont-SeaLevel.org). Sea-level rise, along with tectonic, sediment load and groundwater extraction induced land uplift/subsidence, have exacerbated Bangladesh's coastal vulnerability, affecting 150 million people in one of the world's most densely populated regions. Here we present preliminary results using space geodetic observations, including satellite radar and laser altimetry, GRACE gravity, tide gauge, hydrographic, and GPS/InSAR observed land subsidence, and via fingerprint sea-level adjustment and reconstructed sea-level approaches, for improved quantification of major contributions to, and the projection of relative sea-level rise at the Bangladesh delta, towards addressing its coastal vulnerability and sustainability.

Increased Anti-HSP60 and Anti-HSP70 Antibodies in Women with Unexplained Recurrent Pregnancy Loss.

PubMed

Matsuda, Miwa; Sasaki, Aiko; Shimizu, Keiko; Kamada, Yasuhiko; Noguchi, Soichi; Hiramatsu, Yuji; Nakatsuka, Mikiya

2017-06-01

　Vascular dysfunction has been reported in women with recurrent pregnancy loss (RPL). We investigated the severity of vascular dysfunction in non-pregnant women with RPL and its correlation with anti-heat shock protein (HSP) antibodies that are known to induce arteriosclerosis. We measured the serum anti-HSP60 antibodies, anti-HSP70 antibodies, and anti-phospholipid antibodies (APA) in 68 women with RPL and 29 healthy controls. Among the women with RPL, 14 had a diagnosis of antiphospholipid syndrome (APS), and in the remaining 54, the causes for RPL were unexplained. Compared to the controls, the brachial-ankle pulse wave velocity (baPWV), carotid augmentation index (cAI), and uterine artery pulsatility index (PI) were all significantly higher in the women with both APS and unexplained RPL. Compared to the controls, the anti-HSP60 antibody levels were significantly higher in the APA-positive group of women with unexplained RPL, and the anti-HSP70 antibody levels were significantly higher in APS and APA-positive group of women with unexplained RPL. However, the anti-HSP60 and anti-HSP70 antibody levels did not correlate with the values of baPWV or cAI. Our results demonstrated anti-HSP60 and anti-HSP70 antibodies are increased in women with unexplained RPL. Further studies are needed to elucidate the roles of anti-HSP antibodies and their pathophysiology in unexplained RPL.

Clinical Usefulness of SPECT-CT in Patients with an Unexplained Pain in Metal on Metal (MOM) Total Hip Arthroplasty.

PubMed

Berber, Reshid; Henckel, Johann; Khoo, Michael; Wan, Simon; Hua, Jia; Skinner, John; Hart, Alister

2015-04-01

SPECT-CT is increasingly used to assess painful knee arthroplasties. The aim of this study was to evaluate the clinical usefulness of SPECT-CT in unexplained painful MOM hip arthroplasty. We compared the diagnosis and management plan for 19 prosthetic MOM hips in 15 subjects with unexplained pain before and after SPECT-CT. SPECT-CT changed the management decision in 13 (68%) subjects, Chi-Square=5.49, P=0.24. In 6 subjects (32%) pain remained unexplained however the result reassured the surgeon to continue with non-operative management. SPECT-CT should be reserved as a specialist test to help identify possible causes of pain where conventional investigations have failed. It can help reassure surgeons making management decisions for patients with unexplained pain following MOM hip arthroplasty. Copyright © 2014 Elsevier Inc. All rights reserved.

Multiple myeloma presenting as CEA-producing rectal cancer.

PubMed

Talamo, Giampaolo; Barochia, Amitkumar; Zangari, Maurizio; Loughran, Thomas P

2010-03-31

We report the case of a 57-year-old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA), a tumor antigen more commonly associated with rectal adenocarcinomas.

Inheritance of Febrile Seizures in Sudden Unexplained Death in Toddlers

PubMed Central

Holm, Ingrid A.; Poduri, Annapurna; Crandall, Laura; Haas, Elisabeth; Grafe, Marjorie R.; Kinney, Hannah C.; Krous, Henry F.

2014-01-01

Sudden unexplained death in toddlers has been associated with febrile seizures, family history of febrile seizures, and hippocampal anomalies. We investigated the mode of inheritance for febrile seizures in these families. A three-generation pedigree was obtained from families enrolled in the San Diego Sudden Unexplained Death in Childhood Research Project, involving toddlers with sudden unexplained death, febrile seizures, and family history of febrile seizures. In our six cases, death was unwitnessed and related to sleep. The interval from last witnessed febrile seizure to death ranged from 3 weeks to 6 months. Hippocampal abnormalities were identified in one of three cases with available autopsy sections. Autosomal dominant inheritance of febrile seizures was observed in three families. A fourth demonstrated autosomal dominant inheritance with incomplete penetrance or variable expressivity. In two families, the maternal and paternal sides manifested febrile seizures. In this series, the major pattern of inheritance in toddlers with sudden unexplained death and febrile seizures was autosomal dominant. Future studies should develop markers (including genetic) to identify which patients with febrile seizures are at risk for sudden unexplained death in childhood, and to provide guidance for families and physicians. PMID:22490769

Laparoscopy In Unexplained Abdominal Pain: Surgeon's Perspective.

PubMed

Abdullah, Muhammad Tariq; Waqar, Shahzad Hussain; Zahid, Muhammad Abdul

2016-01-01

Unexplained abdominal pain is a common but difficult presenting feature faced by the clinicians. Such patients can undergo a number of investigations with failure to reach any diagnosis. The objective of this study was to evaluate the use of laparoscopy in the diagnosis and management of patients with unexplained abdominal pain. This cross-sectional study was conducted at Pakistan Institute of Medical Sciences Islamabad from January 2009 to December 2013. This study included 91 patients of unexplained abdominal pain not diagnosed by routine clinical examination and investigations. These patients were subjected to diagnostic laparoscopy for evaluation of their conditions and to confirm the diagnosis. These patients presented 43% of patients undergoing investigations for abdominal pain. Patients diagnosed with gynaecological problems were excluded to see surgeon's perspective. The findings and the outcomes of the laparoscopy were recorded and data was analyzed. Unexplained abdominal pain is common in females than in males. The most common laparoscopic findings were abdominal tuberculosis followed by appendicitis. Ninety percent patients achieved pain relief after laparoscopic intervention. Laparoscopy is both beneficial and safe in majority of patients with unexplained abdominal pain. General surgeons should acquire training and experience in laparoscopic surgery to provide maximum benefit to these difficult patients.

Health care utilization of mexican patients with medically unexplained physical symptoms.

PubMed

Rodriguez González, Azucena Maribel; Ramírez Aranda, José Manuel; de Los Santos Reséndiz, Homero; Lara Duarte, María Yolanda; Pazaran Zanella, Santiago Oscar; Méndez López, Jafet Felipe; Gil Alfaro, Issa; Islas Ruz, Félix Gilberto; Navarrete Floriano, Gloria; Guillen Salomón, Edith; Texon Fernández, Obdulia; Cruz Duarte, Silvia; Romo Salazar, Juan Carlos; Pérez Ruiz, Claudia Elsa; López Salas, Sara de Jesús; Benítez Amaya, Lizbeth; Zapata Gallardo, Javier Nahum

2016-09-30

To determine the prevalence of medically unexplained physical symptoms and the characteristics and use of health services in a group of patients with medically unexplained physical symptoms and a group of patients with other illnesses. This was a cross-sectional, retrospective and multicenter study. We included 1,043 patients over 18 years of age from 30 primary care units of a government health institution, in 11 states of Mexico, attended by 39 family physicians. The prevalence of medically unexplained physical symptoms was determined and both groups with or without symptoms were compared with regard to drug use, laboratory and other studies, leaves of absence, and referrals in the last six months. The group with medically unexplained physical symptoms was diagnosed using the Patient Health Questionnaire and the diagnostic criteria of Reid et al . Emergency or terminal illnesses were excluded. The chi square test was used with a statistical significance of p < 0.05. Medically unexplained physical symptoms was diagnosed in 73 patients (7.0%). The majority were women (91.8%); their predominant symptom was from the gastrointestinal system in 56 (76.7%). This group had a greater use of clinical studies and referrals to other services (mean 1.1 vs. 0.5; p <0.0001 and 0.6 vs. 0.8; p < 0.01, respectively). The prevalence of medically unexplained physical symptoms was low, but with a greater impact on some health services. This could represent an overload in medical costs.

Non-alcoholic Fatty Liver Disease: East Versus West

PubMed Central

Agrawal, Swastik; Duseja, Ajay K

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease worldwide with prevalence ranging from 10% to 30% in various countries. It has become an important cause of unexplained rise in transaminases, cryptogenic cirrhosis, and cryptogenic hepatocellular carcinoma. Pathogenesis is related to obesity, insulin resistance, oxidative stress, lipotoxicity, and resultant inflammation in the liver progressing to fibrosis. Pharmacological treatment in patients with NAFLD is still evolving and the treatment of these patients rests upon lifestyle modification with diet and exercise being the cornerstones of therapy. While there are many similarities between patients with NAFLD from Asia and the West, there are certain features which make the patients with NAFLD from Asia stand apart. This review highlights the data on NAFLD from Asia comparing it with the data from the West. PMID:25755421

Television image of a large upward electrical discharge above a thunderstorm system

NASA Technical Reports Server (NTRS)

Franz, R. C.; Nemzek, R. J.; Winckler, J. R.

1990-01-01

A low light-level TV camera is used to obtain an unusual image of luminous electrical discharge over a thunderstorm 250 km from the observation site. The image is presented and the discharge in the image is described. It is suggested that the image is probably due to two localized electric charge concentrations at the cloud tops. The hazard of these discharges for aircraft and rocket launches is examined. Consideration is given to the possibility that these discharges may account for unexplained photometric observations of distant lightning events that show a low rise rate of the luminous pulse and no electromagnetic sferic pulse like that in cloud-to-earth lightning strokes. The photometric events of this type that occurred on September 22-23, 1989 during hurricane Hugo are noted.

Multiple myeloma presenting as CEA-producing rectal cancer

PubMed Central

Talamo, Giampaolo; Barochia, Amitkumar; Zangari, Maurizio; Loughran, Thomas P

2010-01-01

We report the case of a 57-year-old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA), a tumor antigen more commonly associated with rectal adenocarcinomas. PMID:21139949

Cross-cultural differences in the epidemiology of unexplained fatigue syndromes in primary care.

PubMed

Skapinakis, Petros; Lewis, Glyn; Mavreas, Venetsanos

2003-03-01

Unexplained fatigue has been extensively studied but most of the samples used were from Western countries. To present international data on the prevalence of unexplained fatigue and fatigue as a presenting complaint in primary care. Method Secondary analysis of the World Health Organization study of psychological problems in general health care. A total of 5438 primary care attenders from 14 countries were assessed with the Composite International Diagnostic Interview. The prevalence of unexplained fatigue of 1-month duration differed across centres, with a range between 2.26 (95% CI 1.17-4.33) and 15.05 (95% CI 10.85-20.49). Subjects from more-developed countries were more likely to report unexplained fatigue but less likely to present with fatigue to physicians compared with subjects from less developed countries. In less-developed countries fatigue might be an indicator of unmet psychiatric need, but in more-developed countries it is probably a symbol of psychosocial distress.

Medically unexplained visual loss in a specialist clinic: a retrospective case-control comparison.

PubMed

O'Leary, Éanna D; McNeillis, Benjamin; Aybek, Selma; Riordan-Eva, Paul; David, Anthony S

2016-02-15

To compare the clinical and demographic characteristics of adult patients with nonorganic or medically unexplained visual loss (MUVL) to those with other common conditions presenting to a neuro-ophthalmology clinic. Case-control design: a retrospective review of medical notes on a consecutive case series of 49 patients assessed at the King's College Hospital neuro-ophthalmology clinic with unexplained visual loss and matched with the next assessed patient identified from clinic records. Patients presented post-symptom onset with a mean clinical course of 30 months (SD=67 months) and standard clinical examination used to confirm diagnoses, alongside ancillary investigations if required. Seventy-two percent (n=36) of MUVL patients were female. In comparison with patients with organic visual disorders, MUVL cases presented with significantly higher rates of bilateral (cf. unilateral) visual impairment (41%, n=20), premorbid psychiatric (27%, n=13) as well as functional (24%, n=12) diagnoses and psychotropic medication usage (22%, n=11). Medically unexplained cases were significantly more likely to report preceding psychological stress (n=9; 18%). Medically unexplained visual impairment may be regarded as part of the spectrum of medically unexplained disorders seen in the general hospital setting. Research is needed to determine long-term outcomes and effective tailored interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

Diagnostic value of FDG-PET/(CT) in children with fever of unknown origin and unexplained fever during immune suppression.

PubMed

Blokhuis, Gijsbert J; Bleeker-Rovers, Chantal P; Diender, Marije G; Oyen, Wim J G; Draaisma, Jos M Th; de Geus-Oei, Lioe-Fee

2014-10-01

Fever of unknown origin (FUO) and unexplained fever during immune suppression in children are challenging medical problems. The aim of this study is to investigate the diagnostic value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and FDG-PET combined with computed tomography (FDG-PET/CT) in children with FUO and in children with unexplained fever during immune suppression. All FDG-PET/(CT) scans performed in the Radboud university medical center for the evaluation of FUO or unexplained fever during immune suppression in the last 10 years were reviewed. Results were compared with the final clinical diagnosis. FDG-PET/(CT) scans were performed in 31 children with FUO. A final diagnosis was established in 16 cases (52 %). Of the total number of scans, 32 % were clinically helpful. The sensitivity and specificity of FDG-PET/CT in these patients was 80 % and 78 %, respectively. FDG-PET/(CT) scans were performed in 12 children with unexplained fever during immune suppression. A final diagnosis was established in nine patients (75 %). Of the total number of these scans, 58 % were clinically helpful. The sensitivity and specificity of FDG-PET/CT in children with unexplained fever during immune suppression was 78 % and 67 %, respectively. FDG-PET/CT appears a valuable imaging technique in the evaluation of children with FUO and in the diagnostic process of children with unexplained fever during immune suppression. Prospective studies of FDG-PET/CT as part of a structured diagnostic protocol are warranted to assess the additional diagnostic value.

Common and unique associated factors for medically unexplained chronic widespread pain and chronic fatigue☆

PubMed Central

McBeth, J.; Tomenson, B.; Chew-Graham, C.A.; Macfarlane, G.J.; Jackson, J.; Littlewood, A.; Creed, F.H.

2015-01-01

Objective Chronic widespread pain and chronic fatigue share common associated factors but these associations may be explained by the presence of concurrent depression and anxiety. Methods We mailed questionnaires to a randomly selected sample of people in the UK to identify participants with chronic widespread pain (ACR 1990 definition) and those with chronic fatigue. The questionnaire assessed sociodemographic factors, health status, healthcare use, childhood factors, adult attachment, and psychological stress including anxiety and depression. To identify persons with unexplained chronic widespread pain or unexplained chronic fatigue; we examined participant's medical records to exclude medical illness that might cause these symptoms. Results Of 1443 participants (58.0% response rate) medical records of 990 were examined. 9.4% (N = 93) had unexplained chronic widespread pain and 12.6% (N = 125) had unexplained chronic fatigue. Marital status, childhood psychological abuse, recent threatening experiences and other somatic symptoms were commonly associated with both widespread pain and fatigue. No common effect was found for few years of education and current medical illnesses (more strongly associated with chronic widespread pain) or recent illness in a close relative, neuroticism, depression and anxiety scores (more strongly associated with chronic fatigue). Putative associated factors with a common effect were associated with unexplained chronic widespread pain or unexplained chronic fatigue only when there was concurrent anxiety and/or depression. Discussion This study suggests that the associated factors for chronic widespread pain and chronic fatigue need to be studied in conjunction with concurrent depression/anxiety. Clinicians should be aware of the importance of concurrent anxiety or depression. PMID:26652592

Making sense of medically unexplained symptoms in general practice: a grounded theory study

PubMed Central

2013-01-01

Background General practitioners often encounter patients with medically unexplained symptoms. These patients share many common features, but there is little agreement about the best diagnostic framework for describing them. Aims This study aimed to explore how GPs make sense of medically unexplained symptoms. Design Semi-structured interviews were conducted with 24 GPs. Each participant was asked to describe a patient with medically unexplained symptoms and discuss their assessment and management. Setting The study was conducted among GPs from teaching practices across Australia. Methods Participants were selected by purposive sampling and all interviews were transcribed. Iterative analysis was undertaken using constructivist grounded theory methodology. Results GPs used a variety of frameworks to understand and manage patients with medically unexplained symptoms. They used different frameworks to reason, to help patients make sense of their suffering, and to communicate with other health professionals. GPs tried to avoid using stigmatising labels such as ‘borderline personality disorder’, which were seen to apply a ‘layer of dismissal’ to patients. They worried about missing serious physical disease, but managed the risk by deliberately attending to physical cues during some consultations, and focusing on coping with medically unexplained symptoms in others. They also used referrals to exclude serious disease, but were wary of triggering a harmful cycle of uncoordinated care. Conclusion GPs were aware of the ethical relevance of psychiatric diagnoses, and attempted to protect their patients from stigma. They crafted helpful explanatory narratives for patients that shaped their experience of suffering. Disease surveillance remained an important role for GPs who were managing medically unexplained symptoms. PMID:24427176

Sperm chromatin structure assay results in Nigerian men with unexplained infertility

PubMed Central

Kolade, Charles Oluwabukunmi

2015-01-01

Objective Several publications have established a relationship between sperm DNA damage and male factor infertility, based on data from America, Europe, and Asia. This study aimed to compare the extent of sperm DNA damage in sperm samples from Nigerian men with unexplained infertility and in sperm samples from a fertile group composed of sperm donors who had successfully impregnated a female partner naturally or through assisted conception. Methods A total of 404 men underwent male fertility evaluation at Androcare Laboratories and Cryobank participated in this study. Semen analysis and a sperm chromatin structure assay (SCSA) were performed on all subjects. Results The men in the unexplained infertility group were slightly older than the men in the fertile sperm group (36±10 years vs. 32±6 years, p=0.051). No significant difference was observed between the two groups in semen analysis parameters (p≥0.05). Men in the unexplained infertility group with normal semen parameters had a significantly higher DNA fragmentation index (DFI) than men in the fertile sperm group (27.5%±7.0% vs. 14.1%±5.3%, p<0.05). In the unexplained infertility group, 63% of the men had a DFI greater than 20%, compared to 4% in the fertile sperm group. In the unexplained infertility group, 15.2% of the subjects had a DFI greater than 30%, compared to 1% in the fertile sperm group. Conclusion Our study showed that the SCSA may be a more reliable predictor of fertility potential than traditional semen analysis in cases of unexplained infertility. PMID:26473109

Gold nanoparticle-based low limit of detection Love wave biosensor for carcinoembryonic antigens.

PubMed

Li, Shuangming; Wan, Ying; Su, Yan; Fan, Chunhai; Bhethanabotla, Venkat R

2017-09-15

In this work, a Love wave biosensing platform is described for detecting cancer-related biomarker carcinoembryonic antigen (CEA). An ST 90°-X quartz Love wave device with a layer of SiO 2 waveguide was combined with gold nanoparticles (Au NPs) to amplify the mass loading effect of the acoustic wave sensor to achieve a limit of detection of 37pg/mL. The strategy involves modifying the Au NPs with anti-CEA antibody conjugates to form nanoprobes in a sandwich immunoassay. The unamplified detection limit of the Love wave biosensor is 9.4ng/mL. This 2-3 order of magnitude reduction in the limit of detection brings the SAW platform into the range useful for clinical diagnosis. Measurement electronics and microfluidics are easily constructed for acoustic wave biosensors, such as the Love wave device described here, allowing for robust platforms for point of care applications for cancer biomarkers in general. Copyright © 2017 Elsevier B.V. All rights reserved.

Surface-enhanced Raman scattering study of carcinoembryonic antigen in serum from patients with colorectal cancers

NASA Astrophysics Data System (ADS)

Chen, Gang; Chen, Yanping; Zheng, Xiongwei; He, Cheng; Lu, Jianping; Feng, Shangyuan; Chen, Rong; Zeng, Haisan

2013-12-01

In this work, we developed a SERS platform for quantitative detection of carcinoembryonic antigen (CEA) in serum of patients with colorectal cancers. Anti-CEA-functionalized 4-mercaptobenzoic acid-labeled Au/Ag core-shell bimetallic nanoparticles were prepared first and then used to analyze CEA antigen solutions of different concentrations. A calibration curve was established in the range from 5 × 10-3 to 5 × 105 ng/mL. Finally, this new SERS probe was applied for quantitative detection of CEA in serum obtained from 26 colorectal cancer patients according to the calibration curve. The results were in good agreement with that obtained by electrochemical luminescence method, suggesting that SERS immunoassay has high sensitivity and specificity for CEA detection in serum. A detection limit of 5 pg/ml was achieved. This study demonstrated the feasibility and great potential for developing this new technology into a clinical tool for analysis of tumor markers in the blood.

Polyaniline modified flexible conducting paper for cancer detection

NASA Astrophysics Data System (ADS)

Kumar, Saurabh; Sen, Anindita; Kumar, Suveen; Augustine, Shine; Yadav, Birendra K.; Mishra, Sandeep; Malhotra, Bansi D.

2016-05-01

We report results of studies relating to the fabrication of a flexible, disposable, and label free biosensing platform for detection of the cancer biomarker (carcinoembryonic antigen, CEA). Polyaniline (PANI) has been electrochemically deposited over gold sputtered paper (Au@paper) for covalent immobilization of monoclonal carcinoembryonic antibodies (anti-CEA). The bovine serum albumin (BSA) has been used for blocking nonspecific binding sites at the anti-CEA conjugated PANI/Au@Paper. The PANI/Au@Paper, anti-CEA/PANI/Au@Paper, and BSA/anti-CEA/PANI/Au@Paper platforms have been characterized using scanning electron microscopy, X-ray diffraction, Fourier transmission infrared spectroscopy, chronoamperometry, and electrochemical impedance techniques. The results of the electrochemical response studies indicate that this BSA/anti-CEA/PANI/Au@paper electrode has sensitivity of 13.9 μA ng-1 ml cm2, shelf life of 22 days, and can be used to estimate CEA in the range of 2-20 ng ml-1. This paper sensor has been validated by detection of CEA in serum samples of cancer patients via immunoassay technique.

Adenovirus tumor targeting and hepatic untargeting by a coxsackie/adenovirus receptor ectodomain anti-carcinoembryonic antigen bispecific adapter.

PubMed

Li, Hua-Jung; Everts, Maaike; Pereboeva, Larisa; Komarova, Svetlana; Idan, Anat; Curiel, David T; Herschman, Harvey R

2007-06-01

Adenovirus vectors have a number of advantages for gene therapy. However, because of their lack of tumor tropism and their preference for liver infection following systemic administration, they cannot be used for systemic attack on metastatic disease. Many epithelial tumors (e.g., colon, lung, and breast) express carcinoembryonic antigen (CEA). To block the natural hepatic tropism of adenovirus and to "retarget" the virus to CEA-expressing tumors, we used a bispecific adapter protein (sCAR-MFE), which fuses the ectodomain of the coxsackie/adenovirus receptor (sCAR) with a single-chain anti-CEA antibody (MFE-23). sCAR-MFE untargets adenovirus-directed luciferase transgene expression in the liver by >90% following systemic vector administration. Moreover, sCAR-MFE can "retarget" adenovirus to CEA-positive epithelial tumor cells in cell culture, in s.c. tumor grafts, and in hepatic tumor grafts. The sCAR-MFE bispecific adapter should, therefore, be a powerful agent to retarget adenovirus vectors to epithelial tumor metastases.

Establishment and characterization of a human pancreatic cancer cell line (SUIT-2) producing carcinoembryonic antigen and carbohydrate antigen 19-9.

PubMed

Iwamura, T; Katsuki, T; Ide, K

1987-01-01

A new tumor cell line (SUIT-2) derived from a metastatic liver tumor of human pancreatic carcinoma has been established in tissue culture and in nude mice, and maintained for over five years. In tissue culture, the cells grew in a monolayered sheet with a population doubling time of about 38.2 hr, and floated or piled up to form small buds above the monolayered surface in relatively confluent cultures. Chromosome counts ranged from 34 to 176 with a modal number of 45. Subcutaneous injection of cultured cells into nude mice resulted in tumor formation, histopathologically closely resembling the original neoplasm which had been classified as moderately differentiated tubular adenocarcinoma. Electron microscopic observation of the neoplastic cells revealed a characteristic pancreatic ductal epithelium. SUIT-2 cell line produces and releases at least two tumor markers, carcinoembryonic antigen and carbohydrate antigen 19-9, propagates even in serum-free medium, and metastasizes to the regional lymph nodes in nude mice xenografts.

Model for Spiral Galaxys Rotation Curves

NASA Astrophysics Data System (ADS)

Hodge, John

2003-11-01

A model of spiral galaxy dynamics is proposed. An expression describing the rotation velocity of particles v in a galaxy as a function of the distance from the center r (RC) is developed. The resulting, intrinsic RC of a galaxy is Keplerian in the inner bulge and rising in the disk region without modifying the Newtonian gravitational potential (MOND) and without unknown dark matter. The v^2 is linearly related to r of the galaxy in part of the rapidly rising region of the HI RC (RRRC) and to r^2 in another part of the RRRC. The r to discontinuities in the surface brightness versus r curve is related to the 21 cm line width, the measured mass of the central supermassive black hole (SBH), and the maximum v^2 in the RRRC. The distance to spiral galaxies can be calculated from these relationships that tightly correlates with the distance calculated using Cepheid variables. Differing results in measuring the mass of the SBH from differing measurement procedures are explained. This model is consistent with previously unexplained data, has predicted new relationships, and suggests a new model of the universe. Full text: http://web.infoave.net/ ˜scjh.

Tectonic-driven climate change and the diversification of angiosperms.

PubMed

Chaboureau, Anne-Claire; Sepulchre, Pierre; Donnadieu, Yannick; Franc, Alain

2014-09-30

In 1879, Charles Darwin characterized the sudden and unexplained rise of angiosperms during the Cretaceous as an "abominable mystery." The diversification of this clade marked the beginning of a rapid transition among Mesozoic ecosystems and floras formerly dominated by ferns, conifers, and cycads. Although the role of environmental factors has been suggested [Coiffard C, Gómez B (2012) Geol Acta 10(2):181-188], Cretaceous global climate change has barely been considered as a contributor to angiosperm radiation, and focus was put on biotic factors to explain this transition. Here we use a fully coupled climate model driven by Mesozoic paleogeographic maps to quantify and discuss the impact of continental drift on angiosperm expansion and diversification. We show that the decrease of desertic belts between the Triassic and the Cretaceous and the subsequent onset of long-lasting humid conditions during the Late Cretaceous were driven by the breakup of Pangea and were contemporaneous with the first rise of angiosperm diversification. Positioning angiosperm-bearing fossil sites on our paleobioclimatic maps shows a strong match between the location of fossil-rich outcrops and temperate humid zones, indicating that climate change from arid to temperate dominance may have set the stage for the ecological expansion of flowering plants.

Prevalence of Gilbert syndrome in parents of neonates with pathologic indirect hyperbilirubinemia.

PubMed

Saki, Forough; Hemmati, Fariba; Haghighat, Mahmoud

2011-01-01

The cause of hyperbilirubinemia cannot be found in about 45% of cases of neonatal jaundice. Gilbert syndrome (GS) is the most common congenital disease associated with bilirubin metabolism in the liver. Since the screening value of genetic tests cannot be fully determined until accurate data on the prevalence and penetrance of the GS genotype are known, we sought to estimate whether the prevalence of GS is higher in the parents of neonates with severe unexplained indirect hyperbilirubinemia. Case-control study of parents of neonates with severe unexplained indirect hyperbilirubinemia admitted to a neonatal ward. We used the rifampin test (checked bilirubin before and 4 hours after administration of 600 mg rifampin) for diagnosis of GS in parents of 115 neonates with severe unexplained indirect hyperbilirubinemia. We compared the prevalence of GS in these parents with that of a control group of 115 couples referred for premarital counseling. The 115 neonates were aged 5.2 (1.6) days (mean, standard deviation), all were breast-fed, and males constituted 56.5%. Mean total serum bilirubin (TSB) level was 20.96 (5.48) mg/dL. 14.8% were glucose 6 phosphate dehydrogenase (G6PD) deficiency was present in 14.8%, and 10.4% had A, B or O blood group (ABO) incompatibilities with their mothers. There was no difference in the prevalence of GS between parents of the group with hyperbilirubinemia (22.2%) and the control group (19.13%) (P=.42). Mean TSB in neonates with parents who had GS was more (about 3 mg/dL) than in neonates with normal parents (P=.004). Fathers had GS twice as often as the mothers among the parents of neonates with hyperbilirubinemia (P=.003), among the control group (P=.009) and among neonates (P=.014). This study showed that GS cannot cause severe indirect hyperbilirubinemia by itself, but it may have a summative effect on rising bilirubin when combined with other factors, for example, G6PD. Our results showed that in GS, males are affected about twice as much as the females.

Characteristics of Patients Referred to a Pediatric Infectious Diseases Clinic With Unexplained Fever.

PubMed

Statler, Victoria A; Marshall, Gary S

2016-09-01

Older case series established diagnostic considerations for children meeting a priori definitions of fever of unknown origin (FUO). No recent study has examined the final diagnoses of children referred for unexplained fever. This study was conducted with a retrospective chart review of patients referred to a pediatric infectious diseases clinic from 2008 to 2012 for unexplained fever. Sixty-nine of 221 patients were referred for "prolonged" unexplained fever. Ten of these were not actually having fever, and 11 had diagnoses that were readily apparent at the initial visit. The remaining 48 were classified as having FUO. The median duration of reported fever for these patients was 30 days; 15 had a diagnosis made, 5 of which were serious. None of the serious FUO diagnoses were infections. Of 152 patients with "recurrent" unexplained fever, 92 had an "intermittent" fever pattern, and most of these had sequential, self-limited viral illnesses or no definitive diagnosis made. Twenty of the 60 patients with a "periodic" fever pattern were diagnosed with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. Overall, 166 patients either were not having fever, had self-limited illnesses, or ultimately had no cause of fever discovered. Only 12 had a serious illness, 2 of which were infections (malaria and typhoid fever). Most children referred with unexplained fever had either self-limited illnesses or no specific diagnosis established. Serious diagnoses were unusual, suggesting that these diagnoses rarely present with unexplained fever alone, or that, when they do, the diagnoses are made by primary care providers or other subspecialists. © The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

How do hospital doctors manage patients with medically unexplained symptoms: a qualitative study of physicians.

PubMed

Warner, Alex; Walters, Kate; Lamahewa, Kethakie; Buszewicz, Marta

2017-02-01

Objective Medically unexplained symptoms are a common presentation in medical practice and are associated with significant morbidity and high levels of service use. Most research exploring the attitudes and training of doctors in treating patients with unexplained symptoms has been conducted in primary care. This study aims to explore the ways in which doctors working in secondary care approach and manage patients with medically unexplained symptoms. Design A qualitative study using in-depth interviews and thematic analysis. Setting Three hospitals in the North Thames area. Participants Twenty consultant and training-grade physicians working in cardiology, gastroenterology, rheumatology and neurology. Main outcome measure Physicians' approach to patients with medically unexplained symptoms and their views on managing these patients. Results There was considerable variation in how the physicians approached patients who presented with medically unexplained symptoms. Investigations were often ordered without a clear rationale and the explanations given to patients when results of investigations were normal were highly variable, both within and across specialties. The doctor's level of experience appeared to be a more important factor in their investigation and management strategies than their medical specialty. Physicians reported little or no formal training in how to manage such presentations, with no apparent consistency in how they had developed their approach. Doctors described learning from their own experience and from senior role models. Organisational barriers were identified to the effective management of these patients, particularly in terms of continuity of care. Conclusions Given the importance of this topic, there is a need for serious consideration as to how the management of patients with medically unexplained symptoms is included in medical training and in the planning and delivery of services.

Lower FOXO3 mRNA expression in granulosa cells is involved in unexplained infertility.

PubMed

Yamamoto, Hikaru; Yamashita, Yoshiki; Saito, Natsuho; Hayashi, Atsushi; Hayashi, Masami; Terai, Yoshito; Ohmichi, Masahide

2017-06-01

The aim of this study was to investigate whether FOXO1 and FOXO3 mRNA expression in granulosa cells is the cause of unexplained infertility. Thirty-one patients aged <40 years (13 with unexplained infertility and 18 with male partner infertility as a control group) whose serum anti-Müllerian hormone level was >0.5 ng/μL were enrolled in the study. All patients underwent oocyte retrieval under a short protocol from June 2012 to October 2013. Real-time PCR was carried out using mRNA extracted from granulosa cells retrieved from mature follicles. We compared FOXO1 and FOXO3 mRNA expression ratios in granulosa cells between the unexplained infertility group and the male infertility group. The relation between FOXO1 and FOXO3 mRNA expression ratios in granulosa cells and assisted reproduction technology clinical outcome was also examined. FOXO3 mRNA expression ratio was significantly lower in the unexplained infertility group than in the male infertility group. Moreover, FOXO3 mRNA expression ratio showed a positive correlation with both the number of retrieved oocytes and serum anti-Müllerian hormone level. A positive correlation was also identified between FOXO1 mRNA expression and total dose of hMG. As well, the number of retrieved oocytes in the unexplained infertility group was statistically lower than that in the male infertility group. A lower FOXO3 mRNA expression in granulosa cells leads to poor oocyte development in patients with unexplained infertility undergoing controlled ovarian stimulation for in vitro fertilization-embryo transfer. © 2017 Japan Society of Obstetrics and Gynecology.

Maternal serum amyloid A level as a novel marker of primary unexplained recurrent early pregnancy loss.

PubMed

Ibrahim, Moustafa I; Ramy, Ahmed R; Abdelhamid, Ahmed S; Ellaithy, Mohamed I; Omar, Amna; Harara, Rany M; Fathy, Hayam; Abolouz, Ashraf S

2017-03-01

To assess maternal serum amyloid A (SAA) levels among women with primary unexplained recurrent early pregnancy loss (REPL). A prospective study was conducted among women with missed spontaneous abortion in the first trimester at Ain Shams University Maternity Hospital, Cairo, Egypt, between January 21 and December 25, 2014. Women with at least two consecutive primary unexplained REPLs and no previous live births were enrolled. A control group was formed of women with no history of REPL who had at least one previous uneventful pregnancy with no adverse outcomes. Serum samples were collected to measure SAA levels. The main outcome was the association between SAA and primary unexplained REPL. Each group contained 96 participants. Median SAA level was significantly higher among women with REPL (50.0 μg/mL, interquartile range 26.0-69.0) than among women in the control group (11.6 μg/mL, interquartile range 6.2-15.5; P<0.001). The SAA level was an independent indicator of primary unexplained REPL, after adjusting for maternal age and gestational age (odds ratio 1.12, 95% confidence interval 1.06-1.19; P<0.001). Elevated SAA levels found among women with primary unexplained REPL could represent a novel biomarker for this complication of pregnancy. © 2016 International Federation of Gynecology and Obstetrics.

Multi-symptom illnesses, unexplained illness and Gulf War Syndrome

PubMed Central

Ismail, Khalida; Lewis, Glyn

2006-01-01

Explanatory models for the increased prevalence of ill health in Gulf veterans compared to those not deployed to the Gulf War 1990–1991 remain elusive. This article addresses whether multi-symptom reporting in Gulf veterans are types of medically unexplained symptoms and whether the alleged Gulf War Syndrome is best understood as a medically unexplained syndrome. A review of the epidemiological studies, overwhelmingly cross-sectional, describing ill health was conducted including those that used factor analysis to search for underlying or latent clinical constructs. The overwhelming evidence was that symptoms in Gulf veterans were either in keeping with currently defined psychiatric disorders such as depression and anxiety or were medically unexplained. The application of factor analysis methods had varied widely with a risk of over interpretation in some studies and limiting the validity of their findings. We concluded that ill health in Gulf veterans and the alleged Gulf War Syndrome is best understood within the medically unexplained symptoms and syndromes constructs. The cause of increased reporting in Gulf veterans are still not clear and requires further inquiry into the interaction between sociological factors and symptomatic distress. PMID:16687260

Definition and epidemiology of unexplained infertility.

PubMed

Gelbaya, Tarek A; Potdar, Neelam; Jeve, Yadava B; Nardo, Luciano G

2014-02-01

The diagnosis of unexplained infertility can be made only after excluding common causes of infertility using standard fertility investigations,which include semen analysis, assessment of ovulation, and tubal patency test. These tests have been selected as they have definitive correlation with pregnancy. It is estimated that a standard fertility evaluation will fail to identify an abnormality in approximately 15% to 30% of infertile couples. The reported incidence of such unexplained infertility varies according to the age and selection criteria in the study population. We conducted a review of the literature via MEDLINE. Articles were limited to English-language, human studies published between 1950 and 2013. Since first coined more than 50 years ago, the term unexplained infertility has been a subject of debate. Although additional investigations are reported to explain or define other causes of infertility, these have high false-positive results and therefore cannot be recommended for routine clinical practice. Couples with unexplained infertility might be reassured that even after 12 months of unsuccessful attempts, 50% will conceive in the following 12 months and another 12% in the year after.

Retrospective Validation of a Surveillance System for Unexplained Illness and Death: New Haven County, Connecticut

PubMed Central

Kluger, Michael D.; Sofair, Andre N.; Heye, Constance J.; Meek, James I.; Sodhi, Rajesh K.; Hadler, James L.

2001-01-01

Objectives. This study investigated retrospective validation of a prospective surveillance system for unexplained illness and death due to possibly infectious causes. Methods. A computerized search of hospital discharge data identified patients with potential unexplained illness and death due to possibly infectious causes. Medical records for such patients were reviewed for satisfaction of study criteria. Cases identified retrospectively were combined with prospectively identified cases to form a reference population against which sensitivity could be measured. Results. Retrospective validation was 41% sensitive, whereas prospective surveillance was 73% sensitive. The annual incidence of unexplained illness and death due to possibly infectious causes during 1995 and 1996 in the study county was conservatively estimated to range from 2.7 to 6.2 per 100 000 residents aged 1 to 49 years. Conclusions. Active prospective surveillance for unexplained illness and death due to possibly infectious causes is more sensitive than retrospective surveillance conducted through a published list of indicator codes. However, retrospective surveillance can be a feasible and much less labor-intensive alternative to active prospective surveillance when the latter is not possible or desired. PMID:11499106

Effectiveness of a Blended Multidisciplinary Intervention for Patients with Moderate Medically Unexplained Physical Symptoms (PARASOL): Protocol for a Cluster Randomized Clinical Trial.

PubMed

van Westrienen, Paula Elisabeth; Pisters, Martijn F; Toonders, Suze Aj; Gerrits, Marloes; Veenhof, Cindy; de Wit, Niek J

2018-05-08

Medically unexplained physical symptoms are an important health problem in primary care, with a spectrum from mild to chronic. The burden of chronic medically unexplained physical symptoms is substantial for patients, health care professionals, and society. Therefore, early identification of patients with moderate medically unexplained physical symptoms is needed in order to prevent chronicity. The preventive screening of medically unexplained physical symptoms (PRESUME) screening method was developed using data from the electronic medical record of the patients' general practitioner and demonstrated its prognostic accuracy to identify patients with moderate medically unexplained physical symptoms. In the next step, we developed a proactive blended and integrated mental health and physical therapy intervention program (PARASOL) to reduce complaints of moderate medically unexplained physical symptoms, stimulate self-management, and prevent chronicity. The primary objective of this study is to investigate the effectiveness of the blended PARASOL intervention on the impact of symptoms and quality of life in patients with moderate medically unexplained physical symptoms compared with usual care. Secondary objectives are to study the effect on severity of physical and psychosocial symptoms, general health, physical behavior, illness perception, and self-efficacy in patients with moderate medically unexplained physical symptoms as well as to determine the cost-effectiveness of the program. This paper presents the study protocol of a multicenter cluster randomized clinical trial. Adult patients with moderate medically unexplained physical symptoms will be identified from electronic medical record data using the PRESUME screening method and proactively recruited for participation in the study. Cluster randomization will be performed at the level of the participating health care centers. In total 248 patients with moderate medically unexplained physical symptoms (124 patients per arm) are needed. The PARASOL intervention is a 12-week blended primary care program consisting of 4 face-to-face consultations with the mental health nurse and 5 physical therapy sessions, supplemented with a Web-based program. The Web-based program contains (1) information modules and videos on self-management and educative themes, (2) videos and instructions on prescribed home exercises, and (3) assignments to gradually increase the physical activity. The program is directed at patients' perception of symptoms as well as modifiable prognostic risk factors for chronicity using therapeutic neuroscience education. It encourages self-management, as well as an active lifestyle using a cognitive behavioral approach and graded activity. Primary outcomes are impact of symptoms and quality of life. Secondary outcomes are severity of physical and psychosocial symptoms, general health, physical behavior, illness perceptions, self-efficacy, and cost-effectiveness. All measurements will be performed at baseline, 3 and 12 months after baseline. Retrospective cost questionnaires will also be sent at 6 and 9 months after baseline and these will be used for the cost-effectiveness analysis. The intervention has been developed, and the physical therapists and mental health nurses in the participating experimental health care centers have received two days of training on the content of the blended PARASOL intervention. The recruitment of health care centers started in June 2016 and inclusion of patients began in March 2017. Follow-up assessments of patients are expected to be completed in March 2019. This study is the first randomized clinical trial to determine the effectiveness (including cost-effectiveness) of a proactive, blended, and integrated mental health and physical therapy care program for patients with moderate medically unexplained physical symptoms. The findings will help to improve the treatment for patients with moderate medically unexplained physical symptoms and prevent chronicity. Netherlands Trial Register NTR6755; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6755 (Archived by WebCite at http://www.webcitation.org/6ywporY7u). ©Paula Elisabeth van Westrienen, Martijn F Pisters, Suze AJ Toonders, Marloes Gerrits, Cindy Veenhof, Niek J de Wit. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 08.05.2018.

Somatization disorders in dermatology.

PubMed

Gupta, Madhulika A

2006-02-01

This paper reviews a wide range of somatization-related symptoms that are encountered in dermatology. These include the unexplained cutaneous sensory syndromes especially the cutaneous dysesthesias associated with pain, numbness and pruritus; traumatic memories in post-traumatic stress disorder (PTSD) which are experienced on a sensory level as 'body memories' and may present as local or generalized pruritic states, urticaria and angioedema; and unexplained flushing reactions and profuse perspiration, in addition to unexplained exacerbations of stress-reactive dermatoses such as psoriasis and atopic eczema secondary to the autonomic hyperarousal in PTSD; classic 'pseudoneurologic' symptoms associated with dissociation including unexplained loss of touch or pain, in addition to the self-induced dermatoses such as dermatitis artefacta and trichotillomania that are encountered with dissociative states; and body dysmorphic disorder where the patient often presents with a somatic preoccupation involving the skin or hair.

Natural and Undetermined Sudden Death: Value of Post-Mortem Genetic Investigation

PubMed Central

Fernández-Falgueras, Anna; Sarquella-Brugada, Georgia; Cesar, Sergi; Mademont, Irene; Mates, Jesus; Pérez-Serra, Alexandra; Coll, Monica; Pico, Ferran; Iglesias, Anna; Tirón, Coloma; Allegue, Catarina; Carro, Esther; Gallego, María Ángeles; Ferrer-Costa, Carles; Hospital, Anna; Bardalet, Narcís; Borondo, Juan Carlos; Vingut, Albert; Arbelo, Elena; Brugada, Josep; Castellà, Josep; Medallo, Jordi; Brugada, Ramon

2016-01-01

Background Sudden unexplained death may be the first manifestation of an unknown inherited cardiac disease. Current genetic technologies may enable the unraveling of an etiology and the identification of relatives at risk. The aim of our study was to define the etiology of natural deaths, younger than 50 years of age, and to investigate whether genetic defects associated with cardiac diseases could provide a potential etiology for the unexplained cases. Methods and Findings Our cohort included a total of 789 consecutive cases (77.19% males) <50 years old (average 38.6±12.2 years old) who died suddenly from non-violent causes. A comprehensive autopsy was performed according to current forensic guidelines. During autopsy a cause of death was identified in most cases (81.1%), mainly due to cardiac alterations (56.87%). In unexplained cases, genetic analysis of the main genes associated with sudden cardiac death was performed using Next Generation Sequencing technology. Genetic analysis was performed in suspected inherited diseases (cardiomyopathy) and in unexplained death, with identification of potentially pathogenic variants in nearly 50% and 40% of samples, respectively. Conclusions Cardiac disease is the most important cause of sudden death, especially after the age of 40. Close to 10% of cases may remain unexplained after a complete autopsy investigation. Molecular autopsy may provide an explanation for a significant part of these unexplained cases. Identification of genetic variations enables genetic counseling and undertaking of preventive measures in relatives at risk. PMID:27930701

Screening for Chlamydia trachomatis in Egyptian women with unexplained infertility, comparing real-time PCR techniques to standard serology tests: case control study.

PubMed

Abdella, Rana M A; Abdelmoaty, Hatem I; Elsherif, Rasha H; Sayed, Ahmed Mahmoud; Sherif, Nadine Alaa; Gouda, Hisham M; El Lithy, Ahmed; Almohamady, Maged; Abdelbar, Mostafa; Hosni, Ahmed Naguib; Magdy, Ahmed; Ma, Youssef

2015-06-02

To study the prevalence of Chlamydia infection in women with primary and secondary unexplained infertility using ELISA technique for antibody detection and real time, fully automated PCR for antigen detection and to explore its association with circulating antisperm antibodies (ASA). A total of 50 women with unexplained infertility enrolled in this case control study and a control group of 44 infertile women with a known cause of infertility. Endocervical specimens were collected for Chlamydia antigen detection using PCR and serum samples for antibodies detection. Circulating anti-sperm antibodies were detected using sperm antibody Latex Agglutination tests. The overall prevalence of Chlamydial infection in unexplained infertility cases as detected by both ELISA and PCR was 40 % (20/50). The prevalence of current Chlamydial genital infection as detected by real-time PCR was only 6.0 % (3/50); two of which were also IgM positive. Prevalence of ASA was 6.0 % (3/50); all were sero-negative for anti-C.trachomatis IgM and were PCR negative. The incidence of Chlamydial infection in Egyptian patients with unexplained infertility is relatively high. In the setting of fertility investigations; screening for anti. C.trachomatis antibodies using ELISA, and treatment of positive cases should be considered. The presence of circulating ASA does not correlate with the presence of old or current Chlamydia infection in women with unexplained infertility.

Unexplained Cases of Allergic Reactions Linked to Red Meat

MedlinePlus

... that starts after being bitten by a lone star tick may cause unexplained cases of recurrent anaphylaxis. ... after eating meat. Previous studies have linked lone star tick bites to this unusual food allergy. The ...

Gardner-Diamond syndrome: Difficulties in the management of patients with unexplained medical symptoms

PubMed Central

Meeder, Robert; Bannister, Susan

2006-01-01

The case of an adolescent girl who presented with unexplained bruising is reported. Subsequent investigations failed to elucidate an organic etiology. The diagnosis of Gardner-Diamond syndrome – a syndrome of predictable bruising preceded by pain and warmth at the bruise site, often associated with physical or psychosocial stress – was made. In the present report, the authors use their experience with this rare syndrome to highlight some important ethical and practical considerations with regard to investigation, treatment and communication in illnesses with unexplained medical symptoms. PMID:19030312

A case of anorexia nervosa in an elderly man.

PubMed

Malik, Fahd; Wijayatunga, Uditha; Bruxner, George M

2014-06-01

To explore aspects of anorexia nervosa occurring in older populations, especially men, by reviewing the literature and presenting a case study of an elderly man with unexplained vomiting and weight loss. The literature is reviewed and an illustrative case study of an elderly man with unexplained vomiting and weight loss is described. Anorexia nervosa is an uncommon cause of unexplained weight loss in the elderly, but may be under-recognized and associated with a high level of mortality. © The Royal Australian and New Zealand College of Psychiatrists 2014.

A novel lable-free electrochemical immunosensor for carcinoembryonic antigen based on gold nanoparticles-thionine-reduced graphene oxide nanocomposite film modified glassy carbon electrode.

PubMed

Kong, Fen-Ying; Xu, Mao-Tian; Xu, Jing-Juan; Chen, Hong-Yuan

2011-10-15

In this paper, gold nanoparticle-thionine-reduced graphene oxide (GNP-THi-GR) nanocomposites were prepared to design a label-free immunosensor for the sensitive detection of carcinoembryonic antigen (CEA). The nanocomposites with good biocompatibility, excellent redox electrochemical activity and large surface area were coated onto the glassy carbon electrode (GCE) surface and then CEA antibody (anti-CEA) was immobilized on the electrode to construct the immunosensor. The morphologies and electrochemistry of the formed nanocomposites were investigated by using scanning electron microscopy (SEM), ultraviolet-visible (UV-vis) spectrometry, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). CV and differential pulse voltammetry (DPV) studies demonstrated that the formation of antibody-antigen complexes decreased the peak current of THi in the GNP-THi-GR nanocomposites. The decreased currents were proportional to the CEA concentration in the range of 10-500 pg/mL with a detection limit of 4 pg/mL. The proposed method was simple, fast and inexpensive for the determination of CEA at very low levels. Copyright © 2011 Elsevier B.V. All rights reserved.

Induction of carcinoembryonic antigen expression in a three-dimensional culture system

NASA Technical Reports Server (NTRS)

Jessup, J. M.; Brown, D.; Fitzgerald, W.; Ford, R. D.; Nachman, A.; Goodwin, T. J.; Spaulding, G.

1994-01-01

MIP-101 is a poorly differentiated human colon carcinoma cell line established from ascites that produces minimal amounts of carcinoembryonic antigen (CEA), a 180 kDa glycoprotein tumor marker, and nonspecific cross-reacting antigen (NCA), a related protein that has 50 and 90 kDa isoforms, in vitro in monolayer culture. MIP-101 produces CEA when implanted into the peritoneum of nude mice but not when implanted into subcutaneous tissue. We tested whether MIP-101 cells may be induced to express CEA when cultured on microcarrier beads in three-dimensional cultures, either in static cultures as non-adherent aggregates or under dynamic conditions in a NASA-designed low shear stress bioreactor. MIP- 101 cells proliferated well under all three conditions and increased CEA and NCA production 3 - 4 fold when grown in three-dimensional cultures compared to MIP-101 cells growing logarithmically in monolayers. These results suggest that three-dimensional growth in vitro simulates tumor function in vivo and that three-dimensional growth by itself may enhance production of molecules that are associated with the metastatic process.

Reference Intervals of Alpha-Fetoprotein and Carcinoembryonic Antigen in the Apparently Healthy Population.

PubMed

Zhang, Gao-Ming; Guo, Xu-Xiao; Ma, Xiao-Bo; Zhang, Guo-Ming

2016-12-12

BACKGROUND The aim of this study was to calculate 95% reference intervals and double-sided limits of serum alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) according to the CLSI EP28-A3 guideline. MATERIAL AND METHODS Serum AFP and CEA values were measured in samples from 26 000 healthy subjects in the Shuyang area receiving general health checkups. The 95% reference intervals and upper limits were calculated by using MedCalc. RESULTS We provided continuous reference intervals from 20 years old to 90 years old for AFP and CEA. The reference intervals were: AFP, 1.31-7.89 ng/ml (males) and 1.01-7.10 ng/ml (females); CEA, 0.51-4.86 ng/ml (males) and 0.35-3.45ng/ml (females). AFP and CEA were significantly positively correlated with age in both males (r=0.196 and r=0.198) and females (r=0.121 and r=0.197). CONCLUSIONS Different races or populations and different detection systems may result in different reference intervals for AFP and CEA. Continuous reference intervals of age changes are more accurate than age groups.

[History of tumor markers for cancers of the digestive system].

PubMed

Buzás, György Miklós

2013-05-26

Tumor markers are gene products which signal the occurrence of tumors in different organs as well as their response to surgery and chemotherapy. The discovery of tumor markers occurred after the demonstration of tumor-specific transplantation antigens in chemically or virally induced tumors in syngenic rodents. The history of currently used tumor markers began in the 1940s, the first discovered being alpha-fetoprotein in 1956, followed by that of carcinoembryonic antigen in 1965. Since then the range of tumor markers has widened continously. Their chemical structure and genetics is now well known. Some may play part in tumor growth and development of metastases. The potential uses of tumor markers are general or high risk population screening, adjunct in diagnosis of cancer, preoperative indicator of tumor burden, indicator of therapeutic success, evidence of postoperative recurrences and use in tumor localization. However, there is no ideal tumor marker fulfilling all the criteria. Isotope-labeled anti-carcinoembryonic antigen antibodies and small molecular E-selectin inhibitors could play a role in the molecular radio- and chemotherapy of colon and pancreatic carcinomas.

Polyaniline modified flexible conducting paper for cancer detection

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

Kumar, Saurabh; Sen, Anindita; Kumar, Suveen

We report results of studies relating to the fabrication of a flexible, disposable, and label free biosensing platform for detection of the cancer biomarker (carcinoembryonic antigen, CEA). Polyaniline (PANI) has been electrochemically deposited over gold sputtered paper (Au@paper) for covalent immobilization of monoclonal carcinoembryonic antibodies (anti-CEA). The bovine serum albumin (BSA) has been used for blocking nonspecific binding sites at the anti-CEA conjugated PANI/Au@Paper. The PANI/Au@Paper, anti-CEA/PANI/Au@Paper, and BSA/anti-CEA/PANI/Au@Paper platforms have been characterized using scanning electron microscopy, X-ray diffraction, Fourier transmission infrared spectroscopy, chronoamperometry, and electrochemical impedance techniques. The results of the electrochemical response studies indicate that this BSA/anti-CEA/PANI/Au@paper electrodemore » has sensitivity of 13.9 μA ng{sup −1} ml cm{sup 2}, shelf life of 22 days, and can be used to estimate CEA in the range of 2–20 ng ml{sup −1}. This paper sensor has been validated by detection of CEA in serum samples of cancer patients via immunoassay technique.« less

Kinetics of anti-carcinoembryonic antigen antibody internalization: effects of affinity, bivalency, and stability

PubMed Central

Schmidt, Michael M.; Thurber, Greg M.

2010-01-01

Theoretical analyses suggest that the cellular internalization and catabolism of bound antibodies contribute significantly to poor penetration into tumors. Here we quantitatively assess the internalization of antibodies and antibody fragments against the commonly targeted antigen carcinoembryonic antigen (CEA). Although CEA is often referred to as a non-internalizing or shed antigen, anti-CEA antibodies and antibody fragments are shown to be slowly endocytosed by LS174T cells with a half-time of 10–16 h, a time scale consistent with the metabolic turnover rate of CEA in the absence of antibody. Anti-CEA single chain variable fragments (scFvs) with significant differences in affinity, stability against protease digestion, and valency exhibit similar uptake rates of bound antibody. In contrast, one anti-CEA IgG exhibits unique binding and trafficking properties with twice as many molecules bound per cell at saturation and significantly faster cellular internalization after binding. The internalization rates measured herein can be used in simple computational models to predict the microdistribution of these antibodies in tumor spheroids. PMID:18408925

Hexapeptide fragment of carcinoembryonic antigen which acts as an agonist of heterogeneous ribonucleoprotein M.

PubMed

Palermo, Nicholas Y; Thomas, Peter; Murphy, Richard F; Lovas, Sándor

2012-04-01

Colorectal cancers with metastatic potential secrete the glycoprotein carcinoembryonic antigen (CEA). CEA has been implicated in colorectal cancer metastasis by inducing Kupffer cells to produce inflammatory cytokines which, in turn, make the hepatic micro-environment ideal for tumor cell implantation. CEA binds to the heterogeneous ribonucleoprotein M (hnRNP M) which acts as a cell surface receptor in Kupffer cells. The amino acid sequence in CEA, which binds the hnRNP M receptor, is Tyr-Pro-Glu-Leu-Pro-Lys. In this study, the structure of Ac-Tyr-Pro-Glu-Leu-Pro-Lys-NH₂ (YPELPK) was investigated using electronic circular dichroism, vibrational circular dichroism, and molecular dynamics simulations. The binding of the peptide to hnRNP M was also investigated using molecular docking calculations. The biological activity of YPELPK was studied using differentiated human THP-1 cells, which express hnRNP M on their surface and secrete IL-6 when stimulated by CEA. YPELPK forms a stable polyproline-II helix and stimulates IL-6 production of THP-1 cells at micromolar concentrations. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

Nanogold-enwrapped graphene nanocomposites as trace labels for sensitivity enhancement of electrochemical immunosensors in clinical immunoassays: Carcinoembryonic antigen as a model.

PubMed

Zhong, Zhaoyang; Wu, Wei; Wang, Dong; Wang, Dan; Shan, Jinlu; Qing, Yi; Zhang, Zhimin

2010-06-15

A new, highly sensitive electrochemical immunosensor with a sandwich-type immunoassay format was designed to quantify carcinoembryonic antigen (CEA), as a model tumor marker, using nanogold-enwrapped graphene nanocomposites (NGGNs) as trace labels in clinical immunoassays. The device consisted of a glassy carbon electrode coated with Prussian Blue (PB) on whose surface gold nanoparticles were electrochemically deposited to the further modified with the specific analyte-capturing molecule, anti-CEA antibodies. The immunoassay was performed using horseradish peroxidase (HRP)-conjugated anti-CEA as secondary antibodies attached on the NGGN surface (HRP-anti-CEA-NGGN). The method using HRP-anti-CEA-NGGNs as detection antibodies shows high signal amplification, and exhibits a dynamic working range of 0.05-350 ng/mL with a low detection limit of 0.01 ng/mL CEA (at 3s). The assayed results of serum samples with the sensor received an acceptable agreement with the reference values. Importantly, the methodology provides a promising ultrasensitive assay strategy for clinical applications. Copyright 2010 Elsevier B.V. All rights reserved.

Gestational age of pregnancy loss in women with unexplained recurrent miscarriage.

PubMed

Ticconi, Carlo; Giuliani, Emma; Sorge, Roberto; Patrizi, Lodovico; Piccione, Emilio; Pietropolli, Adalgisa

2016-03-01

The aim of this study was to investigate the gestational age (GA) of pregnancy loss in women with unexplained recurrent miscarriage (RM) and to determine whether the miscarriages occur at similar GA in RM women. This retrospective study was carried out in a university hospital and included 288 women with unexplained RM. The GA at which each miscarriage occurred was carefully determined. Overall, 739 miscarriages were analyzed. RM women had miscarriages at a median GA of 7 weeks (range: 3-20). In RM women, 47.2% (n = 136) experienced miscarriages within a 1-week range of GA and 53.4% (n = 154) had miscarriages in the same period of fetal development (pre-embryonic, embryonic or fetal). Women with unexplained RM tend to have miscarriages at the same GA, which is characteristic for each patient. © 2015 Japan Society of Obstetrics and Gynecology.

Unexplained chronic leukopenia treated with oral iron supplements.

PubMed

Abuirmeileh, Ayman; Bahnassi, Anas; Abuirmeileh, Amjad

2014-04-01

A 67-year-old woman known to have iron deficiency anemia and persistent unexplained chronic leukopenia was cared for by our medical center for about 16 years. During this period she was examined thoroughly and diagnosed to have chronic idiopathic neutropenia (also known as chronic benign neutropenia). Her iron deficiency was attributed to nutritional factors and she was non-compliant with her oral iron supplements. The patient fully received her iron supplement medication by nursing staff for two and a half months during an unexpected prolonged hospital stay after her suffering an acute ischemic cerebrovascular accident. An astonishing outcome was that in addition to having her iron deficiency anemia treated, her long-term unexplained neutropenia was also corrected. Some patients diagnosed with chronic idiopathic neutropenia and clinically present as having unexplained chronic neutropenia might actually be suffering from a form of not yet described iron deficiency induced neutropenia.

Natural history of metastatic biliary tract cancer (BTC) patients with good performance status (PS) who were treated with only best supportive care (BSC).

PubMed

Ji, Jun Ho; Song, Haa-Na; Kim, Rock Bum; Oh, Sung Yong; Lim, Ho Yeong; Park, Joon Oh; Park, Se Hoon; Kim, Moon Jin; Lee, Soon Il; Ryou, Sung Hyeok; Hwang, In Gyu; Jang, Joung-Soon; Kim, Hong Jun; Choi, Jun Young; Kang, Jung-Hun

2015-03-01

Although chemotherapy is widely recommended for patients with metastatic biliary tract cancer, the natural course of these patients, especially those with good performance status who are indicated for chemotherapy, is not known. We retrospectively reviewed patients with metastatic or locally advanced biliary cancer who were diagnosed at six cancer centers. Patients were eligible if they had good performance (ECOG 0-2) and no history of any treatment for cancer. The primary objective was to evaluate the survival time of patients with advanced biliary cancer with good performance who were untreated. Of the 1677 patients, 204 met the inclusion criteria. The median age and overall survival were 72.0 years and 7.1 months. Overall survival (months) by location was 4.7 for intrahepatic, 9.7 for extrahepatic, 4.4 for gallbladder and 11.2 for ampulla of vater cancer. In subgroup analysis, overall survival of locally advanced biliary cancer was 13.8 months and that of patients with normal carcinoembryonic antigen/carbohydrate antigen 19-9 was 10.6 months. In multivariate analysis, variables that were associated with poor prognosis were metastatic biliary cancer [hazard ratio 2.19 (P = 0.001)], high baseline carcinoembryonic antigen level (defined as >4.0 ng/ml) [hazard ratio 1.51 (P = 0.024)] and high baseline carbohydrate antigen 19-9 level (defined as >100 U/ml) [hazard ratio 1.93 (P = 0.001)]. Advanced biliary tract cancer with good performance status showed modest survival without any treatment. Furthermore, subgroup analysis showed that patients with normal carbohydrate antigen 19-9 or carcinoembryonic antigen level or locally advanced status had favorable survival. Further studies comparing the outcome of chemotherapy with that of best supportive care in patients with unresectable biliary tract cancer are warranted. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Unexplained cough: it is time to rule out Sjogren's syndrome.

PubMed

Koslow, Matthew; Kivity, Shaye; Vishnevskia-Dai, Vicktoria; Ben-Dov, Issahar

2018-05-01

Sjogren's syndrome is associated with chronic cough, but sicca symptoms are missing from cough evaluation guidelines. We evaluated patients with unexplained cough for undiagnosed Sjogren's syndrome. Patients referred to our pulmonary clinic (Sheba Medical Center, 2009 to 2012) with unexplained cough and concomitant dry eyes were selected for evaluation. Unexplained cough was defined as chronic cough of unknown etiology despite algorithm-based evaluation and treatment. Patients were evaluated in a dedicated clinic by a pulmonologist, rheumatologist, and ophthalmologist specializing in autoimmune disease. Patients completed the Leicester Cough Questionnaire, spirometry, antibody testing for anti Ro/La, ophthalmologic examination with visual acuity, eyelid, ocular surface fluorescein staining, tear break-up time and Schirmer's test, full slit lamp, and fundus examinations. Four-year follow-up was conducted by telephone questionnaire. We identified 24 patients among which 22 (21 females) agreed for evaluation. Eight patients (36%), seven initially, and one during follow-up were diagnosed with Sjogren's syndrome (SS) (six secondary and two primary SS). At 4-year follow-up, cough tended to persist and improve in only 37% with SS. These include 2 (Scl and RA) who received rituximab and 1 (stage 1 sarcoidosis) with spontaneous improvement. In contrast, cough improved in most (64%) patients without SS; the majority (eight/nine) report intensified disease-specific treatment (five allergic and three GERD). We describe patients in whom unexplained chronic cough was associated with dry eyes. Focused workup revealed undiagnosed Sjogren's syndrome in 36%. Dry eyes, with or without SS, is under-recognized and should be added to diagnostic algorithms for unexplained cough.

Aerodynamic drag crisis and its possible effect on the flight of baseballs

NASA Astrophysics Data System (ADS)

Frohlich, Cliff

1984-04-01

At Reynolds numbers above about 105 the aerodynamic drag force on a sphere drops sharply as the flow begins to become turbulent in the boundary layer. For baseballs, this ``drag crisis'' may occur at speeds which are typical for pitched or batted balls. The effects of the drag reduction on the behavior of both pitched and batted balls is significant, and may explain several features of the game of baseball which previously have been unexplained or attributed to other causes. In particular, the drag reduction may help to explain why pitched fastballs appear to rise, why pitched curve balls appear to drop sharply, and why home run production has increased since the introduction of the alleged ``lively ball.'' Calculations suggest that aerodynamic forces are as important a factor in fastpitch softball as in baseball, and that they are a critical factor in a number of other ball games.

Immediate-type hypersensitivity reactions and hypnosis: problems in methodology.

PubMed

Laidlaw, T M; Richardson, D H; Booth, R J; Large, R G

1994-08-01

Hypnosis has been used to ameliorate skin test reactivity in studies dating back to the 1930s. This study using modern methodology and statistical analyses sets out to test the hypothesis that it was possible to decrease reactions to histamine by hypnotic suggestion. Five subjects, all asthmatic and untrained in hypnosis, were given three hypnotic sessions where they were asked to control their reactions to histamine administered by the Pepys technique to forearm skin. These sessions were to be compared with three non-hypnotic sessions. The flare sizes but not wheal sizes were found to be significantly reduced after the hypnosis sessions, compared to sessions without hypnosis. Skin temperature was correlated with the size of reactions. The day upon which the sessions took place contributed significant amounts of the remaining unexplained variance, giving rise to questions about what could cause these day to day changes.

Carfilzomib and the cardiorenal system in myeloma: an endothelial effect?

PubMed Central

Rosenthal, A; Luthi, J; Belohlavek, M; Kortüm, K M; Mookadam, F; Mayo, A; Fonseca, R; Bergsagel, P L; Reeder, C B; Mikhael, J R; Stewart, A K

2016-01-01

Carfilzomib (Cfz) has been associated with an ~5% incidence of unexplained and unpredictable cardiovascular toxicity in clinical trials. We therefore implemented a detailed, prospective, clinical cardiac and renal evaluation of 62 Cfz-treated myeloma patients, including serial blood pressure (BP), creatinine, troponin, NT-proBNP and pre- and post-treatment echocardiograms, including ejection fraction (EF), average global longitudinal strain and compliance. Pre-treatment elevations in NT-proBNP and BP, as well as abnormal cardiac strain were common. A rise in NT-proBNP occurred frequently post-treatment often without corresponding cardiopulmonary symptoms. A rise in creatinine was common, lessened with hydration and often reversible. All patients had a normal EF pre-treatment. Five patients experienced a significant cardiac event (four decline in EF and one myocardial infarction), of which 2 (3.2%) were considered probably attributable to Cfz. None were rechallenged with Cfz. The ideal strategy for identifying patients at risk for cardiac events, and parameters by which to monitor for early toxicity have not been established; however, it appears baseline echocardiographic testing is not consistently predictive of toxicity. The toxicities observed suggest an endothelial mechanism and further clinical trials are needed to determine whether or not this represents a class effect or is Cfz specific. PMID:26771810

Tectonic-driven climate change and the diversification of angiosperms

PubMed Central

Chaboureau, Anne-Claire; Sepulchre, Pierre; Donnadieu, Yannick; Franc, Alain

2014-01-01

In 1879, Charles Darwin characterized the sudden and unexplained rise of angiosperms during the Cretaceous as an “abominable mystery.” The diversification of this clade marked the beginning of a rapid transition among Mesozoic ecosystems and floras formerly dominated by ferns, conifers, and cycads. Although the role of environmental factors has been suggested [Coiffard C, Gómez B (2012) Geol Acta 10(2):181–188], Cretaceous global climate change has barely been considered as a contributor to angiosperm radiation, and focus was put on biotic factors to explain this transition. Here we use a fully coupled climate model driven by Mesozoic paleogeographic maps to quantify and discuss the impact of continental drift on angiosperm expansion and diversification. We show that the decrease of desertic belts between the Triassic and the Cretaceous and the subsequent onset of long-lasting humid conditions during the Late Cretaceous were driven by the breakup of Pangea and were contemporaneous with the first rise of angiosperm diversification. Positioning angiosperm-bearing fossil sites on our paleobioclimatic maps shows a strong match between the location of fossil-rich outcrops and temperate humid zones, indicating that climate change from arid to temperate dominance may have set the stage for the ecological expansion of flowering plants. PMID:25225405

38 CFR 3.212 - Unexplained absence for 7 years.

Code of Federal Regulations, 2010 CFR

2010-07-01

... continued and unexplained absence of any individual from his or her home and family for a period of 7 years or more and that a diligent search disclosed no evidence of his or her existence after the date of...

38 CFR 3.212 - Unexplained absence for 7 years.

Code of Federal Regulations, 2013 CFR

2013-07-01

... continued and unexplained absence of any individual from his or her home and family for a period of 7 years or more and that a diligent search disclosed no evidence of his or her existence after the date of...

38 CFR 3.212 - Unexplained absence for 7 years.

Code of Federal Regulations, 2014 CFR

2014-07-01

... continued and unexplained absence of any individual from his or her home and family for a period of 7 years or more and that a diligent search disclosed no evidence of his or her existence after the date of...

38 CFR 3.212 - Unexplained absence for 7 years.

Code of Federal Regulations, 2011 CFR

2011-07-01

... continued and unexplained absence of any individual from his or her home and family for a period of 7 years or more and that a diligent search disclosed no evidence of his or her existence after the date of...

38 CFR 3.212 - Unexplained absence for 7 years.

Code of Federal Regulations, 2012 CFR

2012-07-01

... continued and unexplained absence of any individual from his or her home and family for a period of 7 years or more and that a diligent search disclosed no evidence of his or her existence after the date of...

Unexplained Absences and Risk of Death and Injury Among Nursing Home Residents: A Systematic Review.

PubMed

Woolford, Marta H; Weller, Carolina; Ibrahim, Joseph E

2017-04-01

Unexplained absence of nursing home (NH) residents is one of the most challenging issues related to the care of older people. The aim of this review was to examine the death and injury outcomes of unexplained absence of NH residents. We searched MEDLINE, CINAHL, EMBASE, PsycINFO, AgeLine, and Cochrane Library to identify qualitative and quantitative studies published in the English language. Data on death and injury were collated, and aggregate proportions were calculated where possible. Nine studies were identified; most (n = 6) were conducted in the United States. Persons with dementia formed the study population in all studies. There were 1440 individual unexplained absences reported across the 9 studies. We calculated a rate of 82 deaths and 61 injuries per 1000 incidents of unexplained absence. Extreme temperatures were the most common cause of death. Most individuals left by foot, and were found within a 1-mile radius of place last seen in green vegetation and waterways. This review provides valuable insight into death and injury outcomes. Further studies are recommended to improve understanding and prevent adverse outcomes. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Physician Satisfaction in Treating Medically Unexplained Symptoms.

PubMed

Brauer, Simon G; Yoon, John D; Curlin, Farr A

2017-05-01

To determine whether treating conditions having medically unexplained symptoms is associated with lower physician satisfaction and higher ascribed patient responsibility, and to determine whether higher ascribed patient responsibility is associated with lower physician satisfaction in treating a given condition. We surveyed a nationally representative sample of 1504 US primary care physicians. Respondents were asked how responsible patients are for two conditions with more-developed medical explanations (depression and anxiety) and two conditions with less-developed medical explanations (chronic back pain and fibromyalgia), and how much satisfaction they experienced in treating each condition. We used Wald tests to compare mean satisfaction and ascribed patient responsibility between medically explained conditions and medically unexplained conditions. We conducted single-level and multilevel ordinal logistic models to test the relation between ascribed patient responsibility and physician satisfaction. Treating medically unexplained conditions elicited less satisfaction than treating medically explained conditions (Wald P < 0.001). Physicians attribute significantly more patient responsibility to the former (Wald P < 0.005), although the magnitude of the difference is small. Across all four conditions, physicians reported experiencing less satisfaction when treating symptoms that result from choices for which patients are responsible (multilevel odds ratio 0.57, P = 0.000). Physicians experience less satisfaction in treating conditions characterized by medically unexplained conditions and in treating conditions for which they believe the patient is responsible.

Comprehensive analysis of immune, extracellular matrices and pathogens profile in lung granulomatosis of unexplained etiology.

PubMed

da Costa Souza, Paola; Dondo, Patrícia Suemi; Souza, Gabriela; Lopes, Deborah; Moscardi, Marcel; de Miranda Martinho, Vinicius; de Mattos Lourenço, Rodolfo Daniel; Prieto, Tabatha; Balancin, Marcelo Luiz; Assato, Aline Kawassaki; Teodoro, Walcy Rosolia; Rodrigues, Silvia; Lima, Mariana; Castellano, Maria Vera; Coletta, Ester; Parra, Edwin Roger; Capelozzi, Vera Luiza

2018-05-01

This study analyzed the type 1 and type 2T helper (Th1/Th2) cytokines (including interleukins), immune cellular, matrix profile, and pathogens in granulomas with unexplained etiology compared to those with infectious and noninfectious etiology. Surgical lung biopsies from 108 patients were retrospectively reviewed. Histochemistry, immunohistochemistry, immunofluorescence, morphometry and polymerase chain reaction were used, respectively, to evaluate total collagen and elastin fibers, collagen I and III, immune cells, cytokines, matrix metalloproteinase-9, myofibroblasts, and multiple usual and unusual pathogens. No relevant polymerase chain reaction expression was found in unexplained granulomas. A significant difference was found between the absolute number of eosinophils, macrophages, and lymphocytes within granulomas compared to uninvolved lung tissue. Granulomas with unexplained etiology (UEG) presented increased number of eosinophils and high expression of interleukins (ILs) IL-4/IL-5 and transforming growth factor-β. In sarcoidosis, CD4/CD8 cell number was significantly higher within and outside granulomas, respectively; the opposite was detected in hypersensitivity pneumonitis. Again, a significant difference was found between the high number of myofibroblasts and matrix metalloproteinase-9 in UEG, hypersensitivity pneumonitis, and sarcoidosis compared to granulomas of tuberculosis. Granulomas of paracoccidioisis exhibited increased type I collagen and elastic fibers. Th1 immune cellular profile was similar among granulomas with unexplained, infectious, and noninfectious etiology. In contrast, modulation of Th2 and matrix remodeling was associated with more fibroelastogenesis and scarring of lung tissue in UEG compared to infectious and noninfectious. We concluded that IL-4/IL-5 and transforming growth factor-β might be used as surrogate markers of early fibrosis, reducing the need for genotyping, and promise therapeutic target in unexplained granulomas. Copyright © 2018 Elsevier Inc. All rights reserved.

Sexual function in infertile women with polycystic ovary syndrome and unexplained infertility.

PubMed

Diamond, Michael P; Legro, Richard S; Coutifaris, Christos; Alvero, Ruben; Robinson, Randal D; Casson, Peter A; Christman, Gregory M; Huang, Hao; Hansen, Karl R; Baker, Valerie; Usadi, Rebecca; Seungdamrong, Aimee; Bates, G Wright; Rosen, R Mitchell; Schlaff, William; Haisenleder, Daniel; Krawetz, Stephen A; Barnhart, Kurt; Trussell, J C; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

2017-08-01

While female sexual dysfunction is a frequent occurrence, characteristics in infertile women are not well delineated. Furthermore, the impact of infertility etiology on the characteristics in women with differing androgen levels observed in women with polycystic ovary syndrome and unexplained infertility has not been assessed. The objective of the study was to determine the characteristics of sexual dysfunction in women with polycystic ovary syndrome and unexplained infertility. A secondary data analysis was performed on 2 of Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Networks clinical trials: Pregnancy in Polycystic Ovary Syndrome Study II and Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation. Both protocols assessed female sexual function using the Female Sexual Function Inventory and the Female Sexual Distress Scale. Women with polycystic ovary syndrome had higher weight and body mass index than women with unexplained infertility (each P < .001), greater phenotypic (Ferriman-Gallwey hirsutism score, sebum score, and acne score; each P < .001), and hormonal (testosterone, free testosterone, and dehydroepiandrosterone; each P < .001) evidence of androgen excess. Sexual function scores, as assessed by the Female Sexual Function Inventory, were nearly identical. The Female Sexual Distress Scale total score was higher in women with polycystic ovary syndrome. The mean Female Sexual Function Inventory total score increased slightly as the free androgen index increased, mainly as a result of the desire subscore. This association was more pronounced in the women with unexplained infertility. Reproductive-age women with infertility associated with polycystic ovary syndrome and unexplained infertility, despite phenotypic and biochemical differences in androgenic manifestations, do not manifest clinically significant differences in sexual function. Copyright © 2017 Elsevier Inc. All rights reserved.

A Bermuda Triangle of Science

ERIC Educational Resources Information Center

Winkelsas, John

2006-01-01

The Bermuda Triangle is famous for the unexplained disappearances of ships and aircraft, and for strange meteorological phenomena that allegedly have occurred within its boundaries. This article presents an activity wherein students are asked to create their own geographical triangles to research, but instead of focusing on the unexplainable,…

Surface replacement conversion: results depend upon reason for revision.

PubMed

Su, E P; Su, S L

2013-11-01

Surface hip replacement (SHR) is generally used in younger, active patients as an alternative conventional total hip replacement in part because of the ability to preserve femoral bone. This major benefit of surface replacement will only hold true if revision procedures of SHRs are found to provide good clinical results. A retrospective review of SHR revisions between 2007 and 2012 was presented, and the type of revision and aetiologies were recorded. There were 55 SHR revisions, of which 27 were in women. At a mean follow-up of 2.3 years (0.72 to 6.4), the mean post-operative Harris hip score (HHS) was 94.8 (66 to 100). Overall 23 were revised for mechanical reasons, nine for impingement, 13 for metallosis, nine for unexplained pain and one for sepsis. Of the type of revision surgery performed, 14 were femoral-only revisions; four were acetabular-only revisions, and 37 were complete revisions. We did not find that clinical scores were significantly different between gender or different types of revisions. However, the mean post-operative HHS was significantly lower in patients revised for unexplained pain compared with patients revised for mechanical reasons (86.9 (66 to 100) versus 99 (96 to 100); p = 0.029). There were two re-revisions for infection in the entire cohort. Based on the overall clinical results, we believe that revision of SHR can have good or excellent results and warrants a continued use of the procedure in selected patients. Close monitoring of these patients facilitates early intervention, as we believe that tissue damage may be related to the duration of an ongoing problem. There should be a low threshold to revise a surface replacement if there is component malposition, rising metal ion levels, or evidence of soft-tissue abnormalities.

Discrepancy between clinical practice and standardized indications for an implantable loop recorder in patients with unexplained syncope†

PubMed Central

Vitale, Elena; Ungar, Andrea; Maggi, Roberto; Francese, Maura; Lunati, Maurizio; Colaceci, Roberto; Del Rosso, Attilio; Castro, Antonio; Santini, Massimo; Giuli, Silvia; Belgini, Lara; Casagranda, Ivo; Brignole, Michele

2010-01-01

Aim An implantable loop recorder (ILR) is indicated in patients with unexplained syncope after complete conventional work-up. Data from the literature imply that, in clinical practice, the ILR is underused. The aim of the study was to verify if there is any discrepancy between the use of ILRs in clinical practice and the potential indications based on the most potentially appropriate guideline indications. Method and results We compared the prevalence of ILRs actually implanted in patients with unexplained syncope in the Syncope Unit Project (SUP) study and the potential one using the standard given by the guidelines. In the SUP study, 28 (18%) out of 159 patients with unexplained syncope received an ILR. Appropriate criteria for implantation of ILRs according to guidelines were present in 110 (69%) patients. Moreover, 7 (25%) of ILRs actually implanted did not satisfy the guideline standards. During the follow-up, 32% of patients who had received an ILR had a diagnosis compared with 5% of those who did not (P= 0.001). Conclusions The estimated indications were four times higher than those observed. Moreover, in about one quarter of the cases, the use of ILRs proved to be potentially inappropriate according to guideline indications. Two-thirds of patients with unexplained syncope had indications potentially appropriate for ILRs. PMID:20876604

Reference Intervals of Alpha-Fetoprotein and Carcinoembryonic Antigen in the Apparently Healthy Population

PubMed Central

Zhang, Gao-Ming; Guo, Xu-Xiao; Ma, Xiao-Bo; Zhang, Guo-Ming

2016-01-01

Background The aim of this study was to calculate 95% reference intervals and double-sided limits of serum alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) according to the CLSI EP28-A3 guideline. Material/Methods Serum AFP and CEA values were measured in samples from 26 000 healthy subjects in the Shuyang area receiving general health checkups. The 95% reference intervals and upper limits were calculated by using MedCalc. Results We provided continuous reference intervals from 20 years old to 90 years old for AFP and CEA. The reference intervals were: AFP, 1.31–7.89 ng/ml (males) and 1.01–7.10 ng/ml (females); CEA, 0.51–4.86 ng/ml (males) and 0.35–3.45ng/ml (females). AFP and CEA were significantly positively correlated with age in both males (r=0.196 and r=0.198) and females (r=0.121 and r=0.197). Conclusions Different races or populations and different detection systems may result in different reference intervals for AFP and CEA. Continuous reference intervals of age changes are more accurate than age groups. PMID:27941709

Carcinoma-specific Ulex europaeus agglutinin-I binding glycoproteins of human colorectal carcinoma and its relation to carcinoembryonic antigen.

PubMed

Matsushita, Y; Yonezawa, S; Nakamura, T; Shimizu, S; Ozawa, M; Muramatsu, T; Sato, E

1985-08-01

Glycoproteins binding to Ulex europaeus agglutinin-I (UEA-I) lectin, which recognizes the terminal alpha-L-fucose residue, were analyzed in 18 cases of human colorectal carcinoma by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by the Western blotting method. In the distal large bowel (descending and sigmoid colon and rectum), high-molecular-weight glycoproteins binding to UEA-I existed in carcinoma tissue but not in normal mucosa. In the proximal large bowel (ascending and transverse colon), high-molecular-weight glycoproteins binding to UEA-I were found both in normal mucosa and in carcinoma tissue, whereas those from the carcinoma tissue had an apparently lower molecular weight as compared to the weight of those from the normal mucosa. Thus there is a biochemical difference in UEA-I binding glycoproteins between the normal mucosa and the carcinoma tissue, although in our previous histochemical study no difference was observed in UEA-I binding glycoproteins of the proximal large bowel between the carcinoma tissue and the normal mucosa. Furthermore, carcinoembryonic antigen from the carcinoma tissue was found to have the same electrophoretical mobility as the UEA-I binding glycoproteins.

Novel flow cytometric analysis of the progress and route of internalization of a monoclonal anti-carcinoembryonic antigen (CEA) antibody.

PubMed

Ford, C H; Tsaltas, G C; Osborne, P A; Addetia, K

1996-03-01

A flow cytometric method of studying the internalization of a monoclonal antibody (Mab) directed against carcinoembryonic antigen (CEA) has been compared with Western blotting, using three human colonic cancer cell lines which express varying amounts of the target antigen. Cell samples incubated for increasing time intervals with fluoresceinated or unlabelled Mab were analyzed using flow cytometry or polyacrylamide gel electrophoresis and Western blotting. SDS/PAGE analysis of cytosolic and membrane components of solubilized cells from the cell lines provided evidence of non-degraded internalized anti-CEA Mab throughout seven half hour intervals, starting at 5 min. Internalized anti-CEA was detected in the case of high CEA expressing cell lines (LS174T, SKCO1). Very similar results were obtained with an anti-fluorescein flow cytometric assay. Given that these two methods consistently provided comparable results, use of flow cytometry for the detection of internalized antibody is suggested as a rapid alternative to most currently used methods for assessing antibody internalization. The question of the endocytic route followed by CEA-anti-CEA complexes was addressed by using hypertonic medium to block clathrin mediated endocytosis.

Sediment Sulfur Isotopes Reflect Seawater Oxygen Rise in Neoarchean

NASA Astrophysics Data System (ADS)

Fakhraee, M.; Crowe, S.; Katsev, S.

2017-12-01

The oxygenation of the ocean-atmosphere system is recorded in S isotopes preserved in sedimentary pyrites. Disappearance of mass independent fractionation of S (S-MIF) around 2.45 Ga signals the first large-scale oxygenation of the atmosphere (the GOE), while a narrow range of pyritic δ34S during the Archean eon suggests limited oxidative cycling of S. Both δ34S and S-MIF ranges, however, undergo a clear and unexplained expansion in the Neoarchean between 2.7 and 2.45 Ga, indicating a change in global S-cycling. By analyzing the preservation patterns of isotopic signals with a 1D reaction-transport model, we show that the rock record points to the rise of oxygen in shallow marine environments around 2.7 billion years ago. The model tracks d34S and Δ33S isotopic transformations during early diagenesis in a reaction-transport framework. The results indicate that δ34S and MIF signatures in >2.7Ga sulfides require deposition from anoxic or minimally oxygenated seawater, whereas the 2.7-2.4 Ga expansion in both δ34S and D33S ranges points to at least localized accumulation oxygen to low μM levels, accompanied by a moderate rise in sulfate from low μM concentrations to up to 200 μM. In contrast to the role of oxygen in the atmosphere where it suppresses the production of MIF, oxygen in seawater at levels below 25 μM does not necessarily suppress the MIF preservation, which instead depends on the availability of reactive organic matter, sulfate, and electron acceptors for sulfide re-oxidation. The S-isotopes in Neoarchean sulfides thus paint a picture of gradual oxygenation of shallow marine environments under a nearly anoxic atmosphere where the atmospherically produced S isotopic signals are overprinted by increasingly oxidative diagenesis, rising sulfate levels, and increasing organic sedimentation.

Sexual, Physical, Verbal/Emotional Abuse and Unexplained Chest Pain

ERIC Educational Resources Information Center

Eslick, Guy D.; Koloski, Natasha A.; Talley, Nicholas J.

2011-01-01

Objectives: Approximately one third of patients with non cardiac chest pain (NCCP) report a history of abuse, however no data exists on the prevalence of abuse among people with unexplained chest pain in the general population. We aimed to determine if there is a relationship between childhood sexual, physical, emotional abuse and unexplained…

Psychological Mechanisms of Medically Unexplained Symptoms: An Integrative Conceptual Model

ERIC Educational Resources Information Center

Brown, Richard J.

2004-01-01

Theories of medically unexplained illness based on the concepts of dissociation, conversion, and somatization are summarized. Evidence cited in support of these theories is described and the conceptual strengths and shortcomings of each approach are considered. It is argued that each of these approaches adds to the understanding of unexplained…

Dexamethasone in unexplained infertility.

PubMed

Moradan, Sanam; Ghorbani, Raheb

2009-08-01

To determine if dexamethasone could be a suitable option in the treatment of patients with unexplained infertility. This study was carried out in the Obstetrics Department of Amir University Hospital, Semnan, Iran, from April 2001 to May 2008. One hundred and twenty-four cases of unexplained infertility that underwent ovulation induction and intrauterine insemination (IUI) (only one cycle) were evaluated, and divided into 2 groups. Sixteen cases were excluded, as they were unresponsive to the induction ovulation regimen. Group I (n=42) received clomiphene citrate (CC) + dexamethasone, and the control group (group II, n=66) received CC alone. These groups were the same in age, duration of infertility, and body mass index. The clinical pregnancy rates were evaluated in 2 groups by using statistical tests. The clinical pregnancy rate was 21.4% in group I, and 4.5% in group II. There was a significant statistical difference between the groups (relative risk=4.71, 95% confidence interval=1.35-16.42, p=0.0085). The pregnancy rate in women with unexplained infertility that underwent ovulation induction with CC + dexamethasone + IUI was significantly higher than those who underwent ovulation induction with CC alone + IUI.

Unexplained agglutination of stored red blood cells in Alsever's solution caused by the gram-negative bacterium Serratia liquefaciens.

PubMed

Martincic, I; Mastronardi, C; Chung, A; Ramirez-Arcos, S

2008-01-01

Alsever's solution has been used for decades as a preservative solution for storage of RBCs. From October 2005 to January 2006, unexplained hemagglutination of approximately 10 to 20 percent of RBCs stored for several days in a modified version of Alsever's solution was noticed in quality control testing at the Canadian Blood Services Serology Laboratory. An investigation, including microbial testing, was initiated to determine the cause of the unexplained hemagglutination. The gram-negative bacterium Serratia liquefaciens was isolated from supernatant solutions of agglutinated RBCs. Further characterization of this strain revealed that it has the ability to form biofilms; presents high levels of resistance to chloramphenicol, neomycin, and gentamicin; and causes mannose-sensitive hemagglutination. The source of S. liquefaciens contamination in RBC supernatants was not found. However, this bacterium has not been isolated since January 2006 after enhanced cleaning practices were implemented in the serology laboratory where the RBCs are stored. This biofilm-forming, antibiotic-resistant S. liquefaciens strain could be directly linked to the unexplained hemagglutination observed in stored RBCs.

A Practical Methodology for Quantifying Random and Systematic Components of Unexplained Variance in a Wind Tunnel

NASA Technical Reports Server (NTRS)

Deloach, Richard; Obara, Clifford J.; Goodman, Wesley L.

2012-01-01

This paper documents a check standard wind tunnel test conducted in the Langley 0.3-Meter Transonic Cryogenic Tunnel (0.3M TCT) that was designed and analyzed using the Modern Design of Experiments (MDOE). The test designed to partition the unexplained variance of typical wind tunnel data samples into two constituent components, one attributable to ordinary random error, and one attributable to systematic error induced by covariate effects. Covariate effects in wind tunnel testing are discussed, with examples. The impact of systematic (non-random) unexplained variance on the statistical independence of sequential measurements is reviewed. The corresponding correlation among experimental errors is discussed, as is the impact of such correlation on experimental results generally. The specific experiment documented herein was organized as a formal test for the presence of unexplained variance in representative samples of wind tunnel data, in order to quantify the frequency with which such systematic error was detected, and its magnitude relative to ordinary random error. Levels of systematic and random error reported here are representative of those quantified in other facilities, as cited in the references.

[Relationship between unexplained palpitation in 
children and head-up tilt test].

PubMed

Gan, Tuoyu; Wu, Lijia; Zou, Runmei; Lin, Ping; Li, Fang; Yang, Hong; Liu, Ping; Gong, Xiaohui; Wang, Cheng

2018-03-28

To explore the relationship between unexplained palpitation in children and head-up tilt test (HUTT).
 Methods: A total of 142 children with the main symptom of unexplained palpitation were admitted to the Specialist Out-Patient Clinic of Children's Cardiovascular Disease from Sept. 2008 to Feb. 2017 in the Second Xiangya Hospital, Central South University. Among them, 63 cases were male, 79 cases were female, with the mean age of (10.12±2.88) years old. The detailed history, physical examinations, conventional 12 electrocardiogram, chest X-ray, echocardiography, myocardial enzymes and thyroid function were all examined. The disorders of heart disease, systemic disease and drug effect were ruled out. The HUTT inspection was then given to them.
 Results: Among the 142 palpitation cases, 79 cases were HUTT positive (55.6%) and 63 cases were HUTT negative (44.4%). The age in HUTT positive patients was older than that in HUTT negative patients (P<0.05), with no significant difference in gender (P>0.05). There were three types of hemodynamic changes in HUTT positive patients. Among them, 38 cases were postural orthostatic tachycardia syndrome (48.1%), 36 cases were the vasovagal syncope vasodepressive type (45.6%) and 5 cases were the vasovagal syncope mixed type (6.3%). There were no hemodynamic types for vasovagal syncope cardioinhibitory type, orthostatic hypotension and orthostatic hypertension.
 Conclusion: Among the clinically unexplained palpitations children, more than half are caused by unbalanced autonomic nervous function. HUTT can help clear the cause of unexplained palpitations.

Medically unexplained conditions considered by patients in general practice.

PubMed

Tschudi-Madsen, Hedda; Kjeldsberg, Mona; Natvig, Bård; Ihlebaek, Camilla; Straand, Jørund; Bruusgaard, Dag

2014-04-01

Patients frequently present with multiple and 'unexplained' symptoms, often resulting in complex consultations. To better understand these patients is a challenge to health care professionals, in general, and GPs, in particular. In our research on symptom reporting, we wanted to explore whether patients consider that they may suffer from conditions commonly regarded as unexplained, and we explored associations between these concerns and symptom load, life stressors and socio-demographic factors. Consecutive, unselected patients in general practice completed questionnaires addressing eight conditions commonly regarded as unexplained (amalgam poisoning, Candida syndrome, fibromyalgia, food intolerance, electromagnetic hypersensitivity, burnout syndrome, chronic fatigue syndrome and irritable bowel syndrome). With logistic regression, we analysed associations with symptom load, burden of life stressors with negative impact on present health and socio-demographic variables. Out of the 909 respondents (response rate = 88.8%), 863 had complete data. In total, 39.6% of patients had considered that they may suffer from one or more unexplained conditions (UCs). These concerns were strongly and positively associated with recent symptom load and number of life stressors. If we excluded burnout and food intolerance, corresponding associations were found. Patients frequently considered that they may suffer from UCs. The likelihood of such concerns strongly increased with an increasing symptom load and with the number of life stressors with negative impact on present health. Hence, the number of symptoms may be a strong indicator of whether patients consider their symptoms part of such often controversial multisymptom conditions.

Explained and unexplained tissue loss in corals from the Tropical Eastern Pacific

USGS Publications Warehouse

Rodriguez-Villalobos, Jenny Carolina; Work, Thierry M.; Calderon-Aguilera, Luis Eduardo; Reyes-Bonilla, Hector; Hernández, Luis

2015-01-01

Coral reefs rival rainforest in biodiversity, but are declining in part because of disease. Tissue loss lesions, a manifestation of disease, are present in dominant Pocillopora along the Pacific coast of Mexico. We characterized tissue loss in 7 species of Pocillopora from 9 locations (44 sites) spanning southern to northern Mexico. Corals were identified to species, and tissue loss lesions were photographed and classified as those explainable by predation and those that were unexplained. A focal predation study was done concurrently at 3 locations to confirm origin of explained lesions. Of 1054 cases of tissue loss in 7 species of corals, 84% were associated with predation (fish, snails, or seastar) and the remainder were unexplained. Types of tissue loss were not related to coral density; however there was significant geographic heterogeneity in type of lesion; one site in particular (Cabo Pulmo) had the highest prevalence of predator-induced tissue loss (mainly pufferfish predation). Crown-of-thorns starfish, pufferfish, and snails were the most common predators and preferred P. verrucosa, P. meandrina, and P. capitata, respectively. Of the 9 locations, 4 had unexplained tissue loss with prevalence ranging from 1 to 3% with no species predilection. Unexplained tissue loss was similar to white syndrome (WS) in morphology, indicating additional study is necessary to clarify the cause(s) of the lesions and the potential impacts to dominant corals along the Pacific coast of Mexico.

Preovulatory uterine flushing with saline as a treatment for unexplained infertility: a randomised controlled trial protocol.

PubMed

Maheux-Lacroix, Sarah; Dodin, Sylvie; Moore, Lynne; Bujold, Emmanuel; Lefebvre, Jessica; Bergeron, Marie-Ève

2016-01-06

In vitro fertilisation (IVF) is the treatment of choice for unexplained infertility. Preovulatory uterine flushing could reduce intrauterine debris and inflammatory factors preventing pregnancy and constitute an alternative to IVF. Our objective is to assess the efficacy of preovulatory uterine flushing with physiological saline for the treatment of unexplained infertility. We will perform a randomised controlled trial based on consecutive women aged between 18 and 37 years consulting for unexplained infertility for at least 1 year. On the day of their luteinising hormone surge, 192 participants will be randomised in two equal groups to either receive 20 mL of physiological saline by an intrauterine catheter or 10 mL of saline intravaginally. We will assess relative risk of live birth (primary outcome), as well as pregnancy (secondary outcome) over one cycle of treatment. We will report the side effects, complications and acceptability of the intervention. This project was approved by the Ethics committee of the Centre Hospitatlier Universitaire de Quebec (no 2015-1146). Uterine flushing is usually well tolerated by women and would constitute a simple, affordable and minimally invasive treatment for unexplained infertility. We plan to communicate the results of the review by presenting research abstracts at conferences and by publishing the results in a peer-reviewed journal. NCT02539290; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Chronic fatigue in patients with unexplained self-reported food hypersensitivity and irritable bowel syndrome: validation of a Norwegian translation of the Fatigue Impact Scale.

PubMed

Lind, Ragna; Berstad, Arnold; Hatlebakk, Jan; Valeur, Jørgen

2013-01-01

Patients with unexplained self-reported food hypersensitivity and irritable bowel syndrome (IBS) suffer from several health complaints, including fatigue. The aim of the present study was to validate a Norwegian translation of the Fatigue Impact Scale (FIS), and to assess the impact of fatigue in patients with self-reported food hypersensitivity and IBS, as compared with healthy controls. Thirty-eight patients with unexplained self-reported food hypersensitivity and IBS, who participated in the validation of the FIS completed the following additional questionnaires: the Short Form of Nepean Dyspepsia Index for assessment of quality of life, the Subjective Health Complaint Inventory, and questionnaires for diagnosis and severity of IBS. Impact of fatigue was studied in 43 patients with unexplained self-reported food hypersensitivity, 70% diagnosed with IBS, and 42 healthy controls. Cronbach's α for the FIS was 0.98, indicating excellent agreement between individual items. Scores on the FIS correlated with scores on the Short Form of Nepean Dyspepsia Index (r = 0.50, P = 0.001), indicating good convergent validity, and were higher in patients (median 85.0, interquartile range 36.8-105.3) than in controls (median 14.0, interquartile range 3.0-29.0, P ≤ 0.0001). The Norwegian translation of the FIS performed excellently in patients with unexplained self-reported food hypersensitivity and IBS, with patients reporting significantly more impact of chronic fatigue than healthy controls.

Unravelling associations between unassigned mass spectrometry peaks with frequent itemset mining techniques.

PubMed

Vu, Trung Nghia; Mrzic, Aida; Valkenborg, Dirk; Maes, Evelyne; Lemière, Filip; Goethals, Bart; Laukens, Kris

2014-01-01

Mass spectrometry-based proteomics experiments generate spectra that are rich in information. Often only a fraction of this information is used for peptide/protein identification, whereas a significant proportion of the peaks in a spectrum remain unexplained. In this paper we explore how a specific class of data mining techniques termed "frequent itemset mining" can be employed to discover patterns in the unassigned data, and how such patterns can help us interpret the origin of the unexpected/unexplained peaks. First a model is proposed that describes the origin of the observed peaks in a mass spectrum. For this purpose we use the classical correlative database search algorithm. Peaks that support a positive identification of the spectrum are termed explained peaks. Next, frequent itemset mining techniques are introduced to infer which unexplained peaks are associated in a spectrum. The method is validated on two types of experimental proteomic data. First, peptide mass fingerprint data is analyzed to explain the unassigned peaks in a full scan mass spectrum. Interestingly, a large numbers of experimental spectra reveals several highly frequent unexplained masses, and pattern mining on these frequent masses demonstrates that subsets of these peaks frequently co-occur. Further evaluation shows that several of these co-occurring peaks indeed have a known common origin, and other patterns are promising hypothesis generators for further analysis. Second, the proposed methodology is validated on tandem mass spectrometral data using a public spectral library, where associations within the mass differences of unassigned peaks and peptide modifications are explored. The investigation of the found patterns illustrates that meaningful patterns can be discovered that can be explained by features of the employed technology and found modifications. This simple approach offers opportunities to monitor accumulating unexplained mass spectrometry data for emerging new patterns, with possible applications for the development of mass exclusion lists, for the refinement of quality control strategies and for a further interpretation of unexplained spectral peaks in mass spectrometry and tandem mass spectrometry.

Phase I/II combined chemoimmunotherapy with carcinoembryonic antigen-derived HLA-A2-restricted CAP-1 peptide and irinotecan, 5-fluorouracil, and leucovorin in patients with primary metastatic colorectal cancer.

PubMed

Weihrauch, Martin R; Ansén, Sascha; Jurkiewicz, Elke; Geisen, Caroline; Xia, Zhinan; Anderson, Karen S; Gracien, Edith; Schmidt, Manuel; Wittig, Burghardt; Diehl, Volker; Wolf, Juergen; Bohlen, Heribert; Nadler, Lee M

2005-08-15

We conducted a phase I/II randomized trial to evaluate the clinical and immunologic effect of chemotherapy combined with vaccination in primary metastatic colorectal cancer patients with a carcinoembryonic antigen-derived peptide in the setting of adjuvants granulocyte macrophage colony-stimulating factor, CpG-containing DNA molecules (dSLIM), and dendritic cells. HLA-A2-positive patients with confirmed newly diagnosed metastatic colorectal cancer and elevated serum carcinoembryonic antigen (CEA) were randomized to receive three cycles of standard chemotherapy (irinotecan/high-dose 5-fluorouracil/leucovorin) and vaccinations with CEA-derived CAP-1 peptide admixed with different adjuvants [CAP-1/granulocyte macrophage colony-stimulating factor/interleukin-2 (IL-2), CAP-1/dSLIM/IL-2, and CAP-1/IL-2]. After completion of chemotherapy, patients received weekly vaccinations until progression of disease. Immune assessment was done at baseline and after three cycles of combined chemoimmunotherapy. HLA-A2 tetramers complexed with the peptides CAP-1, human T-cell lymphotrophic virus type I TAX, cytomegalovirus (CMV) pp65, and EBV BMLF-1 were used for phenotypic immune assessment. IFN-gamma intracellular cytokine assays were done to evaluate CTL reactivity. Seventeen metastatic patients were recruited, of whom 12 completed three cycles. Therapy resulted in five complete response, one partial response, five stable disease, and six progressive disease. Six grade 1 local skin reactions and one mild systemic reaction to vaccination treatment were observed. Overall survival after a median observation time of 29 months was 17 months with a survival rate of 35% (6 of 17) at that time. Eight patients (47%) showed elevation of CAP-1-specific CTLs. Neither of the adjuvants provided superiority in eliciting CAP-1-specific immune responses. During three cycles of chemotherapy, EBV/CMV recall antigen-specific CD8+ cells decreased by an average 14%. The presented chemoimmunotherapy is a feasible and safe combination therapy with clinical and immunologic efficacy. Despite concurrent chemotherapy, increases in CAP-1-specific T cells were observed in 47% of patients after vaccination.

New parvovirus in child with unexplained diarrhea, Tunisia.

PubMed

Phan, Tung G; Sdiri-Loulizi, Khira; Aouni, Mahjoub; Ambert-Balay, Katia; Pothier, Pierre; Deng, Xutao; Delwart, Eric

2014-11-01

A divergent parvovirus genome was the only eukaryotic viral sequence detected in feces of a Tunisian child with unexplained diarrhea. Tusavirus 1 shared 44% and 39% identity with the nonstructural protein 1 and viral protein 1, respectively, of the closest genome, Kilham rat parvovirus, indicating presence of a new human viral species in the Protoparvovirus genus.

New Parvovirus in Child with Unexplained Diarrhea, Tunisia

PubMed Central

Phan, Tung G.; Sdiri-Loulizi, Khira; Aouni, Mahjoub; Ambert-Balay, Katia; Pothier, Pierre; Deng, Xutao

2014-01-01

A divergent parvovirus genome was the only eukaryotic viral sequence detected in feces of a Tunisian child with unexplained diarrhea. Tusavirus 1 shared 44% and 39% identity with the nonstructural protein 1 and viral protein 1, respectively, of the closest genome, Kilham rat parvovirus, indicating presence of a new human viral species in the Protoparvovirus genus. PMID:25340816

Psychosoma in Crisis: An Autoethnographic Study of Medically Unexplained Symptoms and Their Diverse Contexts

ERIC Educational Resources Information Center

Hills, John; Lees, John; Freshwater, Dawn; Cahill, Jane

2018-01-01

In this study, we examine autoethnographic data from three critical incidents as experienced by the first author demonstrating the importance of context in understanding medically unexplained symptoms, their incidence and underlying patterns. We make the case for ethnographies as a crucial research strand in discerning the finer aspects of the…

Unexplained Deaths and Critical Illnesses of Suspected Infectious Cause, Taiwan, 2000–2005

PubMed Central

Wei, Kuo-Chen; Jiang, Donald Dah-Shyong; Chiu, Chan-Hsian; Chang, Shan-Chwen

2008-01-01

We report 5 years’ surveillance data from the Taiwan Centers for Disease Control on unexplained deaths and critical illnesses suspected of being caused by infection. A total of 130 cases were reported; the incidence rate was 0.12 per 100,000 person-years; and infectious causes were identified for 81 cases (62%). PMID:18826839

Motor selection dynamics in FEF explain the reaction time variance of saccades to single targets

PubMed Central

Hauser, Christopher K; Zhu, Dantong; Stanford, Terrence R

2018-01-01

In studies of voluntary movement, a most elemental quantity is the reaction time (RT) between the onset of a visual stimulus and a saccade toward it. However, this RT demonstrates extremely high variability which, in spite of extensive research, remains unexplained. It is well established that, when a visual target appears, oculomotor activity gradually builds up until a critical level is reached, at which point a saccade is triggered. Here, based on computational work and single-neuron recordings from monkey frontal eye field (FEF), we show that this rise-to-threshold process starts from a dynamic initial state that already contains other incipient, internally driven motor plans, which compete with the target-driven activity to varying degrees. The ensuing conflict resolution process, which manifests in subtle covariations between baseline activity, build-up rate, and threshold, consists of fundamentally deterministic interactions, and explains the observed RT distributions while invoking only a small amount of intrinsic randomness. PMID:29652247

Gulf War syndrome: an emerging threat or a piece of history?

PubMed Central

Greenberg, N; Wessely, S

2008-01-01

‘Gulf War syndrome’ is a phrase coined after the 1991 Gulf War to group together disparate, unexplained health symptoms in Gulf veterans. This paper examines the many hypotheses that have been put forward about the origins of the concept and gives an overview of the studies that have attempted to explain the lasting health effects associated with Gulf service. Our review finds that although in the UK there has not yet been evidence of a new Gulf War syndrome as a result of the current conflicts in Iraq and Afghanistan, there is a rise in post-conflict psychiatric disorders now being reported in the USA. We postulate that after conflicts military personnel will always face some form of post-conflict syndrome and the nature of the threats experienced is likely to dictate the form the syndrome might take. We also postulate that media reporting is likely to have influenced and to continue unhelpfully to influence the health of service personnel. PMID:22460210

Television Image of a Large Upward Electrical Discharge Above a Thunderstorm System

NASA Astrophysics Data System (ADS)

Franz, R. C.; Nemzek, R. J.; Winckler, J. R.

1990-07-01

An image of an unusual luminous electrical discharge over a thunderstorm 250 kilometers from the observing site has been obtained with a low-light-level television camera. The discharge began at the cloud tops at 14 kilometers and extended into the clear air 20 kilometers higher. The image, which had a duration of less than 30 milliseconds, resembled two jets or fountains and was probably caused by two localized electric charge concentrations at the cloud tops. Large upward discharges may create a hazard for aircraft and rocket launches and, by penetrating into the ionosphere, may initiate whistler waves and other effects on a magnetospheric scale. Such upward electrical discharges may account for unexplained photometric observations of distant lightning events that showed a low rise rate of the luminous pulse and no electromagnetic sferic pulse of the type that accompanies cloud-to-earth lightning strokes. An unusually high rate of such photometric events was recorded during the night of 22 to 23 September 1989 during a storm associated with hurricane Hugo.

Television image of a large upward electrical discharge above a thunderstorm system.

PubMed

Franz, R C; Nemzek, R J; Winckler, J R

1990-07-06

An image of an unusual luminous electrical discharge over a thunderstorm 250 kilometers from the observing site has been obtained with a low-light-level television camera. The discharge began at the cloud tops at 14 kilometers and extended into the clear air 20 kilometers higher. The image, which had a duration of less than 30 milliseconds,resembled two jets or fountains and was probably caused by two localizd electric charge concentrations at the cloud tops. Large upward discharges may create a hazard for aircraft and rocket launches and, by penetrating into the ionosphere, may initiate whistler waves and other effects on a magnetospheric scale. Such upward electrical discharges may account for unexplained photometric observations of distant lightning events that showed a low rise rate of the luminous pulse and no electromagnetic sferic pulse of the type that accompanies cloud-to-earth lightning strokes. An unusually high rate of such photometric events was recorded during the night of 22 to 23 September 1989 during a storm associated with hurricane Hugo.

Neuroscience and the soul: competing explanations for the human experience.

PubMed

Preston, Jesse Lee; Ritter, Ryan S; Hepler, Justin

2013-04-01

The development of fMRI techniques has generated a boom of neuroscience research across the psychological sciences, and revealed neural correlates for many psychological phenomena seen as central to the human experience (e.g., morality, agency). Meanwhile, the rise of neuroscience has reignited old debates over mind-body dualism and the soul. While some scientists use neuroscience to bolster a material account of consciousness, others point to unexplained neural phenomena to defend dualism and a spiritual perspective on the mind. In two experiments we examine how exposure to neuroscience research impacts belief in the soul. We find that belief in soul decreases when neuroscience provides strong mechanistic explanations for mind. But when explanatory gaps in neuroscience research are emphasized, belief in soul is enhanced, suggesting that physical and metaphysical explanations may be used reflexively as alternative theories for mind. Implications for the future of belief in soul and neuroscience research are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

Nonlocal Polarization Feedback in a Fractional Quantum Hall Ferromagnet.

PubMed

Hennel, Szymon; Braem, Beat A; Baer, Stephan; Tiemann, Lars; Sohi, Pirouz; Wehrli, Dominik; Hofmann, Andrea; Reichl, Christian; Wegscheider, Werner; Rössler, Clemens; Ihn, Thomas; Ensslin, Klaus; Rudner, Mark S; Rosenow, Bernd

2016-04-01

In a quantum Hall ferromagnet, the spin polarization of the two-dimensional electron system can be dynamically transferred to nuclear spins in its vicinity through the hyperfine interaction. The resulting nuclear field typically acts back locally, modifying the local electronic Zeeman energy. Here we report a nonlocal effect arising from the interplay between nuclear polarization and the spatial structure of electronic domains in a ν=2/3 fractional quantum Hall state. In our experiments, we use a quantum point contact to locally control and probe the domain structure of different spin configurations emerging at the spin phase transition. Feedback between nuclear and electronic degrees of freedom gives rise to memristive behavior, where electronic transport through the quantum point contact depends on the history of current flow. We propose a model for this effect which suggests a novel route to studying edge states in fractional quantum Hall systems and may account for so-far unexplained oscillatory electronic-transport features observed in previous studies.

Diagnostic value of [(18)F]-FDG PET/CT in children with fever of unknown origin or unexplained signs of inflammation.

PubMed

Jasper, Niklas; Däbritz, Jan; Frosch, Michael; Loeffler, Markus; Weckesser, Matthias; Foell, Dirk

2010-01-01

Fever of unknown origin (FUO) and unexplained signs of inflammation are challenging medical problems especially in children and predominantly caused by infections, malignancies or noninfectious inflammatory diseases. The aim of this study was to assess the diagnostic value of (18)F-FDG PET and PET/CT in the diagnostic work-up in paediatric patients. In this retrospective study, 47 FDG PET and 30 PET/CT scans from 69 children (median age 8.1 years, range 0.2-18.1 years, 36 male, 33 female) were analysed. The diagnostic value of PET investigations in paediatric patients presenting with FUO (44 scans) or unexplained signs of inflammation without fever (33 scans) was analysed. A diagnosis in paediatric patients with FUO or unexplained signs of inflammation could be established in 32 patients (54%). Of all scans, 63 (82%) were abnormal, and of the total number of 77 PET and PET/CT scans 35 (45%) were clinically helpful. In patients with a final diagnosis, scans were found to have contributed to the diagnosis in 73%. Laboratory, demographic or clinical parameters of the children did not predict the usefulness of FDG PET scans. This is the first larger study demonstrating that FDG PET and PET/CT may be valuable diagnostic tools for the evaluation of children with FUO and unexplained signs of inflammation. Depicting inflammation in the whole body, while not being traumatic, it is attractive for use especially in children. The combination of PET with CT seems to be superior, since the site of inflammation can be localized more accurately.

May Underdiagnosed Nutrition Imbalances Be Responsible for a Portion of So-Called Unexplained Infertility? From Diagnosis to Potential Treatment Options.

PubMed

Noventa, Marco; Quaranta, Michela; Vitagliano, Amerigo; Cinthya, Vescio; Valentini, Romina; Campagnaro, Tania; Marci, Roberto; Paola, Rossana Di; Alviggi, Carlo; Gangemi, Michele; Saccardi, Carlo; Nardelli, Giovanni Battista; Gizzo, Salvatore

2016-06-01

The aim of the study was to investigate whether women affected by unexplained infertility may have undiagnosed dietary imbalances which negatively affect fertility. Secondarily, we investigated whether varying degrees of nutritional abnormalities may benefit from different periconceptional dietary supplementations, evaluating the most effective intervention in improving pregnancy rate after in vitro fertilization (IVF). We conducted a survey on 2 cohorts of patients (group A: unexplained infertility and group B: healthy first trimester spontaneous pregnancies) with the scope of investigating and comparing their dietary status discriminating women without dietary abnormalities (cohort 1) from those with abnormalities exclusively in micronutrient intake (cohort 2) or combined abnormalities in both micronutrient and macronutrient intake and associated obesity (cohort 3). All women included in group A were offered the opportunity to receive a prescription for one of the 3 designated daily dietary supplementation schemes (subgroups A1, A2, and A3) which were to be implemented in the 3 months immediately prior to beginning IVF treatment. When compared with fertile women, patients having unexplained infertility showed significant abnormalities in dietary habits. These differences ranged from a minimal imbalance in micronutrient intake (potentially avoidable with dietary supplementation) to severe combined macronutrient and micronutrient imbalance frequently associated with obesity (partially amendable by inositol supplementation and frequently requiring long-term dietary reeducation before establishment of fertility). Nutritional investigation and treatment may explain and resolve a portion of cases of unexplained infertility, improving the outcome of IVF treatment and, with minimal imbalances, likely restore spontaneous fertility. © The Author(s) 2015.

[Criteria for somatization studied in an outpatient clinic for general internal medicine].

PubMed

van Hemert, A M; Speckens, A E; Rooijmans, H G; Bolk, J H

1996-06-08

To compare the evolution of bodily symptoms and the frequency of medical consultation using three different operational definitions of 'somatization'. Descriptive follow-up study. General Internal Medicine Outpatient Clinic of Leiden University Hospital, the Netherlands. Information about physical and psychic symptoms and about the somatic-medical diagnosis was collected in a group of 158 newly referred patients. The concept of 'somatization' was operationalized in three ways: a) seeking medical consultation for somatically unexplained symptoms; b) seeking medical consultation for somatically unexplained symptoms combined with an anxiety disorder or a depressive disorder according to the 'present state examination'; c) seeking medical consultation for somatically unexplained symptoms combined with a somatization disorder or hypochondria according to the Diagnostic and statistical manual of mental disorders (DSM) III R criteria. After a follow-up period of 1.2 years, information was collected from the entire study group about the evolution of the physical symptoms and the frequency of medical consultation. Patients with somatically unexplained symptoms combined with a somatization disorder or hypochondria were characterized in the follow-up by numerous physical symptoms and a high frequency of medical consultation. Compared with the other patients with unexplained symptoms, they visited the general practitioner during the follow-up period 2.5 times as often, saw specialists twice as often and were admitted to a 'somatic' hospital, 6 times as often. Using criteria of low restrictiveness for somatization, a large group of patients were identified with a relatively normal (average) illness behaviour. Using more restrictive criteria led to identification of a smaller group with more extreme illness behaviour.

INCIDENCE OF ABNORMAL POSITRON EMISSION TOMOGRAPHY IN PATIENTS WITH UNEXPLAINED CARDIOMYOPATHY AND VENTRICULAR ARRHYTHMIAS

PubMed Central

Tung, Roderick; Bauer, Brenton; Schelbert, Heinrich; Lynch, Joseph; Auerbach, Martin; Gupta, Pawan; Schiepers, Christiaan; Chan, Samantha; Ferris, Julie; Barrio, Martin; Ajijola, Olujimi; Bradfield, Jason; Shivkumar, Kalyanam

2015-01-01

Background The incidence of myocardial inflammation in patients with unexplained cardiomyopathy referred for ventricular arrhythmias (VA) is unknown. Objective To report fasting PET scan findings in consecutive patients referred with unexplained cardiomyopathy and VA. Methods 18-FDG PET/CT scans with a >16 hour fasting protocol were prospectively ordered for patients referred for VA and unexplained cardiomyopathy (EF<55%). Patients with focal myocardial FDG uptake were labeled as arrhythmogenic inflammatory cardiomyopathy (AIC) and classified into four groups based on the presence of lymph node uptake (AIC+) and perfusion abnormalities (early vs late stage). Results Over a 3-year period, 103 PET scan were performed with 49% (AIC+=17, AIC=33) exhibiting focal FDG uptake. The mean age was 52±12 years with an EF of 36±16%. Patients with AIC were more likely to have a history of pacemaker (32% vs 6%, p=0.002) compared to those with normal PET. When biopsy was performed, histologic diagnosis revealed non-granulomatous inflammation in 6 patients and sarcoidosis in 18 patients. 90% of patients with AIC/AIC+ were prescribed immunosuppressive therapy and 58% underwent ablation. Correlation between areas of perfusion abnormalities and FDG uptake with electro-anatomic mapping was observed in 79% patients and MRI findings matched in only 33%. Conclusions Nearly 50% of patients referred with unexplained cardiomyopathy and VA demonstrate ongoing focal myocardial inflammation on FDG PET. These data suggests that a significant proportion of patients labeled “idiopathic” may have occult arrhythmogenic inflammatory cardiomyopathy, which may benefit from early detection and immunosuppressive medical therapy. PMID:26272522

Clinical significance of somatic mutation in unexplained blood cytopenia

PubMed Central

Gallì, Anna; Travaglino, Erica; Ambaglio, Ilaria; Rizzo, Ettore; Molteni, Elisabetta; Elena, Chiara; Ferretti, Virginia Valeria; Catricalà, Silvia; Bono, Elisa; Todisco, Gabriele; Bianchessi, Antonio; Rumi, Elisa; Zibellini, Silvia; Pietra, Daniela; Boveri, Emanuela; Camaschella, Clara; Toniolo, Daniela; Papaemmanuil, Elli; Ogawa, Seishi; Cazzola, Mario

2017-01-01

Unexplained blood cytopenias, in particular anemia, are often found in older persons. The relationship between these cytopenias and myeloid neoplasms like myelodysplastic syndromes is currently poorly defined. We studied a prospective cohort of patients with unexplained cytopenia with the aim to estimate the predictive value of somatic mutations for identifying subjects with, or at risk of, developing a myeloid neoplasm. The study included a learning cohort of 683 consecutive patients investigated for unexplained cytopenia, and a validation cohort of 190 patients referred for suspected myeloid neoplasm. Using granulocyte DNA, we looked for somatic mutations in 40 genes that are recurrently mutated in myeloid malignancies. Overall, 435/683 patients carried a somatic mutation in at least 1 of these genes. Carrying a somatic mutation with a variant allele frequency ≥0.10, or carrying 2 or more mutations, had a positive predictive value for diagnosis of myeloid neoplasm equal to 0.86 and 0.88, respectively. Spliceosome gene mutations and comutation patterns involving TET2, DNMT3A, or ASXL1 had positive predictive values for myeloid neoplasm ranging from 0.86 to 1.0. Within subjects with inconclusive diagnostic findings, carrying 1 or more somatic mutations was associated with a high probability of developing a myeloid neoplasm during follow-up (hazard ratio = 13.9, P < .001). The predictive values of mutation analysis were confirmed in the independent validation cohort. The findings of this study indicate that mutation analysis on peripheral blood granulocytes may significantly improve the current diagnostic approach to unexplained cytopenia and more generally the diagnostic accuracy of myeloid neoplasms. PMID:28424163

Protocol for the "four steps to control your fatigue (4-STEPS)" randomised controlled trial: a self-regulation based physical activity intervention for patients with unexplained chronic fatigue

PubMed Central

2012-01-01

Background Unexplained Chronic Fatigue is a medical condition characterized by the presence of persistent, severe and debilitating medically unexplained fatigue, leading to impaired functioning and lower quality of life. Research suggests that physical activity can contribute to the reduction of fatigue and other somatic symptoms and can thus significantly improve physical functioning and quality of life in these patients. Based on the self-regulation (SR) theory of behaviour change, we developed a brief physical activity program for patients suffering from unexplained chronic fatigue which focuses on the training of self-regulation skills, the "4-STEPS to control your fatigue" program. Methods/Design This is a multi-centre, randomised controlled trial (RCT) that will be carried out in local primary care centres and at the Portuguese Fibromyalgia and Chronic Fatigue Syndrome Patients Association. Patients aged between 18 and 65 and fulfilling operationalized criteria for Idiopathic Chronic Fatigue (ICF) and Chronic Fatigue Syndrome (CFS) will be recruited and randomly allocated to standard care (SC) or standard care plus a self-regulation based physical activity program (4-STEPS). Patients will be assessed at baseline, after the intervention (3 months) and at 12 months follow-up. The primary outcome is fatigue severity. Discussion The results of the RCT will provide information about the effectiveness of a brief self-regulation intervention for promoting physical activity in patients with unexplained chronic fatigue. If the program proves to be effective, it may be considered as an adjunctive treatment for these patients. Trial Registration ISRCTN: ISRCTN70763996 PMID:22429404

Antimüllerian hormone levels and antral follicle counts are not reduced compared with community controls in patients with rigorously defined unexplained infertility.

PubMed

Greenwood, Eleni A; Cedars, Marcelle I; Santoro, Nanette; Eisenberg, Esther; Kao, Chia-Ning; Haisenleder, Daniel J; Diamond, Michael P; Huddleston, Heather G

2017-12-01

To test the hypothesis that women with unexplained infertility demonstrate evidence of diminished ovarian reserve when compared with a population of community controls. Cross-sectional study. Multicenter university-based clinical practices. Study participants included 277 healthy, normo-ovulatory female partners with rigorously defined unexplained infertility randomly selected from a multicenter trial (Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation). Controls included 226 healthy, normo-ovulatory women not seeking treatment for fertility from a community-based cohort (Ovarian Aging study). Serum antimüllerian hormone (AMH) assay at a central laboratory, FSH, fasting serum metabolic testing, transvaginal ultrasonography for antral follicle counts (AFCs), anthropometric measurements. Average AMH, AFC, and AMH/AFC were compared between infertile and control women by age. Analyses of covariance compared these outcomes while controlling for confounders, including age, race, body mass index, smoking history, and study site. In our models, AMH, AFC, and AMH/AFC ovarian reserve indices did not differ between infertile women and community-based controls, after controlling for age, race, body mass index, smoking history, and study site. Currently utilized predictors of ovarian reserve do not discriminate women with rigorously defined unexplained infertility from healthy community-based women of similar demographic characteristics. Contrary to our hypothesis, among women with FSH in the normal range (≤12 IU/L), women with unexplained infertility did not show evidence of decreased ovarian reserve as measured by AMH and AFC. Ovarian reserve markers in isolation may not serve as predictors of future fertility. Copyright © 2017 American Society for Reproductive Medicine. All rights reserved.

Unexplained infertility: overall ongoing pregnancy rate and mode of conception.

PubMed

Brandes, M; Hamilton, C J C M; van der Steen, J O M; de Bruin, J P; Bots, R S G M; Nelen, W L D M; Kremer, J A M

2011-02-01

Unexplained infertility is one of the most common diagnoses in fertility care. The aim of this study was to evaluate the outcome of current fertility management in unexplained infertility. In an observational, longitudinal, multicentre cohort study, 437 couples were diagnosed with unexplained infertility and were available for analysis. They were treated according to their prognosis using standing national treatment protocols: (i) expectant management-IUI-IVF (main treatment route), (ii) IUI-IVF and (iii) directly IVF. Primary outcome measures were: ongoing pregnancy rate, patient flow over the strategies, numbers of protocol violation and drop out rates. A secondary outcome measure was the prediction of ongoing pregnancy and mode of conception. Of all couples 81.5% (356/437) achieved an ongoing pregnancy and 73.9% (263/356) of the pregnancies were conceived spontaneously. There were 408 couples (93.4%) in strategy-1, 21 (5.0%) in strategy-2 and 8 (1.8%) in strategy-3. In total, 33 (7.6%) couples entered the wrong strategy. There were 104 couples (23.8%) who discontinued fertility treatment prematurely: 26 on doctor's advice (with 4 still becoming pregnant) and 78 on their own initiative (with 33 still achieving a pregnancy). Predictors for overall pregnancy chance and mode of conception were duration of infertility, female age and obstetrical history. Overall success rate in couples with unexplained infertility is high. Most pregnancies are conceived spontaneously. We recommend that if the pregnancy prognosis is good, expectant management should be suggested. The prognosis criteria for treatment with IUI or IVF needs to be investigated in randomized controlled trials.

Progress for Women in Academe, Yet Inequities Persist: Evidence from NSOPF:99

ERIC Educational Resources Information Center

Toutkoushian, Robert K.; Conley, Valerie Martin

2005-01-01

In this study, we use data from the 1999 National Study of Postsecondary Faculty (NSOPF:99) to measure the unexplained wage gap between men and women in academe. We pay particular attention to how these unexplained wage gaps have changed over time by comparing the results from the 1999 survey to published results from previous national surveys and…

Education, Occupation and Career Expectations: Determinants of the Gender Pay Gap for UK Graduates. CEE DP 69

ERIC Educational Resources Information Center

Chevalier, Arnaud

2006-01-01

A large proportion of the gender wage gap is usually left unexplained. In this paper, we investigate whether the unexplained component is due to misspecification. Using a sample of recent UK graduates, we introduce variables on career expectations and character traits, variables that are typically not observed. The evidence indicates that women…

A unique and unexplained ricochet leak post PCI - successfully treated with intra-coronary glue.

PubMed

Goel, Pravin K; Syal, Sanjeev K

2014-01-01

We herein describe a unique case of coronary artery perforation treated with covered stent with repeat cardiac tamponade resulting out of a fresh unexplained leak from a remote vessel (Ricochet) and successfully treated with intra-coronary injection of sterile synthetic glue, cyanoacrylate. Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Interferon Regulatory Factor 5 Gene Polymorphisms in Iranian Women with Unexplained Recurrent Pregnancy Loss.

PubMed

Amiri Jahromi, Rakhshan; Nasiri, Mahboobeh; Jahromi, Athar Rasekh

2017-01-01

This study aimed to examine the association of three functional IRF5 rs10954213, rs3757385, and rs41298401 polymorphisms with susceptibility to unexplained recurrent pregnancy loss (RPL) among Iranian women from south of Iran. 176 women with unexplained RPL and 173 healthy postmenopausal controls were enrolled in this case-control study. Genotyping of the polymorphisms rs10954213 and rs3757385 was carried out using touchdown tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS PCR), and polymorphism rs41298401 was typed using PCR-restriction fragment length polymorphism (PCR-RFLP). Genotype frequencies were significantly different between RPL cases and controls regarding AG heterozygote genotype of rs10954213, GT genotype of rs3757385, and GG genotype of rs41298401. In addition, allele variants (G for rs10954213, T for rs3757385, and G for rs41298401) showed protective role against RPL, while GG haplotype of two first variants was shown to be a susceptibility factor for the disease. These data provide the first evidence, to our knowledge, of the protective role of the studied IRF5 gene polymorphisms against unexplained RPL among Iranian women from south of Iran.

A Comparison of Pattern of Pregnancy Loss in Women with Infertility Undergoing IVF and Women with Unexplained Recurrent Miscarriages Who Conceive Spontaneously

PubMed Central

Tamhankar, Vidya A.; Liu, Beiyu; Yan, Junhao; Li, Tin-Chiu

2015-01-01

Objective. Women with infertility and recurrent miscarriages may have an overlapping etiology. The aim of this study was to compare the pregnancy loss in pregnancies after IVF treatment with spontaneous pregnancies in women with recurrent miscarriages and to assess differences related to cause of infertility. Methods. The outcome from 1220 IVF pregnancies (Group I) was compared with 611 spontaneous pregnancies (Group II) in women with recurrent miscarriages. Subgroup analysis was performed in Group I based on cause of infertility: tubal factor (392 pregnancies); male factor (610 pregnancies); and unexplained infertility (218 pregnancies). Results. The clinical pregnancy loss rate in Group I (14.3%) was significantly lower than that of Group II (25.8%, p < 0.001) and this was independent of the cause of infertility. However the timing of pregnancy loss was similar between Groups I and II. The clinical pregnancy loss rate in Group I was similar in different causes of infertility. Conclusions. The clinical pregnancy loss rate following IVF treatment is lower than that of women with unexplained recurrent miscarriages who conceived spontaneously. This difference persists whether the infertility is secondary to tubal factors, male factors, or unexplained cause. PMID:26576157

Expectant management may reduce overtreatment in women affected by unexplained infertility confirmed by diagnostic laparoscopy.

PubMed

De Cicco, S; Tagliaferri, Valeria; Selvaggi, L; Romualdi, D; Di Florio, C; Immediata, V; Lanzone, A; Guido, M

2017-02-01

To determine whether the mini-invasive surgery still play a role in the diagnostic workup and in the management of the couples affected by unexplained infertility. 170 infertile women (age range 25-38 years) with documented normal ovarian, tubal and uterine function underwent combined hysteroscopic and laparoscopic surgery; 100 women refused surgery or ART treatment (control group) choosing expectant management. A retrospective assessment questionnaire was proposed to enrolled women to collect the rate of spontaneous or ART-induced pregnancies. The combined surgery revealed pelvic pathologies in 49.4% of patients, confirming the diagnosis of unexplained infertility only in 86 of studied patients. In this group of 86 selected women, 28 of them achieved a spontaneous pregnancy and 23 women obtained pregnancy after ART. The Chi-square analysis shows that the pregnancy rate was not influenced by the employment of ART. In the group of 100 control women, only 14 (14%) achieved a spontaneous pregnancy after 18 months of expectant management. Combined laparoscopy and hysteroscopy in women with unexplained infertility may reveal previously undiagnosed pathologies that could require ART, and in those without abnormal surgical finding, ART does not improve pregnancy rate.

The correlation of sperm morphology with unexplained recurrent spontaneous abortion: A systematic review and meta-analysis

PubMed Central

Cao, Xiaodan; Cui, Yun; Zhang, Xiaoxia; Lou, Jiangtao; Zhou, Jun; Wei, Renxiong

2017-01-01

Sperm morphology displays a potential impact on sperm function and may ultimately impact reproductive function. Current studies have investigated the correlation between sperm morphology with unexplained recurrent spontaneous abortion (RSA) but have shown inconsistent results. Hence, we systematically searched MEDLINE, EMBASE, CNKI databases, as well as the Cochrane Library for studies that examined the association between sperm morphology and unexplained RSA. Fifteen studies were identified, including 883 cases and 530 controls. Our meta-analysis results indicated that the percentage of normal sperm morphology from men with RSA partners was significantly lower than those from normal controls(SMD [95% CI]: − 0.60 [−0.81, −0.40]; P<0.00001) and the percentage of sperm morphologic alterations was significantly higher in patients with RSA compared with the control group (SMD [95% CI]: 0.92 [0.42, 1.43]; P=0.0004). The present study suggested that the percentage of normal sperm morphology may indeed decrease in men from RSA group compared with controls. However, there were some limitations in the study such as the differences in stain techniques and classification criteria. Further evidences are needed to better elucidate the relationship between sperm morphology and unexplained RSA. PMID:28903451

Do patients with unexplained physical symptoms pressurise general practitioners for somatic treatment? A qualitative study.

PubMed

Ring, Adele; Dowrick, Christopher; Humphris, Gerry; Salmon, Peter

2004-05-01

To identify the ways in which patients with medically unexplained symptoms present their problems and needs to general practitioners and to identify the forms of presentation that might lead general practitioners to feel pressurised to deliver somatic interventions. Qualitative analysis of audiorecorded consultations between patients and general practitioners. 7 general practices in Merseyside, England. 36 patients selected consecutively from 21 general practices, in whom doctors considered that patients' symptoms were medically unexplained. Inductive qualitative analysis of ways in which patients presented their symptoms to general practitioners. Although 34 patients received somatic interventions (27 received drug prescriptions, 12 underwent investigations, and four were referred), only 10 requested them. However, patients presented in other ways that had the potential to pressurise general practitioners, including: graphic and emotional language; complex patterns of symptoms that resisted explanation; description of emotional and social effects of symptoms; reference to other individuals as authority for the severity of symptoms; and biomedical explanations. Most patients with unexplained symptoms received somatic interventions from their general practitioners but had not requested them. Though such patients apparently seek to engage the general practitioner by conveying the reality of their suffering, general practitioners respond symptomatically.

Resection of isolated pelvic recurrences after colorectal surgery: long-term results and predictors of improved clinical outcome.

PubMed

Henry, Leonard R; Sigurdson, Elin; Ross, Eric A; Lee, John S; Watson, James C; Cheng, Jonathan D; Freedman, Gary M; Konski, Andre; Hoffman, John P

2007-07-01

Recurrence in the pelvis after resection of a rectal or rectosigmoid cancer presents a dilemma. Resection offers the only reasonable probability for cure, but at the cost of perioperative morbidity and potential mortality. Clinical decision making remains difficult. Patients resected with curative intent for isolated pelvic recurrences after curative colorectal surgery from 1988 through 2003 were reviewed retrospectively. Clinical and pathologic factors, salvage operations, and complications were recorded. The primary measured outcome was overall survival. Univariate and multivariate analyses were conducted to identify prognostic factors of improved outcome. Ninety patients underwent an attempt at curative resection of a pelvic recurrence with median follow-up of 31 months. Complications occurred in 53% of patients. Operative mortality was 4.4% (4 of 90). Median overall survival was 38 months, and estimated 5-year survival was 40%. A total of 51 of 86 patients had known recurrences (15 local, 16 distant, 20 both). Multivariate analysis revealed that preoperative carcinoembryonic antigen level and final margin status were statistically significant predictors of outcome. The resection of pelvic recurrences after colorectal surgery for cancer can be performed with low mortality and good long-term outcome; however, morbidity from such procedures is high. Low preoperative carcinoembryonic antigen and negative margin of resection predict improved survival.

Resection of isolated pelvic recurrences after colorectal surgery: long-term results and predictors of improved clinical outcome.

PubMed

Henry, Leonard R; Sigurdson, Elin; Ross, Eric A; Lee, John S; Watson, James C; Cheng, Jonathan D; Freedman, Gary M; Konski, Andre; Hoffman, John P

2007-03-01

Recurrence in the pelvis after resection of a rectal or rectosigmoid cancer presents a dilemma. Resection offers the only reasonable probability for cure, but at the cost of marked perioperative morbidity and potential mortality. Clinical decision making remains difficult. Patients who underwent resection with curative intent for isolated pelvic recurrences after curative colorectal surgery from 1988 through 2003 were reviewed retrospectively. Clinical and pathological factors, salvage operations, and complications were recorded. The primary measured outcome was overall survival. Univariate and multivariate analyses were conducted to identify prognostic factors of improved outcome. Ninety patients underwent an attempt at curative resection of a pelvic recurrence; median follow-up was 31 months. Complications occurred in 53% of patients. Operative mortality occurred in 4 (4.4%) of 90 patients. Median overall survival was 38 months, and estimated 5-year survival was 40%. A total of 51 of 86 patients had known recurrences (15 local, 16 distant, 20 both). Multivariate analysis revealed that preoperative carcinoembryonic antigen level and final margin status were statistically significant predictors of outcome. The resection of pelvic recurrences after colorectal surgery for cancer can be performed with low mortality and good long-term outcome; however, morbidity from such procedures is high. Low preoperative carcinoembryonic antigen and negative margin of resection predict improved survival.

Reduced Hepatic Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Level in Obesity.

PubMed

Heinrich, Garrett; Muturi, Harrison T; Rezaei, Khadijeh; Al-Share, Qusai Y; DeAngelis, Anthony M; Bowman, Thomas A; Ghadieh, Hilda E; Ghanem, Simona S; Zhang, Deqiang; Garofalo, Robert S; Yin, Lei; Najjar, Sonia M

2017-01-01

Impairment of insulin clearance is being increasingly recognized as a critical step in the development of insulin resistance and metabolic disease. The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Null deletion or liver-specific inactivation of Ceacam1 in mice causes a defect in insulin clearance, insulin resistance, steatohepatitis, and visceral obesity. Immunohistological analysis revealed reduction of hepatic CEACAM1 in obese subjects with fatty liver disease. Thus, we aimed to determine whether this occurs at the hepatocyte level in response to systemic extrahepatic factors and whether this holds across species. Northern and Western blot analyses demonstrate that CEACAM1 mRNA and protein levels are reduced in liver tissues of obese individuals compared to their lean age-matched counterparts. Furthermore, Western analysis reveals a comparable reduction of CEACAM1 protein in primary hepatocytes derived from the same obese subjects. Similar to humans, Ceacam1 mRNA level, assessed by quantitative RT-PCR analysis, is significantly reduced in the livers of obese Zucker ( fa/fa , ZDF) and Koletsky ( f/f ) rats relative to their age-matched lean counterparts. These studies demonstrate that the reduction of hepatic CEACAM1 in obesity occurs at the level of hepatocytes and identify the reduction of hepatic CEACAM1 as a common denominator of obesity across multiple species.

Combined evaluation of the Glasgow prognostic score and carcinoembryonic antigen concentration prior to hepatectomy predicts postoperative outcomes in patients with liver metastasis from colorectal cancer.

PubMed

Kobayashi, Takashi; Kawakamil, Masayo; Hara, Yoshiaki; Shioiri, Sadaaki; Yasuno, Masamichi; Teruya, Masanori; Kaminishi, Michio

2014-01-01

Little is known about the ability of the inflammation-based Glasgow prognostic score (GPS). 106 patients who underwent curative resection for colorectal liver metastasis (CRLM) were analyzed. Patients with an elevated Creactive protein concentration (>10 mg/L) and hypoalbuminemia (<35 g/L) at admission were assigned a GPS 2, those with only 1 of these biochemical abnormalities were assigned a GPS 1, and those without either abnormality were assigned a GPS 0. Multivariate analysis showed that 2 variables, carcinoembryonic antigen (CEA) concentration > 30 ng/mL and a GPS 1 or 2, were independently prognostic of survival. Patients were classified into 3 groups on the basis of these 2 variables. Patients with GPS 1 or 2 and CEA concentration > 30 ng/mL were assigned a new score of 2, those with either 1 factor were assigned a new score of 1, and those with neither factors were assigned a new score of 0. The 5-year overall survival rates of new scores of 0, 1, 2 were 71.5%, 31.6%, and 0%, respectively (P < 0.0001). This simple staging system may be able to identify a subgroup of patients who are eligible for curative resection but show poor prognosis.

AuNPs/CNOs/SWCNTs/chitosan-nanocomposite modified electrochemical sensor for the label-free detection of carcinoembryonic antigen.

PubMed

Rizwan, Mohammad; Elma, Syazwani; Lim, Syazana Abdullah; Ahmed, Minhaz Uddin

2018-06-01

In this work, a nanocomposite of gold nanoparticles (AuNPs), carbon nano-onions (CNOs), single-walled carbon nanotubes (SWCNTs) and chitosan (CS) (AuNPs/CNOs/SWCNTs/CS) was prepared for the development of highly sensitive electrochemical immunosensor for the detection of carcinoembryonic antigen (CEA), clinical tumor marker. Firstly, layer-by-layer fabrication of the CEA-immunosensors was studied using cyclic voltammetry (CV) and square wave voltammetry (SWV). By combining the advantages of large surface area and electronic properties of AuNPs, CNOs, SWCNTs, and film forming properties of CS, AuNPs/CNOs/SWCNTs/CS-nanocomposite-modified glassy carbon electrode showed a 200% increase in effective surface area and electronic conductivity. The calibration plot gave a negative linear relationship between log[concentration] of CEA and electrical current with a correlation coefficient of 0.9875. The CEA-immunosensor demonstrated a wide linear detection range of 100 fg mL -1 to 400 ng mL -1 with a low detection limit of 100 fg mL -1 . In addition to high sensitivity, reproducibility and large stability, CEA-immunosensor provided an excellent selectivity and resistant-to-interference in the presence of other antigens in serum and hence a potential to be used with real samples. Copyright © 2018 Elsevier B.V. All rights reserved.

A sensitive label-free amperometric CEA immunosensor based on graphene-nafion nanocomposite film as an enhanced sensing platform.

PubMed

Li, Yan; Yang, Wei-Kang; Fan, Man-Qi; Liu, Ao

2011-01-01

A novel approach to fabricate a label-free amperometric immunosensor for the detection of carcinoembryonic antigen (CEA) was described. Herein, methylene blue (MB), gold nanoparticles (AuNPs) and carcinoembryonic antibody (anti-CEA) were layer-by-layer assembled on the graphene-Nafion nanocomposite film-modified electrode by means of a self-assembling technique and the opposite-charged adsorption. Subsequently, the stepwise self-assembling procedure of the immunosensor was further characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The factors influencing the performance of the resulting immunosensor were studied in detail. The developed procedure showed improved features, including larger amount and higher immunoactivity of the immobilized antibody and repeatable regeneration of the sensor, as well as direct, rapid and simple determination for the antigen without multiple separation and labeling steps. The immunosensor could detect the target protein in a range of 0.5 to 120 ng/mL with a limit of 0.17 ng/mL (at 3σ). Finally, the immunosensing system was evaluated on several clinical samples. Analytical results were found to be in satisfactory agreement with those detected by the enzyme-linked immunosorbent assay (ELISA) method, indicating that this new method was a promising alternative tool for clinical diagnosis.

Simultaneous Detection of α-Fetoprotein and Carcinoembryonic Antigen Based on Si Nanowire Field-Effect Transistors.

PubMed

Zhu, Kuiyu; Zhang, Ye; Li, Zengyao; Zhou, Fan; Feng, Kang; Dou, Huiqiang; Wang, Tong

2015-08-05

Primary hepatic carcinoma (PHC) is one of the most common malignancies worldwide, resulting in death within six to 20 months. The survival rate can be improved by effective treatments when diagnosed at an early stage. The α-fetoprotein (AFP) and carcinoembryonic antigen (CEA) have been identified as markers that are expressed at higher levels in PHC patients. In this study, we employed silicon nanowire field-effect transistors (SiNW-FETs) with polydimethylsiloxane (PDMS) microfluidic channels to simultaneously detect AFP and CEA in desalted human serum. Dual-channel PDMS was first utilized for the selective modification of AFP and CEA antibodies on SiNWs, while single-channel PDMS offers faster and more sensitive detection of AFP and CEA in serum. During the SiNW modification process, 0.1% BSA was utilized to minimize nonspecific protein binding from serum. The linear dynamic ranges for the AFP and CEA detection were measured to be 500 fg/mL to 50 ng/mL and 50 fg/mL to 10 ng/mL, respectively. Our work demonstrates the promising potential of fabricated SiNW-FETs as a direct detection kit for multiple tumor markers in serum; therefore, it provides a chance for early stage diagnose and, hence, more effective treatments for PHC patients.

Detection of survivin, carcinoembryonic antigen and ErbB2 level in oral squamous cell carcinoma patients.

PubMed

Li, Shu-Xia; Yang, Yan-Qi; Jin, Li-Jian; Cai, Zhi-Gang; Sun, Zheng

2016-01-01

The aim of this study was to detect the survivin, carcinoembryonic antigen (CEA) and ErbB2 in the saliva, serum and local tumor-exfoliated cells of oral squamous cell carcinoma (OSCC) patients, for providing reliable tumor markers for the early detection of oral malignant cancer. The saliva, serum, and local tumor-exfoliated cell samples of 26 OSCC patients without chemotherapy and 10 non-cancer patients were collected in Department of Oral and Maxillofacial Surgery, School of Stomatology, Peking University. The contents of survivin, CEA and ErbB2 using were detected usingenzyme-linked immunosorbent assay. The survivin and CEA levels in saliva and local tumor-exfoliated cells of OSCC patients were significantly higher than those in the non-cancer patients (P < 0.05), but there was no significant difference in the content of the above factors in the serum sample between two groups. There was no significant difference in the ErbB2 content in the saliva, serum or local tumor-exfoliated cells between two groups. Survivin and CEA levels are significantly increased in the saliva and local tumor-exfoliated cells in OSCC patients, and they can be used as reliable markers for the early detection of oral malignant cancer.

Nanoporous gold as a solid support for protein immobilization and development of an electrochemical immunoassay for prostate specific antigen and carcinoembryonic antigen

PubMed Central

Pandey, Binod; Demchenko, Alexei V.; Stine, Keith J.

2013-01-01

Nanoporous gold (NPG) was utilized as a support for immobilizing alkaline phosphatase (ALP) conjugated to monoclonal antibodies against either prostate specific antigen (PSA) or carcinoembryonic antigen (CEA). The antibody-ALP conjugates were coupled to self-assembled monolayers of lipoic acid and used in direct kinetic assays. Using the enzyme substrate p-aminophenylphosphate, the product p-aminophenol was detected by its oxidation near 0.1 V (vs. Ag|AgCl) using square wave voltammetry. The difference in peak current arising from oxidation of p-aminophenol before and after incubation with biomarker increased with biomarker concentration. The response to these two biomarkers was linear up to 10 ng mL-1 for CEA and up to 30 ng mL-1 for PSA. The effect of interference on the PSA assay was studied using bovine serum albumin (BSA) as a model albumin protein. The effect of interference from a serum matrix was examined for the PSA assay using newborn calf serum. A competitive version of the immunoassay using antigen immobilized onto the NPG surface was highly sensitive at lower antigen concentration. Estimates of the surface coverage of the antibody-ALP conjugates on the NPG surface are presented. PMID:23935216

A high-sensitivity electrochemical aptasensor of carcinoembryonic antigen based on graphene quantum dots-ionic liquid-nafion nanomatrix and DNAzyme-assisted signal amplification strategy.

PubMed

Huang, Jing-Yi; Zhao, Lang; Lei, Wan; Wen, Wei; Wang, Yi-Jia; Bao, Ting; Xiong, Hua-Yu; Zhang, Xiu-Hua; Wang, Sheng-Fu

2018-01-15

In this work, we have developed an electrochemical aptasensor for high-sensitivity determination of carcinoembryonic antigen (CEA) based on lead ion (Pb 2+ )-dependent DNAzyme-assisted signal amplification and graphene quantum dot-ionic liquid-nafion (GQDs-IL-NF) composite film. We designed hairpin DNA containing CEA-specific aptamers and DNAzyme chains. In the presence of CEA, hairpin DNA recognized the target and performed a DNAzyme-assisted signal amplification reaction to yield a large number of single-stranded DNA. The GQDs-IL-NF composite film was immobilized on the glassy carbon electrode for the interaction with single-stranded DNA through noncovalent π-π stacking interaction. Therefore, the methylene blue-labeled substrate DNA (MB-substrate) was fixed on the electrode and exhibited an initial electrochemical signal. Under optimal conditions, the response current change was proportional to the concentration of CEA, demonstrating a wide linear range from 0.5fgmL -1 to 0.5ngmL -1 , with a low detection limit of 0.34fgmL -1 . Furthermore, the proposed aptasensor was successfully applied in determining CEA in serum samples, showing its superior prospects in clinical diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Suppression of Murine Colitis and its Associated Cancer by Carcinoembryonic Antigen-Specific Regulatory T Cells

PubMed Central

Blat, Dan; Zigmond, Ehud; Alteber, Zoya; Waks, Tova; Eshhar, Zelig

2014-01-01

The adoptive transfer of regulatory T cells (Tregs) offers a promising strategy to combat pathologies that are characterized by aberrant immune activation, including graft rejection and autoinflammatory diseases. Expression of a chimeric antigen receptor (CAR) gene in Tregs redirects them to the site of autoimmune activity, thereby increasing their suppressive efficiency while avoiding systemic immunosuppression. Since carcinoembryonic antigen (CEA) has been shown to be overexpressed in both human colitis and colorectal cancer, we treated CEA-transgenic mice that were induced to develop colitis with CEA-specific CAR Tregs. Two disease models were employed: T-cell-transfer colitis as well as the azoxymethane–dextran sodium sulfate model for colitis-associated colorectal cancer. Systemically administered CEA-specific (but not control) CAR Tregs accumulated in the colons of diseased mice. In both model systems, CEA-specific CAR Tregs suppressed the severity of colitis compared to control Tregs. Moreover, in the azoxymethane–dextran sodium sulfate model, CEA-specific CAR Tregs significantly decreased the subsequent colorectal tumor burden. Our data demonstrate that CEA-specific CAR Tregs exhibit a promising potential in ameliorating ulcerative colitis and in hindering colorectal cancer development. Collectively, this study provides a proof of concept for the therapeutic potential of CAR Tregs in colitis patients as well as in other autoimmune inflammatory disorders. PMID:24686242

Demonstration of monoclonal anti-carcinoembryonic antigen (CEA) antibody internalization by electron microscopy, western blotting and radioimmunoassay.

PubMed

Tsaltas, G; Ford, C H; Gallant, M

1992-01-01

One of the important factors affecting the action of monoclonal antibodies (Mabs) or immunoconjugates on tumour sites depends on whether the Mab is internalized by the cancer cells in question. The underexplored subject of internalization is discussed in this paper, and a number of in vitro techniques for investigating internalization are evaluated, using a model which consists of a well characterized anti-carcinoembryonic antigen (anti-CEA) Mab and a number of CEA expressing human cancer cell lines. Employing two alternative radiolabeling assays, evidence for internalization of the anti-CEA Mab by a CEA-positive colorectal cancer cell line (LS174T) was obtained throughout the time intervals examined (5 min to 150 min). Electronmicroscopy employing horseradish-peroxidase labeled anti-CEA Mab and control antibody permitted direct visualization of anti-CEA Mab-related staining in intracellular compartments of a high CEA-expressor human colorectal cell line (SKCO1). Finally Western blots of samples derived from cytosolic and membrane components of solubilized cells from lung and colonic cancer cell lines provided evidence for internalized anti-CEA Mab throughout seven half hour intervals, starting at 5 minutes. Internalized anti-CEA was detected in all CEA expressing cell lines (LS174T, SKCO1, BENN) but not in the case of a very low CEA expressor line (COLO 320).

Comparison of a chimeric anti-carcinoembryonic antigen antibody conjugated with visible or near-infrared fluorescent dyes for imaging pancreatic cancer in orthotopic nude mouse models

NASA Astrophysics Data System (ADS)

Maawy, Ali A.; Hiroshima, Yukihiko; Kaushal, Sharmeela; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael

2013-12-01

The aim of this study was to evaluate a set of visible and near-infrared dyes conjugated to a tumor-specific chimeric antibody for high-resolution tumor imaging in orthotopic models of pancreatic cancer. BxPC-3 human pancreatic cancer was orthotopically implanted into pancreata of nude mice. Mice received a single intravenous injection of a chimeric anti-carcinoembryonic antigen antibody conjugated to one of the following fluorophores: 488-nm group (Alexa Fluor 488 or DyLight 488); 550-nm group (Alexa Fluor 555 or DyLight 550); 650-nm group (Alexa Fluor 660 or DyLight 650), or the 750-nm group (Alexa Fluor 750 or DyLight 755). After 24 h, the Olympus OV100 small-animal imaging system was used for noninvasive and intravital fluorescence imaging of mice. Dyes were compared with respect to depth of imaging, resolution, tumor-to-background ratio (TBR), photobleaching, and hemoglobin quenching. The longer wavelength dyes had increased depth of penetration and ability to detect the smallest tumor deposits and provided the highest TBRs, resistance to hemoglobin quenching, and specificity. The shorter wavelength dyes were more photostable. This study showed unique advantages of each dye for specific cancer imaging in a clinically relevant orthotopic model.

Neem leaf glycoprotein enhances carcinoembryonic antigen presentation of dendritic cells to T and B cells for induction of anti-tumor immunity by allowing generation of immune effector/memory response.

PubMed

Sarkar, Koustav; Goswami, Shyamal; Roy, Soumyabrata; Mallick, Atanu; Chakraborty, Krishnendu; Bose, Anamika; Baral, Rathindranath

2010-08-01

Vaccination with neem leaf glycoprotein matured carcinoembryonic antigen (CEA) pulsed dendritic cells (DCs) enhances antigen-specific humoral and cellular immunity against CEA and restricts the growth of CEA(+) murine tumors. NLGP helps better CEA uptake, processing and presentation to T/B cells. This vaccination (DCNLGPCEA) elicits mitogen induced and CEA specific T cell proliferation, IFN gamma secretion and induces specific cytotoxic reactions to CEA(+) colon tumor cells. In addition to T cell response, DCNLGPCEA vaccine generates anti-CEA antibody response, which is principally IgG2a in nature. This antibody participates in cytotoxicity of CEA(+) cells in antibody-dependent manner. This strong anti-CEA cellular and humoral immunity protects mice from tumor development and these mice remained tumor free following second tumor inoculation, indicating generation of effector memory response. Evaluation of underlying mechanism suggests vaccination generates strong CEA specific CTL and antibody response that can completely prevent the tumor growth following adoptive transfer. In support, significant upregulation of CD44 on the surface of lymphocytes from DCNLGPCEA immunized mice was noticed with a substantial reduction in L-selectin (CD62L). (c) 2010 Elsevier B.V. All rights reserved.

Intermittent hypoxia in patients with unexplained polycythaemia.

PubMed Central

Moore-Gillon, J C; Treacher, D F; Gaminara, E J; Pearson, T C; Cameron, I R

1986-01-01

The aetiology of polycythaemia is unclear in up to 30% of patients. Twenty patients with unexplained polycythaemia were investigated to see whether they had an intermittent hypoxic stimulus to erythropoiesis that was undetected by conventional investigations for hypoxic secondary polycythaemia. Overnight polygraphic sleep studies showed that five patients had prolonged nocturnal hypoxaemia. Their arterial oxygen saturation was below 92%, the level at which appreciable hypoxic stimulation of erythropoiesis occurs, for 26-68% of the time for which they were studied. Considerable evidence is accumulating that intermittent hypoxia is a potent stimulus to erythropoiesis, and clinicians should consider the possibility of nocturnal hypoxia in patients with unexplained polycythaemia. Appropriate investigation will lead to the correct diagnosis of polycythaemia secondary to hypoxia in some cases previously regarded as idiopathic, and treatment may then be planned accordingly. PMID:3092936

Bacterial vaginosis and infertility: cause or association?

PubMed

Salah, Rasheed M; Allam, Abdelmonem M; Magdy, Amin M; Mohamed, Abeer Sh

2013-03-01

To estimate the prevalence of bacterial vaginosis (BV) in infertile women and evaluate the effect of treatment of BV on the pregnancy rate in patients with polycystic ovarian disease (PCOD) and unexplained infertility. Cohort study conducted at the Department of Obstetrics and Gynecology in collaboration with the Microbiology Department of Sohag University Hospital, Egypt. All eligible women with female factor infertility (n=874) were enrolled and all asymptomatic fertile women (n=382) attending the family planning clinic of the study hospital were recruited as a control group. The study was in two phases: the first included screening all participants for BV after Gram-staining of the vaginal discharge. The second phase was concerned with evaluating the effect of treatment of BV on the cumulative pregnancy rate (CPP) in patients with PCOD (group I; n=278) and unexplained infertility (group II; n=170). Each group was divided into three sub-groups: groups Ia (n=129) and IIa (n=73) were BV positive and treated for BV; groups Ib (n=61) and IIb (n=49) were BV positive and did not receive treatment for BV, and groups Ic (n=88) and IIc (n=48) were BV negative. The prevalence of BV was compared using the Chi-square. The long rank test of Kaplan-Meier life table analysis was used to compare the CPR. A multivariate regression model was designed to define the most significant variable which affected the pregnancy rate in patients with PCOD. The prevalence of BV was significantly higher in infertile than fertile women (45.5% vs 15.4%). The highest prevalence was found in patients with PCOD (60.1%) and unexplained infertility (37.4%). The CPR in both patients with PCOD and unexplained infertility were significantly higher in the patients who were treated for BV. Regression model showed that BV was one of the significant factors interfering with pregnancy. BV is strongly implicated in female infertility and is probably an underestimated cause of unexplained infertility. Screening and treatment of BV in patients with PCOD and unexplained infertility improved the pregnancy rate considerably. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Attachment, Symptom Severity, and Depression in Medically Unexplained Musculoskeletal Pain and Osteoarthritis: A Cross-Sectional Study

PubMed Central

Schroeter, Corinna; Ehrenthal, Johannes C.; Giulini, Martina; Neubauer, Eva; Gantz, Simone; Amelung, Dorothee; Balke, Doreen; Schiltenwolf, Marcus

2015-01-01

Background Attachment insecurity relates to the onset and course of chronic pain via dysfunctional reactions to pain. However, few studies have investigated the proportion of insecure attachment styles in different pain conditions, and results regarding associations between attachment, pain severity, and disability in chronic pain are inconsistent. This study aims to clarify the relationships between insecure attachment and occurrence or severity of chronic pain with and without clearly defined organic cause. To detect potential differences in the importance of global and romantic attachment representations, we included both concepts in our study. Methods 85 patients with medically unexplained musculoskeletal pain (UMP) and 89 patients with joint pain from osteoarthritis (OA) completed self-report measures of global and romantic attachment, pain intensity, physical functioning, and depression. Results Patients reporting global insecure attachment representations were more likely to suffer from medically unexplained musculoskeletal pain (OR 3.4), compared to securely attached patients. Romantic attachment did not differ between pain conditions. Pain intensity was associated with romantic attachment anxiety, and this relationship was more pronounced in the OA group compared to the UMP group. Both global and romantic attachment anxiety predicted depression, accounting for 15% and 17% of the variance, respectively. Disability was independent from attachment patterns. Conclusions Our results indicate that global insecure attachment is associated with the experience of medically unexplained musculoskeletal pain, but not with osteoarthritis. In contrast, insecure attachment patterns seem to be linked to pain intensity and pain-related depression in unexplained musculoskeletal pain and in osteoarthritis. These findings suggest that relationship-informed focused treatment strategies may alleviate pain severity and psychological distress in chronic pain independent of underlying pathology. PMID:25807172

Ovulation induction and controlled ovarian stimulation using letrozole gonadotropin combination: A single center retrospective cohort study.

PubMed

Arya, Sushila; Kupesic-Plavsic, Sanja; Mulla, Zuber D; Dwivedi, Alok K; Crisp, Zeni; Jose, Jisha; Noble, Luis S

2017-11-01

To assess the effect of letrozole in combination with low dose gonadotropins for ovulation induction in anovulatory infertility from polycystic ovary syndrome (PCOS) and controlled ovarian stimulation for endometriosis, and unexplained infertility patients. Retrospective cohort study in a setting of private Reproductive Endocrinology and Infertility Clinic affiliated with the University. Three hundred couples (650 cycles) requiring OI/COS for PCOS (92 patients, 195 cycles), endometriosis (89 patients, 217 cycles), and unexplained infertility (119 patients, 238 cycles). Patients received 2.5mg or 5mg letrozole for 5days (D3-D7) and recombinant follicle-stimulating hormone on alternating D3-D7 and human menopausal gonadotropin-highly purified alternating D5-D10 until growth of ideally 2 mature follicles. Ovulation was triggered with 10,000 IU of HCG. Maximum number of cycles per patient was four. Main outcome measures were clinical pregnancy rates, multiple order pregnancy rates, miscarriage rates, number of follicles and endometrial thickness on the day of HCG administration. The cumulative incidence of pregnancy was estimated as 35% (95%CI: 29%-41%) overall and was highest in patients with PCOS (36.6%), followed by unexplained infertility (34.6%) and endometriosis (32.5%). The pregnancy rates per cycle in PCOS, endometriosis and unexplained infertility patients were 17%, 13.2% and 17.2% respectively, no statistically significant difference between the groups. There were three twin pregnancies in PCOS, and one in unexplained infertility group. Monofolliculogenesis was noted in 48% of patients. Letrozole-low dose gonadotropins combination appears to be effective across different causes of infertility for superovulation. The letrozole-low dose gonadotropin combination resulted in high rate of monofolliculogenesis, low occurrence of multiple gestations and no case of OHSS or cycle cancellation. Published by Elsevier B.V.

Characteristics and clinical assessment of unexplained sudden cardiac arrest in the real-world setting: focus on idiopathic ventricular fibrillation

PubMed Central

Waldmann, Victor; Bougouin, Wulfran; Karam, Nicole; Dumas, Florence; Sharifzadehgan, Ardalan; Gandjbakhch, Estelle; Algalarrondo, Vincent; Narayanan, Kumar; Zhao, Alexandre; Amet, Denis; Jost, Daniel; Geri, Guillaume; Lamhaut, Lionel; Beganton, Frankie; Ludes, Bertrand; Bruneval, Patrick; Plu, Isabelle; Hidden-Lucet, Françoise; Albuisson, Juliette; Lavergne, Thomas; Piot, Olivier; Alonso, Christine; Leenhardt, Antoine; Lellouche, Nicolas; Extramiana, Fabrice; Cariou, Alain; Jouven, Xavier; Marijon, Eloi

2018-01-01

Abstract Aims Recent studies have shown that in more than half of apparently unexplained sudden cardiac arrests (SCA), a specific aetiology can be unmasked by a careful evaluation. The characteristics and the extent to which such cases undergo a systematic thorough investigation in real-life practice are unknown. Methods and results Data were analysed from an ongoing study, collecting all cases of out-of-hospital cardiac arrest in Paris area. Investigations performed during the index hospitalization or planned after discharge were gathered to evaluate the completeness of assessment of unexplained SCA. Between 2011 and 2016, among the 18 622 out-of-hospital cardiac arrests, 717 survivors (at hospital discharge) fulfilled the definition of cardiac SCA. Of those, 88 (12.3%) remained unexplained after electrocardiogram, echocardiography, and coronary angiography. Cardiac magnetic resonance imaging yielded the diagnosis in 25 (3.5%) cases, other investigations accounted for 14 (2.4%) additional diagnoses, and 49 (6.8%) patients were labelled as idiopathic ventricular fibrillation (IVF) (48.7 ± 15 years, 69.4% male). Among those labelled IVF, only 8 (16.3%) cases benefited from a complete workup (including pharmacological testing). Younger patients [odds ratio (OR) 6.00, 95% confidence interval (CI) 1.80–22.26] and those admitted to university centres (OR 3.60, 95% CI 1.12–12.45) were more thoroughly investigated. Genetic testing and family screening were initiated in only 9 (18.4%) and 12 (24.5%) cases, respectively. Conclusion Our findings suggest that complete investigations are carried out in a very low proportion of unexplained SCA. Standardized, systematic approaches need to be implemented to ensure that opportunities for specific therapies and preventive strategies (including relatives) are not missed. PMID:29566157

Characteristics and clinical assessment of unexplained sudden cardiac arrest in the real-world setting: focus on idiopathic ventricular fibrillation.

PubMed

Waldmann, Victor; Bougouin, Wulfran; Karam, Nicole; Dumas, Florence; Sharifzadehgan, Ardalan; Gandjbakhch, Estelle; Algalarrondo, Vincent; Narayanan, Kumar; Zhao, Alexandre; Amet, Denis; Jost, Daniel; Geri, Guillaume; Lamhaut, Lionel; Beganton, Frankie; Ludes, Bertrand; Bruneval, Patrick; Plu, Isabelle; Hidden-Lucet, Françoise; Albuisson, Juliette; Lavergne, Thomas; Piot, Olivier; Alonso, Christine; Leenhardt, Antoine; Lellouche, Nicolas; Extramiana, Fabrice; Cariou, Alain; Jouven, Xavier; Marijon, Eloi

2018-06-01

Recent studies have shown that in more than half of apparently unexplained sudden cardiac arrests (SCA), a specific aetiology can be unmasked by a careful evaluation. The characteristics and the extent to which such cases undergo a systematic thorough investigation in real-life practice are unknown. Data were analysed from an ongoing study, collecting all cases of out-of-hospital cardiac arrest in Paris area. Investigations performed during the index hospitalization or planned after discharge were gathered to evaluate the completeness of assessment of unexplained SCA. Between 2011 and 2016, among the 18 622 out-of-hospital cardiac arrests, 717 survivors (at hospital discharge) fulfilled the definition of cardiac SCA. Of those, 88 (12.3%) remained unexplained after electrocardiogram, echocardiography, and coronary angiography. Cardiac magnetic resonance imaging yielded the diagnosis in 25 (3.5%) cases, other investigations accounted for 14 (2.4%) additional diagnoses, and 49 (6.8%) patients were labelled as idiopathic ventricular fibrillation (IVF) (48.7 ± 15 years, 69.4% male). Among those labelled IVF, only 8 (16.3%) cases benefited from a complete workup (including pharmacological testing). Younger patients [odds ratio (OR) 6.00, 95% confidence interval (CI) 1.80-22.26] and those admitted to university centres (OR 3.60, 95% CI 1.12-12.45) were more thoroughly investigated. Genetic testing and family screening were initiated in only 9 (18.4%) and 12 (24.5%) cases, respectively. Our findings suggest that complete investigations are carried out in a very low proportion of unexplained SCA. Standardized, systematic approaches need to be implemented to ensure that opportunities for specific therapies and preventive strategies (including relatives) are not missed.

Ordering blood tests for patients with unexplained fatigue in general practice: what does it yield? Results of the VAMPIRE trial.

PubMed

Koch, Hèlen; van Bokhoven, Marloes A; ter Riet, Gerben; van Alphen-Jager, Jm Tineke; van der Weijden, Trudy; Dinant, Geert-Jan; Bindels, Patrick J E

2009-04-01

Unexplained fatigue is frequently encountered in general practice. Because of the low prior probability of underlying somatic pathology, the positive predictive value of abnormal (blood) test results is limited in such patients. The study objectives were to investigate the relationship between established diagnoses and the occurrence of abnormal blood test results among patients with unexplained fatigue; to survey the effects of the postponement of test ordering on this relationship; and to explore consultation-related determinants of abnormal test results. Cluster randomised trial. General practices of 91 GPs in the Netherlands. GPs were randomised to immediate or postponed blood-test ordering. Patients with new unexplained fatigue were included. Limited and expanded sets of blood tests were ordered either immediately or after 4 weeks. Diagnoses during the 1-year follow-up period were extracted from medical records. Two-by-two tables were generated. To establish independent determinants of abnormal test results, a multivariate logistic regression model was used. Data of 325 patients were analysed (71% women; mean age 41 years). Eight per cent of patients had a somatic illness that was detectable by blood-test ordering. The number of false-positive test results increased in particular in the expanded test set. Patients rarely re-consulted after 4 weeks. Test postponement did not affect the distribution of patients over the two-by-two tables. No independent consultation-related determinants of abnormal test results were found. Results support restricting the number of tests ordered because of the increased risk of false-positive test results from expanded test sets. Although the number of re-consulting patients was small, the data do not refute the advice to postpone blood-test ordering for medical reasons in patients with unexplained fatigue in general practice.

A Randomized Double-Blind Controlled Trial Comparing Davanloo Intensive Short-Term Dynamic Psychotherapy as Internet-Delivered Vs Treatment as Usual for Medically Unexplained Pain: A 6-Month Pilot Study.

PubMed

Chavooshi, Behzad; Mohammadkhani, Parvaneh; Dolatshahi, Behrouz

2016-01-01

Research has shown that Intensive Short-Term Dynamic Psychotherapy (ISTDP) can effectively decrease pain intensity and improve quality of life in patients with medically unexplained pain. Understanding that not all patients with medically unexplained pain have access to in-person ISTDP, this study aims to investigate the efficacy of an Internet-delivered ISTDP for individuals with medically unexplained pain using Skype in comparison with treatment as usual. In this randomized controlled trial, 100 patients were randomly allocated into Internet-delivered ISTDP (n = 50) and treatment-as- usual (n = 50) groups. Treatment intervention consisted of 16 weekly, hour-long therapy sessions. The primary outcome was perceived pain assessed using the Numeric Pain Rating Scale. The secondary outcome included Depression Anxiety Stress Scale-21, Emotion Regulation Questionnaire, Mindful Attention Awareness Scale, and Quality-of-Life Inventory. Blind assessments were conducted at the baseline, posttreatment, and at a 6-month follow-up. In the intention-to-treat analysis, pain symptoms in the intervention group were significantly reduced (p < 0.001), whereas a reduction was not observed in the treatment as usual group (p = 0.651). Moreover, there were significant decreases in depression, anxiety, and stress, as well as a greater increase in emotion regulation functioning, mindfulness, and quality of life observed in the intervention group 6 months after the treatment compared with the treatment as usual condition. The results of this pilot trial demonstrate that 16 weeks of ISTDP delivered by Skype can significantly improve pain intensity and clinical symptoms of medically unexplained pain. Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Unexplained lower abdominal pain associated with sacroiliac joint dysfunction: report of 2 cases.

PubMed

Morimoto, Daijiro; Isu, Toyohiko; Kim, Kyongsong; Matsumoto, Ryoji; Isobe, Masanori

2011-01-01

A 25-year-old woman and a 31-year-old man presented with chronic lower back pain and unexplained lower abdominal pain. Both patients had groin tenderness at the medial border of the anterior superior iliac spine. The results of radiographical and physical examinations suggested sacroiliac joint dysfunction. Sacroiliac joint injection relieved their symptoms, including groin tenderness. In our experience, groin tenderness is highly specific for sacroiliac joint dysfunction. We speculate that spasm of the iliac muscle can cause groin pain and tenderness. Groin pain and a history of unexplained abdominal pain, with lower back pain, are symptoms that suggest sacroiliac joint dysfunction. Additionally, compression of the iliac muscle is a simple and useful maneuver; therefore, it can be used as a screening test for sacroiliac joint dysfunction, alongside other provocation tests.

Solving medical mysteries: hidden stresses and unexplained symptoms.

PubMed

Clarke, David D

2016-09-01

Medically unexplained symptoms and chronic functional syndromes are common but few healthcare professionals have had formal training about their connection to psychosocial issues. A systematic approach to diagnosis and treatment based on experience with over 7000 of these patients is described. Outcomes improve with assessment for and treatment of current life stresses, the prolonged impact of adversity in childhood and somatic presentations of depression, post-traumatic stress, and anxiety disorders.

[The diagnostic value of medical thoracoscopy for unexplained pleural effusion].

PubMed

Jiang, Shu-juan; Mu, Xiao-yan; Zhang, Song; Su, Li-li; Ma, Wei-xia

2013-05-01

To explore the endoscopic features of patients with unexplained pleural effusion, and to evaluate the diagnostic value of medical thoracoscopy. A retrospective analysis of 2380 patients with unexplained pleural effusion (1320 males and 1060 females; age 15-94 years) in Shandong Provincial Hospital from 1992 to 2011 were performed .The diagnosis was confirmed by medical thoracoscopy. The endoscopic findings of malignant pleural effusion mostly showed nodules of varying sizes. The nodules could be grape-like, cauliflower-like, fused into masses, or diffused small nodules . The appearance of cancerous nodules was more diversified compared to tuberculous nodules. Tuberculous pleurisy was manifested as diffuse pleural congestion and miliary changes, multiple small gray-white nodules, fibrin deposition and adhesion in the pleural cavity, pleural thickening and loculation . The pathological diagnosis was as follows: pleural metastases in 899 (37.8%), primary pleural mesothelioma in 439 (18.4%), tuberculous pleurisy in 514 (21.6%), non-specific inflammation in 226 (9.5%), empyema in 190 (8.0%), hepatic pleural effusion in 36 (1.5%) and pleural effusion of unknown causes in 76 (3.2%) cases. The diagnostic positive rate of medical thoracoscopy was 96.8%. No serious complications were observed. Medical thoracoscopy is a relatively safe procedure and has an important application value in the diagnosis of unexplained pleural effusion.

Prevalence and clinical significance of antinuclear antibodies in Iranian women with unexplained recurrent miscarriage

PubMed Central

Molazadeh, Morteza; Karimzadeh, Hadi; Azizi, Mohammad R

2014-01-01

Background: Antinuclear antibodies (ANAs) in women with recurrent miscarriage have been reported. The presence of moderate to high titers of these antibodies represents an autoimmune condition that can endanger the health of the fetus in pregnant women. Objective: In this study, we evaluated the prevalence of ANAs in Iranian women with a history of two or more unexplained abortion. Materials and Methods: 560 women with unexplained recurrent miscarriage and 560 healthy controls accounted for this study over a period of 13 months. ANAs were detected by indirect immunofluorescence technique. Results: ANAs were detected in 74 of 560 (13.21%) patient with recurrent miscarriage, and in only 5 of 560 (0.9%) controls (p<0.001). ANA positivity was generally found with low-positive results (1.40-1.80) in about 38% of positive cases, whereas moderate titres (1.160-1.320) and high titres (>1.640) were seen in about 46% and 16% of cases respectively. Finally evaluating of microscopic ANA patterns revealed that about half of positive cases had antibodies against DNA- histone complex, associated with systemic lupus erythematosus disease. Conclusion: Antinuclear antibodies are not uncommon in women with unexplained recurrent miscarriage, suggesting the possible role of an autoimmune disorder on abortion, at least in a subgroup of patients. PMID:24799884

A research coding method to evaluate medical clinicians conduct of behavioral health care in patients with unexplained symptoms.

PubMed

Grayson-Sneed, Katelyn A; Smith, Robert C

2018-04-01

Develop a reliable coding method of a Behavioral Health Treatment Model for patients with Medically Unexplained Symptoms (BHTM-MUS). Two undergraduates trained for 30h coded videotaped interviews from 161 resident-simulated patient (SP) interactions. Trained on 45 videotapes, coders coded 33 (20%) of 161 study set tapes for the BHTM-MUS. Guetzkow's U, Cohen's Kappa, and percent of agreement were used to measure coders' reliability in unitizing and coding residents' skills for eliciting: education and informing (4 yes/no items), motivating (2), treatment statements (5), commitment and goals (2), negotiates plan (8), non-emotion patient-centered skills (4), and patient-centered emotional skills (8). 60 items were dichotomized a priori from analysis of the BHTM-MUS and were reduced to 33 during training. Guetzkow's U ranged from .00 to .082. Kappa ranged from 0.76 to 0.97 for the 7 variables and 33 individual items. The overall kappa was 0.87, and percent of agreement was 95.7%. Percent of agreement by item ranged from 85 to 100%. A highly reliable coding method is recommended to evaluate medical clinicians' behavioral care skills in patients with unexplained symptoms. A way to rate behavioral care in patients with unexplained symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

Trends in the earnings gender gap among dentists, physicians, and lawyers.

PubMed

Nguyen Le, Thanh An; Lo Sasso, Anthony T; Vujicic, Marko

2017-04-01

The authors examined the factors associated with sex differences in earnings for 3 professional occupations. The authors used a multivariate Blinder-Oaxaca method to decompose the differences in mean earnings across sex. Although mean differences in earnings between men and women narrowed over time, there remained large, unaccountable earnings differences between men and women among all professions after multivariate adjustments. For dentists, the unexplained difference in earnings for women was approximately constant at 62% to 66%. For physicians, the unexplained difference in earnings for women ranged from 52% to 57%. For lawyers, the unexplained difference in earnings for women was the smallest of the 3 professions but also exhibited the most growth, increasing from 34% in 1990 to 45% in 2010. The reduction in the earnings gap is driven largely by a general convergence between men and women in some, but not all, observable characteristics over time. Nevertheless, large unexplained gender gaps in earnings remain for all 3 professions. Policy makers must use care in efforts to alleviate earnings differences for men and women because measures could make matters worse without a clear understanding of the nature of the factors driving the differences. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.

Investigation of fatigue by Australian general practice registrars: a cross-sectional study.

PubMed

Morgan, Simon; Henderson, Kim M; Tapley, Amanda; Thomson, Allison; Wilson, Jessica; Scott, John; Spike, Neil A; McArthur, Lawrie; van Driel, Mieke L; Magin, Parker J

2015-06-01

Fatigue is the most common undifferentiated problem presenting in general practice. Previous studies have shown that this presentation leads to multiple investigations. There is no published literature describing the management of patients with fatigue by general practice (GP) registrars. To document the investigation-ordering behaviour of GP registrars in managing patients with a new diagnosis of unexplained fatigue. This was a cross-sectional analysis of data from Registrar Clinical Encounters in Training (ReCEnT), an ongoing cohort study of GP registrars' consultations. We established the prevalence of new diagnoses of unexplained fatigue and associations with that diagnosis, the rate of test ordering and the number and types of investigations ordered. 644 registrars contributed data from 68 986 encounters. In 0.78% of patient encounters, a new diagnosis of unexplained fatigue was made. Pathology was ordered in 78.4% of these problems (versus 18.1% in non-fatigue problems), at a rate of 488 tests per 100 new fatigue problems. Our study suggests that unexplained fatigue elicits a non-rational approach to test ordering by registrars. These findings contribute to the understanding of GP registrar management of fatigue, and undifferentiated presentations more broadly, and suggest educational approaches to improve practice, including dealing with uncertainty.

High prevalence of antibodies against hepatitis E virus in HIV-infected patients with unexplained liver disease.

PubMed

Merchante, Nicolás; Parra-Sánchez, Manuel; Rivero-Juárez, Antonio; Cifuentes, Celia; Camacho, Ángela; Macías, Juan; Martínez-Dueñas, Loreto; Pérez-Navarro, Elisabet; Rivero, Antonio; Pineda, Juan A

2015-10-01

To look for evidence of hepatitis E virus (HEV) exposure in HIV-infected patients with unexplained elevations of liver stiffness (LS). Case-control study conducted in 31 HIV-infected patients with unexplained elevations of LS and in 31 HIV-controls with normal LS, matched by age, sex and CD4 cell-counts. Serum HEV antibodies were tested by two ELISA procedures and by Immunoblot. We defined exposure to HEV as the detection of serum HEV antibodies by at least one of the two ELISA assays, provided that it was confirmed by Immunoblot. A real-time PCR RNA assay was conducted in all plasma samples to identify subjects with active HEV infection. Exposure to HEV was demonstrated, according to the criteria used in this study, in 9 (29%) of the cases, whereas it was shown in 5 (16%) of the controls (p=.3). Serum HEV RNA was detected in none of the controls and in only in one case. This patient had a documented chronic hepatitis E with progression to cirrhosis. HEV antibodies are frequently found in HIV-infected patients with unexplained liver disease. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Celiac disease and dysfunctional uterine bleeding; the efficiency of gluten free diet.

PubMed

Ehsani-Ardakani, M J; Fallahian, M; Rostami, K; Rostami-Nejad, M; Lotfi, S; Mohaghegh-Shalmani, H; Dabiri, R; Norouzinia, M; Azizpour-Shoobi, F; Zali, M R

2014-01-01

The aim of this study was to investigate the relation between Celiac disease (CD) and unexplained dysfunctional uterine bleeding (DUB) in celiac women. The celiac patients were selected from women who were referred to celiac department. Controls were selected from those women without any signs of celiac disease and matched with age. Meanwhile, a trained physician was ready to explain the study, and then in case of their allowance, a questionnaire was completed by the physician. 24 % of celiac women reported a past history of at least one menstrual cycle disorder vs 10 % of controls reported these problems (p=0.038) and higher percentage of unexplained DUB has been observed in celiac women. All celiac patients were undertaking gluten free diet for at least 3 months and the celiac patients who reported the history of DUB were again interviewed for any signs of unexplained DUB. From 12 celiac women with DUB, 10 patients reported no more unexplained DUB after getting gluten-free diet (83.3 %). The occurrence of a significant correlation between CD and DUB suggests the possibility of considering CD as one of the potential causes of abnormal uterine bleeding. Therefore, celiac disease must be seriously considered in the screening of patients with reproductive disorders (Tab. 2,Ref. 23).

Low molecular weight heparin use in unexplained recurrent miscarriage

PubMed Central

Yuksel, Halide; Kayatas, Semra; Boza, Aysen Telce; Api, Murat; Ertekin, A. Aktug; Cam, Cetin

2014-01-01

Objective: The aim of the study was to investigate whether the use of low molecular weight heparin (LMWH) improve live birth rates when compared with control group in patients with unexplained recurrent miscarriages (URM). Methods: In this prospective observational study 150 women with a history of two or more previous unexplained first trimester pregnancy loss who received LMWH; either enoxaparin (n=50), tinzaparin (n=50) or nothing (n=50) were followed for the pregnancy outcome measures. Only the patients who have used standardized dosage of LMWH (4000 IU/day enoxaparin or 3500 IU/day tinzaparin ) were included to the study. The primary end point was the live birth rate and secondary end points were the side effects, late pregnancy complications and neonatal outcome in the study cohorts. Results: Live birth was achieved 85% of the LMWH group and 66% of the control group (p=0.007). According to the subgroup analysis; live birth rates did not differ significantly between the enoxaparin and tinzaparin group (84% and 86%, respectively). Maternal and neonatal side effects were not statistically significant among the study participants. Conclusion: Thromboprophylaxis with LMWH resulted in a improved live-birth rate in patient with 2 or more consecutive unexplained recurrent pregnancy loss. Nevertheless these findings need to be confirmed in larger randomized trials. PMID:25674114

Paraoxonase-2 and paraoxonase-3: comparison of mRNA expressions in the placentae of unexplained intrauterine growth restricted and noncomplicated pregnancies.

PubMed

Dikbas, Levent; Yapca, Omer Erkan; Dikbas, Neslihan; Gundogdu, Cemal

2017-05-01

Recent evidence suggests that oxidative stress is involved in the pathophysiology of many human diseases. It has been demonstrated that oxidative stress is associated with intrauterine growth restriction (IUGR), and the depletion of placental antioxidant systems has been suggested as a key factor in this disease. Our aims were to explore the possible role of antioxidant paraoxonase-2 (PON2) and paraoxonase-3 (PON3) in the pathophysiology of unexplained IUGR. We have studied the expression of mRNA for PON2, PON3 in placental tissues by using RT-qPCR. Two groups, consisting of normal (n = 18) and unexplained IUGR pregnancies (n = 20) were compared. Our results demonstrated that there were no significant differences in the mRNA expressions of PON2, PON3 between the two groups (p = 0.28, p = 0.90, respectively). PON2 and PON3 were down-regulated in IUGR. Antenatal steroid therapy had no effect on the expression mRNA in placentae of unexplained IUGR pregnancies compared to non-treated group. These results suggest that PON2, PON3 mRNA levels were not changed significantly in placentae of IUGR when compared to normal pregnant women.

High Variability in Nosocomial Clostridium difficile Infection Rates Across Hospitals After Colorectal Resection.

PubMed

Aquina, Christopher T; Probst, Christian P; Becerra, Adan Z; Hensley, Bradley J; Iannuzzi, James C; Noyes, Katia; Monson, John R T; Fleming, Fergal J

2016-04-01

Hospital-acquired Clostridium difficile infection is associated with adverse patient outcomes and high medical costs. The incidence and severity of C. difficile has been rising in both medical and surgical patients. Our aim was to assess risk factors and variation associated with the development of nosocomial C. difficile colitis among patients undergoing colorectal resection. This was a retrospective cohort study. The study included segmental colectomy and proctectomy cases in New York State from 2005 to 2013. The study cohort included 150,878 colorectal resections. Patients with a documented previous history of C. difficile infection or residence outside of New York State were excluded. A diagnosis of C. difficile colitis either during the index hospital stay or on readmission within 30 days was the main measure. C. difficile colitis occurred in 3323 patients (2.2%). Unadjusted C. difficile colitis rates ranged from 0% to 11.3% among surgeons and 0% to 6.8% among hospitals. After controlling for patient, surgeon, and hospital characteristics using mixed-effects multivariable analysis, significant unexplained variation in C. difficile rates remained present across hospitals but not surgeons. Patient factors explained only 24% of the total hospital-level variation, and known surgeon and hospital-level characteristics explained an additional 8% of the total hospital-level variation. Therefore, ≈70% of the hospital variation in C. difficile infection rates remained unexplained by captured patient, surgeon, and hospital factors. Furthermore, there was an ≈5-fold difference in adjusted C. difficile rates across hospitals. A limited set of hospital and surgeon characteristics was available. Colorectal surgery patients appear to be at high risk for C. difficile infection, and alarming variation in nosocomial C. difficile infection rates currently exists among hospitals after colorectal resection. Given the high morbidity and cost associated with C. difficile colitis, adopting institutional quality improvement programs and maintaining strict prevention strategies are of the utmost importance.

"Unexplainable" medical histories and childhood sexual abuse. New doctoral thesis tells you how to investigate the links.

PubMed

Getz, L

1999-06-01

This is a brief summary and a personal reflection on Anne Luise Kirkengen's PhD thesis "Embodiment of sexual boundary violations in childhood". It is written to encourage other clinicians to familiarise themselves with this original and important study. It has high relevance for every clinician who is ever confronted with patients that present medical histories that are "diffuse" or unexplainable according to traditional medical knowledge.

Educational Gradients and Pathways of Disability Onset Among Older Mexicans.

PubMed

Saenz, Joseph L; Wong, Rebeca

2016-04-01

Educational disparities research is less common in developing countries. We evaluate whether educational gradients of disability onset exist in Mexico across groups (birth cohort and sex) and whether the association is unexplained or indirect via health (health behaviors, chronic conditions, and self-rated health) or economic (income, wealth, and health insurance) pathways. Data come from the Mexican Health & Aging study. Activities of daily living are reported in 2001, 2003, and 2012 by respondents and spouses aged 50+ (N = 9,560). Groups are analyzed using logistic regression to test education-disability onset associations. Significant education-ADL onset associations were observed across groups, and much of these associations were direct (unexplained by pathways). Indirect effects operated primarily through the health pathway. Those with less education were disadvantaged in terms of disability across birth cohorts and sex. Unexplained effects of education may suggest unobserved mediators or differential returns to resources by educational level. © The Author(s) 2016.

Blame, shame and hopelessness: medically unexplained symptoms and the 'heartsink' experience.

PubMed

Stone, Louise

2014-04-01

'Heartsink' patients present a moral dilemma. We recognise their suffering, but at the same time struggle with the feelings they trigger in us. Patients also experience negative feelings. Without a diagnosis they lack a narrative or vocabulary to make sense of their own suffering. This article explores some of the challenges faced and strategies utilised when managing patients with medically unexplained symptoms. Doctors and patients often experience frustration and helplessness in consultations around medically unexplained symptoms. Without a diagnosis, patients lack social legitimacy as 'sick' people with 'real' illnesses. They often describe feeling blamed for their own distress. Because of this, they can experience deep feelings of worthlessness and shame. Patients with a history of abuse can be particularly vulnerable. Management includes validating their suffering, helping them construct appropriate explanations for their distress and providing empathic interpersonal care, while minimising the risk of iatrogenic harm.

Increased Prevalence of Celiac Disease in Patients with Unexplained Infertility in the United States: A Prospective Study

PubMed Central

Lebwohl, Benjamin; Wang, Jeffrey; Lee, Susie K.; Murray, Joseph A.; Sauer, Mark V.; Green, Peter H. R.

2011-01-01

Celiac disease is an autoimmune disorder which can present with a variety of non-gastrointestinal manifestations. In women, it may manifest with an assortment of gynecologic or obstetric disorders. Some reports have linked female infertility with undiagnosed celiac disease. Though there are a number of studies from Europe and the Middle East, only two prior American studies have examined the prevalence of “silent” celiac disease in a female infertility population. We prospectively performed serologic screening for celiac disease in 188 infertile women (ages 25–39). While we did not demonstrate an increased prevalence of celiac disease in our overall infertile female population, we were able to detect a significantly increased prevalence (5.9%) of undiagnosed celiac disease among women presenting with unexplained infertility (n=51). Our findings suggest the importance of screening infertile female patients, particularly those with unexplained infertility, for celiac disease. PMID:21682114

Educational Gradients and Pathways of Disability Onset Among Older Mexicans

PubMed Central

Saenz, Joseph L.; Wong, Rebeca

2016-01-01

Introduction Educational disparities research is less common in developing countries. We evaluate whether educational gradients of disability onset exist in Mexico across groups (birth cohort and sex) and whether the association is unexplained or indirect via health (health behaviors, chronic conditions, and self-rated health) or economic (income, wealth, and health insurance) pathways. Method Data come from the Mexican Health & Aging study. Activities of daily living are reported in 2001, 2003, and 2012 by respondents and spouses aged 50+ (N = 9,560). Groups are analyzed using logistic regression to test education–disability onset associations. Results Significant education–ADL onset associations were observed across groups, and much of these associations were direct (unexplained by pathways). Indirect effects operated primarily through the health pathway. Discussion Those with less education were disadvantaged in terms of disability across birth cohorts and sex. Unexplained effects of education may suggest unobserved mediators or differential returns to resources by educational level. PMID:26966253

Elevated Squamous Cell Carcinoma Antigen, Cytokeratin 19 Fragment, and Carcinoembryonic Antigen Levels in Diabetic Nephropathy

PubMed Central

Chen, Jianzhong; Zhang, Bin; Chen, Qingguang; Qiu, Yan; Luo, Qian; Gen, Yanna; Meng, Jiali

2017-01-01

Objective We aimed to explore whether squamous cell carcinoma antigen (SCC), cytokeratin 19 fragment (Cyfra21-1), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) are elevated in diabetic nephropathy (DN) and the association between urinary albumin-to-creatinine ratio (UACR) and tumor markers in diabetic patients. Methods Nondialysis patients with diabetes (n = 261) and 90 healthy controls were enrolled. DN was defined as an UACR ≥ 30 mg/g in the absence of a urinary tract infection or other renal abnormalities. Results Patients with DN had significantly higher serum SCC, Cyfra21-1, and CEA levels than those with normoalbuminuria and healthy controls. The rates of positive SCC, Cyfra21-1, and CEA significantly increased with increasing urinary albumin excretion (all P for trend < 0.001). In contrast, NSE was not affected by DN. SCC, Cyfra21-1, and CEA were significantly and positively correlated with UACR. In logistic regression, after multivariable adjustment, increased UACR was associated with increased odds ratio of elevated tumor marker levels (all P for trend < 0.05). Conclusions Serum levels of SCC, Cyfra21-1, and CEA are markedly increased with increasing urinary albumin excretion, which affects the specificity for diagnosis for lung cancer. Appropriate interpretation of tumor markers in diabetic patients is mandatory to avoid unnecessary and even hazardous biopsies. PMID:28744310

Negative serum carcinoembryonic antigen has insufficient accuracy for excluding recurrence from patients with Dukes C colorectal cancer: analysis with likelihood ratio and posttest probability in a follow-up study.

PubMed

Hara, Masayasu; Kanemitsu, Yukihide; Hirai, Takashi; Komori, Koji; Kato, Tomoyuki

2008-11-01

This study was designed to determine the efficacy of carcinoembryonic antigen (CEA) monitoring for screening patients with colorectal cancer by using posttest probability of recurrence. For this study, 348 (preoperative serum CEA level elevated: CEA+, n = 119; or normal: CEA-, n = 229) patients who had undergone potentially curative surgery for colorectal cancer were enrolled. After five-year follow-up with measurements of serum CEA levels and imaging workup, posttest probabilities of recurrence were calculated. Recurrence was observed in 39 percent of CEA+ patients and 30 percent in CEA- patients, and CEA levels were elevated in 33.3 percent of CEA+ patients and 17.5 percent of CEA- patients. With obtained sensitivity (68.4 percent, CEA+; 41 percent, CEA-), specificity (83 percent, CEA+; 91 percent, CEA-) and likelihood ratio (test positive: 4.0, CEA+; 4.4, CEA-; and test negative: 0.38, CEA+; 0.66, CEA-), posttest probability given the presence of CEA elevation in the CEA+ and CEA- was 72.2 and 65.5 percent, respectively, and that given the absence of CEA elevation was 20 and 22.2 percent, respectively. Whereas postoperative CEA elevation indicates recurrence with high probability, a normal postoperative CEA is not useful for excluding the probability of recurrence.

Lectin-Based Assay for Glycoform-Specific Detection of α2,6-sialylated Transferrin and Carcinoembryonic Antigen in Tissue and Body Fluid.

PubMed

Ito, Hiromi; Hoshi, Kyoka; Honda, Takashi; Hashimoto, Yasuhiro

2018-05-30

Antibodies are useful for detecting glycoprotein antigens, but a conventional antibody recognizes only a protein epitope rather than a glycan. Thus, glycan isoform detection generally requires time- and labor-consuming processes such as lectin affinity column chromatography followed by sandwich ELISA. We recently found antigen-antibody reactions that were inhibited by lectin binding to glycans on the glycoprotein antigen, leading to a convenient glycoform-specific assay. Indeed, Sambucus sieboldiana agglutinin (SSA) lectin, a binder to sialylα2,6galactose residue, inhibited antibody binding to α2,6-sialylated transferrin (Tf) (SSA inhibition). SSA inhibition was not observed with other glycoforms, such as periodate-treated, sialidase-treated and sialidase/galactosidase-treated Tf, suggesting that the assay was glycoform-specific. SSA inhibition was also applicable for visualizing localization of α2,6-sialylated-Tf in a liver section. This is the first immunohistochemical demonstration of glycoform localization in a tissue section. SSA inhibition was utilized for establishing ELISA to quantify α2,6-sialylated carcinoembryonic antigen (CEA), a marker for various cancers. In addition, α2,6-sialylated-CEA was visualized in a colonic adenocarcinoma section by SSA inhibition. The method would further be applicable to a simple and rapid estimation of other α2,6-sialylated glycoproteins and have a potential aid to histopathological diagnosis.

Corticotropin-Releasing Hormone Modulates Human Trophoblast Invasion through Carcinoembryonic Antigen-Related Cell Adhesion Molecule-1 Regulation

PubMed Central

Bamberger, Ana-Maria; Minas, Vassilis; Kalantaridou, Sophia N.; Radde, Jessica; Sadeghian, Helen; Löning, Thomas; Charalampopoulos, Ioannis; Brümmer, Jens; Wagener, Christoph; Bamberger, Christoph M.; Schulte, Heinrich M.; Chrousos, George P.; Makrigiannakis, Antonis

2006-01-01

Abnormalities in the process of trophoblast invasion may result in abnormal placentation. Both the embryonic trophoblast and maternal decidua produce corticotropin-releasing hormone (CRH), which promotes implantation. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), which is expressed in extravillous trophoblasts (EVTs) of normal human placenta, may also function in tro-phoblast/endometrial interactions. We investigated whether locally produced CRH plays a role in trophoblast invasion, primarily by regulating CEACAM1 expression. We examined cultures of freshly isolated human EVTs, which express CEACAM1, and an EVT-based hybridoma cell line, which is devoid of endogenous CEACAM1. CRH inhibited EVT invasion in Matrigel invasion assays, and this effect was blocked by the CRH receptor type 1 (CRHR1)-specific antagonist antalarmin. Additionally, CRH decreased CEACAM1 expression in EVTs in a dose-dependent manner. After transfection of the hybridoma cell line with a CEACAM1 expression vector, the invasiveness of these cells was strongly enhanced. This effect was inhibited by addition of blocking monoclonal antibody against CEACAM1. Furthermore, blocking of endogenous CEACAM1 in EVTs inhibited the invasive potential of these cells. Taken together these findings suggest that CRH inhibits trophoblast invasion by decreasing the expression of CEACAM1 through CRHR1, an effect that might be involved in the pathophysiology of clinical conditions, such as preeclampsia and placenta accreta. PMID:16400017

Cytokine-induced CEACAM1 expression on keratinocytes is characteristic for psoriatic skin and contributes to a prolonged lifespan of neutrophils.

PubMed

Rahmoun, Massilva; Molès, Jean-Pierre; Pedretti, Nathalie; Mathieu, Marc; Fremaux, Isabelle; Raison-Peyron, Nadia; Lecron, Jean-Claude; Yssel, Hans; Pène, Jérôme

2009-03-01

Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) is a cell-surface glycoprotein, belonging to the carcinoembryonic antigen family, expressed by human neutrophils, epithelial cells, activated T and NK cells. CEACAM1 is expressed as a cell-surface molecule with different isoforms or can be secreted as a soluble protein. Here, we show that keratinocytes in the outer epidermal layer of psoriatic skin express CEACAM1, unlike those in healthy skin or in cutaneous lesions of patients with atopic or nummular dermatitis. Stimulation of primary human keratinocytes or in vitro reconstituted epidermis with culture supernatants of activated psoriatic lesion-infiltrating T cells, IFN-gamma or oncostatin M, but not IL-17, induced the expression of transcripts for the CEACAM1-long and -short isoforms and cell-surface CEACAM1, whereas soluble CEACAM1 was not produced. The uppermost layers of the epidermis in psoriatic lesions also contain neutrophils, a cell type with inflammatory and antimicrobial properties. Coculture of CEACAM1-expressing keratinocytes or CHO transfectants with neutrophils delayed spontaneous apoptosis of the latter cells. These results show that cytokine-induced cell-surface expression of CEACAM1 by keratinocytes in the context of a psoriatic environment might contribute to the persistence of neutrophils and thus to ongoing inflammation and the decreased propensity for skin infection, typical for patients with psoriasis.

Effect of heterogeneity of carcinoembryonic antigen on liver cell membrane binding and its kinetics of removal from circulation.

PubMed

Byrn, R A; Medrek, P; Thomas, P; Jeanloz, R W; Zamcheck, N

1985-07-01

Carcinoembryonic antigen (CEA) is a glycoprotein metabolized primarily by the liver. Subcellular fractions of rat liver were examined for CEA binding activity. Hepatocyte plasma membrane and microsome fractions bound CEA, and this binding shared the calcium requirement, neuraminidase sensitivity, and carbohydrate specificity of the hepatocyte asialoglycoprotein receptor. CEA had previously been shown to react with this galactose-specific receptor, in vivo, only following neuraminidase treatment. Galactose receptor binding of CEA was measured in three different purified CEA preparations. The fraction of CEA capable of binding to excess levels of galactose receptor on membranes varied (46.5%, 40.2%, and 4.7% for CEA-1, -2, and -3, respectively). These CEAs were shown to be 2.3%, 7.9%, and 0.7% as effective, respectively, as asialo-alpha 1-acid glycoprotein in inhibiting the binding of radiolabeled asialo-alpha 1-acid glycoprotein to liver cell membranes. Each of the three CEA preparations showed different clearance kinetics from the circulation of mice. Coinjection of asialo-alpha 1-acid glycoprotein with the CEAs revealed differing inhibition of the clearances. These results show that differences in the carbohydrate components of purified CEA preparations affect their rate of removal from circulation and thus possibly the relationship between CEA production and observed plasma levels in patients. The possible origin of these CEA differences is discussed with their clinical implications.

Quantitative analysis of antigen for the induction of tolerance in carcinoembryonic antigen transgenic mice.

PubMed Central

Hasegawa, T; Isobe, K; Nakashima, I; Shimokata, K

1992-01-01

In order to analyse the amounts of antigen in the thymus for the induction of tolerance, several carcinoembryonic antigen (CEA) transgenic lines were established which expressed human CEA antigen with different amounts. The chimeric KSN nude mice transplanted with the thymus of the B601 line (in which CEA mRNA and CEA protein could be detected in various tissues) to kidney capsule showed tolerance to human CEA. On the other hand, the chimeric KSN nude mice transplanted with the thymus of the B602 or BC60 line (in which neither CEA mRNA nor CEA protein could be detected by Northern blot analysis and flow cytometry analysis) or normal C57BL/6 (B6) did not develop the tolerance to human CEA. However, the chimeric KSN nude mice transplanted simultaneously with thymus of the B6 and spleen of the B601 line became tolerant to human CEA antigen. In the case of systemic immunization with cells which had CEA antigen, the B601 line was tolerant to human CEA. Surprisingly, the B602 and BC60 lines were also tolerant to CEA molecule. These results indicate that not only the antigen present in the thymus but also the antigen which flows from the peripheral organs to the thymus may be necessary for the induction of CEA tolerance. Images Figure 1 PMID:1493931

Polyethylene Glycol (PEG) Linked to Near Infrared (NIR) Dyes Conjugated to Chimeric Anti-Carcinoembryonic Antigen (CEA) Antibody Enhances Imaging of Liver Metastases in a Nude-Mouse Model of Human Colon Cancer

PubMed Central

Maawy, Ali A.; Hiroshima, Yukihiko; Zhang, Yong; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael

2014-01-01

We report here that polyethylene glycol (PEG) linked to near infrared dyes conjugated to chimeric mouse-human anti-carcinoembryonic antigen (CEA) antibody greatly improves imaging of liver metastases in a nude mouse model of colon-cancer experimental metastases. PEGylated and non-PEGylated DyLight 650 and 750 dyes were conjugated to the chimeric anti-CEA antibody. The dyes were initially injected intravenously into nude mice without tumors. Tissue biodistribution was determined by tissue sonication and analyzing tissue dye concentration profiles over time. PEGylated dyes had significantly lower accumulation in the liver (p = 0.03 for the 650 dyes; p = 0.002 for the 750 dyes) compared to non-PEGylated dyes. In an experimental liver metastasis model of HT-29 colon cancer, PEGylated dyes conjugated to the anti-CEA antibody showed good labeling of metastatic tumors with high contrast between normal and malignant tissue which was not possible with the non-PEGylated dyes since there was so much non-specific accumulation in the liver. PEGylation of the DyLight 650 and 750 NIR dyes significantly altered tissue biodistribution, allowing brighter tissue labeling, decreased accumulation in normal organs, particularly the liver. This enabled high fidelity and high contrast imaging of liver metastases. PMID:24859320

Importance of the Postoperative Carcinoembryonic Antigen Level during Follow-Up after Curative Resection in Patients with Liver Metastatic Colorectal Carcinoma.

PubMed

Hashimoto, Takuzo; Itabashi, Michio; Ogawa, Shinpei; Hirosawa, Tomoichiro; Bamba, Yoshiko; Kaji, Sanae; Ubukata, Mamiko; Shimizu, Satoru; Sugihara, Kenichi; Kameoka, Shingo

2014-06-01

To validate the conventional Japanese grading of liver metastasis for no residual tumor resection in Stage IV colorectal cancer (CRC) with liver metastasis and to identify risk factors for postoperative recurrence. The subjects of this study were 1792 Stage IV CRC patients with liver metastasis. In 1792 cases, including unresectable cases, there was a significantly different prognosis by grade (P < 0.0001). In 421 R0 cases, there was no significant difference between Grade A and Grade B (P = 0.8527). In 381 cases without extra-hepatic metastasis, the prognosis was not significantly different among three grades. On multivariate analysis, carcinoembryonic antigen within 3 months from R0 operation (3M-CEA) was an independent risk factor regardless of extrahepatic metastasis. There was a significantly different prognosis (P < 0.0001) among Grade A', defined as a normal 3M-CEA level, Grade B', defined as Grade A or B and an abnormal 3M-CEA level, and Grade C', defined as Grade C and an abnormal 3M-CEA level. The postoperative CEA level is an important risk factor during follow-up after curative resection in patients with liver metastatic colorectal carcinoma. The combination of the 3M-CEA level and conventional grading of liver metastasis is useful for follow-up of R0 resection cases.

The course of newly presented unexplained complaints in general practice patients: a prospective cohort study.

PubMed

Koch, H; van Bokhoven, M A; Bindels, P J E; van der Weijden, T; Dinant, G J; ter Riet, G

2009-12-01

Newly presented unexplained complaints (UCs) are common in general practice. Factors influencing the transition of newly presented into persistent UCs have been scarcely investigated. We studied the number and the nature of diagnoses made over time, as well as factors associated with UCs becoming persistent. Finally, we longitudinally studied factors associated with quality of life (QoL). Prospective cohort study in general practice of patients presenting with a new UC. Data sources were case record forms, patient questionnaires and electronic medical registries at inclusion, 1, 6 and 12 months. Presence of complaints and diagnoses made over time were documented. Potential risk factors were assessed in mixed-effect logistic and linear regression models. Sixty-three GPs included 444 patients (73% women; median age 42) with unexplained fatigue (70%), abdominal complaints (14%) and musculoskeletal complaints (16%). At 12 months, 43% of the patients suffered from their initial complaints. Fifty-seven percent of the UCs remained unexplained. UCs had (non-life-threatening) somatic origins in 18% of the patients. QoL was often poor at presentation and tended to remain poor. Being a male [odds ratio (OR) 0.6; 95% confidence interval (CI) 0.4-0.8] and GPs' being more certain about the absence of serious disease (OR 0.9; 95% CI 0.8-0.9) were the strongest predictors of a diminished probability that the complaints would still be present and unexplained after 12 months. The strongest determinants of complaint persistence [regardless of (un)explicability] were duration of complaints >4 weeks before presentation (OR 2.6; 95% CI 1.6-4.3), musculoskeletal complaint at baseline (OR 2.3; 1.2-4.5), while the passage of time acted positively (OR 0.8 per month; 95% CI 0.78-0.84). Musculoskeletal complaints, compared to fatigue, decreased QoL on the physical domain (4.6 points; 2.6-6.7), while presence of psychosocial factors decreased mental QoL (5.0; 3.1-6.9). One year after initial presentation, a large proportion of newly presented UCs remained unexplained and unresolved. We identified determinants that GPs might want to consider in the early detection of patients at risk of UC persistence and/or low QoL.

'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass.

PubMed

Gregson, C L; Steel, S A; O'Rourke, K P; Allan, K; Ayuk, J; Bhalla, A; Clunie, G; Crabtree, N; Fogelman, I; Goodby, A; Langman, C M; Linton, S; Marriott, E; McCloskey, E; Moss, K E; Palferman, T; Panthakalam, S; Poole, K E S; Stone, M D; Turton, J; Wallis, D; Warburton, S; Wass, J; Duncan, E L; Brown, M A; Davey-Smith, G; Tobias, J H

2012-02-01

High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m(2), p < 0.001). Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.

Medically unexplained dyspnoea and panic.

PubMed

Hauzer, Rose; Verheul, Willeke; Griez, Eric; Wesseling, Geertjan; van Duinen, Marlies

2015-07-01

Medically unexplained dyspnoea in the pulmonary setting is often accompanied by considerable levels of anxiety, suggestive of psychopathology, in particular panic disorder (PD). This pilot study investigates the value of the Multidimensional Dyspnea Profile as a tool to facilitate identification of a specific dyspnoea profile suggestive of comorbid PD. The verbal descriptors, feeling depressed, air hunger and concentrating on breathing, significantly differentiated between the two groups of patients with pulmonary disease with and without PD. © 2015 Asian Pacific Society of Respirology.

Medically unexplained physical symptoms, misunderstood and wrongly treated? A semiotic perspective on chronic pain.

PubMed

Busvold, Kari Irene H; Bondevik, Hilde

2018-06-01

Medically unexplained physical symptoms (MUPS) are a significant and increasing health issue in the western world. Chronic pain constitutes a considerable element of these symptoms, and the lack of a biomedical explanation of their cause challenges the clinical encounter. The limitations of biomedicine become evident in these encounters and expose the need for an expanded understanding of body and symptom. Semiotics, as an anti-dualistic meta-theory, closes the gap between natural science and the humanities and views the human body in an evolutionary and existential perspective. By focusing on interpretation and communication of signs as ongoing processes at all levels of life, biology and experience, the subjective and the measurable will be integrated. A special type of sign, the self-referential, is part of the body's internal communication. These signs may be viewed as the body's warnings to itself, for instance when the individual's consciousness, thought and action run counter to the organism's physiological and psychological needs. In a semiotic perspective, existential conditions may also activate the body's defense systems. In this context, the unexplained pain may be understood as a functional warning sign. The enhanced understanding of body and symptom that a semiotic approach calls for is relevant for the work of physiotherapists and may lead to more constructive clinical encounters with patients with unexplained chronic pain.

Ongoing pregnancies in patients with unexplained recurrent pregnancy loss: adverse obstetric outcomes.

PubMed

Cozzolino, Mauro; Rizzello, Francesca; Riviello, Chiara; Romanelli, Chiara; Coccia Elisabetta, Maria

2018-05-25

To investigate the incidence of adverse pregnancy outcomes in couples with an unexplained Recurrent Pregnancy Loss (RPL) history, a retrospective cohort study was conducted between 2014 and 2015. The study group (A) included couples with an unexplained RPL, and the control group (B) was composed of couples who attended the Low-Risk Antenatal Unit during the same period. On the other hand, 53 couples were included in the study group (A) and on the other hand, 65 in the control group (B). Women with previous unexplained recurrent pregnancies loss had a significantly increased risk of gestational diabetes with 12 cases (22.6%) in the study group and 3 cases (4.6%) in the control (OR: 6.048; 95% CI: 1.607-22.762; p = 0.007). A slight increase in the risk of preterm delivery and hepatic cholestasis was observed in the study group (6 cases, 11.3%, in study group and 1 case, 1.5% in the controls (OR: 8.170; 95% CI: 0.951-70.158; p = 0.0555). Women with a history of RPL delivered more frequently by caesarean section (OR: 3.252; 95% CI: 1.460-7.241; p = 0.0039). Women with a history of RPL were at an increased risk for adverse pregnancy outcomes, mainly gestational diabetes. Therefore, a closer surveillance during the antenatal period is recommended in this group of patients.

Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?

PubMed

Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Roussel, Nathalie; De Kooning, Margot; Ickmans, Kelly; Matic, Milica

2011-05-01

Central sensitization accounts for chronic 'unexplained' pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients. This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed. Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2δ) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that - theoretically - desensitize the CNS in humans. To provide a comprehensive treatment for 'unexplained' chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization. © 2011 Informa UK, Ltd

Motilin-induced gastric contractions signal hunger in man.

PubMed

Tack, J; Deloose, E; Ang, D; Scarpellini, E; Vanuytsel, T; Van Oudenhove, L; Depoortere, I

2016-02-01

Hunger is controlled by the brain, which receives input from signals of the GI tract (GIT). During fasting, GIT displays a cyclical motor pattern, the migrating motor complex (MMC), regulated by motilin. To study the relationship between hunger and MMC phases (I-III), focusing on spontaneous and pharmacologically induced phase III and the correlation with plasma motilin and ghrelin levels. The role of phase III was also studied in the return of hunger after a meal in healthy individuals and in patients with loss of appetite. In fasting healthy volunteers, mean hunger ratings during a gastric (62.5±7.5) but not a duodenal (40.4±5.4) phase III were higher (p<0.0005) than during phase I (27.4±4.7) and phase II (37±4.5). The motilin agonist erythromycin, but not the cholinesterase inhibitor neostigmine, induced a premature gastric phase III, which coincided with an increase in hunger scores from 29.2±7 to 61.7±8. The somatostatin analogue octreotide induced a premature intestinal phase III without a rise in hunger scores. Hunger ratings significantly correlated (β=0.05; p=0.01) with motilin plasma levels, and this relationship was lost after erythromycin administration. Motilin, but not ghrelin administration, induced a premature gastric phase III and a rise in hunger scores. In contrast to octreotide, postprandial administration of erythromycin induced a premature gastric phase III accompanied by an early rise in hunger ratings. In patients with unexplained loss of appetite, gastric phase III was absent and hunger ratings were lower. Motilin-induced gastric phase III is a hunger signal from GIT in man. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Can marital selection explain the differences in health between married and divorced people? From a longitudinal study of a British birth cohort.

PubMed

Cheung, Y B

1998-03-01

In view of the rising divorce rates, the impact of divorce on health has an increasing importance in public health. The differentials in health between the married and the divorced may be explained by 'marital selection' and 'marital protection'. Using longitudinal data from a study of the 1958 British birth cohort, factors that select people into divorce were identified from the areas of socio-economic status, health, and attractiveness, which included physical attractiveness, health-related behaviour and temperament. Evidence for both positive and adverse selection is found. The different sets of selection factors for females and males appear to be in line with gender role expectations. The health differentials between married and divorced men were weak and can be explained away by the selection factors. Having controlled for the selection effects, there were still significant associations between divorce and physical and psychological health in women. Though these unexplained differentials cannot be definitely interpreted as the consequences of marital dissolution, this interpretation remains plausible.

Outburst Cycle of the Dwarf Nova SS Cygni

NASA Astrophysics Data System (ADS)

Voikhanskaya, N. F.

2018-01-01

Extensive observational data obtained to date is analyzed with special attention given to space observations. The spectral type of the white dwarf is estimated and it is concluded that accretion of matter on it is the only source of the x-ray flux in the system. The rotation of the secondary is shown to be synchronous and therefore its illumination by hard x-rays results in the formation of stellar wind. This is the main mechanism of mass transfer onto the white dwarf. The geometry of the system prevents the formation of the disk by stellar wind. Instead, stellar wind forms a quasispherical envelope whose variability influences the outburst process. Based on these conclusions, the properties of the system are interpreted, which so far have remained unexplained: short-term appearance of peculiar spectrum during the rising phase of the outburst, rather constant width of absorption lines during the outburst, decrease of the width of emission lines during the outburst, variation of the x-ray and ultraviolet fluxes during ordinary and low-amplitude anomalous outbursts, and, finally, the quasiperiodicity of the outbursts.

Modeling the Population-Level Processes of Biodiversity Gain and Loss at Geological Timescales.

PubMed

Fortelius, Mikael; Geritz, Stefan; Gyllenberg, Mats; Raia, Pasquale; Toivonen, Jaakko

2015-12-01

The path of species diversification is commonly observed by inspecting the fossil record. Yet, how species diversity changes at geological timescales relate to lower-level processes remains poorly understood. Here we use mathematical models of spatially structured populations to show that natural selection and gradual environmental change give rise to discontinuous phenotype changes that can be connected to speciation and extinction at the macroevolutionary level. In our model, new phenotypes arise in the middle of the environmental gradient, while newly appearing environments are filled by existing phenotypes shifting their adaptive optima. Slow environmental change leads to loss of phenotypes in the middle of the extant environmental range, whereas fast change causes extinction at one extreme of the environmental range. We compared our model predictions against a well-known yet partially unexplained pattern of intense hoofed mammal diversification associated with grassland expansion during the Late Miocene. We additionally used the model outcomes to cast new insight into Cope's law of the unspecialized. Our general finding is that the rate of environmental change determines where generation and loss of diversity occur in the phenotypic and physical spaces.

Recent advances in primary ciliary dyskinesia genetics

PubMed Central

Kurkowiak, Małgorzata; Ziętkiewicz, Ewa; Witt, Michał

2015-01-01

Primary ciliary dyskinesia (PCD) is a rare genetically heterogeneous disorder caused by the abnormal structure and/or function of motile cilia. The PCD diagnosis is challenging and requires a well-described clinical phenotype combined with the identification of abnormalities in ciliary ultrastructure and/or beating pattern as well as the recognition of genetic cause of the disease. Regarding the pace of identification of PCD-related genes, a rapid acceleration during the last 2–3 years is notable. This is the result of new technologies, such as whole-exome sequencing, that have been recently applied in genetic research. To date, PCD-causative mutations in 29 genes are known and the number of causative genes is bound to rise. Even though the genetic causes of approximately one-third of PCD cases still remain to be found, the current knowledge can already be used to create new, accurate genetic tests for PCD that can accelerate the correct diagnosis and reduce the proportion of unexplained cases. This review aims to present the latest data on the relations between ciliary structure aberrations and their genetic basis. PMID:25351953

The effectiveness, safety, and economic evaluation of Korean medicine for unexplained infertile women: A multi-center, prospective, observational study protocol.

PubMed

Kim, Su-Hyun; Jo, Junyoung; Kim, Dong-Il

2017-12-01

Infertility is a condition in which a woman has not been pregnant despite having had normal intercourse for 1 year. The number of unexplained infertile females is increasing because of late marriage customs, as well as environmental and lifestyle habits. In Korea, infertile females have been treated with Korean medicine (KM). However, these effects have not been objectively confirmed through clinical trials. Therefore, this study was conducted to demonstrate the effectiveness of herbal medicine treatment in infertile patients and to demonstrate the economic feasibility through economical evaluation with assisted reproductive technology.This study is designed as a multicenter, single-arm clinical trial. All participants included will be from 3 Korean Medicine hospitals in Korea and will voluntarily sign an informed consent agreement. All recruited patients will conduct related surveys and tests, and be provided with treatment according to their menstrual cycle. Patients will take herbal medicines for 4 menstruation cycles and receive acupuncture and moxibustion treatment at 3 times (menstrual cycle day 3, 8, 14) during 4 menstruation cycles. They will also undergo an approximately 4 menstrual cycle treatment period, and 3 menstrual cycle observation period. If pregnant during the study, participants will take the herbal medicine for implantation for about 15 days. In this study, the primary outcome will be the clinical pregnancy rate, whereas the secondary outcome will include the implantation rate, ongoing pregnancy rate, and live birth rate.Ultimately, this study will provide clinical data regarding the effectiveness and safety of KM treatment for females with unexplained infertility and important evidence for establishing standard KM treatments for unexplained infertility. Moreover, we will identify the most cost-effective way to treat unexplained infertility. Korean Clinical Trial Registry (CRIS), Republic of Korea: KCT0002235. Date: February 21, 2017 (retrospectively registered). Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Determinants of fertility and reproductive success after hysteroscopic septoplasty for women with unexplained primary infertility: a prospective analysis of 88 cases.

PubMed

Shokeir, Tarek; Abdelshaheed, Mahmoud; El-Shafie, Mohamed; Sherif, Lotfy; Badawy, Ahmed

2011-03-01

To evaluate prospectively the effect of hysteroscopic septoplasty as therapy for unexplained primary infertility in women with uterine septum as a sole cause for reproductive failure and to define the factors influencing reproductive success. In a prospective comparative study, we enrolled 103 infertile women with uterine septum as a sole cause for reproductive failure. They had had unexplained primary infertility >2 years and a follow-up >12 months. Uterine anomalies were diagnosed by means of hysterosalpingography (HSG) and 2D-transvaginal sonography (TVS) with intrauterine saline infusion. Hysteroscopic septoplasty was performed in the early follicular phase. Pregnancy rates (PR) according to patient and septum characteristics (septum size) were the main outcome measures. Follow-up was complete for 88 patients. The mean (±SD) age of the patients was 36.1±2.1 years. Forty-two patients became pregnant (40.7%). The mean (±SD) delay in conception was 7.5±2.6 months. Nearly 80% of the pregnant women conceived spontaneously. Of 44 pregnancies in 42 women, 36 live newborns were delivered. The PR was significantly higher in women <35 years of age or with <3 years of unexplained primary infertility. Moreover, in women with a septum size larger than one-half of their uterine length the PR was significantly higher than those with septum size <1/2 of their uterus (P=.12). Fertility and pregnancy after hysteroscopic septoplasty in women with unexplained primary infertility and uterine septum as a sole cause for reproductive failure seems to depend on patient age, duration of infertility before septoplasty, and septum size. Women with a septum size larger than one-half of their uterine length have a higher chance of successful pregnancy after hysteroscopic septoplasty. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Kisspeptin: A Potential Factor for Unexplained Infertility and Impaired Embryo Implantation

PubMed Central

Mumtaz, Aaida; Khalid, Aqsa; Jamil, Zehra; Fatima, Syeda Sadia; Arif, Sara; Rehman, Rehana

2017-01-01

Background Kisspeptin (KP) is a neuropeptide that causes the release of the gonadotropin releasing hormone, which controls hypothalamo pituitary ovarian axis and exerts a number of peripheral effects on reproductive organs. The primary objective of this study was to compare baseline KP levels in females with different types of infertility and identify possible correlations with risk of failure to conceive, preclinical abortion and pregnancy after intracytoplasmic sperm injection (ICSI). Materials and Methods A longitudinal cohort study was carried out from August 2014 until May 2015 by recruiting 124 female patients undergoing ICSI, after obtaining ethical approval from the Australian Concept Infertility Medical Center. Cause of infertility due to male, female and unexplained factors was at a frequency of 32 (24%), 33 (31%) and 59 (45%) among the individuals respectively. KP levels were measured by ELISA assay before the initiation of the ICSI treatment protocol. Outcome of ICSI was categorized into three groups of non-pregnant with beta-human chorionic gonadotropin (β-hCG)<5-25 mIU/ml, preclinical abortion with β-hCG>25 mIU/ml and no cardiac activity, and clinical pregnancy declared upon confirmation of cardiac activity. Results based on cause of infertility and outcome groups were analyzed by one-way ANOVA. Results Females with unexplained infertility had significantly lower levels of KP when compared with those with male factor infertility (176.69 ± 5.03 vs. 397.6 ± 58.2, P=0.001). Clinical pregnancy was observed in 28 (23%) females of which 17 (71%) had a female cause of infertility. In the non-pregnant group of 66 (53%) females, common cause of infertility was unexplained 56(85%). A weak positive correlation of KP levels with fertilized oocytes and endometrial thickness was observed (P=0.04 and 0.01 respectively). Conclusion Deficiency of KP in females with unexplained infertility was associated with reduced chances of implantation after ICSI. PMID:28670427

Nonulcer dyspepsia.

PubMed Central

Thompson, W. G.

1984-01-01

One third to one half of cases of dyspepsia remain unexplained. The cause of nonulcer dyspepsia is unknown, but aerophagia, esophageal dysfunction, pyloroduodenal dysmotility and the irritable bowel syndrome may be important factors in some patients. The symptoms are often affected by diet and emotion. History-taking and endoscopy are the most discriminating diagnostic tests. Unexplained dyspepsia tends to be a lifelong disease with few, if any, sequelae. Nevertheless, reassurance and treatment with a placebo, such as an antacid or simethicone, provide effective and safe relief for many patients. PMID:6365298

Endosonography in the diagnosis and management of pancreatic cysts

PubMed Central

Kadiyala, Vivek; Lee, Linda S

2015-01-01

Rapid advances in radiologic technology and increased cross-sectional imaging have led to a sharp rise in incidental discoveries of pancreatic cystic lesions. These cystic lesions include non-neoplastic cysts with no risk of malignancy, neoplastic non-mucinous serous cystadenomas with little or no risk of malignancy, as well as neoplastic mucinous cysts and solid pseudopapillary neoplasms both with varying risk of malignancy. Accurate diagnosis is imperative as management is guided by symptoms and risk of malignancy. Endoscopic ultrasound (EUS) allows high resolution evaluation of cyst morphology and precise guidance for fine needle aspiration (FNA) of cyst fluid for cytological, chemical and molecular analysis. Initially, clinical evaluation and radiologic imaging, preferably with magnetic resonance imaging of the pancreas and magnetic resonance cholangiopancreatography, are performed. In asymptomatic patients where diagnosis is unclear and malignant risk is indeterminate, EUS-FNA should be used to confirm the presence or absence of high-risk features, differentiate mucinous from non-mucinous lesions, and diagnose malignancy. After analyzing the cyst fluid for viscosity, cyst fluid carcinoembryonic antigen, amylase, and cyst wall cytology should be obtained. DNA analysis may add useful information in diagnosing mucinous cysts when the previous studies are indeterminate. New molecular biomarkers are being investigated to improve diagnostic capabilities and management decisions in these challenging cystic lesions. Current guidelines recommend surgical pancreatic resection as the standard of care for symptomatic cysts and those with high-risk features associated with malignancy. EUS-guided cyst ablation is a promising minimally invasive, relatively low-risk alternative to both surgery and surveillance. PMID:25789091

Is postural tremor size controlled by interstitial potassium concentration in muscle?

PubMed Central

Lakie, M; Hayes, N; Combes, N; Langford, N

2004-01-01

Objectives: To determine whether factors associated with postural tremor operate by altering muscle interstitial K+. Methods: An experimental approach was used to investigate the effects of procedures designed to increase or decrease interstitial K+. Postural physiological tremor was measured by conventional means. Brief periods of ischaemic muscle activity were used to increase muscle interstitial K+. Infusion of the ß2 agonist terbutaline was used to decrease plasma (and interstitial) K+. Blood samples were taken for the determination of plasma K+. Results: Ischaemia rapidly reduced tremor size, but only when the muscle was active. The ß2 agonist produced a slow and progressive rise in tremor size that was almost exactly mirrored by a slow and progressive decrease in plasma K+. Conclusions: Ischaemic reduction of postural tremor has been attributed to effects on muscle spindles or an unexplained effect on muscle. This study showed that ischaemia did not reduce tremor size unless there was accompanying muscular activity. An accumulation of K+ in the interstitium of the ischaemic active muscle may blunt the response of the muscle and reduce its fusion frequency, so that the force output becomes less pulsatile and tremor size decreases. When a ß2 agonist is infused, the rise in tremor mirrors the resultant decrease in plasma K+. Decreased plasma K+ reduces interstitial K+ concentration and may produce greater muscular force fluctuation (more tremor). Many other factors that affect postural tremor size may exert their effect by altering plasma K+ concentration, thereby changing the concentration of K+ in the interstitial fluid. PMID:15201362

Investigation of unexplained infant deaths in Jerusalem, Israel 1996–2003

PubMed Central

Eisenstein, Eli M; Haklai, Ziona; Schwartz, Shepard; Klar, Aharon; Stein, Nechama; Kerem, Eitan

2007-01-01

Background Sudden infant death syndrome (SIDS) is a diagnosis of exclusion that may be assigned only after investigations including a forensic autopsy are performed to exclude possible organic and environmental causes of death. Israeli society is influenced by the Jewish and Islamic faiths, which permit autopsy only under selected circumstances. Against this background, we carried out a study to determine what examinations are performed to investigate unexplained infant deaths in Jerusalem, Israel. Methods We examined hospital, Ministry of Health and Ministry of Interior records of unexplained infant deaths in the Jerusalem district from the years 1996–2003. Results Ninety six cases were identified from all sources. Forty nine (51%) infants were brought to a hospital at or near the time of death. Studies to determine the cause of death were performed in 54% of cases for which medical records were available for review. These studies included bacterial cultures (44%), skeletal surveys (12%), computerised tomography (3%) and metabolic studies (3%). Only one forensic autopsy was performed, and in no instance was the death site examined by medical personnel. There was a high rate of retrospective review by district health physicians. The most frequently assigned cause of death was SIDS. Conclusions : The capacity of public health officials and forensic pathologists to investigate unexplained infant deaths is strongly affected by the legal, religious and political milieu in which they work. Efforts should be made to develop socially acceptable methods of improving the quality of infant death investigations in Jerusalem. PMID:17074788

Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: A randomized controlled trial

PubMed Central

2011-01-01

Background The aim of this randomized controlled trial was to compare the efficacy of extended letrozole regimen with clomiphene citrate in women with unexplained infertility undergoing superovulation and intrauterine insemination (IUI). Methods Two hundred and fourteen patients with unexplained infertility were randomized into two equal groups using computer generated list and were treated by either letrozole 2.5 mg/day from cycle day 1 to 9 (extended letrozole group, 211 cycles) or clomiphene citrate 100 mg/day from cycle day 3 to 7 (clomiphene citrate group,210 cycles). Intrauterine insemination was performed 36 to 40 hours after HCG administration. Results Both groups were comparable with regard to number of mature follicles (2.24 +/- 0.80 Vs 2.13 +/- 0.76) and the day of HCG administration. Serum estradiol was significantly greater in clomiphene citrate group (356 +/- 151 Vs 822 +/- 302 pg/ml, P = < 0.001) and the endometrial thickness was significantly greater in extended letrozole group (9.10 +/- 1.84 Vs 8.18 +/- 1.93 mm, P = < 0.001).The pregnancy rate per cycle and cumulative pregnancy rate were significantly greater in extended letrozole group (18.96% Vs 11.43% and 37.73% Vs 22.86%, respectively). Conclusion The extended letrozole regimen had a superior efficacy as compared with clomiphene citrate in patients of unexplained infertility undergoing superovulation and IUI. Trial registration ClinicalTrials.gov, NCT01232075 PMID:21693030

Letrozole versus clomiphene citrate for unexplained infertility: a systematic review and meta-analysis.

PubMed

Liu, Aihai; Zheng, Chao; Lang, Junzhe; Chen, Wenbing

2014-05-01

The objective of this study is to investigate and compare the effectiveness of letrozole and clomiphene citrate for improving fertility outcomes, including pregnancy rate, miscarriage rate, multiple pregnancy rate, and incidence rate of adverse events, number of dominant follicles, endometrial thickness at hCG day and serum E2 on hCG day. MEDLINE, EMBASE, CENTRAL, CNKI and CBMdisc databases were searched up to March 2013. Randomized controlled trials comparing letrozole with clomiphene in women with unexplained infertility were included. Pooled relative risk, mean difference and 95% confidence intervals were calculated. We found that there are no differences in pregnancy, miscarriage and multiple pregnancy rates, incidence rate of adverse events, number of dominant follicles (>18 mm) and endometrial thickness at hCG day in women with unexplained infertility between letrozole and clomiphene regimens. The mean (±standard deviation) concentration of serum E2 on hCG day was lower in those treated with letrozole than those with clomiphene. The subgroup of 2.5 mg letrozole displayed a statistically significant higher rate of clinical pregnancy as compared with 100 mg of clomiphene. The results of this study conclude that letrozole is as effective as clomiphene in women with unexplained infertility. Letrozole at a dose of 2.5 mg seems more effective. Further high-quality studies assessing the possible effectiveness of letrozole in selected groups of patients are warranted. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

[The usefullness of implantable loop recorders for evaluation of unexplained syncope and palpitations].

PubMed

Kristjánsdóttir, Ingibjörg; Reimarsdóttir, Guđrun; Arnar, Davíđ O

2012-09-01

Syncope is a common complaint and determining the underlying cause can be difficult despite extensive evaluation. The purpose of this study was to evaluate the usefulness of an implantable loop recorder for patients with unexplained syncope and palpitations. This was a retrospective analysis of 18 patients, five of whom still have the device implanted. All patients had undergone extensive evaluation for their symptoms before getting the loop recorder implanted and this was therefore a highly select group. Of the thirteen patients where use of the device was completed, the mean age was 65±20 years. The loop recorder was in use for a mean time of 20±13 months. Unexplained syncope, eleven of thirteen, was the most common indication. The other two received the loop recorder for unexplained palpitations. Four patients had sick sinus syndrome during monitoring, three had supraventricular tachycardia and one had ventricular tachycardia. Further three had typical symptoms but no arrhythmia was recorded and excluding that as a cause. Two patients had no symptoms the entire time they had the loop recorder. Of the five patients still with the device three had syncope as the indication for monitoring and two have the device as a means of evaluating the results of treatment for arrhythmia. This study on our initial experience with implantable loop recorders shows that these devices can be useful in the investigation of the causes of syncope and palpitations.

Anxiety and depression predicted by medically unexplained symptoms in Pakistani children: a case-control study.

PubMed

Imran, Nazish; Ani, Cornelius; Mahmood, Zahid; Hassan, Khawaja Amjad; Bhatti, Muhammad Riaz

2014-02-01

To explore association between medically unexplained symptoms in children in Pakistan with emotional difficulties and functional impairments. We conducted a matched three-group case-control study of 186 children aged 8-16 years in Lahore, Pakistan. Cases were 62 children with chronic somatic symptoms for which no organic cause was identified after investigations. Two control groups of 62 children with chronic medical paediatric conditions, and 62 healthy children were identified. Cases and controls were matched for gender, age, and school class. Somatisation was measured with the Children's Somatisation Inventory (CSI-24) while anxiety and depression were measured with the Spencer Children's Anxiety Scale and the Short Mood and Feelings Questionnaire respectively. All questionnaires were translated into Urdu. Mean age was 11.7 years (SD=2.1). Cases scored significantly higher on somatisation (CSI-24), anxiety and depression than both control groups. Paediatric controls scored significantly higher than healthy controls on all three measures. Two hierarchical linear regression models were used to explore if somatisation predicted depression and anxiety while controlling for several confounders. Somatisation (higher CSI-24 scores) independently and significantly predicted higher anxiety (β=.37, p=.0001) and depression (β=.41, p=.0001) scores. This is the first study to show an association between medically unexplained symptoms and anxiety and depression in Pakistani children. This highlights the importance of screening for emotional difficulties in children presenting with unexplained somatic symptoms in this region. Copyright © 2013 Elsevier Inc. All rights reserved.

Opinion paper: the role of work in the management of medically unexplained physical symptoms.

PubMed

Tobback, Els; Mariman, An; Clauwaert, Lies; Godderis, Lode; Heytens, Stefan; Ruppol, Patrick; Spooren, Daniel; Tytgat, Rita; De Muynck, Martine; Vogelaers, Dirk

2018-05-04

Patients with medically unexplained physical symptoms suffer from chronic fatigue and/or pain in combination with a variety of other symptoms. A flexible, biopsychosocial approach is needed for diagnostic screening and global management. It is crucial to involve the direct patient environment, including family, friends, colleagues as well as health providers, evaluation, and reintegration sector. The aim of this paper is to review the importance of work in the management of medically unexplained physical symptoms. In this paper, different actors involved explain their views and handling concerning work in the management of MUPS. Symptom severity and lack of understanding from the environment can negatively impact on earning an independent income from labor for years. Work, whether or not paid, is however, an important life domain with positive effects on physical, psychological, and social well-being. Therefore, health actors are pivotal in starting the professional reintegration process as soon as possible and should discuss this item from the early stage onward. Support services can be consulted in mutual interaction as required. A case manager, acting as a central intermediator within this multidisciplinary approach, may promote effective communication and coordination between the patients and their surrounding actors. The professional reintegration process should start as soon as possible within the management of medically unexplained physical symptoms. As such, the care sector, the evaluation sector, and the professional integration sector should collaborate and effectively communicate with each other.

Slater revisited: 6 year follow up study of patients with medically unexplained motor symptoms.

PubMed

Crimlisk, H L; Bhatia, K; Cope, H; David, A; Marsden, C D; Ron, M A

1998-02-21

To investigate psychiatric and neurological morbidity, diagnostic stability, and indicators of prognosis in patients previously identified as having medically unexplained motor symptoms. Follow up study. National Hospital for Neurology and Neurosurgery, London--a secondary and tertiary referral hospital for neurological disorders. 73 patients with medically unexplained motor symptoms admitted consecutively in 1989-91. 35 (48%) patients had absence of motor function (for example, hemiplegia) and 38 (52%) had abnormal motor activity (for example, tremor, dystonia, or ataxia). Neurological clinical diagnosis at face to face reassessment by a neurologist and a psychiatric diagnosis after a standardised assessment interview--the schedule for affective disorders and schizophrenia--conducted by a psychiatrist. Good follow up data were available for 64 subjects (88%). Only three subjects had new organic neurological disorders at follow up that fully or partly explained their previous symptoms. 44/59 (75%) subjects had had psychiatric disorders; in 33 (75%) patients, the psychiatric diagnosis coincided with their unexplained motor symptoms. 31/59 (45%) patients had a personality disorder. Three subjects had developed new psychiatric illnesses at follow up, but in only one did the diagnosis account for the previous motor symptoms. Resolution of physical symptoms was associated with short length of symptoms, comorbid psychiatric disorder, and a change in marital status during follow up. Unlike Slater's study of 1965, a low incidence of physical or psychiatric diagnoses which explained these patients' symptoms or disability was found. However, a high level of psychiatric comorbidity existed.

Massive immunoglobulin treatment in women with four or more recurrent spontaneous primary abortions of unexplained aetiology.

PubMed

Yamada, H; Kishida, T; Kobayashi, N; Kato, E H; Hoshi, N; Fujimoto, S

1998-09-01

The aim of this trial was to investigate the efficacy of massive i.v. immunoglobulin (MIVIg) treatment for women with a history of recurrent spontaneous abortion (RSA) due to unexplained aetiology. The study included nine women (11 pregnancies) with a history of four or more consecutive RSA with unexplained aetiology and no live births. The mean number of fetal losses was 4.5 (range 4-6 abortions). Over the course of 5 days, immunoglobulin (20 g/day) was infused i.v. at gestational weeks 4-7. No additional infusions were carried out. Two pregnancies out of the 11 conceptions resulted in missed abortions at gestational weeks 6 and 7 respectively. Mosaicism (46XX/ 48XX, +16, +20), and tetraploidy (92XXXX) were found by chromosome analyses of the two aborti. Eight out of the other nine pregnancies resulted in full term deliveries of healthy neonates. One pregnancy developed intrauterine growth retardation and fetal distress, resulting in a premature delivery (30 gestational weeks) by Caesarean section. Thus, excluding the two abortions with chromosome aberrations, the MIVIg treatment was effective in all nine pregnancies of RSA women with unexplained aetiology. This MIVIg treatment (100 g administered in early gestation) may be a beneficial alternative to previous IVIg infusion methods, and should be further evaluated in a multicentric, placebo-controlled study, employing a larger number of homogeneous patients who fall into a high risk category of first trimester abortions.

Investigation of unexplained infant deaths in Jerusalem, Israel 1996-2003.

PubMed

Eisenstein, Eli M; Haklai, Ziona; Schwartz, Shepard; Klar, Aharon; Stein, Nechama; Kerem, Eitan

2007-08-01

Sudden infant death syndrome (SIDS) is a diagnosis of exclusion that may be assigned only after investigations including a forensic autopsy are performed to exclude possible organic and environmental causes of death. Israeli society is influenced by the Jewish and Islamic faiths, which permit autopsy only under selected circumstances. Against this background, we carried out a study to determine what examinations are performed to investigate unexplained infant deaths in Jerusalem, Israel. We examined hospital, Ministry of Health and Ministry of Interior records of unexplained infant deaths in the Jerusalem district from the years 1996-2003. Ninety six cases were identified from all sources. Forty nine (51%) infants were brought to a hospital at or near the time of death. Studies to determine the cause of death were performed in 54% of cases for which medical records were available for review. These studies included bacterial cultures (44%), skeletal surveys (12%), computerised tomography (3%) and metabolic studies (3%). Only one forensic autopsy was performed, and in no instance was the death site examined by medical personnel. There was a high rate of retrospective review by district health physicians. The most frequently assigned cause of death was SIDS. : The capacity of public health officials and forensic pathologists to investigate unexplained infant deaths is strongly affected by the legal, religious and political milieu in which they work. Efforts should be made to develop socially acceptable methods of improving the quality of infant death investigations in Jerusalem.

Hydrotubation in the management of female infertility: outcome in low resource settings.

PubMed

Adesiyun, A G; Cole, B; Ogwuche, P

2009-01-01

To determine the outcome of therapeutic hydrotubation (tubal flushing) in patients with tubal infertility and unexplained infertility. Prospective non-randomised observational study. Alba hospital, a five bed multidisciplinary private hospital in Kaduna city, Nigeria. Infertile women with tubal and unexplained infertility. Two hundred and fifty seven patients that had therapeutic hydrotubation over 7.5 years were analysed. The age range was 21 to 44 years with mean of 34.5 years. Secondary infertility was found in 209 (81.3%) patients and primary infertility in 166 (64.6%) patients. Of the 257 patients, 134 (52.1%) had had induced abortion. Indications for hydrotubation were bilateral perifimbrial adhesion (incomplete tubal occlusion) 47.9%, bilateral fimbrial end occlusion 24.9%, bilateral cornual blockage 16% and unexplained infertility in 11.3% of cases. One hundred and nine conceptions were recorded in this study and the overall conception rate was 42.4%. Likewise, percentage ratio of conception in these 154 patients with evidence of post-hydrotubation tubal patency was 70.8%. Pregnancy outcome of the 109 conceptions are term pregnancy 84.4%, preterm pregnancy 9.2%, miscarriage 4.6% and ectopic pregnancy in 1.8% of the conceptions. Recorded complications were pelvic pain in 177 (68.9%) patients and vaginal bleeding in 63 (24.5%) patients. With good case selection, therapeutic hydrotubation may be beneficial in resource poor countries, especially in patients with incomplete tubal occlusion (bilateral perifimbrial adhesions) and as part of treatment for unexplained infertility.

Highly sensitive and selective lateral flow immunoassay based on magnetic nanoparticles for quantitative detection of carcinoembryonic antigen.

PubMed

Liu, Fangming; Zhang, Honglian; Wu, Zhenhua; Dong, Haidao; Zhou, Lin; Yang, Dawei; Ge, Yuqing; Jia, Chunping; Liu, Huiying; Jin, Qinghui; Zhao, Jianlong; Zhang, Qiqing; Mao, Hongju

2016-12-01

Carcinoembryonic antigen (CEA) is an important biomarker in cancer diagnosis. Here, we present an efficient, selective lateral-flow immunoassay (LFIA) based on magnetic nanoparticles (MNPs) for in situ sensitive and accurate point-of-care detection of CEA. Signal amplification mechanism involved linking of detection MNPs with signal MNPs through biotin-modified single-stranded DNA (ssDNA) and streptavidin. To verify the effectiveness of this modified LFIA system, the sensitivity and specificity were evaluated. Sensitivity evaluation showed a broad detection range of 0.25-1000ng/ml for CEA protein by the modified LFIA, and the limit of detection (LOD) of the modified LFIA was 0.25ng/ml, thus producing significant increase in detection threshold compared with the traditional LFIA. The modified LFIA could selectively recognize CEA in presence of several interfering proteins. In addition, this newly developed assay was applied for quantitative detection of CEA in human serum specimens collected from 10 randomly selected patients. The modified LFIA system detected minimum 0.27ng/ml of CEA concentration in serum samples. The results were consistent with the clinical data obtained using commercial electrochemiluminescence immunoassay (ECLIA) (p<0.01). In conclusion, the MNPs based LFIA system not only demonstrated enhanced signal to noise ratio, it also detected CEA with higher sensitivity and selectivity, and thus has great potential to be commercially applied as a sensitive tumor marker filtration system. Copyright © 2016 Elsevier B.V. All rights reserved.

Concordance of Carcinoembryonic Antigen Ratio and Response Evaluation Criteria in Solid Tumors as Prognostic Surrogate Indicators of Metastatic Colorectal Cancer Patients Treated with Chemotherapy.

PubMed

Huang, Sheng-Chieh; Lin, Jen-Kou; Lin, Tzu-Chen; Chen, Wei-Shone; Yang, Shung-Haur; Wang, Huann-Sheng; Lan, Yuan-Tzu; Lin, Chun-Chi; Jiang, Jeng-Kai; Chang, Shih-Ching

2015-07-01

Carcinoembryonic antigen (CEA) is widely used as a tumor marker in colorectal cancer (CRC). This study aimed to evaluate the role of the degree of change in CEA levels during the treatment period and found that the degree of change highly correlated with disease survival and Response Evaluation Criteria in Solid Tumors (RECIST) criteria in evaluating therapy response. A total of 447 metastatic CRC patients treated with surgery of the primary tumor followed by systemic therapy at a single center from the year 2000 through 2011 were reviewed. The degree of change in CEA levels was expressed as the CEA ratio (post-CEA/pre-CEA) and classified into four groups during the treatment period for further evaluation. The imaging change of the same population was also compared with the CEA ratio during the treatment period. The CEA ratio was significantly correlated with different chemotherapy regimens (p < 0.001), pre-treatment CEA level (p < 0.001), lymphovascular invasion (p = 0.006), and tumor differentiation (p = 0.018). CEA ratio and imaging change according to RECIST criteria were both correlated with overall survival (p < 0.001). These two methods for evaluating treatment response were highly correlated (p < 0.001). CEA ratio was found to be a reliable prognostic factor in stage IV CRC, and was highly correlated with the imaging survey according to RECIST criteria. Further prospective studies are essential to validate these findings.

Evidence for carboxyl-terminal processing and glycolipid-anchoring of human carcinoembryonic antigen.

PubMed

Takami, N; Misumi, Y; Kuroki, M; Matsuoka, Y; Ikehara, Y

1988-09-05

We have investigated the post-translational modification of carcinoembryonic antigen (CEA) for membrane-anchoring in QGP-1 cells derived from a human pancreatic carcinoma. Pulse-chase experiments with [3H]leucine demonstrated that CEA was initially synthesized as a precursor form with Mr 150,000 having N-linked high-mannose-type oligosaccharides, which was then converted to a mature form with Mr 200,000 containing the complex type sugar chains. The mature protein thus labeled was found to be released from the cell surface by treatment with phosphatidylinositol-specific phospholipase C, suggesting that CEA is a phosphatidylinositol-linked membrane protein. This was confirmed by metabolic incorporation into CEA of 3H-labeled compounds such as ethanolamine, myo-inositol, palmitic acid, and stearic acid. The 3H-labeled fatty acids incorporated were specifically removed from the protein by nitrous acid deamination as well as by phosphatidylinositol-specific phospholipase C treatment. Since the available cDNA sequence predicts that CEA contains a single methionine residue only in its carboxyl-terminal hydrophobic domain, processing of the carboxyl terminus was examined by pulse-chase experiments with [35S]methionine. It was found that CEA with Mr 150,000 was initially labeled with [35S]methionine but its radioactivity was immediately lost with chase. Taken together, these results suggest that CEA is anchored to the membrane by simultaneously occurring proteolysis of the carboxyl terminus and replacement by the glycophospholipid immediately after the synthesis.

Continuous intra-arterial 5-FU chemotherapy in a patient with a repeated recurrence of rectal cancer: report of a case.

PubMed

Toh, U; Isomoto, H; Araki, Y; Matsumoto, A; Yasunaga, M; Ogoh, Y; Inuzuka, K; Ozaki, K; Shirouzu, K

2000-06-01

We report a patient with a recurrent pelvic tumor after abdominoperineal resection of a rectal carcinoma who was treated sufficiently by repeated intra-arterial infusions of 5-fluorouracil. A continuous, 24-hour 5-fluorouracil administration was made through the bilateral internal iliac artery at a dosage of 250 mg/m2/day by the subcutaneous reservoir located at both upper legs using a Baxter infusor. In this patient pain in the hip and pelvis was relieved. A complete regression in the infused field of pelvic tumor was observed not only with computed tomography and magnetic resonance imaging but also confirmed by operative findings at the seventh month after the intra-arterial infusion. The abnormal serum level of carcinoembryonic antigen and carbohydrate antigen 19-9 was decreased to within the normal range at the 19th and 3rd week respectively. When the repeated recurrence was suspected in follow-up, normalization of the re-elevated carcinoembryonic antigen and carbohydrate antigen 19-9 levels was also obtained by repeating the same treatment. The side effects and complications were tolerable, consisting of local skin erosion on the hips and lower extremity neuropathy caused by the 5-fluorouracil. Clinical local regression of a pelvic recurrence was observed in a patient with rectal recurrent tumor who received continuous intra-arterial chemotherapy. Local recurrence of rectal cancer may be controlled effectively and safely by repeating long-term, continuous, intra-arterial 5-fluorouracil infusion.

Capillary electrophoresis-chemiluminescence detection for carcino-embryonic antigen based on aptamer/graphene oxide structure.

PubMed

Zhou, Zi-Ming; Feng, Zhe; Zhou, Jun; Fang, Bi-Yun; Qi, Xiao-Xiao; Ma, Zhi-Ya; Liu, Bo; Zhao, Yuan-Di; Hu, Xue-Bin

2015-02-15

A new strategy is proposed for determination of carcino-embryonic antigen (CEA) based on aptamer/graphene oxide (Apt/GO) by capillary electrophoresis-chemiluminescence (CE-CL) detection system. CEA aptamer conjugated with horseradish peroxidase (HRP) firstly mixes with GO, and the CL will be quenched because the stack of HRP-Apt on GO leads to chemiluminescence resonance energy transfer (CRET). When CEA exists, the specific combination of HRP-Apt and CEA can form HRP-Apt-CEA complex, which dissociates from GO. Then, the CL catalyzed by HRP-Apt-CEA complex can be detected without any CRET, and the content of CEA can be estimated by the CL intensity. It has been proved that the interference issue resulted from free HRP-Apt is solved well by mixing GO firstly with HRP-Apt, which blocks the free HRP-Apt's CL signal due to CL quenching effect of GO; and the interference resulted from GO to CL is also solved by CE, then the sensitivity and accuracy can be greatly improved. Results also showed that the CL intensity had a linear relationship with the concentration of CEA in the range from 0.0654 to 6.54 ng/mL, and the limit of detection was approximately 4.8 pg/mL (S/N = 3). This proposed method with high specificity offers a new way for separation and determination of biomolecule, and has good potential in application of biochemistry and bioanalysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Pre-clinical validation study of a miniaturized electrochemical immunoassay based on square wave voltammetry for early detection of carcinoembryonic antigen in human serum.

PubMed

Martínez-Mancera, Flavio Dolores; García-López, Patricia; Hernández-López, José Luis

2015-04-15

The ELISA format for measuring carcinoembryonic antigen (CEA) serves as a reference standard against which other assays are compared. Because the World Health Organization (WHO) increasingly recommends the use of serum CEA as a diagnostic tool for cancer, it is relevant to explore the reliability of the new decentralized CEA point-of-care-testing (POCT) technologies that are available to physicians and patients, in compliance with mandates of the clinical laboratories' regulatory agencies. Electrochemical immunoassay (ECIA) based on trace lead (Pb) analysis by anodic stripping techniques using sandwich-type immunocomplex conjugates: (MB)Ab/AgCEA/Ab(PbS), and a commercial ELISA test system with optical transmission. The ECIA provides better analytical performance than does the ELISA. The within assay precision coefficient of variance (%CVw) of the ECIA is lower than the value recommended by the Hong Kong Association of Medical Laboratories (HKAML), and the recoveries of CEA at 1.0, 5.0, 10.0, 25.0 and 50.0 ng/ml are in the range of 99-110% for control serum samples. The ECIA showed a minimal positive bias of 0.0267 ± 0.3270 ng/ml (P=0.9389). The proposed CEA screening technology can be practically employed for decentralized clinical analysis of CEA in human serum. Therefore, it can be viewed as a control method for personalized therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Magnetic immunoassay coupled with inductively coupled plasma mass spectrometry for simultaneous quantification of alpha-fetoprotein and carcinoembryonic antigen in human serum

NASA Astrophysics Data System (ADS)

Zhang, Xing; Chen, Beibei; He, Man; Zhang, Yiwen; Xiao, Guangyang; Hu, Bin

2015-04-01

The absolute quantification of glycoproteins in complex biological samples is a challenge and of great significance. Herein, 4-mercaptophenylboronic acid functionalized magnetic beads were prepared to selectively capture glycoproteins, while antibody conjugated gold and silver nanoparticles were synthesized as element tags to label two different glycoproteins. Based on that, a new approach of magnetic immunoassay-inductively coupled plasma mass spectrometry (ICP-MS) was established for simultaneous quantitative analysis of glycoproteins. Taking biomarkers of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) as two model glycoproteins, experimental parameters involved in the immunoassay procedure were carefully optimized and analytical performance of the proposed method was evaluated. The limits of detection (LODs) for AFP and CEA were 0.086 μg L- 1 and 0.054 μg L- 1 with the relative standard deviations (RSDs, n = 7, c = 5 μg L- 1) of 6.5% and 6.2% for AFP and CEA, respectively. Linear range for both AFP and CEA was 0.2-50 μg L- 1. To validate the applicability of the proposed method, human serum samples were analyzed, and the obtained results were in good agreement with that obtained by the clinical chemiluminescence immunoassay. The developed method exhibited good selectivity and sensitivity for the simultaneous determination of AFP and CEA, and extended the applicability of metal nanoparticle tags based on ICP-MS methodology in multiple glycoprotein quantifications.

Prognostic Role of Carcinoembryonic Antigen Level after Preoperative Chemoradiotherapy in Patients with Rectal Cancer.

PubMed

Huh, Jung Wook; Yun, Seong Hyeon; Kim, Seok Hyung; Park, Yoon Ah; Cho, Yong Beom; Kim, Hee Cheol; Lee, Woo Yong; Park, Hee Chul; Choi, Doo Ho; Park, Joon Oh; Park, Young Suk; Chun, Ho-Kyung

2018-05-29

The prognostic role of post-chemoradiotherapy (CRT) carcinoembryonic antigen (CEA) level is not clear. We evaluated the prognostic significance of post-CRT CEA level in patients with rectal cancer after preoperative CRT. We reviewed 659 consecutive patients who underwent preoperative CRT and total mesorectal excision for non-metastatic rectal cancer. Patients were categorized into two groups according to post-CRT serum CEA level: low CEA (< 5 ng/mL) and high CEA (≥ 5 ng/mL). Median post-CRT CEA level was 1.7 ng/mL (range, 0.1-207.0). A high post-CRT level was significantly associated with ypStage, ypT category, tumor regression grade, and pre-CRT CEA level. The 5-year overall survival rate of the 659 patients was 87.8% with a median follow-up period of 57.0 months (range, 1.4-176.4). When the post-CRT CEA groups were divided into groups according to pre-CRT CEA level, the 5-year overall survival rates were significantly different (P < 0.001 and P = 0.001, respectively). Post-CRT CEA level was an independent prognostic factor for overall survival. Multivariate analysis revealed that operation method, differentiation, perineural invasion, postoperative chemotherapy, tumor regression grade, and post-CRT CEA level were independent prognostic factors for overall survival. The level of serum CEA after preoperative CRT was an independent prognostic factor for overall survival in patients with rectal cancer.

The predictive value of preoperative carcinoembryonic antigen level in the prognosis of colon cancer.

PubMed

Kirat, Hasan T; Ozturk, Ersin; Lavery, Ian C; Kiran, Ravi P

2012-10-01

We evaluated factors associated with an increased preoperative carcinoembryonic antigen (CEA) level for colon cancer patients undergoing elective curative surgery and assessed whether this was associated with prognosis when accounting for other potential confounders. Prospectively accrued data of patients with stage I, II, and III colon cancer undergoing surgery (1980-2008) were retrieved retrospectively. Patients with a preoperative CEA level greater than 5 ng/mL (group B) were compared with those with a CEA level of 5 ng/mL or less (group A). There were 651 patients (379 men) with a median age of 67 years (range, 21-94 y) and a median follow-up period of 5.9 years. Groups A (n = 451) and B (n = 200) had similar ages and tumor locations. Group B had larger tumors; more patients with T3 and N1/N2; and more patients with stage II/III tumors, and hence greater use of chemotherapy (P = .04). On multivariate analysis, patient age, tumor stage, and differentiation were associated with oncologic outcomes. A CEA level greater than 5 ng/mL was not associated independently with recurrence, recurrence-free survival (P = .47), or overall survival (P = .3). An increased preoperative CEA level is a marker for a more advanced tumor stage. For adequately staged patients, a high preoperative CEA level is not associated independently with oncologic outcomes. Copyright © 2012 Elsevier Inc. All rights reserved.

Dye sensitized photoelectrochemical immunosensor for the tumor marker CEA by using a flower-like 3D architecture prepared from graphene oxide and MoS2.

PubMed

Song, Kaijing; Ding, Chuanmin; Zhang, Bing; Chang, Honghong; Zhao, Zhihuan; Wei, Wenlong; Wang, Junwen

2018-06-01

The authors describe a dye-sensitized photoelectrochemical immunoassay for the tumor marker carcinoembryonic antigen (CEA). The method employs the rhodamine dye Rh123 with red color and absorption maximum at 500 nm for spectral sensitization, and a 3D nanocomposite prepared from graphene oxide and MoS 2 acting as the photoelectric conversion layer. The nanocomposite with flower-like 3D architectures was characterized by transmission electron microscopy, scanning electron microscopy, X-ray powder diffraction, and UV-vis diffuse reflectometry. A photoelectrochemical sandwich immunoassay was developed that is based on the use of the nanocomposite and based on the specific binding of antibody and antigen, and by using a secondary antibody labeled with Rh123 and CdS (Ab 2 -Rh123@CdS). Under optimal conditions and at a typical working voltage of 0 V (vs. Hg/HgCl 2 ), the photocurrent increases linearly 10 pg mL -1 to 80 ng mL -1 CEA concentration range, with a 3.2 pg mL -1 detection limit. Graphical abstract Flower-like GO-MoS 2 complex with high efficiency of electron transport was synthesized to construct photoelectrochemical platform. The sandwich-type immunoassay was built on this platform based on specific binding of antigen and antibody. Carcinoembryonic antigen in sample was detected sensitively by using sensitization of rhodamine dye Rh123 as signal amplification strategy.

Serum CA 19-9 as a prognostic factor in patients with metastatic gastric cancer.

PubMed

Jo, Jae-Cheol; Ryu, Min-Hee; Koo, Dong-Hoe; Ryoo, Baek-Yeol; Kim, Hwa Jung; Kim, Tae Won; Choi, Kee Don; Lee, Gin Hyug; Jung, Hwoon-Yong; Yook, Jeong Hwan; Oh, Sung Tae; Kim, Byung Sik; Kim, Jin-Ho; Kang, Yoon-Koo

2013-12-01

To evaluate tumor markers as prognostic factors in patients with metastatic or recurrent gastric cancer receiving first-line chemotherapy. Between January 2000 and December 2008, 1178 patients with metastatic or recurrent gastric cancer were assayed for expression of three serum tumor markers, CA 19-9, CA 72-4 and carcinoembryonic antigen (CEA), prior to the initiation of first-line chemotherapy. Elevated serum concentrations of carbohydrate antigen (CA) 19-9 (>37 U/mL), CA 72-4 (>4 U/mL) and carcinoembryonic antigen (CEA) (>6 ng/mL) were observed in 38, 56 and 33% of patients, respectively. Univariate analysis showed that elevated serum concentration of each of the three markers, CA 19-9 (P = 0.001), CA 72-4 (P = 0.001) and CEA (P = 0.030), was significantly associated with poor patient prognosis. However, multivariate analysis showed that an elevated CA 19-9 concentration only was significantly associated with shorter survival (hazard ratio [HR] 1.22; 95% CI, 1.08-1.37, P = 0.002). In the good risk and moderate risk groups, previously defined by clinical factors alone, survival was significantly lower in patients with elevated CA 19-9 (P < 0.001 and P = 0.021, respectively), but this difference was not observed in the poor-risk group. Elevated serum CA 19-9 concentration in patients with metastatic or recurrent gastric cancer, especially in good or moderate risk groups, is an independent negative predictor of prognosis. © 2012 Wiley Publishing Asia Pty Ltd.

[Expression of carcinoembryonic antigen receptor in digestive organs].

PubMed

Zhao, Hui-min; Zhang, Sen; Gao, Feng

2010-08-01

To explore the significance of the expression of carcinoembryonic antigen receptors (CEAR) in digestive organs. Specimens were procured from 20 male BALB/c mice including esophagus, small intestine, stomach, colon, pancreas, and liver. Kupffer cells were obtained by density gradient centrifugation following enzymatic digestion of the fresh liver specimen. Immunohistochemistry and immunocytochemistry methods were used to detect CEAR in those organs or Kupffer cells. CEAR was found both in cytoplasm and nuclei of the digestive tract mucosal epithelial cells and pancreas islet cells, but only in the cytoplasm of liver cells, Kupffer cells, and smooth muscle cells of the whole digestive tract. The mean ranks of CEAR expression were 174.33 in the mucosal epithelial cells of colon, 160.70 in epithelial cells of small intestine, 139.18 in Kupffer cells, 137.43 in pancreas islet cells, 131.70 in liver cells, 124.23 in gastric epithelial cells, 77.15 in esophageal epithelial cells and 57.80-71.00 in smooth muscle cells of the entire digestive tract examined. There were significantly differences in the CEAR expression intensity among those positive cells (chi2=99.58, P<0.01) while CEAR was not present in submucosal connective tissue cells, pancreatic exocrine cells, or hepatic sinusoid endothelial cells. There are significantly differences in the expression of CEAR in the main digestive organs according to the different tissue and cells, which may play an important role in the carcinogenesis and hepatic metastasis from tumors of the digestive system.

Heterogeneous RNA-binding protein M4 is a receptor for carcinoembryonic antigen in Kupffer cells.

PubMed

Bajenova, O V; Zimmer, R; Stolper, E; Salisbury-Rowswell, J; Nanji, A; Thomas, P

2001-08-17

Here we report the isolation of the recombinant cDNA clone from rat macrophages, Kupffer cells (KC) that encodes a protein interacting with carcinoembryonic antigen (CEA). To isolate and identify the CEA receptor gene we used two approaches: screening of a KC cDNA library with a specific antibody and the yeast two-hybrid system for protein interaction using as a bait the N-terminal part of the CEA encoding the binding site. Both techniques resulted in the identification of the rat heterogeneous RNA-binding protein (hnRNP) M4 gene. The rat ortholog cDNA sequence has not been previously described. The open reading frame for this gene contains a 2351-base pair sequence with the polyadenylation signal AATAAA and a termination poly(A) tail. The mRNA shows ubiquitous tissue expression as a 2.4-kilobase transcript. The deduced amino acid sequence comprised a 78-kDa membrane protein with 3 putative RNA-binding domains, arginine/methionine/glutamine-rich C terminus and 3 potential membrane spanning regions. When hnRNP M4 protein is expressed in pGEX4T-3 vector system in Escherichia coli it binds (125)I-labeled CEA in a Ca(2+)-dependent fashion. Transfection of rat hnRNP M4 cDNA into a non-CEA binding mouse macrophage cell line p388D1 resulted in CEA binding. These data provide evidence for a new function of hnRNP M4 protein as a CEA-binding protein in Kupffer cells.

The Effects of Total Motile Sperm Count on Spontaneous Pregnancy Rate and Pregnancy After IUI Treatment in Couples with Male Factor and Unexplained Infertility.

PubMed

Hajder, Mithad; Hajder, Elmira; Husic, Amela

2016-02-01

Male infertility factor is defined if the total number of motile spermatozoa (TMSC) < 20 × 10(6)/ejaculated, and unexplained infertility if spermiogram is normal with normal female factor. of this study was to determine the predictive value of TMSC for spontaneous pregnancy (ST) and pregnancy after treatment with intrauterine insemination (IUI) in couples with male factor and unexplained infertility. According to the WHO qualification system abnormal spermiogram can be diagnosed as oligozoospermia (O), asthenozoospermia (A), teratozoospermia (T) or combination (O+A+T) and azoospermia (A). Although this classification indicates the accuracy of findings its relevance for prognosis in infertile couple and the choice of treatment is questionable. The study included 98 couples with male infertility factor (bad spermiogram) and couples with normospermia and normal female factor (unexplained infertility). Testing group is randomized at: group (A) with TMSC> 3,10(6) / ejaculate and a spontaneous pregnancy, group (B) with TMSCl <3 x 10(6) / ejaculate and pregnancy after IUI, plus couples who have not achieved SP with TMSC> 3 x 10(6) / ejaculate and couples who have not achieved pregnancy. From a total of 98 pairs of men's and unexplained infertility, 42 of them (42.8%) achieved spontaneous pregnancy, while 56 (57.2%) pairs did not achieve spontaneous pregnancy. TMSC was significantly higher (42.4 ± 28.4 vs. 26.2 ± 24, p <0.05) in the group A compared to group B. Couples with TMSC 1-5 × 10(6) ejaculate had significantly lower (9.8% vs. 22.2%, p <0.0001) rate of spontaneous pregnancy in comparison to couples after IUI treatment. Couples with unexplained infertility had significantly higher (56.8% vs. 29.9%, p <0.01) spontaneous pregnancy rate compared to couples after IUI treatment. Infertile couples had significant pregnancy rate with TMSC 5-10 x 10(6) / ejaculate (OR = 1.45, 95% CI:1.26-1.78, <0.01); with TMSC 10-20 x 10(6) / ejaculate (OR = 1.36, 95% CI: 1:12 to 1:46, <0.0001) with TMSC> 20 x 10(6) / ejaculate (RR = 1.7, 95% CI: 1.56-1.82, <0.001) after treatment with IUI compared to spontaneous pregnancy. Based on these results we can conclude that couples with the TMSC> 5 x 10(6) / ejaculate are indicated for treatment with IUI. TMSC can be used as the method of choice for diagnosis and treatment of male infertility.

Effect of More vs Less Frequent Follow-up Testing on Overall and Colorectal Cancer-Specific Mortality in Patients With Stage II or III Colorectal Cancer: The COLOFOL Randomized Clinical Trial.

PubMed

Wille-Jørgensen, Peer; Syk, Ingvar; Smedh, Kenneth; Laurberg, Søren; Nielsen, Dennis T; Petersen, Sune H; Renehan, Andrew G; Horváth-Puhó, Erzsébet; Påhlman, Lars; Sørensen, Henrik T

2018-05-22

Intensive follow-up of patients after curative surgery for colorectal cancer is common in clinical practice, but evidence of a survival benefit is limited. To examine overall mortality, colorectal cancer-specific mortality, and colorectal cancer-specific recurrence rates among patients with stage II or III colorectal cancer who were randomized after curative surgery to 2 alternative schedules for follow-up testing with computed tomography and carcinoembryonic antigen. Unblinded randomized trial including 2509 patients with stage II or III colorectal cancer treated at 24 centers in Sweden, Denmark, and Uruguay from January 2006 through December 2010 and followed up for 5 years; follow-up ended on December 31, 2015. Patients were randomized either to follow-up testing with computed tomography of the thorax and abdomen and serum carcinoembryonic antigen at 6, 12, 18, 24, and 36 months after surgery (high-frequency group; n = 1253 patients) or at 12 and 36 months after surgery (low-frequency group; n = 1256 patients). The primary outcomes were 5-year overall mortality and colorectal cancer-specific mortality rates. The secondary outcome was the colorectal cancer-specific recurrence rate. Both intention-to-treat and per-protocol analyses were performed. Among 2555 patients who were randomized, 2509 were included in the intention-to-treat analysis (mean age, 63.5 years; 1128 women [45%]) and 2365 (94.3%) completed the trial. The 5-year overall patient mortality rate in the high-frequency group was 13.0% (161/1253) compared with 14.1% (174/1256) in the low-frequency group (risk difference, 1.1% [95% CI, -1.6% to 3.8%]; P = .43). The 5-year colorectal cancer-specific mortality rate in the high-frequency group was 10.6% (128/1248) compared with 11.4% (137/1250) in the low-frequency group (risk difference, 0.8% [95% CI, -1.7% to 3.3%]; P = .52). The colorectal cancer-specific recurrence rate was 21.6% (265/1248) in the high-frequency group compared with 19.4% (238/1250) in the low-frequency group (risk difference, 2.2% [95% CI, -1.0% to 5.4%]; P = .15). Among patients with stage II or III colorectal cancer, follow-up testing with computed tomography and carcinoembryonic antigen more frequently compared with less frequently did not result in a significant rate reduction in 5-year overall mortality or colorectal cancer-specific mortality. clinicaltrials.gov Identifier: NCT00225641.

Lead poisoning due to bullets lodged in the human body.

PubMed

Gerstner Garcés, Juan Bernardo; Manotas Artuz, Rafael Ignacio

2012-07-01

With the increased violence and use of firearms in Colombia, we may see more cases of lead poisoning in our environment, and must be prepared to diagnose and treat them. Subtle signs and symptoms as unexplained anemia, gastro-intestinal discomfort and abdominal cramps, as well as severe signs such as changes in behavior and neurological status, nephropathy, and unexplained death, may be associated with a history of gunshot wounds and bullets in the human body. We must offer the patient knowledge and management strategies of pathology.

Lead poisoning due to bullets lodged in the human body

PubMed Central

Manotas Artuz, Rafael Ignacio

2012-01-01

With the increased violence and use of firearms in Colombia, we may see more cases of lead poisoning in our environment, and must be prepared to diagnose and treat them. Subtle signs and symptoms as unexplained anemia, gastro-intestinal discomfort and abdominal cramps, as well as severe signs such as changes in behavior and neurological status, nephropathy, and unexplained death, may be associated with a history of gunshot wounds and bullets in the human body. We must offer the patient knowledge and management strategies of pathology. PMID:24893198

Diagnostic value of radiological imaging pre- and post-drainage of pleural effusions.

PubMed

Corcoran, John P; Acton, Louise; Ahmed, Asia; Hallifax, Robert J; Psallidas, Ioannis; Wrightson, John M; Rahman, Najib M; Gleeson, Fergus V

2016-02-01

Patients with an unexplained pleural effusion often require urgent investigation. Clinical practice varies due to uncertainty as to whether an effusion should be drained completely before diagnostic imaging. We performed a retrospective study of patients undergoing medical thoracoscopy for an unexplained effusion. In 110 patients with paired (pre- and post-drainage) chest X-rays and 32 patients with paired computed tomography scans, post-drainage imaging did not provide additional information that would have influenced the clinical decision-making process. © 2015 Asian Pacific Society of Respirology.

[Genetics of sudden unexplained death].

PubMed

Campuzano, Oscar; Allegue, Catarina; Brugada, Ramon

2014-03-20

Sudden unexplained death is defined by death without a conclusive diagnosis after autopsy and it is responsible for a large percentage of sudden deaths. The progressive interaction between genetics and forensics in post-mortem studies has identified inheritable alterations responsible for pathologies associated with arrhythmic sudden death. The genetic diagnosis of the deceased enables the undertaking of preventive measures in family members, many of them asymptomatic but at risk. The implications of this multidisciplinary translational medical approach are complex, requiring the dedication of a specialized team. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Effectiveness of a cognitive behavioral intervention in patients with medically unexplained symptoms: cluster randomized trial

PubMed Central

2012-01-01

Background Medically unexplained symptoms are an important mental health problem in primary care and generate a high cost in health services. Cognitive behavioral therapy and psychodynamic therapy have proven effective in these patients. However, there are few studies on the effectiveness of psychosocial interventions by primary health care. The project aims to determine whether a cognitive-behavioral group intervention in patients with medically unexplained symptoms, is more effective than routine clinical practice to improve the quality of life measured by the SF-12 questionary at 12 month. Methods/design This study involves a community based cluster randomized trial in primary healthcare centres in Madrid (Spain). The number of patients required is 242 (121 in each arm), all between 18 and 65 of age with medically unexplained symptoms that had seeked medical attention in primary care at least 10 times during the previous year. The main outcome variable is the quality of life measured by the SF-12 questionnaire on Mental Healthcare. Secondary outcome variables include number of consultations, number of drug (prescriptions) and number of days of sick leave together with other prognosis and descriptive variables. Main effectiveness will be analyzed by comparing the percentage of patients that improve at least 4 points on the SF-12 questionnaire between intervention and control groups at 12 months. All statistical tests will be performed with intention to treat. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in this analysis. Discussion This study aims to provide more insight to address medically unexplained symptoms, highly prevalent in primary care, from a quantitative methodology. It involves intervention group conducted by previously trained nursing staff to diminish the progression to the chronicity of the symptoms, improve quality of life, and reduce frequency of medical consultations. Trial registration The trial was registered with ClinicalTrials.gov, number NCT01484223 [ http://ClinicalTrials.gov]. PMID:22551252

Juvenile granulosa cell tumor arising from intra-abdominal testis in newborn: case report and review of the literature.

PubMed

Partalis, Nikolaos; Tzardi, Maria; Barbagadakis, Sophia; Sakellaris, George

2012-05-01

In the present case, the neonate presented with a left-sided abdominal mass and an empty left scrotum. Abdominal ultrasonography showed well-defined cystic formation, and laparotomy revealed a tumor arising from an intra-abdominal left testis. The carcinoembryonic antigen and neuron-specific enolase levels were within normal limits, and the serum β-human chorionic gonadotropin and α-fetoprotein levels were within age-related normal values. The findings from the immunochemistry tests confirmed the diagnosis. Copyright © 2012 Elsevier Inc. All rights reserved.

Evidence of small-fiber polyneuropathy in unexplained, juvenile-onset, widespread pain syndromes.

PubMed

Oaklander, Anne Louise; Klein, Max M

2013-04-01

We tested the hypothesis that acquired small-fiber polyneuropathy (SFPN), previously uncharacterized in children, contributes to unexplained pediatric widespread pain syndromes. Forty-one consecutive patients evaluated for unexplained widespread pain beginning before age 21 had medical records comprehensively analyzed regarding objective diagnostic testing for SFPN (neurodiagnostic skin biopsy, nerve biopsy, and autonomic function testing), plus histories, symptoms, signs, other tests, and treatments. Healthy, demographically matched volunteers provided normal controls for SFPN tests. Age at illness onset averaged 12.3 ± 5.7 years; 73% among this poly-ethnic sample were female (P = .001). Sixty-eight percent were chronically disabled, and 68% had hospitalizations. Objective testing diagnosed definite SFPN in 59%, probable SFPN in 17%, and possible SFPN in 22%. Only 1 of 41 had entirely normal SFPN test results. Ninety-eight percent of patients had other somatic complaints consistent with SFPN dysautonomia (90% cardiovascular, 82% gastrointestinal, and 34% urologic), 83% reported chronic fatigue, and 63% had chronic headache. Neurologic examinations identified reduced sensation in 68% and vasomotor abnormalities in 55%, including 23% with erythromelalgia. Exhaustive investigations for SFPN causality identified only history of autoimmune illnesses in 33% and serologic markers of disordered immunity in 89%. Treatment with corticosteroids and/or intravenous immune globulin objectively and subjectively benefited 80% of patients (12/15). More than half among a large series of patients with childhood-onset, unexplained chronic widespread pain met rigorous, multitest, diagnostic criteria for SFPN, which extends the age range of acquired SFPN into early childhood. Some cases appeared immune-mediated and improved with immunomodulatory therapies.

Insertable cardiac monitors in the diagnosis of syncope and the detection of atrial fibrillation: A systematic review and meta-analysis.

PubMed

Burkowitz, Jörg; Merzenich, Carina; Grassme, Kathrin; Brüggenjürgen, Bernd

2016-08-01

Insertable or implantable cardiac monitors (ICMs) continuously monitor the heart rhythm and record irregularities over 3 years, enabling the diagnosis of infrequent rhythm abnormalities associated with syncope and stroke. The enhanced recognition capabilities of recent ICM models are able to accurately detect atrial fibrillation (AF) and have led to new applications of ICMs for the detection and monitoring of AF. Based on a systematic literature search, two indications were identified for ICMs for which considerable evidence, including randomized studies, exists: diagnosing the underlying cardiac cause of unexplained recurrent syncope and detecting AF in patients after cryptogenic stroke (CS). Three randomized controlled trials (RCTs) were identified that compared the effectiveness of ICMs in diagnosing patients with unexplained syncope (n = 556) to standard of care. A meta-analysis was conducted in order to generate an overall effect size and confidence interval of the diagnostic yield of ICMs versus conventional monitoring. In the indication CS, one RCT and five observational studies were included in order to assess the performance of ICMs in diagnosing patients with AF (n = 1129). Based on these studies, there is strong evidence that ICMs provide a higher diagnostic yield for detecting arrhythmias in patients with unexplained syncope and for detection of AF in patients after CS compared to conventional monitoring. Prolonged monitoring with ICMs is an effective tool for diagnosing the underlying cardiac cause of unexplained syncope and for detecting AF in patients with CS. In all RCTs, ICMs have a superior diagnostic yield compared to conventional monitoring. © The European Society of Cardiology 2016.

Frequency of and reasons for paroxysmal nocturnal haemoglobinuria screening in patients with unexplained anaemia.

PubMed

England, James T; Dalal, Bakul; Leitch, Heather A

2018-04-01

Referral to hematology for anemia is common. In paroxysmal nocturnal hemoglobinuria (PNH), cells deficient in the glycosylphosphatidyl inositol (GPI) anchor are lysed by complement. Eculizumab improves overall survival and quality of life while reducing hemolysis, transfusion requirements, and thrombosis. We evaluated the frequency of screening for PNH in patients with unexplained anemia. Key clinical features, laboratory data, and investigations were recorded for patients referred for anemia since 2010, without a specific cause found. PNH testing was done by flow cytometry. 540 patients had: anemia not yet diagnosed (NYD, n=318 (including unexplained iron deficiency, n=92; DAT-negative hemolysis, n=9)); anemia of chronic disease, n=173; and pancytopenia NYD, n=49. 82.4% had LDH testing done; 85.0% total bilirubin; 78.7% reticulocyte counts; and 40.6% haptoglobin level; 131 (24.2%) had possible hemolysis. PNH testing was done in 56 (10.4%). Those screened for PNH were more likely to have: younger age (P=0.04); a history of thrombosis (P<0.001); undergone a BMBx (P<0.001); received RBC transfusions (P=0.0018); or evidence of DAT-negative hemolysis (P<0.001). In summary, PNH was tested for in a minority of patients with unexplained anemia (10.4%) despite potential indicators of hemolysis in 24.2%. Increased screening could identify patients who would benefit from treatment and should be considered. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Projecting the potential impact of the Cap-Score™ on clinical pregnancy, live births, and medical costs in couples with unexplained infertility.

PubMed

Babigumira, Joseph B; Sharara, Fady I; Garrison, Louis P

2018-01-01

The Cap-Score™ was developed to assess the capacitation status of men, thereby enabling personalized management of unexplained infertility by choosing timed intrauterine insemination (IUI), versus immediate in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in individuals with a low Cap-Score™. The objective of this study was to estimate the differences in outcomes and costs comparing the use of the Cap-Score™ with timed IUI (CS-TI) and the standard of care (SOC), which was assumed to be three IUI cycles followed by three IVF-ICSI cycles. We developed and parameterized a decision-analytic model of management of unexplained infertility for women based on data from the published literature. We calculated the clinical pregnancy rates, live birth rates, and medical costs comparing CS-TI and SOC. We used Monte Carlo simulation to quantify uncertainty in projected estimates and performed univariate sensitivity analysis. Compared to SOC, CS-TI was projected to increase the pregnancy rate by 1-26%, marginally reduce live birth rates by 1-3% in couples with women below 40 years, increase live birth rates by 3-7% in couples with women over 40 years, reduce mean medical costs by $4000-$19,200, reduce IUI costs by $600-$1370, and reduce IVF costs by $3400-$17,800, depending on the woman's age. The Cap-Score™ is a potentially valuable clinical tool for management of unexplained infertility because it is projected to improve clinical pregnancy rates, save money, and, depending on the price of the test, increase access to treatment for infertility.

Un-explained visual loss following silicone oil removal: results of the Pan American Collaborative Retina Study (PACORES) Group.

PubMed

Roca, Jose A; Wu, Lihteh; Berrocal, Maria; Rodriguez, Francisco; Alezzandrini, Arturo; Alvira, Gustavo; Velez-Montoya, Raul; Quiroz-Mercado, Hugo; Fernando Arevalo, J; Serrano, Martín; Lima, Luiz H; Figueroa, Marta; Farah, Michel; Chico, Giovanna

2017-01-01

To report the incidence and clinical features of patients that experienced un-explained visual loss following silicone oil (SO) removal. Multicenter retrospective study of patients that underwent SO removal during 2000-2012. Visual loss of ≥2 lines was considered significant. A total of 324 eyes of 324 patients underwent SO removal during the study period. Forty two (13%) eyes suffered a significant visual loss following SO removal. Twenty three (7.1%) of these eyes lost vision secondary to known causes. In the remaining 19 (5.9%) eyes, the loss of vision was not explained by any other pathology. Eleven of these 19 patients (57.9%) were male. The mean age of this group was 49.2 ± 16.4 years. Eyes that had an un-explained visual loss had a mean IOP while the eye was filled with SO of 19.6 ± 6.9 mm Hg. The length of time that the eye was filled with SO was 14.8 ± 4.4 months. In comparison, eyes that did not experience visual loss had a mean IOP of 14 ± 7.3 mm Hg ( p  < 0.0002) and a mean tamponade duration of 9.3 ± 10.9 months ( p  < 0.0001). An un-explained visual loss after SO removal was observed in 5.9% of eyes. Factors associated with this phenomenon included a higher IOP and longer SO tamponade duration.

An Evaluation of Factors Associated With Pathogenic PRSS1, SPINK1, CTFR, and/or CTRC Genetic Variants in Patients With Idiopathic Pancreatitis.

PubMed

Jalaly, Niloofar Y; Moran, Robert A; Fargahi, Farshid; Khashab, Mouen A; Kamal, Ayesha; Lennon, Anne Marie; Walsh, Christi; Makary, Martin A; Whitcomb, David C; Yadav, Dhiraj; Cebotaru, Liudmila; Singh, Vikesh K

2017-08-01

We evaluated factors associated with pathogenic genetic variants in patients with idiopathic pancreatitis. Genetic testing (PRSS1, CFTR, SPINK1, and CTRC) was performed in all eligible patients with idiopathic pancreatitis between 2010 to 2015. Patients were classified into the following groups based on a review of medical records: (1) acute recurrent idiopathic pancreatitis (ARIP) with or without underlying chronic pancreatitis; (2) idiopathic chronic pancreatitis (ICP) without a history of ARP; (3) an unexplained first episode of acute pancreatitis (AP)<35 years of age; and (4) family history of pancreatitis. Logistic regression analysis was used to determine the factors associated with pathogenic genetic variants. Among 197 ARIP and/or ICP patients evaluated from 2010 to 2015, 134 underwent genetic testing. A total of 88 pathogenic genetic variants were found in 64 (47.8%) patients. Pathogenic genetic variants were identified in 58, 63, and 27% of patients with ARIP, an unexplained first episode of AP <35 years of age, and ICP without ARP, respectively. ARIP (OR: 18.12; 95% CI: 2.16-151.87; P=0.008) and an unexplained first episode of AP<35 years of age (OR: 2.46; 95% CI: 1.18-5.15; P=0.017), but not ICP, were independently associated with pathogenic genetic variants in the adjusted analysis. Pathogenic genetic variants are most likely to be identified in patients with ARIP and an unexplained first episode of AP<35 years of age. Genetic testing in these patient populations may delineate an etiology and prevent unnecessary diagnostic testing and procedures.

Evidence of Small-Fiber Polyneuropathy in Unexplained, Juvenile-Onset, Widespread Pain Syndromes

PubMed Central

Klein, Max M.

2013-01-01

OBJECTIVE: We tested the hypothesis that acquired small-fiber polyneuropathy (SFPN), previously uncharacterized in children, contributes to unexplained pediatric widespread pain syndromes. METHODS: Forty-one consecutive patients evaluated for unexplained widespread pain beginning before age 21 had medical records comprehensively analyzed regarding objective diagnostic testing for SFPN (neurodiagnostic skin biopsy, nerve biopsy, and autonomic function testing), plus histories, symptoms, signs, other tests, and treatments. Healthy, demographically matched volunteers provided normal controls for SFPN tests. RESULTS: Age at illness onset averaged 12.3 ± 5.7 years; 73% among this poly-ethnic sample were female (P = .001). Sixty-eight percent were chronically disabled, and 68% had hospitalizations. Objective testing diagnosed definite SFPN in 59%, probable SFPN in 17%, and possible SFPN in 22%. Only 1 of 41 had entirely normal SFPN test results. Ninety-eight percent of patients had other somatic complaints consistent with SFPN dysautonomia (90% cardiovascular, 82% gastrointestinal, and 34% urologic), 83% reported chronic fatigue, and 63% had chronic headache. Neurologic examinations identified reduced sensation in 68% and vasomotor abnormalities in 55%, including 23% with erythromelalgia. Exhaustive investigations for SFPN causality identified only history of autoimmune illnesses in 33% and serologic markers of disordered immunity in 89%. Treatment with corticosteroids and/or intravenous immune globulin objectively and subjectively benefited 80% of patients (12/15). CONCLUSIONS: More than half among a large series of patients with childhood-onset, unexplained chronic widespread pain met rigorous, multitest, diagnostic criteria for SFPN, which extends the age range of acquired SFPN into early childhood. Some cases appeared immune-mediated and improved with immunomodulatory therapies. PMID:23478869

Do alterations in follicular fluid proteases contribute to human infertility?

PubMed

Cookingham, Lisa Marii; Van Voorhis, Bradley J; Ascoli, Mario

2015-05-01

Cathepsin L and ADAMTS-1 are known to play critical roles in follicular rupture, ovulation, and fertility in mice. Similar studies in humans are limited; however, both are known to increase during the periovulatory period. No studies have examined either protease in the follicular fluid of women with unexplained infertility or infertility related to advanced maternal age (AMA). We sought to determine if alterations in cathepsin L and/or ADAMTS-1 existed in these infertile populations. Patients undergoing in vitro fertilization (IVF) for unexplained infertility or AMA-related infertility were prospectively recruited for the study; patients with tubal or male factor infertility were recruited as controls. Follicular fluid was collected to determine gene expression (via quantitative polymerase chain reaction), enzyme concentrations (via enzyme-linked immunosorbent assays), and enzymatic activities (via fluorogenic enzyme cleavage assay or Western blot analysis) of cathepsin L and ADAMTS-1. The analysis included a total of 42 patients (14 per group). We found no statistically significant difference in gene expression, enzyme concentration, or enzymatic activity of cathepsin L or ADAMTS-1 in unexplained infertility or AMA-related infertility as compared to controls. We also found no statistically significant difference in expression or concentration with advancing age. Cathepsin L and ADAMTS-1 are not altered in women with unexplained infertility or AMA-related infertility undergoing IVF, and they do not decline with advancing age. It is possible that differences exist in natural cycles, contributing to infertility; however, our findings do not support a role for protease alterations as a common cause of infertility.

Cost-effectiveness analysis of preimplantation genetic screening and in vitro fertilization versus expectant management in patients with unexplained recurrent pregnancy loss.

PubMed

Murugappan, Gayathree; Ohno, Mika S; Lathi, Ruth B

2015-05-01

To determine whether in vitro fertilization with preimplantation genetic screening (IVF/PGS) is cost effective compared with expectant management in achieving live birth for patients with unexplained recurrent pregnancy loss (RPL). Decision analytic model comparing costs and clinical outcomes. Academic recurrent pregnancy loss programs. Women with unexplained RPL. IVF/PGS with 24-chromosome screening and expectant management. Cost per live birth. The IVF/PGS strategy had a live-birth rate of 53% and a clinical miscarriage rate of 7%. Expectant management had a live-birth rate of 67% and clinical miscarriage rate of 24%. The IVF/PGS strategy was 100-fold more expensive, costing $45,300 per live birth compared with $418 per live birth with expectant management. In this model, IVF/PGS was not a cost-effective strategy for increasing live birth. Furthermore, the live-birth rate with IVF/PGS needs to be 91% to be cost effective compared with expectant management. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Severe oligohydramnios with intact membranes: an indication for diagnostic amnioinfusion.

PubMed

Pryde, P G; Hallak, M; Lauria, M R; Littman, L; Bottoms, S F; Johnson, M P; Evans, M I

2000-01-01

To quantify the improvement in ultrasonographic fetal imaging following diagnostic amnioinfusion for the indication of unexplained midtrimester oligohydramnios. Patients referred for unexplained midtrimester oligohydramnios were retrospectively reviewed. Videotapes of those undergoing diagnostic antenatal amnioinfusion were analyzed for quality of visualization of routinely imaged structures before and after the infusion procedure. The overall rate of adequate visualization of fetal structures improved from 50.98 to 76.79% (p < 0.0001). In fetuses having preinfusion-identified obstructive uropathy, there was improvement in identification of associated anomalies from 11.8 to 31.3%. Several authors have suggested that diagnostic amnioinfusion can facilitate fetal imaging and increase diagnostic precision in the setting of unexplained severe oligohydramnios. We have quantified the improvement in the rate of optimal visualization of fetal structures which likely translates, in experienced hands, into this observed improved diagnostic precision. Of particular importance is the improvement in appreciation of associated anomalies in cases of obstructive uropathy in which such findings may determine whether or not invasive fetal therapy is indicated. Copyright 2000 S. Karger AG, Basel.

Patients' 'thingification', unexplained symptoms and response-ability in the clinical context: in response to 'Patients' substantialization of disease, the hybrid symptom and the metaphysical care', by Alexandra Parvan.

PubMed

Eriksen, Thor Eirik; Kirkengen, Anna Luise

2016-08-01

The types of diseases, or categories of suffering, referred to as medically unexplained symptoms or syndromes (MUS) are the focus for the following commentary. Such cases seem to invite reflection. The very nature of such complex patterns of disease and suffering raises a number of fundamental epistemological and ontological issues. Furthermore, such health challenges can serve as the basis for an exploration of how the suffering person as well as the medical caretaker comes to grip with disease, incapacitation or suffering. We have structured our comments into two parts: first, we will describe medically unexplained health problems as the background for an inquiry into a process wherein patients reify their suffering in order to meet their doctors on equal terms, which carries a potential for alienation. Second, we will reflect on Alexandra Parvan's text as regards patients' 'substantialization' of their disease, the resulting 'hybrid symptom' and a proposed model for care and healing. © 2015 John Wiley & Sons, Ltd.

An experiential mind-body approach to the management of medically unexplained symptoms.

PubMed

Bakal, D; Steiert, M; Coll, P; Schaefer, J

2006-01-01

This article outlines an experiential mind-body framework for understanding and treating patients with medically unexplained symptoms. The model relies on somatic awareness, a normal part of consciousness, to resolve the mind-body dualism inherent in conventional multidisciplinary approaches. Somatic awareness represents a guiding healing heuristic which allows for a linear treatment application of the biopsychosocial model. The heuristic acknowledges the validity of the patient's physical symptoms and identifies psychological and social factors needed for the healing process. Somatic awareness is used to direct changes in coping styles, illness beliefs, medication dependence and personal dynamics that are necessary to achieve symptom control. The mind-body concept is consistent with and supported by neurobiological models which draw on central nervous system mechanisms to explain medically unexplained symptoms. The concept is also supported by a recent hypothesis concerning the role peripheral connective tissue may play in influencing illness and well-being. Finally, somatic awareness is described as having potential to enhance understanding and conscious use of inner healing mechanisms at the basis of the placebo effect.

Dielectric Spectroscopic Detection of Early Failures in 3-D Integrated Circuits.

PubMed

Obeng, Yaw; Okoro, C A; Ahn, Jung-Joon; You, Lin; Kopanski, Joseph J

The commercial introduction of three dimensional integrated circuits (3D-ICs) has been hindered by reliability challenges, such as stress related failures, resistivity changes, and unexplained early failures. In this paper, we discuss a new RF-based metrology, based on dielectric spectroscopy, for detecting and characterizing electrically active defects in fully integrated 3D devices. These defects are traceable to the chemistry of the insolation dielectrics used in the through silicon via (TSV) construction. We show that these defects may be responsible for some of the unexplained early reliability failures observed in TSV enabled 3D devices.

Positron emission tomography/computed tomography with 18F-fluorocholine improve tumor staging and treatment allocation in patients with hepatocellular carcinoma.

PubMed

Chalaye, Julia; Costentin, Charlotte E; Luciani, Alain; Amaddeo, Giuliana; Ganne-Carrié, Nathalie; Baranes, Laurence; Allaire, Manon; Calderaro, Julien; Azoulay, Daniel; Nahon, Pierre; Seror, Olivier; Mallat, Ariane; Soussan, Michael; Duvoux, Christophe; Itti, Emmanuel; Nault, Jean Charles

2018-03-06

Hepatocellular carcinoma (HCC) staging according to the Barcelona Clinical Liver Cancer (BCLC) classification is based on conventional imaging. The aim of our study was to assess the impact of dual-tracer 18F-fluorocholine and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) on tumor staging and treatment allocation. A total of 192 dual-tracer PET/CT scans (18F-fluorocholine and 18F-fluorodeoxyglucose PET/CT) were performed in 177 patients with HCC. BCLC staging and treatment proposal were retrospectively collected based on conventional imaging, along with any new lesions detected, and changes in BCLC classification or treatment allocation based on dual-tracer PET/CT. Patients were primarily men (87.5%) with cirrhosis (71%) due to alcohol ± non-alcoholic steatohepatitis (26%), viral infection (62%) or unknown causes (12%). Among 122 patients with PET/CT performed for staging, BCLC stage based on conventional imaging was 0/A in 61 patients (50%), B in 32 patients (26%) and C in 29 patients (24%). Dual-tracer PET/CT detected new lesions in 26 patients (21%), upgraded BCLC staging in 14 (11%) and modified treatment strategy in 17 (14%). In addition, dual-tracer PET/CT modified the final treatment in 4/9 (44%) patients with unexplained elevation of alpha-fetoprotein (AFP), 10/25 patients (40%) with doubtful lesions on conventional imaging and 3/36 patients (8%) waiting for liver transplantation without active HCC after tumor response following bridging therapy. When used for HCC staging, dual-tracer PET/CT enabled BCLC upgrading and treatment modification in 11% and 14% of patients, respectively. Dual-tracer PET/CT might also be useful in specific situations (an unexplained rise in AFP, doubtful lesions or pre-transplant evaluation of patients without active HCC). Using a combination of tracers 18F-fluorocholine and 18F-fluorodeoxyglucose when performing positron emission tomography/computed tomography (PET/CT), often called a PET scan, helps to identify new tumor lesions in patients with hepatocellular carcinoma. This technique enabled staging modification of patients' tumors and led to changes in treatment allocation in certain patients. Copyright © 2018. Published by Elsevier B.V.

Value of combining serum carcinoembryonic antigen and PET/CT in predicting EGFR mutation in non-small cell lung cancer.

PubMed

Gu, Jincui; Xu, Siqi; Huang, Lixia; Li, Shaoli; Wu, Jian; Xu, Junwen; Feng, Jinlun; Liu, Baomo; Zhou, Yanbin

2018-02-01

We sought to investigate the associations between pretreatment serum Carcinoembryonic antigen (CEA) level, 18 F-Fluoro-2-deoxyglucose ( 18 F-FDG) uptake value of primary tumor and epidermal growth factor receptor ( EGFR ) mutation status in non-small cell lung cancer (NSCLC). We retrospectively reviewed medical records of 210 NSCLC patients who underwent EGFR mutation test and 18 F-FDG positron emission tomography/computed tomography (PET/CT) scan before anti-tumor therapy. The associations between EGFR mutations and patients' characteristics, serum CEA, PET/CT imaging characteristics maximal standard uptake value (SUVmax) of the primary tumor were analyzed. Receiver-operating characteristic (ROC) curve was used to assess the predictive value of these factors. EGFR mutations were found in 70 patients (33.3%). EGFR mutations were more common in high CEA group (CEA ≥7.0 ng/mL) than in low CEA group (CEA <7.0 ng/mL) (40.4% vs . 27.6%; P=0.05). Females (P<0.001), non-smokers (P<0.001), patients with adenocarcinoma (P<0.001) and SUVmax <9.0 (P=0.001) were more likely to be EGFR mutation-positive. Multivariate analysis revealed that gender, tumor histology, pretreatment serum CEA level, and SUVmax were the most significant predictors for EGFR mutations. The ROC curve revealed that combining these four factors yielded a higher calculated AUC (0.80). Gender, histology, pretreatment serum CEA level and SUVmax are significant predictors for EGFR mutations in NSCLC. Combining these factors in predicting EGFR mutations has a moderate diagnostic accuracy, and is helpful in guiding anti-tumor treatment.

A monoclonal antibody against neem leaf glycoprotein recognizes carcinoembryonic antigen (CEA) and restricts CEA expressing tumor growth.

PubMed

Das, Arnab; Barik, Subhasis; Banerjee, Saptak; Bose, Anamika; Sarkar, Koustav; Biswas, Jaydip; Baral, Rathindranath; Pal, Smarajit

2014-10-01

Carcinoembryonic antigen (CEA) is one of the promising tumor antigens mainly associated with carcinoma of the colon, lung, breast, etc. and received wide attention for cancer immunotherapy. Neem leaf glycoprotein (NLGP), an effective immunomodulator, is able to generate humoral and cellular immune responses in murine tumor models. We have generated a monoclonal antibody (mAb) against NLGP by fusing NLGP-immunized mice splenocytes with nonsecretory myeloma cells. A highly anti-NLGP mAb secreting clone (1C8; IgG2a in nature) has been identified and propagated in culture. 1C8 recognizes human CEA as good as NLGP by enzyme linked immunosorbent assay, Western blotting, and immunoprecipitation. 1C8 detects CEA on colon cancer tissues by immunochistochemistry. By flow cytometry, 1C8 specifically reacts with CEA(+) human (Colo-205, HCT-116, and HT-29) and mouse (CT-26) colon cancer cells, but it showed minimum reactivity with CEA(-) human (MCF7, SiHa, and SCC084) and mouse (B16MelF10) cancer cells. This anti-NLGP 1C8 mAb revealed significant antitumor activity and better survivability in vivo in animals bearing mouse (CT-26 in BALB/c) and human (Colo-205 in athymic nude) CEA(+) cancer cells. 1C8 has no direct influence on proliferation and migration of CEA(+) cells, however, NK cell-dependent strong antibody-dependent cellular cytotoxicity reaction toward CEA(+) cells and normalization of angiogenesis are chiefly associated with tumor growth restriction. Obtained results provided a new immunotherapeutic approach for the effective management of CEA(+) tumors.

Increased mortality associated with elevated carcinoembryonic antigen in insurance applicants.

PubMed

Stout, Robert L; Fulks, Michael; Dolan, Vera F; Magee, Mark E; Suarez, Luis

2007-01-01

Determine the relationship between the carcinoembryonic antigen (CEA) value and all-cause mortality in life insurance applicants aged 50 years and over. By use of the Social Security Master Death Index, mortality was examined in 115,590 insurance applicants aged 50 and up for whom blood samples for CEA were submitted to the Clinical Reference Laboratory. Results were stratified by CEA value (<5 ng/mL, 5 to 9.9 ng/mL, 10+ ng/mL), smoking status, and age groups (50-59 years, 60-69 years, and 70 years and up). Relative mortality is increased at CEA values between 5 and 9.9 ng/mL and further increased at 10+ ng/mL for all age groups, with the most dramatic increase at the youngest ages. Excess mortality appears to last at least 3 to 4 years after the elevated result. Five-year all-cause mortality in applicants with CEA values of 10+ ng/mL is 25.2% with a mortality ratio relative to those with a CEA <5 ng/mL of 1156%. This study shows that CEA can detect the risk of early excess mortality in life insurance applicants; CEA levels of 5 ng/mL and over may be of concern. CEA testing beginning at age 50 years for life insurance applicants could capture 4.6% of early mortality if the threshold for further evaluation was set at 10 ng/mL. Only 0.4% of all applicants aged 50 and over have CEA values at or above this threshold.

Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

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

Bajenova, Olga, E-mail: o.bazhenova@spbu.ru; Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg 199034; Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178

2014-06-10

Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA andmore » beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein.« less

A synergistic interferon-γ production is induced by mouse hepatitis virus in interleukin-12 (IL-12)/IL-18-activated natural killer cells and modulated by carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1a receptor

PubMed Central

Jacques, Alexandre; Bleau, Christian; Turbide, Claire; Beauchemin, Nicole; Lamontagne, Lucie

2009-01-01

The production of interferon-γ (IFN-γ) by infiltrating natural killer (NK) cells in liver is involved in the control of mouse hepatitis virus (MHV) infection. The objectives of this study were to identify the mechanisms used by MHV type 3 to modulate the production of IFN-γ by NK cells during the acute hepatitis in susceptible C57BL/6 mice. Ex vivo and in vitro experiments revealed that NK cells, expressing carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1a (the MHV receptor), can produce a higher level of IFN-γ in the presence of both L2-MHV3 and interleukin-12 (IL-12)/IL-18. The synergistic production of IFN-γ by NK cells depends on viral replication rather than viral fixation only, because it is inhibited or not induced in cells infected with ultraviolet-inactivated viruses and in cells from Ceacam1a−/− mice infected with virulent viruses. The synergistic IFN-γ production involves the p38 mitogen-activated protein kinase (MAPK) rather than the extracellular signal-regulated kinase-1/2 MAPK signalling pathway. However, the signal triggered through the engagement of CEACAM1a decreases the production of IFN-γ, when these molecules are cross-linked using specific monoclonal antibodies. These results suggest that control of acute hepatitis by IFN-γ-producing NK cells may depend on both production of IL-12 and IL-18 in the liver environment and viral infection of NK cells. PMID:19740316

Preoperative Carcinoembryonic Antigen and Prognosis of Colorectal Cancer. An Independent Prognostic Factor Still Reliable

PubMed Central

Li Destri, Giovanni; Rubino, Antonio Salvatore; Latino, Rosalia; Giannone, Fabio; Lanteri, Raffaele; Scilletta, Beniamino; Di Cataldo, Antonio

2015-01-01

To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this—to date—has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging. PMID:25875542

Preoperative carcinoembryonic antigen and prognosis of colorectal cancer. An independent prognostic factor still reliable.

PubMed

Li Destri, Giovanni; Rubino, Antonio Salvatore; Latino, Rosalia; Giannone, Fabio; Lanteri, Raffaele; Scilletta, Beniamino; Di Cataldo, Antonio

2015-04-01

To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this-to date-has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging.

Specific tumor labeling enhanced by polyethylene glycol linkage of near infrared dyes conjugated to a chimeric anti-carcinoembryonic antigen antibody in a nude mouse model of human pancreatic cancer

NASA Astrophysics Data System (ADS)

Maawy, Ali A.; Hiroshima, Yukihiko; Zhang, Yong; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael

2014-10-01

Labeling of metastatic tumors can aid in their staging and resection of cancer. Near infrared (NIR) dyes have been used in the clinic for tumor labeling. However, there can be a nonspecific uptake of dye by the liver, lungs, and lymph nodes, which hinders detection of metastasis. In order to overcome these problems, we have used two NIR dyes (DyLight 650 and 750) conjugated to a chimeric anti-carcinoembryonic antigen antibody to evaluate how polyethylene glycol linkage (PEGylation) can improve specific tumor labeling in a nude mouse model of human pancreatic cancer. The conjugated PEGylated and non-PEGylated DyLight 650 and 750 dyes were injected intravenously into non-tumor-bearing nude mice. Serum samples were collected at various time points in order to determine serum concentrations and elimination kinetics. Conjugated PEGylated dyes had significantly higher serum dye concentrations than non-PEGylated dyes (p=0.005 for the 650 dyes and p<0.001 for the 750 dyes). Human pancreatic tumors subcutaneously implanted into nude mice were labeled with antibody-dye conjugates and serially imaged. Labeling with conjugated PEGylated dyes resulted in significantly brighter tumors compared to the non-PEGylated dyes (p<0.001 for the 650 dyes; p=0.01 for 750 dyes). PEGylation of the NIR dyes also decreased their accumulation in lymph nodes, liver, and lung. These results demonstrate enhanced selective tumor labeling by PEGylation of dyes conjugated to a tumor-specific antibody, suggesting their future clinical use in fluorescence-guided surgery.

Degranulation and shrinkage of dark cells in eccrine glands and elevated serum carcinoembryonic antigen in patients with acquired idiopathic generalized anhidrosis.

PubMed

Sano, K; Asahina, M; Uehara, T; Matsumoto, K; Araki, N; Okuyama, R

2017-12-01

Acquired idiopathic generalized anhidrosis (AIGA) is characterized by anhidrosis/hypohidrosis without other autonomic and neurological dysfunctions. Pathologically, AIGA is considered to usually present no significant morphological alterations in eccrine glands, the secretory portion which consists of clear cells, dark cells, and myoepithelial cells. AIGA patients recently have been reported to show high serum concentrations of carcinoembryonic antigen (CEA). Our aim is to reveal morphological abnormalities of dark cells and investigate their relationship with serum CEA. We performed comparative analysis of eccrine glands between sweat-preserved and non-sweating skin in four AIGA patients. Serum CEA concentrations in 22 cases with AIGA were measured with healthy volunteers. Furthermore, we semiquantitatively investigated dermcidin, FoxA1 and CEA expression in eccrine glands of 12 cases with AIGA and 5 cases with non-AIGA. Marked degranulation and shrinkage of dark cells consistently occurred in AIGA. Furthermore, high serum CEA concentrations were found in 14 of 22 AIGA patients (over 60%), but serum CEA levels were not correlated with CEA expression in eccrine glands. Dermcidin expression in dark cells apparently decreased in AIGA patients, severely in those with high serum CEA and moderately in those with low serum CEA, while well-preserved expression was found in non-AIGA subjects. Our study suggests morphological damage and molecular dysregulation of dark cells, leading to impairment of their functions in AIGA patients. Severely damaged dark cells correspond to high serum CEA. Accordingly, these pathological changes in eccrine dark cells may be involved in anhidrosis/hypohidrosis of AIGA. © 2017 European Academy of Dermatology and Venereology.

A sensorimotor account of vision and visual consciousness.

PubMed

O'Regan, J K; Noë, A

2001-10-01

Many current neurophysiological, psychophysical, and psychological approaches to vision rest on the idea that when we see, the brain produces an internal representation of the world. The activation of this internal representation is assumed to give rise to the experience of seeing. The problem with this kind of approach is that it leaves unexplained how the existence of such a detailed internal representation might produce visual consciousness. An alternative proposal is made here. We propose that seeing is a way of acting. It is a particular way of exploring the environment. Activity in internal representations does not generate the experience of seeing. The outside world serves as its own, external, representation. The experience of seeing occurs when the organism masters what we call the governing laws of sensorimotor contingency. The advantage of this approach is that it provides a natural and principled way of accounting for visual consciousness, and for the differences in the perceived quality of sensory experience in the different sensory modalities. Several lines of empirical evidence are brought forward in support of the theory, in particular: evidence from experiments in sensorimotor adaptation, visual "filling in," visual stability despite eye movements, change blindness, sensory substitution, and color perception.

JSA guideline for the management of malignant hyperthermia crisis 2016.

PubMed

2017-04-01

Malignant hyperthermia (MH) can be fatal if the crisis is not appropriately treated. It is an inherited disease usually triggered by the administration of volatile inhalational anesthetics and/or succinylcholine, a muscle relaxant. In a patient with suspected MH, the mechanism of calcium release from storage in the sarcoplasmic reticulum in the skeletal muscle is abnormally accelerated. Unexplained hypercarbia representing >55 mmHg of end-tidal carbon dioxide, tachycardia, and muscle rigidity (including masseter muscle rigidity) are early signs of the initiation of MH, because the metabolism is accelerated. The body temperature can rise by >0.5 °C/15 min and may reach ≥40 °C. Respiratory and metabolic acidosis, arrhythmia, cola-colored urine, increased levels of serum potassium, and tented T-waves on electrocardiogram are common and can lead to cardiac arrest. MH should be treated by discontinuation of the triggering agents, administration of intravenous dantrolene (initially 1 mg/kg), and reduction of the body temperature. Early diagnosis and sufficient dantrolene with body temperature reduction are essential to relieve the patient's MH crisis. This guideline in Japanese translation has been posted on the website: http://www.anesth.or.jp/guide/pdf/guideline_akuseikounetsu.pdf .

A fast dynamic grid adaption scheme for meteorological flows

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

Fiedler, B.H.; Trapp, R.J.

1993-10-01

The continuous dynamic grid adaption (CDGA) technique is applied to a compressible, three-dimensional model of a rising thermal. The computational cost, per grid point per time step, of using CDGA instead of a fixed, uniform Cartesian grid is about 53% of the total cost of the model with CDGA. The use of general curvilinear coordinates contributes 11.7% to this total, calculating and moving the grid 6.1%, and continually updating the transformation relations 20.7%. Costs due to calculations that involve the gridpoint velocities (as well as some substantial unexplained costs) contribute the remaining 14.5%. A simple way to limit the costmore » of calculating the grid is presented. The grid is adapted by solving an elliptic equation for gridpoint coordinates on a coarse grid and then interpolating the full finite-difference grid. In this application, the additional costs per grid point of CDGA are shown to be easily offset by the savings resulting from the reduction in the required number of grid points. In simulation of the thermal costs are reduced by a factor of 3, as compared with those of a companion model with a fixed, uniform Cartesian grid. 8 refs., 8 figs.« less

Glucose acutely decreases pH of secretory granules in mouse pancreatic islets. Mechanisms and influence on insulin secretion.

PubMed

Stiernet, Patrick; Guiot, Yves; Gilon, Patrick; Henquin, Jean-Claude

2006-08-04

Glucose-induced insulin secretion requires a rise in beta-cell cytosolic Ca2+ ([Ca2+]c) that triggers exocytosis and a mechanistically unexplained amplification of the action of [Ca2+]c. Insulin granules are kept acidic by luminal pumping of protons with simultaneous Cl- uptake to maintain electroneutrality. Experiments using patched, dialyzed beta-cells prompted the suggestion that acute granule acidification by glucose underlies amplification of insulin secretion. However, others found glucose to increase granular pH in intact islets. In this study, we measured islet granular pH with Lysosensor DND-160, a fluorescent dye that permits ratiometric determination of pH < 6 in acidic compartments. Stimulation of mouse islets with glucose reversibly decreased granular pH by mechanisms that are dependent on metabolism and Cl- ions but independent of changes in [Ca2+]c and protein kinase A or C activity. Granular pH was increased by concanamycin (blocker of the vesicular type H+-ATPase) > methylamine (weak base) > Cl- omission. Concanamycin and methylamine did not alter glucose-induced [Ca2+]c increase in islets but strongly inhibited the two phases of insulin secretion. Omission of Cl- did not affect the first phase but decreased the second phase of both [Ca2+]c and insulin responses. Neither experimental condition affected the [Ca2+]c rise induced by 30 mM KCl, but the insulin responses were inhibited by concanamycin > methylamine and not affected by Cl- omission. The amplification of insulin secretion by glucose was not suppressed. We conclude that an acidic granular pH is important for insulin secretion but that the acute further acidification produced by glucose is not essential for the augmentation of secretion via the amplifying pathway.

Pharmacokinetic interaction between domperidone and ketoconazole leads to QT prolongation in healthy volunteers: a randomized, placebo-controlled, double-blind, crossover study

PubMed Central

Boyce, Malcolm J; Baisley, Kathy J; Warrington, Steven J

2012-01-01

AIMS To assess the steady-state pharmacokinetic and QTc effects of domperidone and ketoconazole, given alone and together. METHODS A randomized, placebo-controlled, double-blind, crossover study was carried out. Healthy subjects (14 men, 10 women; age 18–39 years; mean weight 73.5 kg, range 53.8–98.8 kg; 23 Europid, 1 Afro-Caribbean) received orally, for 7 days each, placebo, domperidone 10 mg, four doses daily, at 4 h intervals, ketoconazole 200 mg 12-hourly and domperidone and ketoconazole together. The washout period was 15 days. Pharmacokinetics and serial 12-lead ECGs were assessed on day 7, and serial ECGs on day −1 and at follow-up. Two subjects withdrew before the third treatment period, so data were available for 22–24 subjects. RESULTS Ketoconazole tripled domperidone concentrations at steady-state. Domperidone, ketoconazole and their combination significantly increased QTcF in men. Overall adjusted mean differences from placebo were 4.20 (95% CI 0.77, 7.63), 9.24 (95% CI 5.85, 12.63) and 15.90 (95% CI 12.47, 19.33) ms, respectively. In women, QTcF was not significantly different from placebo on either domperidone or ketoconazole alone, or in combination. However, QTc was positively correlated with plasma drug concentrations, in both men and women. ΔQTcF increased by about 2 ms per 10 ng ml–1 rise in domperidone concentration, and per 1 µg ml–1 rise in ketoconazole concentration. CONCLUSIONS Ketoconazole tripled the plasma concentrations of domperidone. Domperidone and ketoconazole increased QTcF in men, whether given together or separately. The effect of domperidone alone was below the level of clinical importance. The negative result in women is unexplained. PMID:21883386

Myxedema coma and cardiac ischemia in relation to thyroid hormone replacement therapy in a 38-year-old Japanese woman.

PubMed

Taguchi, Takafumi; Iwasaki, Yasumasa; Asaba, Koichi; Takao, Toshihiro; Hashimoto, Kozo

2007-12-01

Although thyroid hormone deficiency, either clinical or subclinical, is an established risk factor for cardiovascular disease, coronary ischemia in a premenopausal woman in her 30s is relatively rare. A 38-year-old woman was referred to our hospital with severe breathlessness and depressed consciousness. Physical examination found facial, abdominal, and pretibial edema; coarse hair, hoarse voice, and dry skin; engorged jugular veins; a distant heart sound; and reduced bilateral entry of air into the chest. Laboratory examinations revealed severe hypothyroidism, hyperlipidemia, and elevated serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125). A computed tomography scan showed massive pleural and pericardial effusions. After 3 months of levothyroxine replacement therapy (initial dose: 12.5 microg/d; maintenance dose: 125 microg/d), all abnormal laboratory values associated with hypothyroidism returned to within normal ranges, with the exception of a transient and paradoxical rise in serum thyroid-stimulating hormone levels. However, 3 weeks after the initiation of therapy, the patient reported intermittent chest pains during the course of therapy, and a coronary artery angiogram revealed diffuse stenosis of all 3 branches. The patient underwent coronary artery bypass grafting, with subsequent improvement in coronary perfusion. Careful cardiovascular evaluation is recommended before the start of thyroid hormone replacement therapy. In addition, care should be taken in the interpretation of serum biomarkers of malignancy (eg, CEA, CA125) in patients with myxedema, as values may be elevated in a hypothyroid state. Long-standing hypothyroidism may be associated with severe coronary atherosclerosis, even in a relatively young, premenopausal woman. The potential adverse cardiovascular effects of thyroid hormone must be considered during replacement therapy, even in relatively young patients.

Characterizing sudden death and dead-in-bed syndrome in Type 1 diabetes: analysis from two childhood-onset Type 1 diabetes registries.

PubMed

Secrest, A M; Becker, D J; Kelsey, S F; Laporte, R E; Orchard, T J

2011-03-01

Type 1 diabetes mellitus increases the risk for sudden unexplained death, generating concern that diabetes processes and/or treatments underlie these deaths. Young (< 50 years) and otherwise healthy patients who are found dead in bed have been classified as experiencing 'dead-in-bed' syndrome. We thus identified all unwitnessed deaths in two related registries (the Children's Hospital of Pittsburgh and Allegheny County) yielding 1319 persons with childhood-onset (age < 18 years) Type 1 diabetes diagnosed between 1965 and 1979. Cause of death was determined by a Mortality Classification Committee (MCC) of at least two physician epidemiologists, based on the death certificate and additional records surrounding the death. Of the 329 participants who had died, the Mortality Classification Committee has so far reviewed and assigned a final cause of death to 255 (78%). Nineteen (8%) of these were sudden unexplained deaths (13 male) and seven met dead-in-bed criteria. The Mortality Classification Committee adjudicated cause of death in the seven dead-in-bed persons as: diabetic coma (n =4), unknown (n=2) and cardiomyopathy (n=1, found on autopsy). The three dead-in-bed individuals who participated in a clinical study had higher HbA(1c) , lower BMI and higher daily insulin dose compared with both those dying from other causes and those surviving. Sudden unexplained death in Type 1 diabetes seems to be increased 10-fold and associated with male sex, while dead-in-bed individuals have a high HbA(1c) and insulin dose and low BMI. Although sample size is too small for definitive conclusions, these results suggest specific sex and metabolic factors predispose to sudden unexplained death and dead-in-bed death. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

A prospective cohort study to refine and validate the Panic Screening Score for identifying panic attacks associated with unexplained chest pain in the emergency department

PubMed Central

Foldes-Busque, Guillaume; Denis, Isabelle; Poitras, Julien; Fleet, Richard P; Archambault, Patrick; Dionne, Clermont E

2013-01-01

Introduction Panic-like anxiety (panic attacks with or without panic disorder), a highly treatable condition, is the most prevalent condition associated with unexplained chest pain in the emergency department. Panic-like anxiety may be responsible for a significant portion of the negative consequences of unexplained chest pain, such as functional limitations and chronicity. However, more than 92% of panic-like anxiety cases remain undiagnosed at the time of discharge from the emergency department. The 4-item Panic Screening Score (PSS) questionnaire was derived in order to increase the identification of panic-like anxiety in emergency department patients with unexplained chest pain. Methods and analysis The goals of this prospective cohort study were to (1) refine the PSS; (2) validate the revised version of the PSS; (3) measure the reliability of the revised version of the PSS and (4) assess the acceptability of the instrument among emergency physicians. Eligible and consenting patients will be administered the PSS in a large emergency department. Patients will be contacted by phone for administration of the criterion standard for panic attacks as well as by a standardised interview to collect information for other predictors of panic attacks. Multivariate analysis will be used to refine the PSS. The new version will be prospectively validated in an independent sample and inter-rater agreement will be assessed in 10% of cases. The screening instrument acceptability will be assessed with the Ottawa Acceptability of Decision Rules Instrument. Ethics and dissemination This study protocol has been reviewed and approved by the Alphonse-Desjardins research ethics committee. The results of the study will be presented in scientific conferences and published in peer-reviewed scientific journals. Further dissemination via workshops and a dedicated website is planned. PMID:24163208

Antenatal testing to predict outcome in pregnancies with unexplained antepartum haemorrhage.

PubMed

Ajayi, R A; Soothill, P W; Campbell, S; Nicolaides, K H

1992-02-01

To investigate whether Doppler studies of placental perfusion and antenatal tests for fetal hypoxia can identify reduced placental functional reserve in women with unexplained antepartum haemorrhage (APH). A prospective, longitudinal study. Fetal Surveillance Unit, King's College Hospital, London. 48 women with bleeding from the genital tract after 26 weeks gestation without a clinical diagnosis of abruption or ultrasound evidence of placenta praevia. Fetal surveillance by Doppler measurements of the umbilical and uterine arteries, biophysical profile scoring and computerized measurement of the mean minute range of FHR variation. A poor outcome was defined by one or more of the following: (i) birthweight greater than 2SD below the normal mean for gestational age and sex, (ii) abnormal FHR pattern in labour resulting in operative delivery, (iii) umbilical vein blood pH at delivery less than 7.15, (iv) a 5-min Apgar score less than 7. Fifteen of the 48 pregnancies had a poor outcome; seven occurred in the 10 women delivered preterm (less than 37 weeks) and eight in the 36 women delivered between 37 and 42 weeks. Two women were delivered after 42 weeks and both infants had a good outcome. The results of Doppler studies of uterine and umbilical arteries, fetal biophysical profile or FHR variation were not significantly different between the two outcome groups. The 36 pregnancies delivered between 37 and 42 weeks were matched retrospectively for maternal age, parity and race with 36 pregnancies without APH; there was no significant difference in outcome between the women with unexplained APH and the matched comparison group. Morbidity related to unexplained APH is associated with preterm delivery rather than with damage to utero-placental function.

Cost-effectiveness of primary offer of IVF vs. primary offer of IUI followed by IVF (for IUI failures) in couples with unexplained or mild male factor subfertility.

PubMed

Pashayan, Nora; Lyratzopoulos, Georgios; Mathur, Raj

2006-06-23

In unexplained and mild male factor subfertility, both intrauterine insemination (IUI) and in-vitro fertilisation (IVF) are indicated as first line treatments. Because the success rate of IUI is low, many couples failing IUI subsequently require IVF treatment. In practice, it is therefore important to examine the comparative outcomes (live birth-producing pregnancy), costs, and cost-effectiveness of primary offer of IVF, compared with primary offer of IUI followed by IVF for couples failing IUI. Mathematical modelling was used to estimate comparative clinical and cost effectiveness of either primary offer of one full IVF cycle (including frozen cycles when applicable) or "IUI + IVF" (defined as primary IUI followed by IVF for IUI failures) to a hypothetical cohort of subfertile couples who are eligible for both treatment strategies. Data used in calculations were derived from the published peer-reviewed literature as well as activity data of local infertility units. Cost-effectiveness ratios for IVF, "unstimulated-IUI (U-IUI) + IVF", and "stimulated IUI (S-IUI) + IVF" were 12,600 pounds sterling, 13,100 pound sterling and 15,100 pound sterling per live birth-producing pregnancy respectively. For a hypothetical cohort of 100 couples with unexplained or mild male factor subfertility, compared with primary offer of IVF, 6 cycles of "U-IUI + IVF" or of "S-IUI + IVF" would cost an additional 174,200 pounds sterling and 438,000 pounds sterling, representing an opportunity cost of 54 and 136 additional IVF cycles and 14 to 35 live birth-producing pregnancies respectively. For couples with unexplained and mild male factor subfertility, primary offer of a full IVF cycle is less costly and more cost-effective than providing IUI (of any modality) followed by IVF.

Cost-effectiveness of primary offer of IVF vs. primary offer of IUI followed by IVF (for IUI failures) in couples with unexplained or mild male factor subfertility

PubMed Central

Pashayan, Nora; Lyratzopoulos, Georgios; Mathur, Raj

2006-01-01

Background In unexplained and mild male factor subfertility, both intrauterine insemination (IUI) and in-vitro fertilisation (IVF) are indicated as first line treatments. Because the success rate of IUI is low, many couples failing IUI subsequently require IVF treatment. In practice, it is therefore important to examine the comparative outcomes (live birth-producing pregnancy), costs, and cost-effectiveness of primary offer of IVF, compared with primary offer of IUI followed by IVF for couples failing IUI. Methods Mathematical modelling was used to estimate comparative clinical and cost effectiveness of either primary offer of one full IVF cycle (including frozen cycles when applicable) or "IUI + IVF" (defined as primary IUI followed by IVF for IUI failures) to a hypothetical cohort of subfertile couples who are eligible for both treatment strategies. Data used in calculations were derived from the published peer-reviewed literature as well as activity data of local infertility units. Results Cost-effectiveness ratios for IVF, "unstimulated-IUI (U-IUI) + IVF", and "stimulated IUI (S-IUI) + IVF" were £12,600, £13,100 and £15,100 per live birth-producing pregnancy respectively. For a hypothetical cohort of 100 couples with unexplained or mild male factor subfertility, compared with primary offer of IVF, 6 cycles of "U-IUI + IVF" or of "S-IUI + IVF" would cost an additional £174,200 and £438,000, representing an opportunity cost of 54 and 136 additional IVF cycles and 14 to 35 live birth-producing pregnancies respectively. Conclusion For couples with unexplained and mild male factor subfertility, primary offer of a full IVF cycle is less costly and more cost-effective than providing IUI (of any modality) followed by IVF. PMID:16796733

Occult thyroid eye disease in patients with unexplained ocular misalignment identified by standardized orbital echography.

PubMed

Volpe, Nicholas J; Sbarbaro, James A; Gendron Livingston, Kym; Galetta, Steven L; Liu, Grant T; Balcer, Laura J

2006-07-01

To describe the clinical presentation, orbital echography (OE) findings, and neuroimaging results of patients with chronic unexplained ocular misalignment, which includes patients with clinically occult thyroid eye disease (TED) that is identifiable through a characteristic OE appearance. Retrospective observational case series. Seventy-eight patients with chronic ocular misalignment suspected of TED because of a history of systemic thyroid disease, proptosis, dysmotility, positive forced ductions, or eyelid retraction or lag were categorized as TED positive, negative, and indeterminate with the use of standardized OE. Demographic, clinical, OE, computed tomography, and magnetic resonance imaging information was collected. Analyses determined the prevalence of TED and differences between TED positive, negative, and indeterminate groups. Fifty-five percent of the findings were suspicious for and most consistent with TED (TED positive); 26% of the findings were TED negative, and 19% of the findings were TED indeterminate. Of 30 patients with newly diagnosed TED by OE, 70% had no lid retraction, and 20% had no other findings of TED. The inferior rectus followed by the superior rectus/levator complex, medial rectus, and lateral rectus muscles were the most frequently involved muscles. Neuroimaging that was performed in only 26 of 78 patients (33%) did not appear to yield additional diagnostic information. TED is a potential cause of chronic unexplained ocular misalignment in a substantial proportion of patients. These patients frequently present in an occult fashion without other clinical findings that are typical of TED. In these patients, a diagnosis of TED by OE can reduce further costly evaluation. OE appears to have significant clinical usefulness in the diagnosis of TED in patients with unexplained ocular misalignment.

Association of uterine fibroids and pregnancy outcomes after ovarian stimulation-intrauterine insemination for unexplained infertility.

PubMed

Styer, Aaron K; Jin, Susan; Liu, Dan; Wang, Baisong; Polotsky, Alex J; Christianson, Mindy S; Vitek, Wendy; Engmann, Lawrence; Hansen, Karl; Wild, Robert; Legro, Richard S; Coutifaris, Christos; Alvero, Ruben; Robinson, Randal D; Casson, Peter; Christman, Gregory M; Christy, Alicia; Diamond, Michael P; Eisenberg, Esther; Zhang, Heping; Santoro, Nanette

2017-03-01

To investigate the association of non-cavity-distorting uterine fibroids and pregnancy outcomes after ovarian stimulation-intrauterine insemination (OS-IUI) in couples with unexplained infertility. Secondary analysis from a prospective, randomized, multicenter clinical trial investigating fertility outcomes after OS-IUI. Reproductive Medicine Network clinical sites. Nine hundred couples with unexplained infertility who participated in the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial. Participants were randomized to one of three arms (clomiphene citrate, letrozole, or gonadotropins), and treatment was continued for up to four cycles or until pregnancy was achieved. Conception (serum hCG increase), clinical pregnancy (fetal cardiac activity), and live birth rates. A total of 102/900 participants (11.3%) had at least one documented fibroid and a normal uterine cavity. Women with fibroids were older, more likely to be African American, had a greater uterine volume, lower serum antimüllerian hormone levels, and fewer antral follicles than women without fibroids. In conception cycles, clinical pregnancy rates were significantly lower in participants with fibroids than in those without uterine fibroids. Pregnancy loss before 12 weeks was more likely in African American women with fibroids compared with non-African American women with fibroids. There was no difference in conception and live birth rates in subjects with and without fibroids. No differences were observed in conception and live birth rates in women with non-cavity-distorting fibroids and those without fibroids. These findings provide reassurance that pregnancy success is not impacted in couples with non-cavity-distorting fibroids undergoing OS-IUI for unexplained infertility. NCT01044862. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Within-Tunnel Variations in Pressure Data for Three Transonic Wind Tunnels

NASA Technical Reports Server (NTRS)

DeLoach, Richard

2014-01-01

This paper compares the results of pressure measurements made on the same test article with the same test matrix in three transonic wind tunnels. A comparison is presented of the unexplained variance associated with polar replicates acquired in each tunnel. The impact of a significance component of systematic (not random) unexplained variance is reviewed, and the results of analyses of variance are presented to assess the degree of significant systematic error in these representative wind tunnel tests. Total uncertainty estimates are reported for 140 samples of pressure data, quantifying the effects of within-polar random errors and between-polar systematic bias errors.

Check-Standard Testing Across Multiple Transonic Wind Tunnels with the Modern Design of Experiments

NASA Technical Reports Server (NTRS)

Deloach, Richard

2012-01-01

This paper reports the result of an analysis of wind tunnel data acquired in support of the Facility Analysis Verification & Operational Reliability (FAVOR) project. The analysis uses methods referred to collectively at Langley Research Center as the Modern Design of Experiments (MDOE). These methods quantify the total variance in a sample of wind tunnel data and partition it into explained and unexplained components. The unexplained component is further partitioned in random and systematic components. This analysis was performed on data acquired in similar wind tunnel tests executed in four different U.S. transonic facilities. The measurement environment of each facility was quantified and compared.

Clinical perspectives on osteogenesis imperfecta versus non-accidental injury.

PubMed

Pereira, Elaine Maria

2015-12-01

Although non-accidental injuries (NAI) are more common in cases of unexplained fractures than rare disorders such as osteogenesis imperfecta (OI), ruling out OI and other medical causes of fracture is always indicated. The majority of OI patients can be diagnosed with the help of family history, physical examination, and radiographic findings. In particular, there are a few radiological findings which are seen more commonly in NAI than in OI which may help guide clinician considerations regarding the probability of either of these diagnoses. At the same time, molecular testing still merits careful consideration in cases with unexplained fractures without obvious additional signs of abuse. © 2015 Wiley Periodicals, Inc.

Sudden onset unexplained encephalopathy in infants: think of cannabis intoxication.

PubMed

Lavi, Eran; Rekhtman, David; Berkun, Yackov; Wexler, Isaiah

2016-03-01

The use of cannabis as both a therapeutic agent and recreational drug is common, and its availability is increasing as a result of legalization in many countries. Among older children, the manifestations of cannabis intoxication are numerous and include both neurological and systemic manifestations that are frequently non-specific. There have been only a few reports detailing cannabis intoxication in infants and toddlers. We describe three infants who presented to the emergency department with encephalopathic signs without prominent systemic manifestations. During the initial interview of caregivers, no history of exposure to neurotoxic agents was obtained. All three patients were subsequently diagnosed with cannabis intoxication based on urine toxic screens for delta-9-tetrahydrocannabinol (THC). The infants recovered with supportive care that included fluids and monitoring. The non-specific symptomatology of cannabis intoxication in infants together with the wide differential for unexplained acute onset encephalopathy may delay diagnosis and lead to inappropriate procedures and interventions such as antimicrobial treatments and imaging studies. Healthcare personnel of emergency rooms, urgent care centers, and general clinics should be aware of the potential risk of cannabis ingestion in young infants. A thorough medical history and toxic screen are warranted in all infants with unexplained decreased sensorium.

Assessment of Somatization and Medically Unexplained Symptoms in Later Life

PubMed Central

van Driel, T. J. W.; Hilderink, P. H.; Hanssen, D. J. C.; de Boer, P.; Rosmalen, J. G. M.; Oude Voshaar, R. C.

2017-01-01

The assessment of medically unexplained symptoms and “somatic symptom disorders” in older adults is challenging due to somatic multimorbidity, which threatens the validity of somatization questionnaires. In a systematic review study, the Patient Health Questionnaire–15 (PHQ-15) and the somatization subscale of the Symptom Checklist 90-item version (SCL-90 SOM) are recommended out of 40 questionnaires for usage in large-scale studies. While both scales measure physical symptoms which in younger persons often refer to unexplained symptoms, in older persons, these symptoms may originate from somatic diseases. Using empirical data, we show that PHQ-15 and SCL-90 SOM among older patients correlate with proxies of somatization as with somatic disease burden. Updating the previous systematic review, revealed six additional questionnaires. Cross-validation studies are needed as none of 46 identified scales met the criteria of suitability for an older population. Nonetheless, specific recommendations can be made for studying older persons, namely the SCL-90 SOM and PHQ-15 for population-based studies, the Freiburg Complaint List and somatization subscale of the Brief Symptom Inventory 53-item version for studies in primary care, and finally the Schedule for Evaluating Persistent Symptoms and Somatic Symptom Experiences Questionnaire for monitoring treatment studies. PMID:28745072

Efficacy of cognitive-behavioural therapy by general practitioners for unexplained fatigue among employees: Randomised controlled trial.

PubMed

Huibers, Marcus J H; Beurskens, Anna J H M; Van Schayck, Constant P; Bazelmans, Ellen; Metsemakers, Job F M; Knottnerus, J Andre; Bleijenberg, Gijs

2004-03-01

Fatigue is a common complaint that may lead to long-term sick leave and work disability. To assess the efficacy of cognitive-behavioural therapy by general practitioners for unexplained, persistent fatigue among employees. A randomised controlled trial, using a pre-randomisation design in primary care, investigated 151 employees on sick leave with fatigue. Participants in the experimental group were offered five to seven 30 min sessions of cognitive-behavioural therapy by a general practitioner; those in the control group were offered no treatment. Main outcome measures (fatigue severity, self-reported absenteeism, registered absenteeism and clinical recovery) were assessed at 4 months, 8 months and 12 months. At baseline, 44% of the patients already met research criteria for chronic fatigue syndrome. There was no significant difference between the experimental group and the control group on primary or secondary outcomes at any point. Cognitive-behavioural therapy by general practitioners for unexplained, persistent fatigue did not prove to be an effective intervention. Since these doctors were unable to deliver this therapy effectively under ideal circumstances, it is unlikely that doctors in routine practice would be more successful in doing so.

Clinical application of hysteroscopic hydrotubation for unexplained infertility in the mare.

PubMed

Inoue, Y; Sekiguchi, M

2017-11-07

Therapeutic techniques for oviductal obstruction in the mare are limited. Nonsurgical and retrograde flushing may be an attractive alternative to current treatment methods for oviductal blockage. To evaluate hysteroscopic selective hydrotubation as a treatment option for presumptive equine oviductal blockage. Retrospective case series. A quantity of 10 mL of saline was flushed through the oviducts in 28 standing sedated mares, which had reproductive histories of unexplained subfertility, by inserting a catheter into the uterotubal junction under endoscopic guidance. All mares in the study had been mated through several cycles (2-20 oestrous cycles) by known fertile stallions prior to treatment, with no evidence of conception. The average number of cycles for each mare prior to treatment was 6.5 ± 4.5. Saline was successfully infused into a total of 50 oviducts. Of 28 mares, 26 conceived after the treatment. The average number of cycles for each mare to become pregnant after treatment was 1.8 ± 0.8. Diagnosis of blocked oviducts was presumptive, and pretreatment infertility was used as the control. This study revealed that hysteroscopic hydrotubation using saline improved pregnancy rates in mares in which oviductal blockage was suspected as a cause of unexplained subfertility. © 2017 EVJ Ltd.

Sickness absence, marginality, and medically unexplained physical symptoms: a focus-group study of patients' experiences.

PubMed

Aamland, Aase; Werner, Erik L; Malterud, Kirsti

2013-06-01

Medically unexplained physical symptoms (MUPS) form a major cause of sickness absence. The purpose of this study was to explore factors which may influence further marginalization among patients with MUPS on long-term sickness absence. Two focus-group discussions were conducted with a purposive sample of 12 participants, six men and six women, aged 24-59 years. Their average duration of sickness absence was 10.5 months. Participants were invited to share stories about experiences from the process leading to the ongoing sickness absence, with a focus on the causes being medically unexplained. Systematic text condensation was applied for analysis. Inspired by theories of marginalization and coping, the authors searched for knowledge of how patients' positive resources can be mobilized to counteract processes of marginality. Analysis revealed how invisible symptoms and lack of objective findings were perceived as an additional burden to the sickness absence itself. Factors that could counteract further marginalization were a supportive social network, positive coping strategies such as keeping to the daily schedule and physical activity, and positive attention and confidence from professionals. Confidence from both personal and professional contacts is crucial. GPs have an important and appreciated role in this aspect.

Irinotecan as a new agent for urachal cancer.

PubMed

Kume, Haruki; Tomita, Kyoichi; Takahashi, Sayuri; Fukutani, Keiko

2006-01-01

The urachal carcinoma, in a 64-year-old male with multiple lung metastases, had shown the resistance to several anti-neoplastic agents including cisplatinum, methotrexate, 5-FU, doxorubicin, epirubicin, and mitomycin C. Because the tumor was adenocarcinoma producing mucin and serum carcinoembryonic antigen (CEA) increased, which resembled colorectal carcinoma, we administrated Irinotecan, which was very effective as the CEA decreased from 98.3 to 38.7 ng/ml and the pulmonary metastatic lesions were reduced by 60%. To our knowledge, this is the first case with urachal carcinoma in which Irinotecan was effective. Copyright (c) 2006 S. Karger AG, Basel.

Combination of long noncoding RNA MALAT1 and carcinoembryonic antigen for the diagnosis of malignant pleural effusion caused by lung cancer.

PubMed

Wang, Wan-Wei; Zhou, Xi-Lei; Song, Ying-Jian; Yu, Chang-Hua; Zhu, Wei-Guo; Tong, Yu-Suo

2018-01-01

Long noncoding RNAs (lncRNAs) are present in body fluids, but their potential as tumor biomarkers has never been investigated in malignant pleural effusion (MPE) caused by lung cancer. The aim of this study was to assess the clinical significance of lncRNAs in pleural effusion, which could potentially serve as diagnostic and predictive markers for lung cancer-associated MPE (LC-MPE). RNAs from pleural effusion were extracted in 217 cases of LC-MPE and 132 cases of benign pleural effusion (BPE). Thirty-one lung cancer-associated lncRNAs were measured using quantitative real-time polymerase chain reaction (qRT-PCR). The level of carcinoembryonic antigen (CEA) was also determined. The receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were established to evaluate the sensitivity and specificity of the identified lncRNAs and other biomarkers. The correlations between baseline pleural effusion lncRNAs expression and response to chemotherapy were also analyzed. Three lncRNAs ( MALAT1 , H19 , and CUDR ) were found to have potential as diagnostic markers in LC-MPE. The AUCs for MALAT1 , H19 , CUDR , and CEA were 0.891, 0.783, 0.824, and 0.826, respectively. Using a logistic model, the combination of MALAT1 and CEA (AUC, 0.924) provided higher sensitivity and accuracy in predicting LC-MPE than CEA (AUC, 0.826) alone. Moreover, baseline MALAT1 expression in pleural fluid was inversely correlated with chemotherapy response in patients with LC-MPE. Pleural effusion lncRNAs were effective in differentiating LC-MPE from BPE. The combination of MALAT1 and CEA was more effective for LC-MPE diagnosis.

Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells

PubMed Central

Lee, Hsin-chung; Ling, Qing-Dong; Yu, Wan-Chun; Hung, Chunh-Ming; Kao, Ta-Chun; Huang, Yi-Wei; Higuchi, Akon

2013-01-01

Purpose We evaluated the higher levels of carcinoembryonic antigen (CEA) secreted by the LoVo human colon carcinoma cells in a medium containing anticancer drugs. Drug-resistant LoVo cells were analyzed by subcutaneously xenotransplanting them into mice. The aim of this study was to evaluate whether the drug-resistant cells isolated in this study were cancer-initiating cells, known also as cancer stem cells (CSCs). Methods The production of CEA was investigated in LoVo cells that were cultured with 0–10 mM of anticancer drugs, and we evaluated the increase in CEA production by the LoVo cells that were stimulated by anticancer drug treatment. The expression of several CSC markers in LoVo cells treated with anticancer drugs was also evaluated. Following anticancer drug treatment, LoVo cells were injected subcutaneously into the flanks of severe combined immunodeficiency mice in order to evaluate the CSC fraction. Results Production of CEA by LoVo cells was stimulated by the addition of anticancer drugs. Drug-resistant LoVo cells expressed lower levels of CSC markers, and LoVo cells treated with any of the anticancer drugs tested did not generate tumors within 8 weeks from when the cells were injected subcutaneously into severe combined immunodeficiency mice. These results suggest that the drug-resistant LoVo cells have a smaller population of CSCs than the untreated LoVo cells. Conclusion Production of CEA by LoVo cells can be stimulated by the addition of anticancer drugs. The drug-resistant subpopulation of LoVo colon cancer cells could stimulate the production of CEA, but these cells did not act as CSCs in in vivo tumor generation experiments. PMID:23818760

Clinical significance of preoperative carcinoembryonic antigen level in patients with clinical stage IA non-small cell lung cancer.

PubMed

Maeda, Ryo; Suda, Takashi; Hachimaru, Ayumi; Tochii, Daisuke; Tochii, Sachiko; Takagi, Yasushi

2017-01-01

The objective of this study was to assess the preoperative serum carcinoembryonic antigen (CEA) level in patients with clinical stage IA non-small cell lung cancer (NSCLC) and to evaluate its clinical significance. Between January 2005 and December 2014, a total of 378 patients with clinical stage IA NSCLC underwent complete resection with systematic node dissection. The survival rate was estimated starting from the date of surgery to the date of either death or the last follow-up by the Kaplan-Meier method. Univariate analyses by log-rank tests were used to determine prognostic factors. Cox proportional hazards ratios were used to identify independent predictors of poor prognosis. Clinicopathological predictors of lymph node metastases were evaluated by logistic regression analyses. The 5-year survival rate of patients with an elevated preoperative serum CEA level was significantly lower than that of patients with a normal CEA level (75.5% vs. 87.7%; P=0.02). However, multivariate analysis did not show the preoperative serum CEA level to be an independent predictor of poor prognosis. Postoperative pathological factors, including lymphatic permeation, visceral pleural invasion, and lymph node metastases, tended to be positive in patients with an elevated preoperative serum CEA level. In addition, the CEA level was a statistically significant independent clinical predictor of lymph node metastases. The preoperative serum CEA level was not an independent predictor of poor prognosis in patients with pathological stage IA NSCLC but was an important clinical predictor of tumor invasiveness and lymph node metastases in patients with clinical stage IA NSCLC. Therefore, measurement of the preoperative serum CEA level should be considered even for patients with early-stage NSCLC.

Surveillance of colorectal cancer: effectiveness of early detection of intraluminal recurrences on prognosis and survival of patients treated for cure.

PubMed

Barillari, P; Ramacciato, G; Manetti, G; Bovino, A; Sammartino, P; Stipa, V

1996-04-01

The authors evaluate the effectiveness of routine colonoscopy and marker evaluation in diagnosis of intraluminal recurrent cancer. Chart review was conducted on 481 patients who underwent curative resection for colorectal cancer between 1980 and 1990. Clinical visits were scheduled and carcinoembryonic antigen evaluation was performed every three months, and colonoscopy was performed preoperatively, 12 to 15 months after surgical treatment, and then with intervals of 12 to 24 months or when symptoms appeared. About 10 percent of patients developed intraluminal recurrences. More than one-half of metachronous lesions arose within the first 24 months, and median time to diagnosis was 25 months. Patients with left-sited tumors in the advanced stage had a higher risk of developing recurrent intraluminal disease. Twenty-nine patients underwent a second surgical operation, of which 17 cases were radical. In this group, the five-year survival was 70.6 percent, although no nonradically treated or nonresected patients survived longer than 31 months. Twenty-two patients were asymptomatic at time of diagnosis of recurrence, and of these, 12 patients underwent radical operation; on the other hand, of the 24 symptomatic patients, only 5 were treated radically. Carcinoembryonic antigen was the first sign of recurrence in eight cases. Colonoscopy must be performed within the first 12 to 15 months after operation, whereas an interval of 24 months between examinations seems sufficient to guarantee early detection of metachronous lesions. Serial tumor marker evaluation is of help in earlier diagnosis of local recurrences. Asymptomatic patients more frequently undergo another operation for cure and thus have a better survival rate.

NLRC5 deficiency protects against acute kidney injury in mice by mediating carcinoembryonic antigen-related cell adhesion molecule 1 signaling.

PubMed

Li, Quanxin; Wang, Ziying; Zhang, Yan; Zhu, Jiaqing; Li, Liang; Wang, Xiaojie; Cui, Xiaoyang; Sun, Yu; Tang, Wei; Gao, Chengjiang; Ma, Chunhong; Yi, Fan

2018-06-12

There is significant progress in understanding the structure and function of NLRC5, a member of the nucleotide oligomerization domain-like receptor family. However, in the context of MHC class I gene expression, the functions of NLRC5 in innate and adaptive immune responses beyond the regulation of MHC class I genes remain controversial and unresolved. In particular, the role of NLRC5 in the kidney is unknown. NLRC5 was significantly upregulated in the kidney from mice with renal ischemia/reperfusion injury. NLRC5 deficient mice significantly ameliorated renal injury as evidenced by decreased serum creatinine levels, improved morphological injuries, and reduced inflammatory responses versus wild type mice. Similar protective effects were also observed in cisplatin-induced acute kidney injury. Mechanistically, NLRC5 contributed to renal injury by promoting tubular epithelial cell apoptosis and reducing inflammatory responses were, at least in part, associated with the negative regulation of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). To determine the relative contribution of NLRC5 expression by parenchymal cells or leukocytes to renal damage during ischemia/reperfusion injury, we generated bone marrow chimeric mice. NLRC5 deficient mice engrafted with wild type hematopoietic cells had significantly lower serum creatinine and less tubular damage than wild type mice reconstituted with NLRC5 deficient bone marrow. This suggests that NLRC5 signaling in renal parenchymal cells plays the dominant role in mediating renal damage. Thus, modulation of the NLRC5-mediated pathway may have important therapeutic implications for patients with acute kidney injury. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

A filamentous bacteriophage targeted to carcinoembryonic antigen induces tumor regression in mouse models of colorectal cancer.

PubMed

Murgas, Paola; Bustamante, Nicolás; Araya, Nicole; Cruz-Gómez, Sebastián; Durán, Eduardo; Gaete, Diana; Oyarce, César; López, Ernesto; Herrada, Andrés Alonso; Ferreira, Nicolás; Pieringer, Hans; Lladser, Alvaro

2018-02-01

Colorectal cancer is a deadly disease, which is frequently diagnosed at advanced stages, where conventional treatments are no longer effective. Cancer immunotherapy has emerged as a new form to treat different malignancies by turning-on the immune system against tumors. However, tumors are able to evade antitumor immune responses by promoting an immunosuppressive microenvironment. Single-stranded DNA containing M13 bacteriophages are highly immunogenic and can be specifically targeted to the surface of tumor cells to trigger inflammation and infiltration of activated innate immune cells, overcoming tumor-associated immunosuppression and promoting antitumor immunity. Carcinoembryonic antigen (CEA) is highly expressed in colorectal cancers and has been shown to promote several malignant features of colorectal cancer cells. In this work, we targeted M13 bacteriophage to CEA, a tumor-associated antigen over-expressed in a high proportion of colorectal cancers but largely absent in normal cells. The CEA-targeted M13 bacteriophage was shown to specifically bind to purified CEA and CEA-expressing tumor cells in vitro. Both intratumoral and systemic administration of CEA-specific bacteriophages significantly reduced tumor growth of mouse models of colorectal cancer, as compared to PBS and control bacteriophage administration. CEA-specific bacteriophages promoted tumor infiltration of neutrophils and macrophages, as well as maturation dendritic cells in tumor-draining lymph nodes, suggesting that antitumor T-cell responses were elicited. Finally, we demonstrated that tumor protection provided by CEA-specific bacteriophage particles is mediated by CD8 + T cells, as depletion of circulating CD8 + T cells completely abrogated antitumor protection. In summary, we demonstrated that CEA-specific M13 bacteriophages represent a potential immunotherapy against colorectal cancer.

EphA2 signaling is impacted by carcinoembryonic antigen cell adhesion molecule 1-L expression in colorectal cancer liver metastasis in a cell context-dependent manner.

PubMed

Arabzadeh, Azadeh; McGregor, Kevin; Breton, Valérie; Van Der Kraak, Lauren; Akavia, Uri David; Greenwood, Celia M T; Beauchemin, Nicole

2017-11-28

We have shown that carcinoembryonic antigen cell adhesion molecule 1 long isoform (CEACAM1-L) expression in MC38 metastatic colorectal cancer (CRC) cells results in liver metastasis inhibition via CCL2 and STAT3 signaling. But other molecular mechanisms orchestrating CEACAM1-L-mediated metastasis inhibition remain to be defined. We screened a panel of mouse and human CRC cells and evaluated their metastatic outcome after CEACAM1 overexpression or downregulation. An unbiased transcript profiling and a phospho-receptor tyrosine kinase screen comparing MC38 CEACAM1-L-expressing and non-expressing (CT) CRC cells revealed reduced ephrin type-A receptor 2 (EPHA2) expression and activity. An EPHA2-specific inhibitor reduced EPHA2 downstream signaling in CT cells similar to that in CEACAM1-L cells with decreased proliferation and migration. Human CRC patients exhibiting high CEACAM1 in combination with low EPHA2 expression benefited from longer time to first recurrence/metastasis compared to those with high EPHA2 expression. With the added interaction of CEACAM6 , we denoted that CEACAM1 high- and EPHA2 low-expressing patient samples with lower CEACAM6 expression also exhibited a longer time to first recurrence/metastasis. In HT29 human CRC cells, down-regulation of CEACAM1 along with CEA and CEACAM6 up-regulation led to higher metastatic burden. Overall, CEACAM1-L expression in poorly differentiated CRC can inhibit liver metastasis through cell context-dependent EPHA2-mediated signaling. However, CEACAM1's role should be considered in the presence of other CEACAM family members.

Combined Blockade of T Cell Immunoglobulin and Mucin Domain 3 and Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Results in Durable Therapeutic Efficacy in Mice with Intracranial Gliomas.

PubMed

Li, Jinhu; Liu, Xiaodong; Duan, Yijun; Liu, Yueting; Wang, Hongqin; Lian, Shizhong; Zhuang, Guotao; Fan, Yimin

2017-07-24

BACKGROUND Glioblastoma multiforme (GBM) evades immune surveillance by inducing immunosuppression via receptor-ligand interactions between immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3) is a key checkpoint receptor responsible for exhaustion and dysfunction of T cells and plays a critical role in immunosuppression. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been recently identified as a heterophilic ligand for Tim-3. MATERIAL AND METHODS We established an intracranial GBM model using C57BL/6 mice and GL261 cells, and treated the mice with single or combined monoclonal antibodies (mAbs) against Tim-3/CEACAM1. The CD4+, CD8+, and regulatory T cells in brain-infiltrating lymphocytes were analyzed using flow cytometry, and the effector function of T cells was assessed using ELISA. We performed a rechallenge by subcutaneous injection of GL261 cells in the "cured" (>90 days post-orthotopic tumor implantation) and naïve mice. RESULTS The mean survival time in the control, anti-Tim-3, anti-CEACAM1, and combined treatment groups was 29.8, 43.4, 42.3, and 86.0 days, respectively, with 80% of the mice in the combined group becoming long-term survivors showing immune memory against glioma cells. Infiltrating CD4+ and CD8+ T cells increased and immunosuppressive Tregs decreased with the combined therapy, which resulted in a markedly elevated ratio of CD4+ and CD8+ cells to Tregs. Additionally, plasma IFN-γ and TGF-β levels were upregulated and downregulated, respectively. CONCLUSIONS Our data indicate that combined blockade of Tim-3 and CEACAM1 generates robust therapeutic efficacy in mice with intracranial tumors, and provides a promising option for GBM immunotherapy.

Simultaneous quantitation of cytokeratin-19 fragment and carcinoembryonic antigen in human serum via quantum dot-doped nanoparticles.

PubMed

Chen, Zhenhua; Liang, Rongliang; Guo, Xinxin; Liang, Junyu; Deng, Qiaoting; Li, Min; An, Taixue; Liu, Tiancai; Wu, Yingsong

2017-05-15

A novel quantum dot-doped polystyrene nanoparticles-based lateral flow test strips (QPs-LFTS) system was developed to simultaneously detect a cytokeratin-19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA) in human serum to aid the diagnosis and prognosis of lung cancer. Quantum dot-doped carboxylate-functionalized polystyrene nanoparticles (QPs) were prepared and introduced as fluorescent reporters in QPs-LFTS. The detection was based on a sandwich immunoassay and performed on lateral flow test strips, with an assay time of 15min. The strips were read by a fluorescence strip reader to obtain the fluorescence peak heights of the test lines (H T ) and the control line (H C ). The ratio of H T /H C was used for quantitation. The QPs showed excellent photoproperties and good performance. Under optimal conditions, the QPs-LFTS system exhibited a wide linear range for CYFRA 21-1 (1.3-480ng/mL) and CEA (2.8-680ng/mL). The detection limits for CYFRA 21-1 and CEA were 0.16 and 0.35ng/mL, respectively. The recovery and reproducibility of the method were satisfactory. Furthermore, excellent correlations (n =120, R 2 =0.9862, P<0.0001 for CYFRA 21-1; n =70, R 2 =0.9509, P<0.0001 for CEA) were obtained between the QPs-LFTS and commercially available chemiluminescence immunoassay kits in clinical serum testing. The results indicate that this developed test system is highly efficient and is expected to be useful for early screening and prognosis evaluation for lung cancer patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Proper exercise decreases plasma carcinoembryonic antigen levels with the improvement of body condition in elderly women.

PubMed

Ko, Il-Gyu; Park, Eung-Mi; Choi, Hye-Jung; Yoo, Jaehyun; Lee, Jong-Kyun; Jee, Yong-Seok

2014-05-01

Aging increases the risk of chronic diseases including cancers. Physical exercise has the beneficial effects for the elderly susceptible to the development of cancers, through maintaining a healthy body condition and improving the immune system. However, excessive or insufficient exercise might increase the risk for cancer. In the present study, we investigated what exercise frequency improves cancer-related biomarkers, such as carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), red blood cell (RBC), and white blood cell (WBC), and the body composition of elderly women. Fifty-four females, aged 70 to 77 years, were divided into 4 groups: control, 1-day exercise (1E), 2-3-day exercise (2-3E), and 5-day exercise (5E) groups. The control group did not participate in any physical activity, while the subjects in the exercise groups underwent the exercise program for 12 weeks. As results, CEA was significantly decreased in the exercise groups, with the lowest values in 2-3E group. In contrast, AFP, RBC and WBC were not significantly changed. CEA is an oncofetal glycoprotein that is overexpressed in adenocarcinomas. Although the function of CEA has not been fully understood, CEA has been suggested to be involved in the release of pro-inflammatory cytokines via stimulating monocytes and macrophages. Moreover, body weight and body mass index were improved in the exercise groups, with the lowest levels in 5E group. Thus, we suggest that exercise for 2-3 days per week decreases the expression of CEA and improves body condition, without loading fatigue or stress, which may contribute to preventing cancer in the elderly women.

Glycosylation Alters Dimerization Properties of a Cell-surface Signaling Protein, Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1).

PubMed

Zhuo, You; Yang, Jeong-Yeh; Moremen, Kelley W; Prestegard, James H

2016-09-16

Human carcinoembryonic antigen-related cell adhesion molecule 1 (C?/Au: EACAM1) is a cell-surface signaling molecule involved in cell adhesion, proliferation, and immune response. It is also implicated in cancer angiogenesis, progression, and metastasis. This diverse set of effects likely arises as a result of the numerous homophilic and heterophilic interactions that CEACAM1 can have with itself and other molecules. Its N-terminal Ig variable (IgV) domain has been suggested to be a principal player in these interactions. Previous crystal structures of the β-sandwich-like IgV domain have been produced using Escherichia coli-expressed material, which lacks native glycosylation. These have led to distinctly different proposals for dimer interfaces, one involving interactions of ABED β-strands and the other involving GFCC'C″ β-strands, with the former burying one prominent glycosylation site. These structures raise questions as to which form may exist in solution and what the effect of glycosylation may have on this form. Here, we use NMR cross-correlation measurements to examine the effect of glycosylation on CEACAM1-IgV dimerization and use residual dipolar coupling (RDC) measurements to characterize the solution structure of the non-glycosylated form. Our findings demonstrate that even addition of a single N-linked GlcNAc at potential glycosylation sites inhibits dimer formation. Surprisingly, RDC data collected on E. coli expressed material in solution indicate that a dimer using the non-glycosylated GFCC'C″ interface is preferred even in the absence of glycosylation. The results open new questions about what other factors may facilitate dimerization of CEACAM1 in vivo, and what roles glycosylation may play in heterophylic interactions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Pretargeting of carcinoembryonic antigen-expressing cancers with a trivalent bispecific fusion protein produced in myeloma cells.

PubMed

Rossi, Edmund A; Chang, Chien-Hsing; Losman, Michele J; Sharkey, Robert M; Karacay, Habibe; McBride, William; Cardillo, Thomas M; Hansen, Hans J; Qu, Zhengxing; Horak, Ivan D; Goldenberg, David M

2005-10-01

To characterize a novel trivalent bispecific fusion protein and evaluate its potential utility for pretargeted delivery of radionuclides to tumors. hBS14, a recombinant fusion protein that binds bispecifically to carcinoembryonic antigen (CEA) and the hapten, histamine-succinyl-glycine (HSG), was produced by transgenic myeloma cells and purified to near homogeneity in a single step using a novel HSG-based affinity chromatography system. Biochemical characterization included size-exclusion high-performance liquid chromatography (SE-HPLC), SDS-PAGE, and isoelectric focusing. Functional characterization was provided by BIAcore and SE-HPLC. The efficacy of hBS14 for tumor pretargeting was evaluated in CEA-expressing GW-39 human colon tumor-bearing nude mice using a bivalent HSG hapten (IMP-241) labeled with (111)In. Biochemical analysis showed that single-step affinity chromatography provided highly purified material. SE-HPLC shows a single protein peak consistent with the predicted molecular size of hBS14. SDS-PAGE analysis shows only two polypeptide bands, which are consistent with the calculated molecular weights of the hBS14 polypeptides. BIAcore showed the bispecific binding properties and suggested that hBS14 possesses two functional CEA-binding sites. This was supported by SE-HPLC immunoreactivity experiments. All of the data suggest that the structure of hBS14 is an 80 kDa heterodimer with one HSG and two CEA binding sites. Pretargeting experiments in the mouse model showed high uptake of radiopeptide in the tumor, with favorable tumor-to-nontumor ratios as early as 3 hours postinjection. The results indicate that hBS14 is an attractive candidate for use in a variety of pretargeting applications, particularly tumor therapy with radionuclides and drugs.

Mouse models expressing human carcinoembryonic antigen (CEA) as a transgene: Evaluation of CEA-based cancer vaccines

PubMed Central

Hance, Kenneth W.; Zeytin, Hasan E.; Greiner, John W.

2010-01-01

In recent years, investigators have carried out several studies designed to evaluate whether human tumor-associated antigens might be exploited as targets for active specific immunotherapy, specifically human cancer vaccines. Not too long ago such an approach would have been met with considerable skepticism because the immune system was believed to be a rigid discriminator between self and non-self which, in turn, protected the host from a variety of pathogens. That viewpoint has been challenged in recent years by a series of studies indicating that antigenic determinants of self have not induced absolute host immune tolerance. Moreover, under specific conditions that evoke danger signals, peptides from self-antigen can be processed by the antigen-presenting cellular machinery, loaded onto the major histocompatibility antigen groove to serve as targets for immune intervention. Those findings provide the rationale to investigate a wide range of tumor-associated antigens, including differentiation antigens, oncogenes, and tumor suppressor genes as possible immune-based targets. One of those tumor-associated antigens is the carcinoembryonic antigen (CEA). Described almost 40 years ago, CEA is a Mr 180–200,000 oncofetal antigen that is one of the more widely studied human tumor-associated antigens. This review will provide: (i) a brief overview of the CEA gene family, (ii) a summary of early preclinical findings on overcoming immune tolerance to CEA, and (iii) the rationale to develop mouse models which spontaneously develop gastrointestinal tumors and express the CEA transgene. Those models have been used extensively in the study of overcoming host immune tolerance to CEA, a self, tumor-associated antigen, and the experimental findings have served as the rationale for the design of early clinical trials to evaluate CEA-based cancer vaccines. PMID:15888344

Precision cancer immunotherapy: optimizing dendritic cell-based strategies to induce tumor antigen-specific T-cell responses against individual patient tumors.

PubMed

Osada, Takuya; Nagaoka, Koji; Takahara, Masashi; Yang, Xiao Yi; Liu, Cong-Xiao; Guo, Hongtao; Roy Choudhury, Kingshuk; Hobeika, Amy; Hartman, Zachary; Morse, Michael A; Lyerly, H Kim

2015-05-01

Most dendritic cell (DC)-based vaccines have loaded the DC with defined antigens, but loading with autologos tumor-derived antigens would generate DCs that activate personalized tumor-specific T-cell responses. We hypothesized that DC matured with an optimized combination of reagents and loaded with tumor-derived antigens using a clinically feasible electroporation strategy would induce potent antitumor immunity. We first studied the effects on DC maturation and antigen presentation of the addition of picibanil (OK432) to a combination of zoledronic acid, tumor necrosis factor-α, and prostaglandin E2. Using DC matured with the optimized combination, we tested 2 clinically feasible sources of autologous antigen for electroloading, total tumor mRNA or total tumor lysate, to determine which stimulated more potent antigen-specific T cells in vitro and activated more potent antitumor immunity in vivo. The combination of tumor necrosis factor-α/prostaglandin E2/zoledronic acid/OK432 generated DC with high expression of maturation markers and antigen-specific T-cell stimulatory function in vitro. Mature DC electroloaded with tumor-derived mRNA [mRNA electroporated dendritic cell (EPDC)] induced greater expansion of antigen-specific T cells in vitro than DC electroloaded with tumor lysate (lysate EPDC). In a therapeutic model of MC38-carcinoembryonic antigen colon cancer-bearing mice, vaccination with mRNA EPDC induced the most efficient anti-carcinoembryonic antigen cellular immune response, which significantly suppressed tumor growth. In conclusion, mature DC electroloaded with tumor-derived mRNA are a potent cancer vaccine, especially useful when specific tumor antigens for vaccination have not been identified, allowing autologous tumor, and if unavailable, allogeneic cell lines to be used as an unbiased source of antigen. Our data support clinical testing of this strategy.

Identification and verification of heat shock protein 60 as a potential serum marker for colorectal cancer

PubMed Central

Hamelin, Céline; Cornut, Emilie; Poirier, Florence; Pons, Sylvie; Beaulieu, Corinne; Charrier, Jean-Philippe; Haïdous, Hader; Cotte, Eddy; Lambert, Claude; Piard, Françoise; Ataman-Önal, Yasemin; Choquet-Kastylevsky, Geneviève

2011-01-01

Colorectal cancer (CRC) is a major public health issue worldwide, and novel tumor markers may contribute to its efficient management by helping in early detection, prognosis or surveillance of disease. The aim of our study was to identify new serum biomarkers for CRC, and we followed a phased biomarker discovery and validation process to obtain an accurate preliminary assessment of potential clinical utility. We compared colonic tumors and matched normal tissue from 15 CRC patients, using two-dimensional difference gel electrophoresis (2D-DIGE), and identified 17 proteins that had significant differential expression. These results were further confirmed by western blotting for heat shock protein (HSP) 60, glutathione-S-transferase Pi, α-enolase, T-complex protein 1 subunit β, and leukocyte elastase inhibitor, and by immunohistochemistry for HSP60. Using mAbs raised against HSP60, we developed a reliable (precision of 5–15%) and sensitive (0.3 ng·mL−1) immunoassay for the detection of HSP60 in serum. Elevated levels of HSP60 were found in serum from CRC patients in two independent cohorts; the receiver-operating characteristic curve obtained in 112 patients with CRC and 90 healthy controls had an area under the curve (AUC) of 0.70, which was identical to the AUC of carcinoembryonic antigen. Combination of serum markers improved clinical performance: the AUC of a three-marker logistic regression model combining HSP60, carcinoembryonic antigen and carbohydrate antigen 19-9 reached 0.77. Serum HSP60 appeared to be more specific for late-stage CRC; therefore, future studies should evaluate its utility for determining prognosis or monitoring therapy rather than early detection. PMID:21973086

Characteristics of cell lines established from human colorectal carcinoma.

PubMed

Park, J G; Oie, H K; Sugarbaker, P H; Henslee, J G; Chen, T R; Johnson, B E; Gazdar, A

1987-12-15

We have characterized 14 human colorectal carcinoma cell lines established from primary and metastatic sites by us during the years 1982 to 1985. Five lines were established in fully defined ACL-4 medium and 9 in serum supplemented R10 medium. However, after establishment, cultures could be grown interchangeably in either medium. The lines grew as floating cell aggregates in ACL-4 medium, while most demonstrated substrate adherence in R10 medium. The lines had relatively long doubling times and low cloning efficiencies. Twelve were tumorigenic in athymic nude mice when injected s.c., and two grew i.p. as well. Based on culture, xenograft, and ultrastructural morphologies, the 14 lines could be subtyped as follows: 4 were well differentiated; 5 were moderately differentiated; 4 were poorly differentiated; and 1 was a mucinous carcinoma. Membrane associated antigens characteristic for gastrointestinal cells (carcinoembryonic antigen, CA 19-9, and TAG-72 antigens) were expressed by 50-71% of the lines. Lines expressing carcinoembryonic antigen and CA 19-9 actively secreted these antigens into the supernatant fluids while TAG-72 antigen was not secreted. Surprisingly, 5 of 7 of the original tumor samples tested and 13 of 14 cultured lines expressed L-dopa decarboxylase activity, which is a characteristic enzyme marker of neuroendocrine cells and tumors. In addition, one poorly differentiated cell line contained dense core granules, characteristic of endocrine secretion. Preliminary cytogenetic analyses indicated that 9 of 11 lines examined contained double minute chromosomes. In addition, 3 of the 9 lines with double minutes also had homogeneously staining regions. These findings indicate a high incidence of amplification of one or more as yet unidentified genes.

Glycosylation Alters Dimerization Properties of a Cell-surface Signaling Protein, Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1)*

PubMed Central

Zhuo, You; Yang, Jeong-Yeh; Moremen, Kelley W.; Prestegard, James H.

2016-01-01

Human carcinoembryonic antigen-related cell adhesion molecule 1 (C?/Au: EACAM1) is a cell-surface signaling molecule involved in cell adhesion, proliferation, and immune response. It is also implicated in cancer angiogenesis, progression, and metastasis. This diverse set of effects likely arises as a result of the numerous homophilic and heterophilic interactions that CEACAM1 can have with itself and other molecules. Its N-terminal Ig variable (IgV) domain has been suggested to be a principal player in these interactions. Previous crystal structures of the β-sandwich-like IgV domain have been produced using Escherichia coli-expressed material, which lacks native glycosylation. These have led to distinctly different proposals for dimer interfaces, one involving interactions of ABED β-strands and the other involving GFCC′C″ β-strands, with the former burying one prominent glycosylation site. These structures raise questions as to which form may exist in solution and what the effect of glycosylation may have on this form. Here, we use NMR cross-correlation measurements to examine the effect of glycosylation on CEACAM1-IgV dimerization and use residual dipolar coupling (RDC) measurements to characterize the solution structure of the non-glycosylated form. Our findings demonstrate that even addition of a single N-linked GlcNAc at potential glycosylation sites inhibits dimer formation. Surprisingly, RDC data collected on E. coli expressed material in solution indicate that a dimer using the non-glycosylated GFCC′C″ interface is preferred even in the absence of glycosylation. The results open new questions about what other factors may facilitate dimerization of CEACAM1 in vivo, and what roles glycosylation may play in heterophylic interactions. PMID:27471271

Two-color immunostaining of liver fine needle aspiration biopsies with CD34 and carcinoembryonic antigen. Potential utilization in the diagnosis of primary hepatocellular carcinoma vs. metastatic tumor.

PubMed

Yoder, Michael; Zimmerman, Robert L; Bibbo, Marluce

2004-04-01

To examine immunohistochemical staining of cell block material with antibodies against vascular marker CD34 and polyclonal carcinoembryonic antigen (pCEA) for their clinical utility as part of a 2-color staining protocol in fine needle aspiration (FNA) biopsy of liver masses to distinguish metastases from primary hepatocellular carcinoma (HCC). The authors obtained cell block material from 96 liver FNAs and performed simultaneous (i.e., "dual-color") immunohistochemical staining utilizing antibodies against vascular marker CD34 and pCEA. Cases were blinded and evaluated by the authors for staining pattern and intensity. A consensus was obtained, the results were unblinded, and the diagnoses were correlated. After staining, 89 cases had sufficient tissue for evaluation. Of the 19 HCC cases, 16 (84%) showed peripheral staining with CD34, and 13 (68%) showed a canalicular or mixed canalicular-cytoplasmic staining pattern for pCEA. Thirteen cases (68%) showed staining for both antigens. All HCC exhibited immunostaining for at least 1 antibody in an appropriate staining pattern. Of the 67 cases of metastatic malignancy, 5 (7%) showed a predominantly transgressing pattern of CD34 staining, 43 (64%) showed a predominantly cytoplasmic or mixed cytoplasmic-canalicular pattern of pCEA staining, and 2 cases (3%) showed staining for both antigens in a transgressing CD34 pattern and cytoplasmic pCEA pattern. None of the 3 normal liver tissue blocks showed staining with either antigen. Two-color immunohistochemical staining of liver cell block material obtained by FNA with antibodies to CD34 and pCEA can be helpful in differentiating metastatic tumors vs. primary HCC.

Detection of carcinoembryonic antigen messenger RNA in blood using quantitative real-time reverse transcriptase-polymerase chain reaction to predict recurrence of gastric adenocarcinoma

PubMed Central

2010-01-01

Background The existence of circulating tumor cells (CTCs) in peripheral blood as an indicator of tumor recurrence has not been clearly established, particularly for gastric cancer patients. We conducted a retrospective analysis of the relationship between CTCs in peripheral blood at initial diagnosis and clinicopathologic findings in patients with gastric carcinoma. Methods Blood samples were obtained from 123 gastric carcinoma patients at initial diagnosis. mRNA was extracted and amplified for carcinoembryonic antigen (CEA) mRNA detection using real-time RT-PCR. Periodic 3-month follow-up examinations included serum CEA measurements and imaging. Results The minimum threshold for corrected CEA mRNA score [(CEA mRNA/GAPDH mRNA) × 106] was set at 100. Forty-five of 123 patients (36.6%) were positive for CEA mRNA expression. CEA mRNA expression significantly correlated with T stage and postoperative recurrence status (P = 0.001). Recurrent disease was found in 44 of 123 cases (35.8%), and 25 of these (56.8%) were positive for CEA mRNA. Of these patients, CEA mRNA was more sensitive than serum CEA in indicating recurrence. Three-year disease-free survival of patients positive for CEA mRNA was significantly poorer than of patients negative for CEA mRNA (P < 0.001). Only histological grade and CEA mRNA positivity were independent factors for disease-free survival using multivariate analysis. Conclusions CEA mRNA copy number in peripheral blood at initial diagnosis was significantly associated with disease recurrence in gastric adenocarcinoma patients. Real-time RT-PCR detection of CEA mRNA levels at initial diagnosis appears to be a promising predictor for disease recurrence in gastric adenocarcinoma patients. PMID:21040522

Detection of carcinoembryonic antigen messenger RNA in blood using quantitative real-time reverse transcriptase-polymerase chain reaction to predict recurrence of gastric adenocarcinoma.

PubMed

Qiu, Miao-Zhen; Li, Zhuang-Hua; Zhou, Zhi-Wei; Li, Yu-Hong; Wang, Zhi-Qiang; Wang, Feng-Hua; Huang, Peng; Aziz, Fahad; Wang, Dao-Yuan; Xu, Rui-Hua

2010-10-31

The existence of circulating tumor cells (CTCs) in peripheral blood as an indicator of tumor recurrence has not been clearly established, particularly for gastric cancer patients. We conducted a retrospective analysis of the relationship between CTCs in peripheral blood at initial diagnosis and clinicopathologic findings in patients with gastric carcinoma. Blood samples were obtained from 123 gastric carcinoma patients at initial diagnosis. mRNA was extracted and amplified for carcinoembryonic antigen (CEA) mRNA detection using real-time RT-PCR. Periodic 3-month follow-up examinations included serum CEA measurements and imaging. The minimum threshold for corrected CEA mRNA score [(CEA mRNA/GAPDH mRNA) × 106] was set at 100. Forty-five of 123 patients (36.6%) were positive for CEA mRNA expression. CEA mRNA expression significantly correlated with T stage and postoperative recurrence status (P = 0.001). Recurrent disease was found in 44 of 123 cases (35.8%), and 25 of these (56.8%) were positive for CEA mRNA. Of these patients, CEA mRNA was more sensitive than serum CEA in indicating recurrence. Three-year disease-free survival of patients positive for CEA mRNA was significantly poorer than of patients negative for CEA mRNA (P < 0.001). Only histological grade and CEA mRNA positivity were independent factors for disease-free survival using multivariate analysis. CEA mRNA copy number in peripheral blood at initial diagnosis was significantly associated with disease recurrence in gastric adenocarcinoma patients. Real-time RT-PCR detection of CEA mRNA levels at initial diagnosis appears to be a promising predictor for disease recurrence in gastric adenocarcinoma patients.

Top-down nanofabrication of silicon nanoribbon field effect transistor (Si-NR FET) for carcinoembryonic antigen detection.

PubMed

Bao, Zengtao; Sun, Jialin; Zhao, Xiaoqian; Li, Zengyao; Cui, Songkui; Meng, Qingyang; Zhang, Ye; Wang, Tong; Jiang, Yanfeng

2017-01-01

Sensitive and quantitative detection of tumor markers is highly required in the clinic for cancer diagnosis and consequent treatment. A field-effect transistor-based (FET-based) nanobiosensor emerges with characteristics of being label-free, real-time, having high sensitivity, and providing direct electrical readout for detection of biomarkers. In this paper, a top-down approach is proposed and implemented to fulfill a novel silicon nano-ribbon FET, which acts as biomarker sensor for future clinical application. Compared with the bottom-up approach, a top-down fabrication approach can confine width and length of the silicon FET precisely to control its electrical properties. The silicon nanoribbon (Si-NR) transistor is fabricated on a Silicon-on-Insulator (SOI) substrate by a top-down approach with complementary metal oxide semiconductor (CMOS)-compatible technology. After the preparation, the surface of Si-NR is functionalized with 3-aminopropyltriethoxysilane (APTES). Glutaraldehyde is utilized to bind the amino terminals of APTES and antibody on the surface. Finally, a microfluidic channel is integrated on the top of the device, acting as a flowing channel for the carcinoembryonic antigen (CEA) solution. The Si-NR FET is 120 nm in width and 25 nm in height, with ambipolar electrical characteristics. A logarithmic relationship between the changing ratio of the current and the CEA concentration is measured in the range of 0.1-100 ng/mL. The sensitivity of detection is measured as 10 pg/mL. The top-down fabricated biochip shows feasibility in direct detecting of CEA with the benefits of real-time, low cost, and high sensitivity as a promising biosensor for tumor early diagnosis.

Up-regulation of tumor suppressor carcinoembryonic antigen-related cell adhesion molecule 1 in human colon cancer Caco-2 cells following repetitive exposure to dietary levels of a polyphenol-rich chokeberry juice.

PubMed

Bermúdez-Soto, María J; Larrosa, Mar; Garcia-Cantalejo, Jesús M; Espín, Juan C; Tomás-Barberan, Francisco A; García-Conesa, María T

2007-04-01

Consumption of berries and red fruits rich in polyphenols may contribute to the reduction of colon cancer through mechanisms not yet understood. In this study, we investigated the response of subconfluent Caco-2 cells (a human colon carcinoma model) to repetitive exposure (2 h a day for a 4-day period) of a subtoxic dose of a chokeberry (Aronia melanocarpa) juice containing mixed polyphenols. To mimic physiological conditions, we subjected the chokeberry juice to in vitro gastric and pancreatic digestion. The effects on viability, proliferation and cell cycle were determined, and changes in the expression of genes in response to the chokeberry treatment were screened using Affymetrix oligonucleotide microarrays. Exposure to the chokeberry juice inhibited Caco-2 cell proliferation by causing G(2)/M cell cycle arrest. We detected changes in the expression of a group of genes involved in cell growth and proliferation and cell cycle regulation, as well as those associated to colorectal cancer. A selection of these genes was further confirmed by quantitative RT-PCR. Among these, the tumor suppressor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), whose expression is known to be reduced in the majority of early adenomas and carcinomas, was up-regulated by the treatment both at the mRNA and protein levels (as shown by flow cytometry analysis). CEACAM1, with a significant regulatory role on cell proliferation of particular interest at early stages of cancer development, may be a potential target for chemoprevention by food components such as those present in polyphenol-rich fruits.

Difficulty in diagnosis and different prognoses between colorectal cancer with ovarian metastasis and advanced ovarian cancer: An empirical study of different surgical adoptions.

PubMed

Lee, Ko-Chao; Lin, Hao; ChangChien, Chan-Chao; Fu, Hung-Chun; Tsai, Ching-Chou; Wu, Chen-Hsuan; Ou, Yu-Che

2017-02-01

To determine the clinical manifestations and optimal management of female patients with advanced colorectal cancer (CRC) metastasis in ovaries mimicking advanced ovarian malignancy. A retrospective medical records review of female patients with primary CRC metastasis to ovaries, which were initially diagnosed as ovarian malignancy, and treated between 2001 and 2013. Clinical presentations, pathologic findings, and treatment outcomes were analyzed. In total, 19 cases were collected in the study through a hospital tumor registry. The mean age of the patients at the time of diagnosis was 45 years (range, 28-63 years). The most common symptoms were abdominal pain or increased abdominal girth (63%). None of them had rectal bleeding. The ratio of cancer antigen-125 to carcinoembryonic antigen was available in 13 out 19 patients (less than 25 in 76.9%). Barium enema or colonoscopic exam was only performed in 10 outpatients. None of them had a positive finding. All 19 patients went for surgery, all of them had ovarian metastasis but only eight of them had bilateral involvement, and 14 of them had carcinomatosis. All patients went for either optimal cytoreduction surgery or suboptimal cytoreduction surgery. The patients who received optimal cytoreduction surgery had a significant better progression-free and overall survival than those who did not. Clinical manifestations of primary CRC with ovarian metastasis may be confused with advanced ovarian cancer. Negative barium enema or colonoscopic exam cannot rule out the possibility of CRC. For patients with a cancer antigen-125 to carcinoembryonic antigen ratio less than 25, 76% are good reference of CRC metastasis to ovaries. Optimal cytoreduction surgery like that used for treating advanced ovarian cancer had a better prognosis than suboptimal cytoreduction colorectal cancer treatment. Copyright © 2017. Published by Elsevier B.V.

The diagnostic value of cytokeratins and carcinoembryonic antigen immunostaining in differentiating hepatocellular carcinomas from intrahepatic cholangiocarcinomas.

PubMed

Stroescu, Cezar; Herlea, Vlad; Dragnea, Adrian; Popescu, Irinel

2006-03-01

To study the differences between the hepatocellular carcinoma (HCC) and peripheral type of cholangiocarcinoma (CHC) using cytokeratin (CK) and carcinoembryonic antigen (CEA) expressions and assessing their accuracy on paraffin sections in the differential diagnosis. The following antibodies were analyzed: AB1 complex (anti CK9-CK20), AB2 complex (anti CK1-CK8), pCEA, and the monoclonal antibodies against cytokeratins CK7, CK8/18, CK17 and CK19. In the mmunohistochemical studies, 15 selected surgically resected liver tumors, 10 HCCs and 5 CHCs, with well established diagnosis (by morphological criteria) were included. Other markers, such as AFP si CA 19-9, were not available. No CHC, but 50% of HCCs were positive for CEA, presenting a canalicular staining pattern. For CK 7, all but one (which was focally positive), meaning 80% of CHCs were diffusely positive, whereas only two HCCs were positive. For CK 19, 80% of CHCs were diffusely positive, while all but two HCCs (a moderately and a poorly differentiated tumor) were negative. For CK 8/18, 70% of HCCs were diffusely positive, whereas only 20% of CHCs were positive. For CK 17, 60% of CHCs were positive, while all HCCs were negative. 80% of CHCs were positive for AB1 anti-CKs complex, whereas only 50% of HCCs were positive, and relating to AB2 anti-CKs complex, 50% of HCCs were diffusely positive and only 20% of CHCs. The immunohistochemical expression of CKs and CEA might be considered helpful in addition to other diagnostic criteria for the differential diagnosis of primary carcinomas of the liver, especially in difficult cases.

Chemopreventive effect of chrysin, a dietary flavone against benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice.

PubMed

Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Barua, Chandan C; Madhana, Rajaram Mohanrao; Dahiya, Vicky; Budhani, Mukesh Kumar; Mallugari, Ramana Reddy; Maramreddy, Suseela Reddy; Gogoi, Ranadeep

2016-04-01

Chemoprevention is considered as one of the most promising and realistic approaches in the prevention of lung cancer. Chrysin, a naturally occurring dietary flavone widely found in Passiflora family of plants and honey, has been studied extensively for its chemopreventive properties. The objective of present study is to divulge the chemopreventive role of chrysin against benzo(a)pyrene [B(a)P] induced lung carcinogenesis in Swiss albino mice. B(a)P was administered orally (50mg/kg body weight) twice a week for four weeks to induce lung cancer in mice. The body weight, lung weight, tumor incidence, lipid peroxidation, carcinoembryonic antigen, enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase) and non-enzymatic antioxidants (reduced glutathione, vitamin E and vitamin C) were estimated. Further, histopathological analysis of lung tissue and western blotting analysis of PCNA, COX-2 and NF-κB were also carried out. Administration of B(a)P resulted in increased lipid peroxides and carcinoembryonic antigen with concomitant decrease in the levels of both enzymatic antioxidants and non-enzymatic antioxidants. Chrysin treatment (250mg/kg body weight) significantly attenuated all these changes thereby showing potent anti lung cancer effect. Further, the anticancer effect of chrysin was confirmed by histopathology of lungs, and immunoblotting analysis of PCNA, COX-2 and NF-κB, where chrysin supplementation downregulated the expression of these proteins and maintained cellular homeostasis. Overall, these findings confirm the chemopreventive potential of chrysin against B(a)P induced lung cancer in Swiss albino mice. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Macrophage interleukin-6 and tumour necrosis factor-α are induced by coronavirus fixation to Toll-like receptor 2/heparan sulphate receptors but not carcinoembryonic cell adhesion antigen 1a

PubMed Central

Jacques, Alexandre; Bleau, Christian; Turbide, Claire; Beauchemin, Nicole; Lamontagne, Lucie

2009-01-01

A rapid antiviral immune response may be related to viral interaction with the host cell leading to activation of macrophages via pattern recognition receptors (PPRs) or specific viral receptors. Carcinoembryonic cell adhesion antigen 1a (CEACAM1a) is the specific receptor for the mouse hepatitis virus (MHV), a coronavirus known to induce acute viral hepatitis in mice. The objective of this study was to understand the mechanisms responsible for the secretion of high-pathogenic MHV3-induced inflammatory cytokines. We report that the induction of the pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor (TNF)-α in peritoneal macrophages does not depend on CEACAM1a, as demonstrated in cells isolated from Ceacam1a−/− mice. The induction of IL-6 and TNF-α production was related rather to the fixation of the spike (S) protein of MHV3 on Toll-like receptor 2 (TLR2) in regions enriched in heparan sulphate and did not rely on viral replication, as demonstrated with denatured S protein and UV-inactivated virus. High levels of IL-6 and TNF-α were produced in livers from infected C57BL/6 mice but not in livers from Tlr2−/− mice. The histopathological observations were correlated with the levels of those inflammatory cytokines. Depending on mouse strain, the viral fixation to heparan sulfate/TLR2 stimulated differently the p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB in the induction of IL-6 and TNF-α. These results suggest that TLR2 and heparan sulphate receptors can act as new viral PPRs involved in inflammatory responses. PMID:19740307

Loss of Mammal-specific Tectorial Membrane Component Carcinoembryonic Antigen Cell Adhesion Molecule 16 (CEACAM16) Leads to Hearing Impairment at Low and High Frequencies*

PubMed Central

Kammerer, Robert; Rüttiger, Lukas; Riesenberg, Rainer; Schäuble, Constanze; Krupar, Rosemarie; Kamp, Annegret; Sunami, Kishiko; Eisenried, Andreas; Hennenberg, Martin; Grunert, Fritz; Bress, Andreas; Battaglia, Sebastiano; Schrewe, Heinrich; Knipper, Marlies; Schneider, Marlon R.; Zimmermann, Wolfgang

2012-01-01

The vertebrate-restricted carcinoembryonic antigen gene family evolves extremely rapidly. Among their widely expressed members, the mammal-specific, secreted CEACAM16 is exceptionally well conserved and specifically expressed in the inner ear. To elucidate a potential auditory function, we inactivated murine Ceacam16 by homologous recombination. In young Ceacam16−/− mice the hearing threshold for frequencies below 10 kHz and above 22 kHz was raised. This hearing impairment progressed with age. A similar phenotype is observed in hearing-impaired members of Family 1070 with non-syndromic autosomal dominant hearing loss (DFNA4) who carry a missense mutation in CEACAM16. CEACAM16 was found in interdental and Deiters cells and was deposited in the tectorial membrane of the cochlea between postnatal days 12 and 15, when hearing starts in mice. In cochlear sections of Ceacam16−/− mice tectorial membranes were significantly more often stretched out as compared with wild-type mice where they were mostly contracted and detached from the outer hair cells. Homotypic cell sorting observed after ectopic cell surface expression of the carboxyl-terminal immunoglobulin variable-like N2 domain of CEACAM16 indicated that CEACAM16 can interact in trans. Furthermore, Western blot analyses of CEACAM16 under reducing and non-reducing conditions demonstrated oligomerization via unpaired cysteines. Taken together, CEACAM16 can probably form higher order structures with other tectorial membrane proteins such as α-tectorin and β-tectorin and influences the physical properties of the tectorial membrane. Evolution of CEACAM16 might have been an important step for the specialization of the mammalian cochlea, allowing hearing over an extended frequency range. PMID:22544735

In vitro autoradiography of carcinoembryonic antigen in tissue from patients with colorectal cancer using multifunctional antibody TF2 and 67/68Ga-labeled haptens by pretargeting

PubMed Central

Hall, Håkan; Velikyan, Irina; Blom, Elisabeth; Ulin, Johan; Monazzam, Azita; Påhlman, Lars; Micke, Patrick; Wanders, Alkwin; McBride, William; Goldenberg, David M.; Långström, Bengt

2012-01-01

The carcinoembryonic antigen (CEA) was visualized in vitro in tissue from patients with colorectal cancer with trivalent bispecific antibody TF2 and two hapten molecules, [67/68Ga]Ga-IMP461 and [67/68Ga]Ga-IMP485 by means of pretargeting. Colorectal cancer tissue samples obtained from surgery at Uppsala University Hospital, were frozen fresh and cryosectioned. The two hapten molecules comprising 1,4,7-triazacyclononanetriacetic acid chelate moiety (NOTA) were labeled with 67Ga or 68Ga. The autoradiography was conducted by incubating the tissue samples with the bispecific antibody TF2, followed by washing and incubation with one of the radiolabeled hapten molecules. After washing, drying and exposure to phosphor imager plates, the autoradiograms were analyzed and compared to standard histochemistry (hematoxylin-eosin). Pronounced binding was found in the tissue from colorectal cancer using the bispecific antibody TF2 and either of the haptens [67/68Ga]Ga-IMP461 and [67/68Ga]Ga-IMP485. Distinct binding was also detected in the epithelium of most samples of neighboring tissue, taken at a minimum of 10 cm from the site of the tumor. It is concluded that pretargeting CEA with the bispecific antibody TF2 followed by the addition of 67/68Ga-labeled hapten is extremely sensitive for visualizing this marker for colorectal cancer. This methodology is therefore a very specific complement to other histochemical techniques in the diagnosis of biopsies or in samples taken from surgery. Use of the pretargeting technique in vivo may also be an advance in diagnosing patients with colorectal cancer, either using 67Ga and SPECT or 68Ga and PET. PMID:23133809

Crystal structure of the anti-(carcinoembryonic antigen) single-chain Fv antibody MFE-23 and a model for antigen binding based on intermolecular contacts.

PubMed

Boehm, M K; Corper, A L; Wan, T; Sohi, M K; Sutton, B J; Thornton, J D; Keep, P A; Chester, K A; Begent, R H; Perkins, S J

2000-03-01

MFE-23 is the first single-chain Fv antibody molecule to be used in patients and is used to target colorectal cancer through its high affinity for carcinoembryonic antigen (CEA), a cell-surface member of the immunoglobulin superfamily. MFE-23 contains an N-terminal variable heavy-chain domain joined by a (Gly(4)Ser)(3) linker to a variable light-chain (V(L)) domain (kappa chain) with an 11-residue C-terminal Myc-tag. Its crystal structure was determined at 2.4 A resolution by molecular replacement with an R(cryst) of 19.0%. Five of the six antigen-binding loops, L1, L2, L3, H1 and H2, conformed to known canonical structures. The sixth loop, H3, displayed a unique structure, with a beta-hairpin loop and a bifurcated apex characterized by a buried Thr residue. In the crystal lattice, two MFE-23 molecules were associated back-to-back in a manner not seen before. The antigen-binding site displayed a large acidic region located mainly within the H2 loop and a large hydrophobic region within the H3 loop. Even though this structure is unliganded within the crystal, there is an unusually large region of contact between the H1, H2 and H3 loops and the beta-sheet of the V(L) domain of an adjacent molecule (strands DEBA) as a result of intermolecular packing. These interactions exhibited remarkably high surface and electrostatic complementarity. Of seven MFE-23 residues predicted to make contact with antigen, five participated in these lattice contacts, and this model for antigen binding is consistent with previously reported site-specific mutagenesis of MFE-23 and its effect on CEA binding.

Surface expression of heterogeneous nuclear RNA binding protein M4 on Kupffer cell relates to its function as a carcinoembryonic antigen receptor.

PubMed

Bajenova, Olga; Stolper, Eugenia; Gapon, Svetlana; Sundina, Natalia; Zimmer, Regis; Thomas, Peter

2003-11-15

Elevated concentrations of carcinoembryonic antigen (CEA) in the blood are associated with the development of hepatic metastases from colorectal cancers. Clearance of circulating CEA occurs through endocytosis by liver macrophages, Kupffer cells. Previously we identified heterogeneous nuclear ribonucleoproteins M4 (hnRNP M4) as a receptor (CEAR) for CEA. HnRNP M4 has two isoform proteins (p80, p76), the full-length hnRNP M4 (CEARL) and a truncated form (CEARS) with a deletion of 39 amino acids between RNA binding domains 1 and 2, generated by alternative splicing. The present study was undertaken to clarify any isoform-specific differences in terms of their function as CEA receptor and localization. We develop anti-CEAR isoform-specific antibodies and show that both CEAR splicing isoforms are expressed on the surface of Kupffer cells and can function as CEA receptor. Alternatively, in P388D1 macrophages CEARS protein has nuclear and CEARL has cytoplasmic localization. In MIP101 colon cancer and HeLa cells the CEARS protein is localized to the nucleus and CEARL to the cytoplasm. These findings imply that different functions are assigned to CEAR isoforms depending on the cell type. The search of 39 amino acids deleted region against the Prosite data base revealed the presence of N-myristylation signal PGGPGMITIP that may be involved in protein targeting to the plasma membrane. Overall, this report demonstrates that the cellular distribution, level of expression, and relative amount of CEARL and CEARS isoforms determine specificity for CEA binding and the expression of alternative spliced forms of CEAR is regulated in a tissue-specific manner.

Identification of preoperative prediction factors of tumor subtypes for patients with solitary ground-glass opacity pulmonary nodules.

PubMed

Li, Meishuang; Wang, Yanan; Chen, Yulong; Zhang, Zhenfa

2018-01-17

Recent wide spread use of low-dose helical computed tomography for the screening of lung cancer have led to an increase in the detection rate of very faint and smaller lesions known as ground-glass opacity nodules. The purpose of this study was to investigate the clinical factors of lung cancer patients with solitary ground-glass opacity pulmonary nodules on computed tomography. A total of 423 resected solitary ground-glass opacity nodules were retrospectively evaluated. We analyzed the clinical, imaging and pathological data and investigated the clinical differences in patient with adenocarcinoma in situ / minimally invasive adenocarcinoma and those with invasive adenocarcinoma. Three hundred and ninety-three adenocarcinomas (92.9%) and 30 benign nodules were diagnosed. Age, the history of family cancer, serum carcinoembryonic antigen level, tumor size, ground-glass opacity types, and bubble-like sign in chest CT differed significantly between adenocarcinoma in situ / minimally invasive adenocarcinoma and invasive adenocarcinoma (p:0.008, 0.046, 0.000, 0.000, 0.000 and 0.001). Receiver operating characteristic curves and univariate analysis revealed that patients with more than 58.5 years, a serum carcinoembryonic antigen level > 1.970 μg/L, a tumor size> 13.50 mm, mixed ground-glass opacity nodules and a bubble-like sign were more likely to be diagnosed as invasive adenocarcinoma. The combination of five factors above had an area under the curve of 0.91, with a sensitivity of 82% and a specificity of 87%. The five-factor combination helps us to distinguish adenocarcinoma in situ / minimally invasive adenocarcinoma from invasive adenocarcinoma and to perform appropriate surgery for solitory ground-glass opacity nodules.

Collecting Protein Biomarkers in Breath Using Electret Filters: A Preliminary Method on New Technical Model and Human Study.

PubMed

Li, Wang; Pi, Xitian; Qiao, Panpan; Liu, Hongying

2016-01-01

Biomarkers in exhaled breath are useful for respiratory disease diagnosis in human volunteers. Conventional methods that collect non-volatile biomarkers, however, necessitate an extensive dilution and sanitation processes that lowers collection efficiencies and convenience of use. Electret filter emerged in recent decade to collect virus biomarkers in exhaled breath given its simplicity and effectiveness. To investigate the capability of electret filters to collect protein biomarkers, a model that consists of an atomizer that produces protein aerosol and an electret filter that collects albumin and carcinoembryonic antigen-a typical biomarker in lung cancer development- from the atomizer is developed. A device using electret filter as the collecting medium is designed to collect human albumin from exhaled breath of 6 volunteers. Comparison of the collecting ability between the electret filter method and other 2 reported methods is finally performed based on the amounts of albumin collected from human exhaled breath. In conclusion, a decreasing collection efficiency ranging from 17.6% to 2.3% for atomized albumin aerosol and 42% to 12.5% for atomized carcinoembryonic antigen particles is found; moreover, an optimum volume of sampling human exhaled breath ranging from 100 L to 200 L is also observed; finally, the self-designed collecting device shows a significantly better performance in collecting albumin from human exhaled breath than the exhaled breath condensate method (p<0.05) but is not significantly more effective than reported 3-stage impactor method (p>0.05). In summary, electret filters are potential in collecting non-volatile biomarkers in human exhaled breath not only because it was simpler, cheaper and easier to use than traditional methods but also for its better collecting performance.

Chromosomal Microarray Testing in 42 Korean Patients with Unexplained Developmental Delay, Intellectual Disability, Autism Spectrum Disorders, and Multiple Congenital Anomalies.

PubMed

Lee, Sun Ho; Song, Wung Joo

2017-09-01

Chromosomal microarray (CMA) is a high-resolution, high-throughput method of identifying submicroscopic genomic copy number variations (CNVs). CMA has been established as the first-line diagnostic test for individuals with developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), and multiple congenital anomalies (MCAs). CMA analysis was performed in 42 Korean patients who had been diagnosed with unexplained DD, ID, ASDs, and MCAs. Clinically relevant CNVs were discovered in 28 patients. Variants of unknown significance were detected in 13 patients. The diagnostic yield was high (66.7%). CMA is a superior diagnostic tool compared with conventional karyotyping and fluorescent in situ hybridization.

Pioneer Venus 12.5 km Anomaly Workshop Report, volume 1

NASA Technical Reports Server (NTRS)

Seiff, A.; Sromovsky, L.; Borucki, W.; Craig, R.; Juergens, D.; Young, R. E.; Ragent, B.

1995-01-01

A workshop was convened at Ames Research Center on September 28 and 29, 1993, to address the unexplained electrical anomalies experienced in December 1978 by the four Pioneer Venus probes below a Venus altitude of 12.5 km. These anomalies caused the loss of valuable data in the deep atmosphere, and, if their cause were to remain unexplained, could reoccur on future Venus missions. The workshop participants reviewed the evidence and studied all identified mechanisms that could consistently account for all observed anomalies. Both hardware problems and atmospheric interactions were considered. Based on a workshop recommendation, subsequent testing identified the cause as being an insulation failure of the external harness. All anomalous events are now explained.

Medically unexplained physical symptoms: toward an alternative paradigm for diagnosis and treatment.

PubMed

Ballas, Christos A; Staab, Jeffrey P

2003-12-01

The treatment of patients with unexplained medical symptoms is difficult because there is neither a clear etiology for the symptoms, nor a useful paradigm with which to understand and treat them. Patients with such symptoms are often referred to psychiatry with vague diagnoses of "somatization" or "hypochondriasis." Rather than considering somatoform diagnoses based on the number or diversity of physical symptoms, evolving research suggests an emphasis on the type of physical symptom as an indicator of Axis I pathology. This article links specific symptomatic complaints, such as chronic pain, chest pain, and dizziness, to the respective Axis I disorders associated with them, such as depression, panic disorder, and anxiety disorders.

Genetic investigation of 100 heart genes in sudden unexplained death victims in a forensic setting

PubMed Central

Christiansen, Sofie Lindgren; Hertz, Christin Løth; Ferrero-Miliani, Laura; Dahl, Morten; Weeke, Peter Ejvin; LuCamp; Ottesen, Gyda Lolk; Frank-Hansen, Rune; Bundgaard, Henning; Morling, Niels

2016-01-01

In forensic medicine, one-third of the sudden deaths remain unexplained after medico-legal autopsy. A major proportion of these sudden unexplained deaths (SUD) are considered to be caused by inherited cardiac diseases. Sudden cardiac death (SCD) may be the first manifestation of these diseases. The purpose of this study was to explore the yield of next-generation sequencing of genes associated with SCD in a cohort of SUD victims. We investigated 100 genes associated with cardiac diseases in 61 young (1–50 years) SUD cases. DNA was captured with the Haloplex target enrichment system and sequenced using an Illumina MiSeq. The identified genetic variants were evaluated and classified as likely, unknown or unlikely to have a functional effect. The criteria for this classification were based on the literature, databases, conservation and prediction of the effect of the variant. We found that 21 (34%) individuals carried variants with a likely functional effect. Ten (40%) of these variants were located in genes associated with cardiomyopathies and 15 (60%) of the variants in genes associated with cardiac channelopathies. Nineteen individuals carried variants with unknown functional effect. Our findings indicate that broad genetic investigation of SUD victims increases the diagnostic outcome, and the investigation should comprise genes involved in both cardiomyopathies and cardiac channelopathies. PMID:27650965

Prediction of thrombophilia in patients with unexplained recurrent pregnancy loss using a statistical model.

PubMed

Wang, Tongfei; Kang, Xiaomin; He, Liying; Liu, Zhilan; Xu, Haijing; Zhao, Aimin

2017-09-01

To establish a statistical model to predict thrombophilia in patients with unexplained recurrent pregnancy loss (URPL). A retrospective case-control study was conducted at Ren Ji Hospital, Shanghai, China, from March 2014 to October 2016. The levels of D-dimer (DD), fibrinogen degradation products (FDP), activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fg), and platelet aggregation in response to arachidonic acid (AA) and adenosine diphosphate (ADP) were collected. Receiver operating characteristic curve analysis was used to analyze data from 158 UPRL patients (≥3 previous first trimester pregnancy losses with unexplained etiology) and 131 non-RPL patients (no history of recurrent pregnancy loss). A logistic regression model (LRM) was built and the model was externally validated in another group of patients. The LRM included AA, DD, FDP, TT, APTT, and PT. The overall accuracy of the LRM was 80.9%, with sensitivity and specificity of 78.5% and 78.3%, respectively. The diagnostic threshold of the possibility of the LRM was 0.6492, with a sensitivity of 78.5% and a specificity of 78.3%. Subsequently, the LRM was validated with an overall accuracy of 83.6%. The LRM is a valuable model for prediction of thrombophilia in URPL patients. © 2017 International Federation of Gynecology and Obstetrics.

Celiac disease presenting as rickets in Saudi children.

PubMed

Assiri, Asaad; Saeed, Anjum; AlSarkhy, Ahmed; El Mouzan, Mohammed Issa; El Matary, Wael

2013-01-01

Rickets is commonly seen as a sign of malabsorption like celiac disease if it is not treated appropriately with vitamin D and calcium supplements. The aim of this study was to examine the frequency of diagnosis of celiac disease among children with unexplained rickets in Saudi children at a tertiary hospital setting. Retrospective review of records of patients referred over 10 years to a pediatric gastroenterology and hepatology unit. The study included all patients referred for evaluation of unexplained rickets and osteomalacia and screened for celiac disease. The diagnosis of rickets was made on the basis of history, physical examination, biochemical and radiological investigations. The diagnosis of celiac disease was made based on the ESPGHAN (European Society for Pediatric Gastroenterology, Hepatology, and Nutrition) criteria. Twenty-six children with a mean (SD) age of 9.5 (4.6) years (5 males, range 1-15 years) were referred for evaluation of unexplained rickets and were screened for celiac disease. The diagnosis of celiac disease based on small bowel biopsy findings was confirmed in 10 (38.4%) patients with rickets. Serological markers for celiac disease including antiendomyseal antibodies and antitissue transglutaminase antibodies were positive in all ten children. Rickets is not an uncommon presentation of celiac disease in Saudi children and pediatricians should consider celiac disease as an underlying cause for rickets.

The most popular terms for medically unexplained symptoms: the views of CFS patients.

PubMed

Picariello, Federica; Ali, Sheila; Moss-Morris, Rona; Chalder, Trudie

2015-05-01

Medically unexplained symptoms/syndromes are common, highly distressing and are often associated with profound disability. One of the controversies surrounding this area relates to which umbrella term should be used to group such symptoms. The purpose of this research was to establish the preferences of patients with chronic fatigue syndrome (CFS) for an umbrella term for medically unexplained symptoms. A cross-sectional mixed methods survey design was used. Participants were asked to indicate their three most preferred terms out of a list of commonly used terms and to provide any extra comments. Frequency analysis was employed to look at the preferences of terms for each rank. Comments were analysed using principles of inductive thematic analysis. Eighty-seven patients with CFS completed a self-report survey. The term "Persistent Physical Symptoms" was the most popular first choice term chosen by 20.7% of patients. Terms containing the word "physical" were consistently more likely to be chosen. Three main themes emerged from the thematic analysis: 1) Physical nature of the illness, 2) Stigma, and 3) Evaluation of the terms, giving a more in-depth understanding of the findings. According to CFS patients, an umbrella term has to reflect the physical experience of MUS. Copyright © 2015 Elsevier Inc. All rights reserved.

Phenotypic Analysis of Korean Patients with Abnormal Chromosomal Microarray in Patients with Unexplained Developmental Delay/Intellectual Disability.

PubMed

Kim, Hyo Jeong; Park, Chang Il; Lim, Jae Woo; Lee, Gyung Min; Cho, Eunhae; Kim, Hyon J

2018-05-01

The present study aimed to investigate chromosomal microarray (CMA) and clinical data in patients with unexplained developmental delay/intellectual disability (DD/ID) accompanying dysmorphism, congenital anomalies, or epilepsy. We also aimed to evaluate phenotypic clues in patients with pathogenic copy number variants (CNVs). We collected clinical and CMA data from patients at Konyang University Hospital between September 2013 and October 2014. We included patients who had taken the CMA test to evaluate the etiology of unexplained DD/ID. All of the 50 patients identified had DD/ID. Thirty-nine patients had dysmorphism, 19 patients suffered from epilepsy, and 12 patients had congenital anomalies. Twenty-nine of the 50 patients (58%) showed abnormal results. Eighteen (36%) were considered to have pathogenic CNVs. Dysmorphism (p=0.028) was significantly higher in patients with pathogenic CNVs than in those with normal CMA. Two or more clinical features were presented by 61.9% (13/21) of the patients with normal CMA and by 83.3% (15/18) of the patients with pathogenic CMA. Dysmorphism can be a phenotypic clue to pathogenic CNVs. Furthermore, pathogenic CNV might be more frequently found if patients have two or more clinical features in addition to DD/ID. © Copyright: Yonsei University College of Medicine 2018.

Sickness absence, marginality, and medically unexplained physical symptoms: A focus-group study of patients’ experiences

PubMed Central

2013-01-01

Abstract Purpose Medically unexplained physical symptoms (MUPS) form a major cause of sickness absence. The purpose of this study was to explore factors which may influence further marginalization among patients with MUPS on long-term sickness absence. Methods Two focus-group discussions were conducted with a purposive sample of 12 participants, six men and six women, aged 24–59 years. Their average duration of sickness absence was 10.5 months. Participants were invited to share stories about experiences from the process leading to the ongoing sickness absence, with a focus on the causes being medically unexplained. Systematic text condensation was applied for analysis. Inspired by theories of marginalization and coping, the authors searched for knowledge of how patients’ positive resources can be mobilized to counteract processes of marginality. Results Analysis revealed how invisible symptoms and lack of objective findings were perceived as an additional burden to the sickness absence itself. Factors that could counteract further marginalization were a supportive social network, positive coping strategies such as keeping to the daily schedule and physical activity, and positive attention and confidence from professionals. Conclusions Confidence from both personal and professional contacts is crucial. GPs have an important and appreciated role in this aspect. PMID:23659708

Genetic investigation of 100 heart genes in sudden unexplained death victims in a forensic setting.

PubMed

Christiansen, Sofie Lindgren; Hertz, Christin Løth; Ferrero-Miliani, Laura; Dahl, Morten; Weeke, Peter Ejvin; LuCamp; Ottesen, Gyda Lolk; Frank-Hansen, Rune; Bundgaard, Henning; Morling, Niels

2016-12-01

In forensic medicine, one-third of the sudden deaths remain unexplained after medico-legal autopsy. A major proportion of these sudden unexplained deaths (SUD) are considered to be caused by inherited cardiac diseases. Sudden cardiac death (SCD) may be the first manifestation of these diseases. The purpose of this study was to explore the yield of next-generation sequencing of genes associated with SCD in a cohort of SUD victims. We investigated 100 genes associated with cardiac diseases in 61 young (1-50 years) SUD cases. DNA was captured with the Haloplex target enrichment system and sequenced using an Illumina MiSeq. The identified genetic variants were evaluated and classified as likely, unknown or unlikely to have a functional effect. The criteria for this classification were based on the literature, databases, conservation and prediction of the effect of the variant. We found that 21 (34%) individuals carried variants with a likely functional effect. Ten (40%) of these variants were located in genes associated with cardiomyopathies and 15 (60%) of the variants in genes associated with cardiac channelopathies. Nineteen individuals carried variants with unknown functional effect. Our findings indicate that broad genetic investigation of SUD victims increases the diagnostic outcome, and the investigation should comprise genes involved in both cardiomyopathies and cardiac channelopathies.

Unexplained metabolic acidosis in critically ill patients: the role of pyroglutamic acid.

PubMed

Mizock, Barry A; Belyaev, Stanislav; Mecher, Carter

2004-03-01

To determine the role of pyroglutamic acid (PGA) in the pathogenesis of unexplained metabolic acidosis in critically ill patients. Case series in the medical ICU of an urban hospital. 23 patients admitted to the medical ICU with acidemia (pH <7.35 or HC0(3) < or = 16 mEq/l) not explained by the presence of ketoacidosis, lactic acidosis, renal failure or ingestion of drugs or toxins and who had an increase in the strong ion gap (SIG) greater than 5. Plasma levels of sodium, potassium, chloride, bicarbonate, calcium (ionized), magnesium, lactate, phosphate, albumin, blood urea nitrogen, and creatinine were measured. Arterial blood gases and urine dipstick for ketones were also analyzed. Plasma was assayed for PGA using gas chromatography. The patient's history and Kardex were reviewed for evidence of acetaminophen administration. The plasma PGA level was found to be very low in all patients studied. The correlation between SIG and PGA (r) was -0.01 (95% CI: -0.42 to 0.40). PGA therefore did not account for the observed increase in the SIG. There appeared to be no obvious influence of acetaminophen intake on levels of PGA in the plasma. We were unable to confirm the importance of PGA as a cause of unexplained metabolic acidosis and increased SIG in our critically ill patients.

The effect of luteal-phase support with vaginal progesterone on pregnancy rates in gonadotropin and clomiphene citrate/intra-uterine insemination cycles in unexplained infertility: A prospective randomised study.

PubMed

Karadag, Burak; Dilbaz, Berna; Karcaaltincaba, Deniz; Sahin, Elif Gulsah; Ercan, Fedi; Karasu, Yetkin; Tonyalı, Nazan Vanlı

2016-08-01

The purpose of this study is to analyse the effect of luteal-phase support on pregnancy rates in gonadotropin + intra-uterine insemination (Gn/IUI) and clomiphene citrate (CC) +IUI (CC/IUI) cycles in patients with unexplained infertility. Equal numbers of patients were recruited in two treatment arms (CC/IUI and Gn/IUI) (n = 100, n = 100, respectively). In each group, 50 patients received vaginal progesterone for 14 days (Crinone 8% vaginal gel, 90 mg per day) for luteal-phase support from the day after IUI and continued until menstruation or the 10th week of gestation if pregnant. There were 29 clinical pregnancies among 200 patients. Pregnancy rates were 12% in CC/IUI cycles, 10% in luteal-phase-supported CC/IUI cycles 16% in Gn/IUI cycles and 20% in luteal-phase-supported Gn/IUI cycles. Although pregnancy rates were higher in Gn/IUI cycles compared to CC/IUI cycles, luteal-phase support did not significantly affect the pregnancy rates in both groups. This study implies that luteal-phase support with progesterone has no pronounced beneficial effect on pregnancy rates in either CC/IUI or Gn/IUI cycles in patients with unexplained infertility.

Basic psychological need experiences, fatigue, and sleep in individuals with unexplained chronic fatigue.

PubMed

Campbell, Rachel; Tobback, Els; Delesie, Liesbeth; Vogelaers, Dirk; Mariman, An; Vansteenkiste, Maarten

2017-12-01

Grounded in self-determination theory, this study tested the hypothesis that the satisfaction and frustration of the psychological needs for autonomy, competence, and relatedness would relate to fatigue and subjective and objective sleep parameters, with stress and negative sleep cognitions playing an explanatory role in these associations. During a stay at a sleep laboratory in Belgium, individuals with unexplained chronic fatigue (N = 160; 78% female) underwent polysomnography and completed a questionnaire at 3 different points in time (i.e., after arrival in the sleep lab, before bedtime, and the following morning) that assessed their need-based experiences and stress during the previous week, fatigue during the preceding day, and sleep-related cognitions and sleep during the previous night. Results indicated that need frustration related to higher stress, which in turn, related to higher evening fatigue. Need frustration also related to poorer subjective sleep quality and shorter sleep duration, as indicated by both subjective and objective shorter total sleep time and subjective (but not objective) longer sleep latency. These associations were accounted for by stress and negative sleep cognitions. These findings suggest that health care professionals working with individuals with unexplained chronic fatigue may consider focusing on basic psychological needs within their therapeutic approach. Copyright © 2017 John Wiley & Sons, Ltd.

Yield and Pitfalls of Ajmaline Testing in the Evaluation of Unexplained Cardiac Arrest and Sudden Unexplained Death: Single-Center Experience With 482 Families.

PubMed

Tadros, Rafik; Nannenberg, Eline A; Lieve, Krystien V; Škorić-Milosavljević, Doris; Lahrouchi, Najim; Lekanne Deprez, Ronald H; Vendrik, Jeroen; Reckman, Yolan J; Postema, Pieter G; Amin, Ahmad S; Bezzina, Connie R; Wilde, Arthur A M; Tan, Hanno L

2017-12-11

This study evaluated the yield of ajmaline testing and assessed the occurrence of confounding responses in a large cohort of families with unexplained cardiac arrest (UCA) or sudden unexplained death (SUD). Ajmaline testing to diagnose Brugada syndrome (BrS) is routinely used in the evaluation of SUD and UCA, but its yield, limitations, and appropriate dosing have not been studied in a large cohort. We assessed ajmaline test response and genetic testing results in 637 individuals from 482 families who underwent ajmaline testing for SUD or UCA. Overall, 89 individuals (14%) from 88 families (18%) had a positive ajmaline test result. SCN5A mutations were identified in 9 of 86 ajmaline-positive cases (10%). SCN5A mutation carriers had positive test results at significantly lower ajmaline doses than noncarriers (0.75 [range: 0.64 to 0.98] mg/kg vs. 1.03 [range: 0.95 to 1.14] mg/kg, respectively; p < 0.01). In 7 of 88 families (8%), it was concluded that the positive ajmaline response was a confounder, either in the presence of an alternative genetic diagnosis accounting for UCA/SUD (5 cases) or noncosegregation of positive ajmaline response and arrhythmia (2 cases). The rate of confounding responses was significantly higher in positive ajmaline responses obtained at >1 mg/kg than in those obtained at ≤1 mg/kg (7 of 48 vs. 0 of 41 individuals; Fisher's exact test: p = 0.014). In line with previous, smaller studies, a positive ajmaline response was observed in a large proportion of UCA/SUD families. Importantly, our data emphasize the potential for confounding possibly false-positive ajmaline responses in this population, particularly at high doses, which could possibly lead to a misdiagnosis. Clinicians should consider all alternative causes in UCA/SUD and avoid ajmaline doses >1 mg/kg. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Expression of retinoid-related orphan receptor (ROR)γt on NK22 cells in the peripheral blood and uterine endometrium of women with unexplained recurrent pregnancy loss and unexplained infertility.

PubMed

Fuchinoue, Kohei; Fukui, Atsushi; Chiba, Hitomi; Kamoi, Mai; Funamizu, Ayano; Taima, Ayako; Fukuhara, Rie; Mizunuma, Hideki

2016-11-01

Recently, NK22 cells, a subset of interleukin (IL)-22-producing natural killer (NK) cells, were identified. We have previously reported the higher percentage of NK22 cells in women suffering recurrent pregnancy loss (RPL). Moreover, we have also reported lower expression of NKp46, a kind of natural cytotoxicity receptor (NCR), on NK cells and the changes of NK cell producing cytokines in women who experience RPL. NK22 cells express NCRs, such as NKp44 or NKp46. Retinoid-related orphan receptor γt (RORγt) is known as a regulator of NK22 cells; however, in NK22 cells of peripheral blood (PB) and the uterine endometrium (UE), the relationship between NCRs and RORγt is unclear. We investigate RORγt expression NK22 cells in the PB and UE of women with unexplained infertility (uI) or unexplained RPL (uRPL). Lymphocytes were extracted from PB and UE, derived from women with uI or uRPL. Expression of RORγt and NCRs in NK cells and NK cell-produced cytokines were analyzed by flow cytometry. CD56 + /NKp46 + /RORγt + cells were positively correlated with CD56 + /IL-22 + cells in both PB and UE. CD56 bright /NKp46 bright /RORγt + cells were significantly higher in uRPL than in uI, and endometrial CD56 bright /NKp46 bright /RORγt + cells were positively correlated with PB. In UE, CD56 bright /RORγt + cells were negatively correlated with CD56 bright /interferon-γ + and CD56 bright /tumor necrosis factor-α + cells of uRPL. RORγt may be associated with NK22 cells in reproduction. Particularly, higher expression of RORγt may be associated with elevated NK22 cells in uRPL. © 2016 Japan Society of Obstetrics and Gynecology.

Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility.

PubMed

Diamond, Michael P; Legro, Richard S; Coutifaris, Christos; Alvero, Ruben; Robinson, Randal D; Casson, Peter; Christman, Gregory M; Ager, Joel; Huang, Hao; Hansen, Karl R; Baker, Valerie; Usadi, Rebecca; Seungdamrong, Aimee; Bates, G Wright; Rosen, R Mitchell; Haisenleder, Daniel; Krawetz, Stephen A; Barnhart, Kurt; Trussell, J C; Ohl, Dana; Jin, Yufeng; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

2015-09-24

The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates. We enrolled couples with unexplained infertility in a multicenter, randomized trial. Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were randomly assigned to ovarian stimulation (up to four cycles) with gonadotropin (301 women), clomiphene (300), or letrozole (299). The primary outcome was the rate of multiple gestations among women with clinical pregnancies. After treatment with gonadotropin, clomiphene, or letrozole, clinical pregnancies occurred in 35.5%, 28.3%, and 22.4% of cycles, and live birth in 32.2%, 23.3%, and 18.7%, respectively; pregnancy rates with letrozole were significantly lower than the rates with standard therapy (gonadotropin or clomiphene) (P=0.003) or gonadotropin alone (P<0.001) but not with clomiphene alone (P=0.10). Among ongoing pregnancies with fetal heart activity, the multiple gestation rate with letrozole (9 of 67 pregnancies, 13%) did not differ significantly from the rate with gonadotropin or clomiphene (42 of 192, 22%; P=0.15) or clomiphene alone (8 of 85, 9%; P=0.44) but was lower than the rate with gonadotropin alone (34 of 107, 32%; P=0.006). All multiple gestations in the clomiphene and letrozole groups were twins, whereas gonadotropin treatment resulted in 24 twin and 10 triplet gestations. There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications. In women with unexplained infertility, ovarian stimulation with letrozole resulted in a significantly lower frequency of multiple gestation but also a lower frequency of live birth, as compared with gonadotropin but not as compared with clomiphene. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01044862.).

Response of unexplained chest pain to proton pump inhibitor treatment in patients with and without objective evidence of gastro-oesophageal reflux disease.

PubMed

Kahrilas, Peter J; Hughes, Nesta; Howden, Colin W

2011-11-01

Unexplained chest pain is potentially attributable to gastro-oesophageal reflux disease (GORD) or oesophageal motility disorders. Reflux chest pain may occur without heartburn. We explored the response of unexplained chest pain to proton pump inhibitor (PPI) therapy in randomised clinical trials (RCTs), differentiating patients with and without objective evidence of GORD. PubMed and Embase were systematically searched for RCTs that reported chest pain response to PPIs in patients who had had pH-monitoring and/or endoscopy to differentiate GORD-positive from GORD-negative subpopulations. Heterogeneity among studies was assessed using the Cochran Q and I(2) statistics, and a fixed effect model was applied. Possible publication bias was assessed by Egger's test. Six RCTs met the inclusion criteria. All used 24 h pH monitoring and/or endoscopy to define GORD-positive patients and improvement in chest pain to define response (five used ≥50%; one used ≥ 20%). The therapeutic gain of >50% improvement with PPIs relative to placebo was 56-85% in GORD-positive and 0-17% in GORD-negative patients. The RR of >50% improvement in chest pain with PPI versus placebo was 4.3 (95% CI 2.8 to 6.7; p<0.0001) for GORD-positive and 0.4 (95% CI 0.3 to 0.7; p=0.0004) for GORD-negative patients. Concomitant heartburn varied among trials from being an exclusion criterion to being essentially concordant with GORD-positive status. Unexplained chest pain in patients with endoscopic or pH-monitoring evidence of GORD tends to improve, but not resolve, with PPI therapy, whereas GORD-negative patients have little or no response. Heartburn was a poor predictor of whether patients with chest pain were GORD-positive or GORD-negative by objective testing.

Premature coronary heart disease and autosomal dominant hypercholesterolemia: Increased risk in women with LDLR mutations.

PubMed

Ahmad, Zahid; Li, Xilong; Wosik, Jedrek; Mani, Preethi; Petr, Joye; McLeod, George; Murad, Shatha; Song, Li; Adams-Huet, Beverley; Garg, Abhimanyu

2016-01-01

For patients with autosomal dominant hypercholesterolemia (ADH), it remains unclear whether differences exist in the risk of premature coronary heart disease (CHD) between patients with confirmed mutations in low-density lipoprotein receptor (LDLR) vs those without detectable mutations. This study sought to assess the risk of premature CHD in ADH patients with mutations in LDLR (referred to as familial hypercholesterolemia [FH]) vs those without detectable mutations (unexplained ADH), stratified by sex. Comparative study of premature CHD in a multiethnic cohort of 111 men and 165 women meeting adult Simon-Broome criteria for ADH. Women with FH (n = 51) had an increased risk of premature CHD compared with unexplained ADH women (n = 111; hazard ratio [HR], 2.74; 95% confidence interval, 1.40-5.34; P = .003) even after adjustment for lipid levels and traditional CHD risk factors (HR, 2.53 [1.10-5.83]; P = .005). Men with FH (n = 42), in contrast, had a similar risk of premature CHD when compared with unexplained ADH men (n = 66; unadjusted: HR, 1.48 [0.84-2.63]; P = .18; adjusted: HR, 1.04 [0.46-2.37]; P = .72). To address whether mutation status provides additional information beyond LDL-cholesterol level, we analyzed premature CHD risk for FH vs unexplained ADH at various percentiles of LDL-cholesterol: the risk ratios were significant for women at 25th percentile (HR, 4.90 [1.69-14.19]) and 50th percentile (HR, 3.44 [1.42-8.32]) but not at 75th percentile (HR, 1.99 [0.95-4.17]), and were not significant for men at any percentile. Our findings suggest that genetic confirmation of ADH may be important to identify patient's risk of CHD, especially for female LDLR mutation carriers. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Undiagnosed pancreatic exocrine insufficiency and chronic pancreatitis in functional GI disorder patients with diarrhea or abdominal pain.

PubMed

Talley, Nicholas J; Holtmann, Gerald; Nguyen, Quoc Nam; Gibson, Peter; Bampton, Peter; Veysey, Martin; Wong, James; Philcox, Stephen; Koloski, Natasha; Bunby, Lisa; Jones, Michael

2017-11-01

A previous UK study showed that 6.1% of patients with diarrhea-predominant irritable bowel syndrome (IBS-D) had evidence of severe pancreatic exocrine insufficiency (PEI), but these findings need replication. We aimed to identify the prevalence of PEI based on fecal elastase stool testing in consecutive outpatients presenting with chronic unexplained abdominal pain and/or diarrhea and/or IBS-D. Patients aged over 40 years presenting to hospital outpatient clinics from six sites within Australia with unexplained abdominal pain and/or diarrhea for at least 3 months and/or IBS-D were studied. Patients completed validated questionnaires and donated a stool sample in which elastase concentration was measured by ELISA. A concentration of < 100 mcg/g stool represented severe and < 200 mcg/g mild to moderate PEI. Patients whose fecal elastase was < 200 mcg/g underwent testing for pancreatic pathology with an endoscopic ultrasound or abdominal CT. Two hundred eighteen patients (mean age of 60 years, 29.4% male) were studied. PEI was found in 4.6% (95% CI 2.2-8.3%) (n = 10), with five patients (2.3% (95% CI 0.8-5.3%) having severe PEI. Only male sex and heavy alcohol use were significantly associated with abnormal versus normal pancreatic functioning. Of seven patients who underwent endoscopic ultrasound or CT, two had features indicative of chronic pancreatitis. One in 50 patients with IBS-D or otherwise unexplained abdominal pain or diarrhea have an abnormal fecal elastase, but unexpected pancreatic insufficiency was detected in only a minority of these. This study failed to confirm the high prevalence of PEI among patients with unexplained GI symptoms previously reported. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Birth characteristics in a clinical sample of women seeking infertility treatment: a case-control study.

PubMed

Vikström, Josefin; Hammar, Mats; Josefsson, Ann; Bladh, Marie; Sydsjö, Gunilla

2014-03-10

To determine the distribution of low birth weight (LBW), preterm birth, small for gestational age (SGA) and large for gestational age (LGA) by main cause of infertility (female, combined, male, unexplained) in women seeking infertility treatment. A case-control study. A Centre for Reproductive Medicine in Sweden. All women (n=1293) born in Sweden in 1973 or later and who were part of heterosexual couples seeking infertility treatment at a Centre of Reproductive Medicine from 2005 to 2010 were asked to participate. Those who had not begun the diagnostic process and who declined participation in the study were excluded. In total, 1206 women (94.5%) participated in the study. Main cause of infertility (female, combined, male, unexplained) collected from the patients' medical charts. LBW (<2500 g), preterm birth (<37 weeks), SGA (<-2SD of the mean weight for the gestational length) and LGA (>+2SD of the mean weight for the gestational length), collected from the Swedish Medical Birth Register. The risk of being born with LBW was increased about 2.4 times (OR=2.40, CI 1.13 to 5.07, p=0.02) in women seeking treatment for infertility due to female causes rather than for male or unexplained causes. Women with a female infertility factor were 2.7 times more likely to be born SGA (OR=2.73, CI 1.02 to 7.34, p=0.047) compared with those in whom the cause of infertility was unexplained. Women born with LBW or SGA seem to suffer an increased risk of infertility due to a female factor. Thus, infants born with birth characteristics that deviate from the norm may be at greater risk of difficulties in childbearing later on in life. Since this study is the first of its kind, more studies are needed to verify the associations found in this study and to determine their nature.

Medical student attitudes about mental illness: does medical-school education reduce stigma?

PubMed

Korszun, Ania; Dinos, Sokratis; Ahmed, Kamran; Bhui, Kamaldeep

2012-05-01

Reducing stigma associated with mental illness is an important aim of medical education, yet evidence indicates that medical students' attitudes toward patients with mental health problems deteriorate as they progress through medical school. Authors examined medical students' attitudes to mental illness, as compared with attitudes toward other medical illness, and the influence of the number of years spent in medical school, as well as of several key socio-demographic, ethnic, and cultural variables. A group of 760 U.K. medical students completed a nationwide on-line survey examining their attitudes toward patients with five conditions (pneumonia, depression, psychotic symptoms, intravenous drug use, long-standing unexplained abdominal complaints), using the Medical Condition Regard Scale (MCRS). Students were also asked whether they had completed the psychiatry rotation or had personal experience of mental disorders themselves or among their friends or family members. They were also asked about their ethnic group (using U.K. national census categories), religious affiliation, and how important religion was in their lives. Independent-samples t-tests and one-way ANOVA were used to compare differences between groups on the MCRS. Students showed the highest regard for patients with pneumonia and lowest regard for patients with long-standing, unexplained abdominal complaints. Although attitudes toward pneumonia were more positive in fifth-year students than in first-year students, attitudes toward unexplained chronic abdominal pain were worse in fifth-year students than in first-year students. Personal experience of mental health treatment, or that among family and friends, were associated with less stigmatizing attitudes. Men showed more stigmatization than women for nearly all conditions; Chinese and South Asian students showed more stigmatizing attitudes toward delusions and hallucinations than their white British counterparts. Medical students in this survey showed the lowest regard for patients with unexplained abdominal pain, and these attitudes were worse in the most experienced medical students. Students' gender, culture and direct or indirect experience of mental illness influenced stigmatizing attitudes.

Mental health care use in medically unexplained and explained physical symptoms: findings from a general population study

PubMed Central

van Eck van der Sluijs, Jonna F; ten Have, Margreet; Rijnders, Cees A; van Marwijk, Harm WJ; de Graaf, Ron; van der Feltz-Cornelis, Christina M

2016-01-01

Objective The aim of this study was to explore mental health care utilization patterns in primary and specialized mental health care of people with unexplained or explained physical symptoms. Methods Data were derived from the first wave of the Netherlands Mental Health Survey and Incidence Study-2, a nationally representative face-to-face cohort study among the general population aged 18–64 years. We selected subjects with medically unexplained symptoms (MUS) only (MUSonly; n=177), explained physical symptoms only (PHYonly, n=1,952), combined MUS and explained physical symptoms (MUS + PHY, n=209), and controls without physical symptoms (NONE, n=4,168). We studied entry into mental health care and the number of treatment contacts for mental problems, in both primary care and specialized mental health care. Analyses were adjusted for sociodemographic characteristics and presence of any 12-month mental disorder assessed with the Composite International Diagnostic Interview 3.0. Results At the primary care level, all three groups of subjects with physical symptoms showed entry into care for mental health problems significantly more often than controls. The adjusted odds ratios were 2.29 (1.33, 3.95) for MUSonly, 1.55 (1.13, 2.12) for PHYonly, and 2.25 (1.41, 3.57) for MUS + PHY. At the specialized mental health care level, this was the case only for MUSonly subjects (adjusted odds ratio 1.65 [1.04, 2.61]). In both the primary and specialized mental health care, there were no significant differences between the four groups in the number of treatment contacts once they entered into treatment. Conclusion All sorts of physical symptoms, unexplained as well as explained, were associated with significant higher entry into primary care for mental problems. In specialized mental health care, this was true only for MUSonly. No differences were found in the number of treatment contacts. This warrants further research aimed at the content of the treatment contacts. PMID:27574433

Overtreatment in couples with unexplained infertility.

PubMed

Kersten, F A M; Hermens, R P G M; Braat, D D M; Hoek, A; Mol, B W J; Goddijn, M; Nelen, W L D M

2015-01-01

What is the percentage of overtreatment, i.e. fertility treatment started too early, in couples with unexplained infertility who were eligible for tailored expectant management? Overtreatment occurred in 36% of couples with unexplained infertility who were eligible for an expectant management of at least 6 months. Prognostic models in reproductive medicine can help to identify infertile couples that would benefit from fertility treatment. In couples with unexplained infertility with a good chance of natural conception within 1 year, based on the Hunault prediction model, an expectant management of 6-12 months, as recommended in international fertility guidelines, prevents unnecessary treatment. A retrospective cohort study in 25 participating clinics, with follow-up of all couples who were seen for infertility in 2011-2012. In all, 9818 couples were seen for infertility in the participating clinics. Couples were eligible to participate if they were diagnosed with unexplained infertility and had a good prognosis of natural conception (>30%) within 1 year based on the Hunault prediction model. Data to assess overtreatment were collected from medical records. Multilevel regression analyses were performed to investigate associations of overtreatment with patient and clinic characteristics. Five hundred and forty-four couples eligible for expectant management were included in this study. Among these, overtreatment, i.e. starting medically assisted reproduction within 6 months, occurred in 36%. The underlying quality indicators showed that in 34% no prognosis was calculated and that in 42% expectant management was not recommended. Finally, 16% of the couples for whom a correct recommendation of expectant management for at least 6 months was made, started treatment within 6 months anyway. Overtreatment was associated with childlessness, higher female age and a longer duration of infertility. No associations between overtreatment and clinic characteristics were found. The response rate was low compared with other fertility studies. Evaluation of possible selection bias showed that responders had a higher socio-economic status than non-responders. Our findings show that developing and publishing guideline recommendations on tailored expectant management (TEM) is not enough and that overtreatment still occurs frequently. Future research should focus on tailored efforts to implement guideline recommendations on TEM. Supported by Netherlands Organisation for Health Research and Development (ZonMW). ZonMW had no role in designing the study, data collection, analysis and interpretation of data or writing of the report. Competing interests: none. www.trialregister.nl NTR3405. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Nodular hidradenocarcinoma with prominent squamous differentiation: case report and immunohistochemical study.

PubMed

Park, H J; Kim, Y C; Cinn, Y W

2000-09-01

We report the case of a 24-year-old woman with nodular hidradenocarcinoma on the scalp. While histopathology of the tumor showed a circumscribed, lobulated intradermal mass with prominent squamous differentiation, the immunohistochemical study with antibodies to cytokeratins, CAM 5.2 and 19, epithelial membrane antigen, carcinoembryonic antigen, S-100 protein and p53 all demonstrated positivity. These findings confirmed that the tumor was of eccrine sweat gland origin and it was thought to be a nodular hidradenocarcinoma differentiating toward the eccrine duct and/or secretory portions. She was treated with a wide local excision and no recurrence was observed 18 months after excision.

IVF or IUI as first-line treatment in unexplained subfertility: the conundrum of treatment selection markers.

PubMed

Tjon-Kon-Fat, R I; Tajik, P; Zafarmand, M H; Bensdorp, A J; Bossuyt, P M M; Oosterhuis, G J E; van Golde, R; Repping, S; Lambers, M D A; Slappendel, E; Perquin, D; Pelinck, M J; Gianotten, J; Maas, J W M; Eijkemans, M J C; van der Veen, F; Mol, B W; van Wely, M

2017-05-01

Are there treatment selection markers that could aid in identifying couples, with unexplained or mild male subfertility, who would have better chances of a healthy child with IVF with single embryo transfer (IVF-SET) than with IUI with ovarian stimulation (IUI-OS)? We did not find any treatment selection markers that were associated with better chances of a healthy child with IVF-SET instead of IUI-OS in couples with unexplained or mild male subfertility. A recent trial, comparing IVF-SET to IUI-OS, found no evidence of a difference between live birth rates and multiple pregnancy rates. It was suggested that IUI-OS should remain the first-line treatment instead of IVF-SET in couples with unexplained or mild male subfertility and female age between 18 and 38 years. The question remains whether there are some couples that may have higher pregnancy chances if treated with IVF-SET instead of IUI. We performed our analyses on data from the INeS trial, where couples with unexplained or mild male subfertility and an unfavourable prognosis for natural conception were randomly allocated to IVF-SET, IVF in a modified natural cycle or IUI-OS. In view of the aim of this study, we only used data of the comparison between IVF-SET (201 couples) and IUI-OS (207 couples). We pre-defined the following baseline characteristics as potential treatment selection markers: female age, ethnicity, smoking status, type of subfertility (primary/secondary), duration of subfertility, BMI, pre-wash total motile count and Hunault prediction score. For each potential treatment selection marker, we explored the association with the chances of a healthy child after IVF-SET and IUI-OS and tested if there was an interaction with treatment. Given the exploratory nature of our analysis, we used a P-value of 0.1. None of the markers were associated with higher chances of a healthy child from IVF-SET compared to IUI-OS (P-value for interaction >0.10). Since this is the first large study that looked at potential treatment selection markers for IVF-SET compared to IUI-OS, we had no data on which to base a power calculation. The sample size was limited, making it difficult to detect any smaller associations. We could not identify couples with unexplained or mild male subfertility who would have had higher chances of a healthy child from immediate IVF-SET than from IUI-OS. As in the original trial IUI-OS had similar effectiveness and was less costly compared to IVF-SET, IUI-OS should remain the preferred first-line treatment in these couples. The study was supported by a grant from the Netherlands Organization for Health Research and Development, and a grant from the Netherlands' association of health care insurers. There are no conflicts of interest. The trial was registered at the Dutch trial registry (NTR939). © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

D-xylose absorption

MedlinePlus

Xylose tolerance test; Diarrhea - xylose; Malnutrition - xylose; Sprue - xylose; Celiac - xylose ... test if you have: Persistent diarrhea Signs of malnutrition Unexplained weight loss This test is primarily used ...

Anomalous rise in algal production linked to lakewater calcium decline through food web interactions

PubMed Central

Korosi, Jennifer B.; Burke, Samantha M.; Thienpont, Joshua R.; Smol, John P.

2012-01-01

Increased algal blooms are a threat to aquatic ecosystems worldwide, although the combined effects of multiple stressors make it difficult to determine the underlying causes. We explore whether changes in trophic interactions in response to declining calcium (Ca) concentrations, a water quality issue only recently recognized in Europe and North America, can be linked with unexplained bloom production. Using a palaeolimnological approach analysing the remains of Cladocera (herbivorous grazers) and visual reflectance spectroscopically inferred chlorophyll a from the sediments of a Nova Scotia (Canada) lake, we show that a keystone grazer, Daphnia, declined in the early 1990s and was replaced by a less effective grazer, Bosmina, while inferred chlorophyll a levels tripled at constant total phosphorus (TP) concentrations. The decline in Daphnia cannot be attributed to changes in pH, thermal stratification or predation, but instead is linked to declining lakewater [Ca]. The consistency in the timing of changes in Daphnia and inferred chlorophyll a suggests top-down control on algal production, providing, to our knowledge, the first evidence of a link between lakewater [Ca] decline and elevated algal production mediated through the effects of [Ca] decline on Daphnia. [Ca] decline has severe implications for whole-lake food webs, and presents yet another mechanism for potential increases in algal blooms. PMID:21957138

Inland thinning on the Greenland ice sheet controlled by outlet glacier geometry

NASA Astrophysics Data System (ADS)

Felikson, Denis; Bartholomaus, Timothy C.; Catania, Ginny A.; Korsgaard, Niels J.; Kjær, Kurt H.; Morlighem, Mathieu; Noël, Brice; van den Broeke, Michiel; Stearns, Leigh A.; Shroyer, Emily L.; Sutherland, David A.; Nash, Jonathan D.

2017-04-01

Greenland’s contribution to future sea-level rise remains uncertain and a wide range of upper and lower bounds has been proposed. These predictions depend strongly on how mass loss--which is focused at the termini of marine-terminating outlet glaciers--can penetrate inland to the ice-sheet interior. Previous studies have shown that, at regional scales, Greenland ice sheet mass loss is correlated with atmospheric and oceanic warming. However, mass loss within individual outlet glacier catchments exhibits unexplained heterogeneity, hindering our ability to project ice-sheet response to future environmental forcing. Using digital elevation model differencing, we spatially resolve the dynamic portion of surface elevation change from 1985 to present within 16 outlet glacier catchments in West Greenland, where significant heterogeneity in ice loss exists. We show that the up-glacier extent of thinning and, thus, mass loss, is limited by glacier geometry. We find that 94% of the total dynamic loss occurs between the terminus and the location where the down-glacier advective speed of a kinematic wave of thinning is at least three times larger than its diffusive speed. This empirical threshold enables the identification of glaciers that are not currently thinning but are most susceptible to future thinning in the coming decades.

Unusual Presentation of Unilateral Isolated Probable Lyme Optic Neuritis.

PubMed

Burakgazi, Ahmet Z; Henderson, Carl S

2016-01-01

Optic neuritis (ON) is one of the most common manifestations of central nervous system involvement caused by various etiologies. Lyme ON is an exceedingly rare ocular manifestation of Lyme disease (LD) and only a few cases have been published in the literature. Lyme ON is very rare but should be included in the differential diagnosis in unexplained cases, particularly in Lyme endemic areas. Careful and detailed examination and investigation are warranted to make the diagnosis. We report this case to increase awareness of clinicians to include Lyme disease in differential diagnosis of ON for unexplained cases of ON. Herein we present a unique case with a unilateral ON caused by LD along with pre- and posttreatment findings and literature review.

The $16,819 pay gap for newly trained physicians: the unexplained trend of men earning more than women.

PubMed

Lo Sasso, Anthony T; Richards, Michael R; Chou, Chiu-Fang; Gerber, Susan E

2011-02-01

Prior research has suggested that gender differences in physicians' salaries can be accounted for by the tendency of women to enter primary care fields and work fewer hours. However, in examining starting salaries by gender of physicians leaving residency programs in New York State during 1999-2008, we found a significant gender gap that cannot be explained by specialty choice, practice setting, work hours, or other characteristics. The unexplained trend toward diverging salaries appears to be a recent development that is growing over time. In 2008, male physicians newly trained in New York State made on average $16,819 more than newly trained female physicians, compared to a $3,600 difference in 1999.

Hyperactivity, unexplained speech delay, and coarse facies--is it Sanfilippo syndrome?

PubMed

Saini, Arushi Gahlot; Singhi, Pratibha; Sahu, Jitendra Kumar; Ganesan, Saptharishi L; Vyas, Sameer; Rao, Sandeep; Sachdeva, Man Updesh Singh

2014-08-01

Mucopolysaccharidosis-IIIB or Sanfilippo-B syndrome is caused by deficiency of lysosomal α-N-acetylglucosaminidase that leads to accumulation of heparan-sulphate and degeneration of central nervous system with progressive dementia, hyperactivity, and aggressive behavior. Mucopolysaccharidosis-III remains underdiagnosed as a cause of developmental delay and hyperactivity both in adults and children because in contrast to other mucopolysaccharidoses, they have little somatic disease, coarse facial features, hepatosplenomegaly or skeletal changes, and a high incidence of false-negative results on the urinary screening tests. We describe here a girl with the classic phenotype of mucopolysaccharidosis-IIIB to alert pediatricians to the possibility of this disorder in children with unexplained speech delay and hyperactivity and prevent unnecessary investigations. © The Author(s) 2013.

Unexplained sudden death, focussing on genetics and family phenotyping.

PubMed

Raju, Hariharan; Behr, Elijah R

2013-01-01

Unexplained sudden death and the sudden arrhythmic death syndrome (SADS) affect a small but significant proportion of young and apparently healthy individuals. This review revisits the causes underlying such deaths and the investigational strategies that identify surviving family who may be at risk. Recent epidemiological data is available from case series or government records. The yield from familial cardiological evaluation for inherited conditions has been supported by additional small series. The greatest advance has come with molecular autopsy studies, which have utilized various methodologies and candidate genes to investigate SADS cases and their families. The latest research replicates and extends the existing knowledge regarding epidemiology and familial evaluation of SADS, whilst genetic studies support a role for the molecular autopsy.

Potentially harmful side-effects: medically unexplained symptoms, somatization, and the insufficient illness narrative for viewers of mystery diagnosis.

PubMed

Farkas, Carol-Ann

2013-09-01

Illness narrative has often been found to play a positive role in both patients' and providers' efforts to find meaning in the illness experience. However, illness narrative can sometimes become counterproductive, even pathological, particularly in cases of medical mystery--cases wherein biopsychosocial factors blur the distinction between bodily dysfunction and somatizing behavior. In this article, the author draws attention to two examples of medical mystery, the clinical presentation of medically unexplained symptoms, and the popular reality television program Mystery Diagnosis, to demonstrate the potentially harmful effects of illness narrative. The medical mystery's complex narrative structure reflects and tends to reinforce providers' and patients' mistaken assumptions, anxieties, and conflicts in ways which obstruct, rather than facilitate, healing.

Left dominant arrhythmogenic cardiomyopathy: a morbid association of ventricular arrhythmias and unexplained infero-lateral T-wave inversion.

PubMed

Protonotarios, Alexandros; Patrianakos, Alexandros; Spanoudaki, Elpida; Kochiadakis, Georgios; Michalodimitrakis, Emmanouel; Vardas, Panagiotis

2013-01-01

Left-dominant arrhythmogenic cardiomyopathy is a subtype of arrhythmogenic right ventricular cardiomyopathy characterized by early predominant left ventricular involvement. Α 34-year-old man presented with palpitations and a history of frequent ventricular extrasystoles of both LBBB and RBBB configuration. Cardiac workup revealed repolarization abnormalities at infero-lateral leads in the absence of diagnostic structural/functional alterations or obstructive coronary artery disease. Six months later he died suddenly. Histopathology was diagnostic for arrhythmogenic right ventricular cardiomyopathy affecting predominantly the left ventricle at subepicardial/midwall myocardial layers. Thus, ventricular arrhythmias accompanied by unexplained infero-lateral T-wave inversion should warn of a possible morbid association underlying left-dominant arrhythmogenic cardiomyopathy. Copyright © 2013 Elsevier Inc. All rights reserved.

Deep seafloor arrivals: an unexplained set of arrivals in long-range ocean acoustic propagation.

PubMed

Stephen, Ralph A; Bolmer, S Thompson; Dzieciuch, Matthew A; Worcester, Peter F; Andrew, Rex K; Buck, Linda J; Mercer, James A; Colosi, John A; Howe, Bruce M

2009-08-01

Receptions, from a ship-suspended source (in the band 50-100 Hz) to an ocean bottom seismometer (about 5000 m depth) and the deepest element on a vertical hydrophone array (about 750 m above the seafloor) that were acquired on the 2004 Long-Range Ocean Acoustic Propagation Experiment in the North Pacific Ocean, are described. The ranges varied from 50 to 3200 km. In addition to predicted ocean acoustic arrivals and deep shadow zone arrivals (leaking below turning points), "deep seafloor arrivals," that are dominant on the seafloor geophone but are absent or very weak on the hydrophone array, are observed. These deep seafloor arrivals are an unexplained set of arrivals in ocean acoustics possibly associated with seafloor interface waves.

Anovulatory and ovulatory infertility: results with simplified management.

PubMed Central

Hull, M G; Savage, P E; Bromham, D R

1982-01-01

A simplified scheme for the management of anovulatory and of ovulatory (usually called unexplained) infertility was evaluated in 244 women. Eighteen patients were excluded because of primary ovarian failure, 164 were treated for ovulatory failure, and 62 with ovulatory infertility remained untreated. Twenty-five patients had a properly validated negative postcoital test. In the remaining 201 patients the two-year conception rates were 96% in patients with amenorrhoea, 83% in those with oligomenorrhoea, 74% in those with luteal deficiency, and 88% in those with ovulatory infertility. Comparison with normal rates implied that amenorrhoea represents a pure form of ovulatory failure that is completely correctable whereas in other conditions unexplained factors also contribute to infertility though to a much smaller extent than was previously thought. PMID:6805656

ESR

MedlinePlus

Erythrocyte sedimentation rate; Sed rate; Sedimentation rate ... Reasons why a "sed rate" may be done include: Unexplained fevers Certain types of arthritis Muscle symptoms Other vague symptoms that cannot be explained This ...

Elder Abuse

MedlinePlus

... homes. The mistreatment may be Physical, sexual, or emotional abuse Neglect or abandonment Financial abuse - stealing of money or belongings Possible signs of elder abuse include unexplained bruises, burns, and injuries. There ...

Fetal karyotyping for chromosome abnormalities after an unexplained elevated maternal serum alpha-fetoprotein screening.

PubMed

Feuchtbaum, L B; Cunningham, G; Waller, D K; Lustig, L S; Tompkinson, D G; Hook, E B

1995-08-01

To study the chromosome abnormality rate among women with elevated levels of maternal serum alpha-fetoprotein (MSAFP) and the types of chromosome abnormalities in this population, and to compare this rate with reports in the literature and the rate observed in the general population. We studied 8097 women who chose to undergo amniocentesis and fetal karyotyping after having an elevated MSAFP test of 2.5 multiples of the median (MOM) or higher. All abnormal karyotypes were reviewed and grouped according to whether the elevated MSAFP value could be explained by a ventral wall or neural tube defect. The overall chromosome abnormality rate was 13.83 per 1000 amniocenteses. The rate in the "unexplained" group was 10.92 per 1000 amniocenteses. Just over half (53%) of the abnormal karyotypes were autosomal anomalies, and 47% were sex chromosome abnormalities. The autosomal aneuploidies observed most frequently were triploidy and trisomy 13. The sex chromosome abnormalities observed most frequently were the XXY and XYY karyotypes. Women who have unexplained elevated MSAFP values of 2.5 MOM or greater have a twofold increase in the rate of chromosome abnormalities in their fetuses compared with the general population (P < or = .001). This rate is consistent with other studies that used a 2.5 MOM cutoff. Studies that used a 2.0 MOM cutoff have reported chromosome abnormality rates that do not vary from general population estimates.

Inherited and acquired thrombophilia in Indian women experiencing unexplained recurrent pregnancy loss.

PubMed

Patil, Rucha; Ghosh, Kanjaksha; Vora, Sonal; Shetty, Shrimati

2015-10-01

The most frequently hypothesized cause of unexplained recurrent pregnancy loss (RPL) refers to a defective maternal haemostatic response leading to uteroplacental thrombosis. Approximately 20% women suffering from pregnancy loss (PL) are associated with autoimmune disorders and more than 50% remain idiopathic after common traditional investigations. The present study aims to investigate the prevalence of different genetic and acquired thrombophilia markers in a large series of Indian women with RPL. Such studies will help analyze the markers which pose maximum risk and help in the appropriate treatment in subsequent pregnancies. The study comprised of 587 women with no apparent etiological causes of RPL and 115 healthy women controls. p values were calculated with two tailed Fisher's exact test; statistical significance was assumed at p<0.05, 95% confidence interval. Relative risks were also calculated. Among genetic thrombophilia, the risk of PL was highest with protein S deficiency (16%, p=0.006) followed by plasminogen activator inhibitor-1 4G/4G (23%, p=0.007) polymorphism. Among acquired markers, the risk of PL was the highest in women with anti-cardiolipin antibodies (24%, p=0.0001), followed by anti-annexin V antibodies (23%, p=0.0009) and lupus anticoagulants (8%, p=0.02). Thrombophilia, inherited and acquired, is an important contributing factor in unexplained RPL and should be screened in the order of its prevalence. Copyright © 2015 Elsevier Inc. All rights reserved.

Classification of stillbirths is an ongoing dilemma.

PubMed

Nappi, Luigi; Trezza, Federica; Bufo, Pantaleo; Riezzo, Irene; Turillazzi, Emanuela; Borghi, Chiara; Bonaccorsi, Gloria; Scutiero, Gennaro; Fineschi, Vittorio; Greco, Pantaleo

2016-10-01

To compare different classification systems in a cohort of stillbirths undergoing a comprehensive workup; to establish whether a particular classification system is most suitable and useful in determining cause of death, purporting the lowest percentage of unexplained death. Cases of stillbirth at gestational age 22-41 weeks occurring at the Department of Gynecology and Obstetrics of Foggia University during a 4 year period were collected. The World Health Organization (WHO) diagnosis of stillbirth was used. All the data collection was based on the recommendations of an Italian diagnostic workup for stillbirth. Two expert obstetricians reviewed all cases and classified causes according to five classification systems. Relevant Condition at Death (ReCoDe) and Causes Of Death and Associated Conditions (CODAC) classification systems performed best in retaining information. The ReCoDe system provided the lowest rate of unexplained stillbirth (14%) compared to de Galan-Roosen (16%), CODAC (16%), Tulip (18%), Wigglesworth (62%). Classification of stillbirth is influenced by the multiplicity of possible causes and factors related to fetal death. Fetal autopsy, placental histology and cytogenetic analysis are strongly recommended to have a complete diagnostic evaluation. Commonly employed classification systems performed differently in our experience, the most satisfactory being the ReCoDe. Given the rate of "unexplained" cases, none can be considered optimal and further efforts are necessary to work out a clinically useful system.

Detection of cardiovascular shunts by transesophageal echocardiography in patients with pulmonary hypertension of unexplained cause.

PubMed

Chen, W J; Chen, J J; Lin, S C; Hwang, J J; Lien, W P

1995-01-01

The purpose of this study was to validate the usefulness of transesophageal echocardiography (TEE) in the assessment of cardiovascular shunts in patients with pulmonary hypertension (PH) of unexplained cause. Twenty-four adult patients, 16 women, 8 men; 15 to 70 years of age, with PH of unexplained cause were studied. All were examined by transthoracic echocardiography (TTE) and TEE. TTE showed the ventricular septal defect in two patients, muscular type in one and perimembranous type in the other. TEE showed the atrial septal defect in eight patients (secundum type in six and primum type in the remaining) and the patient ductus arteriosus in six patients, which were not seen by TTE. The ventricular septal defect shown by TTE was also found by TEE. Patients with a ventricular septal defect were also associated with a patient ductus arteriosus. Among 14 patients with cardiovascular lesions, nine patients displayed a pattern of bidirectional shunt, four a pure left-to-right shunt, and the remaining one a pure right-to-left shunt. All of the cardiovascular defects could be confirmed by passage of the catheter across the defect at cardiac catheterization. In light of PH, transthoracic identification of cardiovascular shunts is difficult because of the low velocity across the defect. In this study, we found that TEE was superior to TTE in detecting and localizing cardiovascular malformations in patient with PH.

Polymorphisms in the methylene tetrahydrofolate reductase and methionine synthase reductase genes and their correlation with unexplained recurrent spontaneous abortion susceptibility.

PubMed

Zhu, L

2015-07-28

We aimed to explore the correlation between unexplained recurrent spontaneous abortion and polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes. A case control study was conducted in 118 patients with unexplained recurrent spontaneous abortion (abortion group) and 174 healthy women (control group). The genetic material was extracted from the oral mucosal epithelial cells obtained from all subjects. The samples were subjected to fluorescence quantitative PCR to detect the single nucleotide polymorphisms (SNPs) in the MTHFR (C677T and A1298C) and MTRR (A66G) gene loci. The distribution frequency (18/118, 15.3%) of the MTHFR 677TT genotype was significantly higher in the abortion group (χ2 = 11.006, P = 0.004) than in the control group (2/174, 1.1%); on the other hand, the distribution frequency of the MTHFR A1298C genotype did not significantly differ between the abortion and control groups (χ(2) = 0.441, P = 0.507). The distribution frequency of the MTRR A66G genotype was also significantly higher in the abortion group (14/118, 11.9%; χ(2) = 10.503, P = 0.005) than in the control group (8/174, 4.6%). The MTHFR C677T and MTRR A66G polymorphisms are significantly correlated with the occurrence of spontaneous abortion.

Correlation between three-dimensional power Doppler and morphometric measurement of endometrial vascularity at the time of embryo implantation in women with unexplained recurrent miscarriage.

PubMed

Chen, Xiaoyan; Saravelos, Sotirios H; Liu, Yingyu; Huang, Jin; Wang, Chi Chiu; Li, Tin Chiu

2017-06-01

Power Doppler in combination with three-dimensional (3D-PD) ultrasonography has been used as a noninvasive tool to evaluate the vascularity. However, it is unclear whether 3D-PD can accurately reflect endometrial vascularization and replace the invasive endometrial biopsy. This study aims to investigate the correlation between 3D-PD and micro vessel morphometric measurement of endometrial vascularity. Twenty-five women with unexplained recurrent miscarriage were recruited for 3D-PD and endometrial biopsy on precisely day LH + 7. Immunohistochemistry using vWF was employed to identify micro vessels in endometrial biopsy specimens followed by the use of morphometric technique to measure the mean vessel diameter and volume fractions. The vascularization index (VI), flow index (FI) and vascularization flow index (VFI) assessed by 3D-PD were calculated for both the endometrial and sub-endometrial regions. There were no significant correlations between any of the ultrasonographic measurements (endometrial thickness, endometrial volume, endometrial VI/FI/VFI, sub-endometrial volume, sub-endometrial VI/FI/VFI) and morphometric features (number of micro vessel, mean diameter of micro vessel and volume fraction measurement of vessel). This study indicates that endometrial vascularity assessed by 3D-PD could not be used to reflect changes in micro vessels of the endometrium at the time of embryo implantation in women with unexplained recurrent miscarriage.

Recurrent unexplained palpitations (RUP) study comparison of implantable loop recorder versus conventional diagnostic strategy.

PubMed

Giada, Franco; Gulizia, Michele; Francese, Maura; Croci, Francesco; Santangelo, Lucio; Santomauro, Maurizio; Occhetta, Eraldo; Menozzi, Carlo; Raviele, Antonio

2007-05-15

The aim of the study was to compare the diagnostic yield and the costs of implantable loop recorder (ILR) with those of the conventional strategy in patients with unexplained palpitations. In patients with unexplained palpitations, especially in those with infrequent symptoms, the conventional strategy, including short-term ambulatory electrocardiogram (ECG) monitoring and electrophysiological study, sometimes fails to establish a diagnosis. We studied 50 patients with infrequent (< or =1 episode/month), sustained (>1 min) palpitations. Before enrollment, patients had a negative initial evaluation, including history, physical examination, and ECG. Patients were randomized either to conventional strategy (24-h Holter recording, a 4-week period of ambulatory ECG monitoring with an external recorder, and electrophysiological study) (n = 24) or to ILR implantation with 1-year monitoring (n = 26). Hospital costs of the 2 strategies were calculated. A diagnosis was obtained in 5 patients in the conventional strategy group, and in 19 subjects in the ILR group (21% vs. 73%, p < 0.001). Despite the higher initial cost, the cost per diagnosis in the ILR group was lower than in the conventional strategy group (euro 3,056 +/- euro 363 vs. euro 6,768 +/- euro 6,672, p = 0.012). In subjects without severe heart disease and with infrequent palpitations, ILR is a safe and more cost-effective diagnostic approach than conventional strategy.

Body composition: A predictive factor of cycle fecundity

PubMed Central

Kayatas, Semra; Api, Murat; Kurt, Didar; Eroglu, Mustafa; Arınkan, Sevcan Arzu

2014-01-01

Objective To study the effect of body composition on reproduction in women with unexplained infertility treated with a controlled ovarian hyperstimulation and intrauterine insemination programme. Methods This prospective observational study was conducted on 308 unexplained infertile women who were scheduled for a controlled ovarian hyperstimulation and intrauterine insemination programme and were grouped as pregnant and non-pregnant. Anthropometric measurements were performed using TANITA-420MA before the treatment cycle. Body composition was determined using a bioelectrical impedance analysis system. Results Body fat mass was significantly lower in pregnant women than in non-pregnant women (15.61±3.65 vs.18.78±5.97, respectively) (p=0.01). In a multiple regression analysis, body fat mass proved to have a stronger association with fecundity than the percentage of body fat, body mass index, or the waist/hip ratio (standardized regression coefficient≥0.277, t-value≥2.537; p<0.05). The cut-off value of fat mass, which was evaluated using the receiver operating characteristics curve, was 16.65 with a sensitivity of 61.8% and a specificity of 70.2%. Below this cut-off value, the odds of the pregnancy occurrence was found to be 2.5 times more likely. Conclusion Body fat mass can be predictive for pregnancy in patients with unexplained infertility scheduled for a controlled ovarian hyperstimulation and intrauterine insemination programme. PMID:25045631

Hydatidiform mole

MedlinePlus

... hands , or unexplained weight loss Symptoms similar to preeclampsia that occur in the first trimester or early ... always a sign of a hydatidiform mole, because preeclampsia is extremely rare this early in a normal ...

Age and disability: explaining the wage differential.

PubMed

Gannon, Brenda; Munley, Margaret

2009-07-01

This paper estimates the level of explained and unexplained factors that contribute to the wage gap between workers with and without disabilities, providing benchmark estimates for Ireland. It separates out the confounding impact of productivity differences between disabled and non-disabled, by comparing wage differentials across three groups, disabled with limitations, disabled without limitations and non-disabled. Furthermore, data are analysed for the years 1995-2001 and two sub-samples pre and post 1998 allow us to decompose wage differentials before and after the Employment Equality Act 1998. Results are comparable to those of the UK and the unexplained component (upper bound of discrimination) is lower once we control for productivity differences. The lower bound level depends on the contribution of unobserved effects and the validity of the selection component in the decomposition model.

Stress and fertility: some modalities of investigation and treatment in couples with unexplained infertility in Dublin.

PubMed

Harrison, R F; O'Moore, R R; O'Moore, A M

1986-01-01

The role of stress in infertility, and its treatment, is reviewed in various groups of couples labeled "unexplained infertile." A simplified profile of stress markers based upon basal prolactin estimations and psychological measurements found infertile couples more stressed than fertile controls and revealed a sub-group of women characterized as having significantly high psychological stress scores and intermittent elevations of prolactin (spikers). This group was effectively treated with a combination of clomiphene citrate and bromocriptine. However, attention to the failures as well as the successes suggests optimum benefit to the patients might involve not only provision of a good clinic ambiance and pharmacological preparations, but also relaxation therapies such as Autogenic Training, which significantly lowered psychological and biochemical stress marker scores.

Time-resolved laser-induced incandescence characterization of metal nanoparticles

NASA Astrophysics Data System (ADS)

Sipkens, T. A.; Singh, N. R.; Daun, K. J.

2017-01-01

This paper presents a comparative analysis of time-resolved laser-induced incandescence measurements of iron, silver, and molybdenum aerosols. Both the variation of peak temperature with fluence and the temperature decay curves strongly depend on the melting point and latent heat of vaporization of the nanoparticles. Recovered nanoparticle sizes are consistent with ex situ analysis, while thermal accommodation coefficients follow expected trends with gas molecular mass and structure. Nevertheless, there remain several unanswered questions and unexplained behaviors: the radiative properties of laser-energized iron nanoparticles do not match those of bulk molten iron; the absorption cross sections of molten iron and silver at the excitation laser wavelength exceed theoretical predictions; and there is an unexplained feature in the temperature decay of laser-energized molybdenum nanoparticles immediately following the laser pulse.

Imaging of a parapharyngeal hemangiopericytoma. Radioimmunoscintigraphy (SPECT) with indium-111-labeled anti-CEA antibody, and comparison to digital subtraction angiography, computed tomography, and immunohistochemistry

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

Kairemo, K.J.; Hopsu, E.V.; Melartin, E.J.

1991-01-01

A 27-year-old male patient with a parapharyngeal hemangiopericytoma was investigated radiologically with orthopantomography, computed tomography, and digital subtraction angiography before the operation. Because a malignancy was suspected, the patient was imaged with gamma camera using radiolabeled monoclonal anticarcinoembryonal antigen antibody including single photon emission computed tomography. The radioantibody accumulated strongly into the neoplasm. Tumor to background ratio was 2.2. Samples of the excised tumor were stained immunohistochemically for desmin, vimentin, muscle actin, cytokeratin, CEA (carcinoembryonic antigen), and factor VIII. They showed that the antibody uptake was of unspecific nature and not due to CEA expression in the tumor.

Neuroendocrine carcinoma of the apocrine glands of the anal sac in a dog.

PubMed

Ogawa, Bunichiro; Taniai, Eriko; Hayashi, Hitomi; Imaoka, Masako; Machida, Noboru; Mitsumori, Kunitoshi; Shibutani, Makoto

2011-07-01

A perianal subcutaneous tumor involving the anal sac developed in an 8-year-old male mixed Labrador Retriever dog. Histologically, this tumor showed typical features of the solid-type carcinoma of the apocrine glands of the anal sac. However, neoplastic cells were immunoreactive for cytokeratin 8, chromogranin A, vasoactive intestinal peptide, neuron-specific enolase, and synaptophysin, and negative for S-100 protein, α-smooth muscle actin, vimentin, glucagon, insulin, somatostatin, carcinoembryonic antigen, serotonin, and parathyroid hormone-related protein. Considering the distribution of chromogranin A-positive cells within the anal sac apocrine glands, this tumor was diagnosed as neuroendocrine carcinoma originating from the apocrine glands of the anal sac.

Primary focal T-cell lymphoma of the liver: a case report and review of the literature.

PubMed

Cerban, Razvan; Gheorghe, Liana; Becheanu, Gabriel; Serban, Valentin; Gheorghe, Cristian

2012-06-01

We present the case of a previously healthy 62 year old man who developed primary non-Hodgkin lymphoma of the liver. Biopsy confirmed that it was a diffuse large anaplastic T-cell lymphoma of an extremely rare type. The diagnosis of this type of lesions is suggested by the presence of a hepatic mass without lymphadenopathy, splenomegaly or bone marrow involvement associated with normal tumor markers (carcinoembryonic antigen, alpha-fetoprotein and CA 19-9 levels). Histological examination of tissue is essential to confirm the diagnosis. Treatment options are surgical resection and/or chemotherapy but the rate of response to treatment varies widely. Some patients can achieve prolonged remission.

Mass Spectrometry for Paper-Based Immunoassays: Toward On-Demand Diagnosis.

PubMed

Chen, Suming; Wan, Qiongqiong; Badu-Tawiah, Abraham K

2016-05-25

Current analytical methods, either point-of-care or centralized detection, are not able to meet recent demands of patient-friendly testing and increased reliability of results. Here, we describe a two-point separation on-demand diagnostic strategy based on a paper-based mass spectrometry immunoassay platform that adopts stable and cleavable ionic probes as mass reporter; these probes make possible sensitive, interruptible, storable, and restorable on-demand detection. In addition, a new touch paper spray method was developed for on-chip, sensitive, and cost-effective analyte detection. This concept is successfully demonstrated via (i) the detection of Plasmodium falciparum histidine-rich protein 2 antigen and (ii) multiplexed and simultaneous detection of cancer antigen 125 and carcinoembryonic antigen.

Association of Testosterone Levels With Anemia in Older Men

PubMed Central

Roy, Cindy N.; Snyder, Peter J.; Stephens-Shields, Alisa J.; Artz, Andrew S.; Bhasin, Shalender; Cohen, Harvey J.; Farrar, John T.; Gill, Thomas M.; Zeldow, Bret; Cella, David; Barrett-Connor, Elizabeth; Cauley, Jane A.; Crandall, Jill P.; Cunningham, Glenn R.; Ensrud, Kristine E.; Lewis, Cora E.; Matsumoto, Alvin M.; Molitch, Mark E.; Pahor, Marco; Swerdloff, Ronald S.; Cifelli, Denise; Hou, Xiaoling; Resnick, Susan M.; Walston, Jeremy D.; Anton, Stephen; Basaria, Shehzad; Diem, Susan J.; Wang, Christina; Schrier, Stanley L.; Ellenberg, Susan S.

2017-01-01

Importance In one-third of older men with anemia, no recognized cause can be found. Objective To determine if testosterone treatment of men 65 years or older with unequivocally low testosterone levels and unexplained anemia would increase their hemoglobin concentration. Design, Setting, and Participants A double-blinded, placebo-controlled trial with treatment allocation by minimization using 788 men 65 years or older who have average testosterone levels of less than 275 ng/dL. Of 788 participants, 126 were anemic (hemoglobin Š12.7 g/dL), 62 of whom had no known cause. The trial was conducted in 12 academic medical centers in the United States from June 2010 to June 2014. Interventions Testosterone gel, the dose adjusted to maintain the testosterone levels normal for young men, or placebo gel for 12 months. Main Outcomes and Measures The percent of men with unexplained anemia whose hemoglobin levels increased by 1.0 g/dL or more in response to testosterone compared with placebo. The statistical analysis was intent-to-treat by a logistic mixed effects model adjusted for balancing factors. Results The men had a mean age of 74.8 years and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30.7; 84.9% were white. Testosterone treatment resulted in a greater percentage of men with unexplained anemia whose month 12 hemoglobin levels had increased by 1.0 g/dL or more over baseline (54%) than did placebo (15%) (adjusted OR, 31.5; 95% CI, 3.7-277.8; P = .002) and a greater percentage of men who at month 12 were no longer anemic (58.3%) compared with placebo (22.2%) (adjusted OR, 17.0; 95% CI, 2.8-104.0; P = .002). Testosterone treatment also resulted in a greater percentage of men with anemia of known cause whose month 12 hemoglobin levels had increased by 1.0 g/dL or more (52%) than did placebo (19%) (adjusted OR, 8.2; 95% CI, 2.1-31.9; P = .003). Testosterone treatment resulted in a hemoglobin concentration of more than 17.5 g/dL in 6 men who had not been anemic at baseline. Conclusions and Relevance Among older men with low testosterone levels, testosterone treatment significantly increased the hemoglobin levels of those with unexplained anemia as well as those with anemia from known causes. These increases may be of clinical value, as suggested by the magnitude of the changes and the correction of anemia in most men, but the overall health benefits remain to be established. Measurement of testosterone levels might be considered in men 65 years or older who have unexplained anemia and symptoms of low testosterone levels. PMID:28241237

No evidence for mutations in NLRP7, NLRP2 or KHDC3L in women with unexplained recurrent pregnancy loss or infertility.

PubMed

Aghajanova, L; Mahadevan, S; Altmäe, S; Stavreus-Evers, A; Regan, L; Sebire, N; Dixon, P; Fisher, R A; Van den Veyver, I B

2015-01-01

Are mutations in NLRP2/7 (NACHT, LRR and PYD domains-containing protein 2/7) or KHDC3L (KH Domain Containing 3 Like) associated with recurrent pregnancy loss (RPL) or infertility? We found no evidence for mutations in NLRP2/7 or KHDC3L in unexplained RPL or infertility. Mutations in NLRP7 and KHDC3L are known to cause biparental hydatidiform moles (BiHMs), a rare form of pregnancy loss. NLRP2, while not associated with the BiHM pathology, is known to cause recurrent Beckwith Weidemann Syndrome (BWS). Ninety-four patients with well characterized, unexplained infertility were recruited over a 9-year period from three IVF clinics in Sweden. Blood samples from 24 patients with 3 or more consecutive miscarriages of unknown etiology were provided by the Recurrent Miscarriage Clinic at St Mary's Hospital, London, UK. Patients were recruited into both cohorts following extensive clinical studies. Genomic DNA was isolated from peripheral blood and subject to Sanger sequencing of NLRP2, NLRP7 and KHDC3L. Sequence electropherograms were analyzed by Sequencher v5.0 software and variants compared with those observed in the 1000 Genomes, single nucleotide polymorphism database (dbSNP) and HapMap databases. Functional effects of non-synonymous variants were predicted using Polyphen-2 and sorting intolerant from tolerant (SIFT). No disease-causing mutations were identified in NLRP2, NLRP7 and KHDC3L in our cohorts of unexplained infertility and RPL. Due to the limited patient size, it is difficult to conclude if the low frequency single nucleotide polymorphisms observed in the present study are causative of the phenotype. The design of the present study therefore is only capable of detecting highly penetrant mutations. The present study supports the hypothesis that mutations in NLRP7 and KHDC3L are specific for the BiHM phenotype and do not play a role in other adverse reproductive outcomes. Furthermore, to date, mutations in NLRP2 have only been associated with the imprinting disorder BWS in offspring and there is no evidence for a role in molar pregnancies, RPL or unexplained infertility. This study was funded by the following sources: Estonian Ministry of Education and Research (Grant SF0180044s09), Enterprise Estonia (Grant EU30020); Mentored Resident research project (Department of Obstetrics and Gynecology, Baylor College of Medicine); Imperial NIHR Biomedical Research Centre; Grant Number C06RR029965 from the National Center for Research Resources (NCCR; NIH). No competing interests declared. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Swollen lymph nodes

MedlinePlus

... lymph nodes, including: Seizure medicines such as phenytoin Typhoid immunization Which lymph nodes are swollen depends on ... hard, irregular, or fixed in place. You have fever, night sweats, or unexplained weight loss. Any node ...

Infertility Fact Sheet

MedlinePlus

... Couples with unexplained infertility What is assisted reproductive technology (ART)? Assisted reproductive technology (ART) is a group ... the woman's body. How often is assisted reproductive technology (ART) successful? Success rates vary and depend on ...

Vulvovaginitis - overview

MedlinePlus

... all age groups, but is most common in young girls before puberty, especially girls with poor genital hygiene. ... longer recovery. Sexual abuse should be considered in young girls with unusual infections and repeated episodes of unexplained ...

Genomic Analyses of Patients With Unexplained Early-Onset Scoliosis.

PubMed

Gao, Xiaochong; Gotway, Garrett; Rathjen, Karl; Johnston, Charles; Sparagana, Steven; Wise, Carol A

2014-09-01

To test for rare genetic mutations, a cohort of patients with unexplained early-onset scoliosis (EOS) was screened using high-density microarray genotyping. A cohort of patients with adolescent idiopathic scoliosis (AIS) was similarly screened and the results were compared. Patients with scoliosis in infancy or early childhood (EOS) are at high risk for progressive deformity and associated problems including respiratory compromise. Early-onset scoliosis is frequently associated with genetic disorders but many patients present with nonspecific clinical features and without an associated diagnosis. The authors hypothesized that EOS in these patients may be caused by rare genetic mutations detectable by next-generation genomic methods. The researchers identified 24 patients with unexplained EOS from pediatric orthopedic clinics. They genotyped them, along with 39 connecting family members, using the Illumina OmniExpress-12, version 1.0 beadchip. Resulting genotypes were analyzed for chromosomal changes, specifically copy number variation and absence of heterozygosity. They screened 482 adolescent idiopathic scoliosis (AIS) patients and 744 healthy controls, who were similarly genotyped with the same beadchip, for chromosomal changes identified in the EOS cohort. Copy number variation and absence of heterozygosity analyses revealed a genetic diagnosis of chromosome 15q24 microdeletion syndrome in 1 patient and maternal uniparental disomy of chromosome 14 in a second one. Prior genetic testing and clinical evaluations had been negative in both cases. A large novel chromosome 10 deletion was likely causal in a third EOS patient. These mutations identified in the EOS patients were absent in AIS patients and controls, and thus were not associated with AIS or found in asymptomatic individuals. These data underscore the usefulness of updated genetic evaluations including high-density microarray-based genotyping and other next-generation methods in patients with unexplained EOS, even when prior genetic studies were negative. These data also suggest the intriguing possibility that other mutations detectable by whole genome sequencing, as well as epigenetic effects, await discovery in the EOS population. Copyright © 2014 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Disturbed EEG sleep, paranoid cognition and somatic symptoms identify veterans with post-traumatic stress disorder

PubMed Central

Rothman, Lorne; Kleinman, Robert; Rhind, Shawn G.; Richardson, J. Donald

2016-01-01

Background Chronic post-traumatic stress disorder (PTSD) behavioural symptoms and medically unexplainable somatic symptoms are reported to occur following the stressful experience of military combatants in war zones. Aims To determine the contribution of disordered EEG sleep physiology in those military combatants who have unexplainable physical symptoms and PTSD behavioural difficulties following war-zone exposure. Method This case-controlled study compared 59 veterans with chronic sleep disturbance with 39 veterans with DSM-IV and clinician-administered PTSD Scale diagnosed PTSD who were unresponsive to pharmacological and psychological treatments. All had standardised EEG polysomnography, computerised sleep EEG cyclical alternating pattern (CAP) as a measure of sleep stability, self-ratings of combat exposure, paranoid cognition and hostility subscales of Symptom Checklist-90, Beck Depression Inventory and the Wahler Physical Symptom Inventory. Statistical group comparisons employed linear models, logistic regression and chi-square automatic interaction detection (CHAID)-like decision trees. Results Veterans with PTSD were more likely than those without PTSD to show disturbances in non-rapid eye movement (REM) and REM sleep including delayed sleep onset, less efficient EEG sleep, less stage 4 (deep) non-REM sleep, reduced REM and delayed onset to REM. There were no group differences in the prevalence of obstructive sleep apnoeas/hypopnoeas and periodic leg movements, but sleep-disturbed, non-PTSD military had more EEG CAP sleep instability. Rank order determinants for the diagnosis of PTSD comprise paranoid thinking, onset to REM sleep, combat history and somatic symptoms. Decision-tree analysis showed that a specific military event (combat), delayed onset to REM sleep, paranoid thinking and medically unexplainable somatic pain and fatigue characterise chronic PTSD. More PTSD veterans reported domestic and social misbehaviour. Conclusions Military combat, disturbed REM/non-REM EEG sleep, paranoid ideation and medically unexplained chronic musculoskeletal pain and fatigue are key factors in determining PTSD disability following war-zone exposure. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:29018561

CMR assessment of the left ventricle apical morphology in subjects with unexplainable giant T-wave inversion and without apical wall thickness ≥15 mm.

PubMed

Wu, Bailin; Lu, Minjie; Zhang, Yan; Song, Bo; Ling, Jian; Huang, Jinghan; Yin, Gang; Lan, Tian; Dai, Linlin; Song, Lei; Jiang, Yong; Wang, Hao; He, Zuoxiang; Lee, Jongmin; Yong, Hwan Seok; Patel, Mehul B; Zhao, Shihua

2017-02-01

Patients with unexplainable giant T-wave inversion in the precordial leads and apical wall thickness <15 mm have been reported. These patients cannot be diagnosed as apical hypertrophic cardiomyopathy (AHCM) according to the current criteria. The objective of this study was to evaluate the apical morphological features of this type of patients using cardiac magnetic resonance. Institutional ethics approval and written informed consent were obtained. A total of 60 subjects with unexplainable giant T-wave inversion and 76 healthy volunteers were prospectively enrolled in the study. The segmented left ventricular (LV) wall thickness was measured according to the American Heart Association 17-segmented model. The apical angle (apA) as well as the regional variations in LV wall thickness was analysed. Considerable variation in LV wall thickness in normals was observed with progressive thinning from the base to apex (male and female, P < 0.01). The apical thickness of subjects with giant T-wave inversion was 8.10 ± 1.67 mm in male, which is thicker than that of controls (4.14 ± 1.17 mm, P < 0.01). In female, the apical thickness was also significantly different from controls (5.85 ± 2.16 vs. 2.99 ± 0.65 mm, P < 0.01). Compared with normals, the apA decreased significantly in male (87.44 ± 13.86 vs.115.03 ± 9.90°, P < 0.01) and female (90.69 ± 8.84 vs. 110.07 ± 13.58°, P < 0.01) subjects, respectively. Although the absolute thickness of apical wall was below the current diagnostic criteria of AHCM, the apical morphological features of subjects with unexplainable giant T-wave inversion were significantly different from normals. Whether these subjects should be included into a preclinical scope of AHCM needs further investigations. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

[Application of single nucleotide polymorphism-microarray and target gene sequencing in the study of genetic etiology of children with unexplained intellectual disability or developmental delay].

PubMed

Gao, Z J; Jiang, Q; Cheng, D Z; Yan, X X; Chen, Q; Xu, K M

2016-10-02

Objective: To evaluate the application of single nucleotide polymorphism (SNP)-microarray and target gene sequencing technology in the clinical molecular genetic diagnosis of unexplained intellectual disability(ID) or developmental delay (DD). Method: Patients with ID or DD were recruited in the Department of Neurology, Affiliated Children's Hospital of Capital Institute of Pediatrics between September 2015 and February 2016. The intellectual assessment of the patients was performed using 0-6-year-old pediatric examination table of neuropsychological development or Wechsler intelligence scale (>6 years). Patients with a DQ less than 49 or IQ less than 51 were included in this study. The patients were scanned by SNP-array for detection of genomic copy number variations (CNV), and the revealed genomic imbalance was confirmed by quantitative real time-PCR. Candidate gene mutation screening was carried out by target gene sequencing technology.Causal mutations or likely pathogenic variants were verified by polymerase chain reaction and direct sequencing. Result: There were 15 children with ID or DD enrolled, 9 males and 6 females. The age of these patients was 7 months-16 years and 9 months. SNP-array revealed that two of the 15 patients had genomic CNV. Both CNV were de novo micro deletions, one involved 11q24.1q25 and the other micro deletion located on 21q22.2q22.3. Both micro deletions were proved to have a clinical significance due to their association with ID, brain DD, unusual faces etc. by querying Decipher database. Thirteen patients with negative findings in SNP-array were consequently examined with target gene sequencing technology, genotype-phenotype correlation analysis and genetic analysis. Five patients were diagnosed with monogenic disorder, two were diagnosed with suspected genetic disorder and six were still negative. Conclusion: Sequential use of SNP-array and target gene sequencing technology can significantly increase the molecular genetic etiologic diagnosis rate of the patients with unexplained ID or DD. Combined use of these technologies can serve as a useful examinational method in assisting differential diagnosis of children with unexplained ID or DD.

MMP13 is potentially a new tumor marker for breast cancer diagnosis.

PubMed

Chang, Hui-Jen; Yang, Ming-Je; Yang, Yu-Hsiang; Hou, Ming-Feng; Hsueh, Er-Jung; Lin, Shiu-Ru

2009-11-01

Within the past decade, the incidence of breast cancer in Taiwan has been rising year after year. Breast cancer is the first most prevalent cancer and the fourth leading cause of cancer-related deaths among women in Taiwan. The early stage of breast cancer not only have a wider range of therapeutic options, but also obtain a higher success rate of therapy than those with advanced breast cancer. A test for tumor markers is the most convenient method to screen for breast cancer. However, the tumor markers currently available for breast cancer detection include carcinoembryonic antigen (CEA), carbohydrate antigen 15.3 (CA15.3), and carbohydrate antigen 27.29 (CA27.29) exhibited certain limitations. Poor sensitivity and specificity greatly limits the diagnostic accuracy of these markers. This study aims to identify potential tumor markers for breast cancer. At first, we analyzed genes expression in infiltrating lobular carcinoma, metaplastic carcinoma, and infiltrating ductal carcinoma of paired specimens (tumor and normal tissue) from breast cancer patients using microarray technology. We selected 371 overexpressed genes in all of the three cell type. In advanced breast cancer tissue, we detected four genes MMP13, CAMP, COL10A1 and FLJ25416 from 25 overexpressed genes which encoded secretion protein more specifically for breast cancer than other genes. After validation with 15 pairs of breast cancer tissue and paired to normal adjacent tissues by membrane array and quantitative RT-PCR, we found MMP13 was 100% overexpressed and confirmed to be a secreted protein by Western blot analysis of the cell culture medium. The expression level of MMP13 was also measured by immunohistochemical staining. We suggest that MMP13 is a highly overexpressed secretion protein in breast cancer tissue. It has potential to be a new tumor marker for breast cancer diagnosis.

Brief resolved unexplained event - BRUE

MedlinePlus

... Allergic reactions A brain, nerve, or muscle disorder Child abuse Certain uncommon genetic disorders A specific cause of ... by a trained provider was needed Signs of child abuse If risk factors are present, testing that may ...

Diagnosis of antenatal Bartter syndrome.

PubMed

Narayan, R; Peres, M; Kesby, G

2016-01-01

Bartter syndrome is a rare heterogeneous group of autosomal-recessive salt-losing renal tubular disorders that can present in fetal life (antenatal Bartter syndrome; ABS) as "unexplained" early-onset polyhydramnios, often associated with growth restriction. Prenatal diagnosis of the condition involves assessment of amniotic fluid biochemistry in a setting of polyuric polyhydramnios; with elevated chloride levels considered a consistent and diagnostic finding. Other amniotic fluid biochemical markers have been described, notably increased aldosterone levels, and low total protein levels. NOVEL INSIGHT: Antenatal Bartter syndrome is a heterogeneous group of renal disorders. While certain biochemical features in amniotic fluid might heighten suspicion, final diagnosis can only be made in the postnatal setting. In the setting of unexplained severe polyhydramnios, clinicians should continue to entertain the diagnosis of antenatal Bartter Syndrome and maintain neonatal surveillance, even if amniotic fluid markers do not support the diagnosis.

Unexplained Excess of Electronlike Events from a 1-GeV Neutrino Beam

NASA Astrophysics Data System (ADS)

Aguilar-Arevalo, A. A.; Anderson, C. E.; Bazarko, A. O.; Brice, S. J.; Brown, B. C.; Bugel, L.; Cao, J.; Coney, L.; Conrad, J. M.; Cox, D. C.; Curioni, A.; Djurcic, Z.; Finley, D. A.; Fleming, B. T.; Ford, R.; Garcia, F. G.; Garvey, G. T.; Green, C.; Green, J. A.; Hart, T. L.; Hawker, E.; Imlay, R.; Johnson, R. A.; Karagiorgi, G.; Kasper, P.; Katori, T.; Kobilarcik, T.; Kourbanis, I.; Koutsoliotas, S.; Laird, E. M.; Linden, S. K.; Link, J. M.; Liu, Y.; Liu, Y.; Louis, W. C.; Mahn, K. B. M.; Marsh, W.; McGregor, G.; Metcalf, W.; Meyers, P. D.; Mills, F.; Mills, G. B.; Monroe, J.; Moore, C. D.; Nelson, R. H.; Nguyen, V. T.; Nienaber, P.; Nowak, J. A.; Ouedraogo, S.; Patterson, R. B.; Perevalov, D.; Polly, C. C.; Prebys, E.; Raaf, J. L.; Ray, H.; Roe, B. P.; Russell, A. D.; Sandberg, V.; Schirato, R.; Schmitz, D.; Shaevitz, M. H.; Shoemaker, F. C.; Smith, D.; Sodeberg, M.; Sorel, M.; Spentzouris, P.; Stancu, I.; Stefanski, R. J.; Sung, M.; Tanaka, H. A.; Tayloe, R.; Tzanov, M.; van de Water, R.; Wascko, M. O.; White, D. H.; Wilking, M. J.; Yang, H. J.; Zeller, G. P.; Zimmerman, E. D.

2009-03-01

The MiniBooNE Collaboration observes unexplained electronlike events in the reconstructed neutrino energy range from 200 to 475 MeV. With 6.46×1020 protons on target, 544 electronlike events are observed in this energy range, compared to an expectation of 415.2±43.4 events, corresponding to an excess of 128.8±20.4±38.3 events. The shape of the excess in several kinematic variables is consistent with being due to either νe and ν¯e charged-current scattering or νμ neutral-current scattering with a photon in the final state. No significant excess of events is observed in the reconstructed neutrino energy range from 475 to 1250 MeV, where 408 events are observed compared to an expectation of 385.9±35.7 events.

Clinical assessment of the male fertility

PubMed Central

Khatun, Amena; Rahman, Md Saidur

2018-01-01

The evaluation of infertility in males consists of physical examination and semen analyses. Standardized semen analyses depend on the descriptive analysis of sperm motility, morphology, and concentration, with a threshold level that must be surpassed to be considered a fertile spermatozoon. Nonetheless, these conventional parameters are not satisfactory for clinicians since 25% of infertility cases worldwide remain unexplained. Therefore, newer tests methods have been established to investigate sperm physiology and functions by monitoring characteristics such as motility, capacitation, the acrosome reaction, reactive oxygen species, sperm DNA damage, chromatin structure, zona pellucida binding, and sperm-oocyte fusion. After the introduction of intracytoplasmic sperm injection technique, sperm maturity, morphology, and aneuploidy conditions have gotten more attention for investigating unexplained male infertility. In the present article, recent advancements in research regarding the utilization of male fertility prediction tests and their role and accuracy are reviewed. PMID:29564308

Why Bioethics Should Be Concerned With Medically Unexplained Symptoms.

PubMed

O'Leary, Diane

2018-05-01

Biomedical diagnostic science is a great deal less successful than we've been willing to acknowledge in bioethics, and this fact has far-reaching ethical implications. In this article I consider the surprising prevalence of medically unexplained symptoms, and the term's ambiguous meaning. Then I frame central questions that remain answered in this context with respect to informed consent, autonomy, and truth-telling. Finally, I show that while considerable attention in this area is given to making sure not to provide biological care to patients without a need, comparatively little is given to the competing, ethically central task of making sure never to obstruct access to biological care for those with diagnostically confusing biological conditions. I suggest this problem arises from confusion about the philosophical value of vagueness when it comes to the line between biological and psychosocial needs.

Clinical value of jointly detection serum lactate dehydrogenase/pleural fluid adenosine deaminase and pleural fluid carcinoembryonic antigen in the identification of malignant pleural effusion.

PubMed

Zhang, Fan; Hu, Lijuan; Wang, Junjun; Chen, Jian; Chen, Jie; Wang, Yumin

2017-09-01

Limited data are available for the diagnostic value, and for the diagnostic sensitivity and specificity of joint detection of serum lactate dehydrogenase (sLDH)/pleural fluid adenosine deaminase (pADA) and pleural fluid carcinoembryonic antigen (pCEA) in malignant pleural effusion (MPE). We collected 987 pleural effusion specimens (of which 318 were malignant pleural effusion, 374 were tubercular pleural effusion, and 295 were parapneumonic effusion specimens) from the First Affiliated Hospital of Wenzhou Medical University from July 2012 to March 2016. The pADA, sLDH, pleural fluid LDH (pLDH), serum C-reactive protein (sCRP), pleural fluid protein, pCEA, white blood cell (WBC), and red blood cell (RBC) were analyzed, and the clinical data of each group were collected for statistical analysis. The level of sLDH/pADA, pCEA, and RBC from the MPE group was markedly higher than the tuberculosis pleural effusion (TB) group (Mann-Whitney U=28422.000, 9278.000, 30518, P=.000, .000, .000) and the parapneumonic pleural fluid group (Mann-Whitney U=5972.500, 7113.000, 36750.500, P=.000, .000, .000). The receiver operating characteristic curve ROC showed that the area under the ROC curve (AUC) (=0.924, 0.841) of pCEA and sLDH/pADA (cutoff=4.9, 10.6) were significantly higher than other markers for the diagnosis of MPE. Thus, joint detection of pCEA and sLDH/pADA suggested that the sensitivity, specificity, and AUC was 0.94, 81.70, and 94.32 at the cutoff 0.16 and diagnostic performance was higher than pCEA or sLDH/pADA. Joint detection of sLDH/pADA and pCEA can be used as a good indicator for the identification of benign and MPE with higher sensitivity and specificity than pCEA or sLDH/pADA. © 2016 Wiley Periodicals, Inc.

Prognostic value of carcinoembryonic antigen level in patients with colorectal cancer liver metastasis treated with percutaneous microwave ablation under ultrasound guidance.

PubMed

Peng, Shaoyong; Huang, Pinzhu; Yu, Huichuan; Wen, Yanlin; Luo, Yanxin; Wang, Xiaolin; Zhou, Jiaming; Qin, Si; Li, Tuoyang; Chen, Yao; Liu, Guangjian; Huang, Meijin

2018-03-01

Thermal ablation is an alternative treatment for colorectal cancer liver metastasis (CRLM). However, prognostic factors in patients with CRLM who have undergone microwave ablation (MWA) have not been clearly defined. Therefore, this study aimed to analyze the risk factors associated with early recurrence in patients with CRLM treated with MWA.Herein, we retrospectively analyzed data for 140 patients with CRLM who underwent MWA from 2013 to 2015 in our institution. Patients were grouped by median pretreatment carcinoembryonic antigen (CEA) level into the high CEA level (>3.7 ng/mL) group and low CEA level (≤3.7 ng/mL) group. Variables that might affect overall survival were subjected to univariable and multivariable Cox regression analysis.Our results showed a median progression-free survival (PFS) and median liver progression-free survival (LPFS) of 9 and 11.5 months, respectively, for the 99 CRLM patients analyzed. Both the median PFS duration (7.5 vs. 12.0 months; hazard ratio [HR]: 1.852; 95% confidence interval [CI]: 1.131-3.034; P = .014) and LPFS duration (7.5 vs 14.0 months; HR: 2.117; 95% CI: 1.247-3.593; P = .005) were significantly shorter in the high CEA level group than in the low level group. In multivariable analysis, high CEA level, >3 tumors, and positive node status for the primary tumor were independent factors for PFS, with corrected HRs of 2.11 (95% CI: 1.257-3.555; P = .005), 2.450 (95% CI: 1.420-4.226; P = .001), and 2.265 (95% CI: 1.304-3.935; P = .004), respectively. However, age, tumor size, regional lymph node were not associated with LPFS.CEA level could be a valuable prognostic factor for early recurrence in patients with CRLM after MWA irrespective of the presence of early local recurrence in the liver or disease progression.

The carcinoembryonic antigen IgV-like N domain plays a critical role in the implantation of metastatic tumor cells.

PubMed

Abdul-Wahid, Aws; Huang, Eric H-B; Cydzik, Marzena; Bolewska-Pedyczak, Eleonora; Gariépy, Jean

2014-03-01

The human carcinoembryonic antigen (CEA) is a cell adhesion molecule involved in both homotypic and heterotypic interactions. The aberrant overexpression of CEA on adenocarcinoma cells correlates with their increased metastatic potential. Yet, the mechanism(s) by which its adhesive properties can lead to the implantation of circulating tumor cells and expansion of metastatic foci remains to be established. In this study, we demonstrate that the IgV-like N terminal domain of CEA directly participates in the implantation of cancer cells through its homotypic and heterotypic binding properties. Specifically, we determined that the recombinant N terminal domain of CEA directly binds to fibronectin (Fn) with a dissociation constant in the nanomolar range (K(D) 16 ± 3 nM) and interacts with itself (K(D) 100 ± 17 nM) and more tightly to the IgC-like A(3) domain (K(D) 18 ± 3 nM). Disruption of these molecular associations through the addition of antibodies specific to the CEA N or A(3)B(3) domains, or by adding soluble recombinant forms of the CEA N, A(3) or A(3)B(3) domains or a peptide corresponding to residues 108-115 of CEA resulted in the inhibition of CEA-mediated intercellular aggregation and adherence events in vitro. Finally, pretreating CEA-expressing murine colonic carcinoma cells (MC38.CEA) with rCEA N, A3 or A(3)B(3) modules blocked their implantation and the establishment of tumor foci in vivo. Together, these results suggest a new mechanistic insight into how the CEA IgV-like N domain participates in cellular events that can have a macroscopic impact in terms of cancer progression and metastasis. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Development of new multivalent-bispecific agents for pretargeting tumor localization and therapy.

PubMed

Rossi, Edmund A; Sharkey, Robert M; McBride, William; Karacay, Habibe; Zeng, Li; Hansen, Hans J; Goldenberg, David M; Chang, Chien-Hsing

2003-09-01

Two bispecific diabodies (BS1.5 and BS1.5H) and two bispecific trivalent proteins (BS6 and BS8) were produced and tested as potential agents for pretargeted delivery of radiolabeled bivalent haptens to tumors expressing carcinoembryonic antigen. Each of the four proteins was expressed in Escherichia coli and purified from the soluble fraction. BS1.5 and BS1.5H (a humanized version of BS1.5) were evaluated in the GW-39 human colonic tumor-nude mouse model using a di-HSG-1,4,7,10-tetra-azacyclododecane-N,N',N" N"'-tetraacetic acid peptide (IMP-241) radiolabeled with (111)In. The biodistribution and T/NT ratios were compared with those of hMN-14 x m679 (Fab' x Fab') prepared chemically. In animals, both BS1.5 and BS1.5H cleared more rapidly than hMN-14 x m679 and showed tumor to nontumor ratios far superior to those of hMN-14 x m679. For example, with BS1.5 injected 8 h before (111)In-IMP-241, the tumor uptake of (111)In was 10.3 +/- 2.7 and 6.3 +/- 2.2% ID/g at 3 and 24 h, respectively, with the tumor to blood ratios being 167 +/- 35 at 3 h and 631 +/- 231 at 24 h. In comparison, the tumor to blood ratios of (111)In observed for hMN-14 x m679 given 24 h earlier were 8 +/- 2 at 3 h and 16 +/- 3 at 24 h. These results indicate that BS1.5 and BS1.5H are promising candidates for use in a variety of pretargeting applications, including tumor therapy with radionuclides and drugs. BS6 and BS8 may be even more attractive because of their potential to achieve higher levels of tumor uptake because of divalent carcinoembryonic antigen binding.

Imaging of colorectal carcinoma with radiolabeled antibodies.

PubMed

Goldenberg, D M; Goldenberg, H; Sharkey, R M; Lee, R E; Higgenbotham-Ford, E; Horowitz, J A; Hall, T C; Pinsky, C M; Hansen, H J

1989-10-01

Colorectal cancer has been the tumor type most frequently studied with radiolabeled antibodies. Among the various antibodies, a majority of patients with colorectal cancer have received xenogeneic polyclonal or monoclonal antibodies against carcino-embryonic antigen. This review summarizes the current status of colorectal cancer imaging with radiolabeled antibodies, ie, radioimmunodetection (RAID), and examines the published studies involving carcinoembryonic antigen (CEA) antibodies and 17-1A, 19-9, and B72.3, and other monoclonal antibodies. In order to better address the issue of the current and future clinical usefulness of this emerging technology, particular attention is given to the protocols, methods, and results of the published studies. Despite differences in study parameters, antibodies and forms, labels, administration routes and doses, and scanning instruments and methods, it has been found that (1) almost no adverse reactions have been evident; (2) antibody fragments are preferred over whole immunoglobulin G reagents because they achieve higher tumor-to-background ratios earlier, thus reducing or precluding the need for dual-isotope subtraction methods or long delays before imaging; (3) use of antibody fragments, including the monovalent Fab' form, permits imaging with short-lived radionuclides of excellent photon properties, such as 123I and 99mTc; (4) circulating antigens against which the imaging antibody is directed can complex with the injected antibody, but such complexes have not prevented successful RAID; (5) patients with high serum titers of the appropriate antigen target usually have higher rates of positive RAID; (6) patients who are seronegative for the tumor antigen being studied can have positive RAID findings, which can represent the detection of occult lesions; (7) single photon emission computed tomography appears to provide better image resolution than planar scanning; (8) regardless of the sensitivity reported in any particular study, almost all investigators have observed the disclosure of occult neoplasms by RAID; and (9) RAID, a more functional test of usually high specificity, can complement other radiological methods, such as computed tomography scans, which are limited to structural information.

Serum carcinoembryonic antigen levels before initial treatment are associated with EGFR mutations and EML4- ALK fusion gene in lung adenocarcinoma patients.

PubMed

Wang, Wen-Tao; Li, Yin; Ma, Jie; Chen, Xiao-Bing; Qin, Jian-Jun

2014-01-01

Epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) define specific molecular subsets of lung adenocarcinomas with distinct clinical features. Our purpose was to analyze clinical features and prognostic value of EGFR gene mutations and the EML4-ALK fusion gene in lung adenocarcinoma. EGFR gene mutations and the EML4-ALK fusion gene were detected in 92 lung adenocarcinoma patients in China. Tumor marker levels before first treatment were measured by electrochemiluminescence immunoassay. EGFR mutations were found in 40.2% (37/92) of lung adenocarcinoma patients, being identified at high frequencies in never-smokers (48.3% vs. 26.5% in smokers; P=0.040) and in patients with abnormal serum carcinoembryonic antigen (CEA) levels before the initial treatment (58.3% vs. 28.6%, P=0.004). Multivariate analysis revealed that a higher serum CEA level before the initial treatment was independently associated with EGFR gene mutations (95%CI: 1.476~11.343, P=0.007). We also identified 8 patients who harbored the EML4-ALK fusion gene (8.7%, 8/92). In concordance with previous reports, younger age was a clinical feature for these (P=0.008). Seven of the positive cases were never smokers, and no coexistence with EGFR mutation was discovered. In addition, the frequency of the EML4-ALK fusion gene among patients with a serum CEA concentration below 5 ng/ml seemed to be higher than patients with a concentration over 5 ng/ml (P=0.021). No significant difference was observed for time to progression and overall survival between EML4-ALK-positive group and EML4-ALK-negative group or between patients with and without an EGFR mutation. The serum CEA level before the initial treatment may be helpful in screening population for EGFR mutations or EML4-ALK fusion gene presence in lung adenocarcinoma patients.

Anti-idiotype antibody induced cellular immunity in mice transgenic for human carcinoembryonic antigen.

PubMed

Saha, Asim; Chatterjee, Sunil K; Foon, Kenneth A; Bhattacharya-Chatterjee, Malaya

2006-08-01

In the present study, we have analysed the detailed cellular immune mechanisms involved in tumour rejection in carcinoembryonic antigen (CEA) transgenic mice after immunization with dendritic cells (DC) pulsed with an anti-idiotype (Id) antibody, 3H1, which mimics CEA. 3H1-pulsed DC vaccinations resulted in induction of CEA specific cytotoxic T lymphocyte (CTL) responses in vitro and the rejection of CEA-transfected MC-38 murine colon carcinoma cells, C15, in vivo (Saha et al.,Cancer Res 2004; 64: 4995-5003). These CTL mediated major histocompatibility complex (MHC) class I-restricted tumour cell lysis, production of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), and expression of Fas ligand (FasL) and TNF-related apoptosis-inducing ligand (TRAIL) in response to C15 cells. CTL used perforin-, FasL-, and TRAIL-mediated death pathways to lyse C15 cells, although perforin-mediated killing was the predominant lytic mechanism in vitro. The cytokines IFN-gamma and TNF-alpha synergistically enhanced surface expression of Fas, TRAIL receptor, MHC class I and class II on C15 cells that increased the sensitivity of tumour cells to CTL lysis. CTL activity generated in 3H1-pulsed DC immunized mice was directed against an epitope defined by the idio-peptide LCD-2, derived from 3H1. In vivo lymphocyte depletion experiments demonstrated that induction of CTL response and antitumour immunity was dependent on both CD4+ and CD8+ T cells. The analysis of splenocytes of immunized mice that had rejected C15 tumour growth revealed up-regulated surface expression of memory phenotype Ly-6C and CD44 on both CD4+ and CD8+ T cells. The adoptive transfer experiments also suggested the role of both CD4+ and CD8+ T cells in this model system. Furthermore, mice that had rejected C15 tumour growth, developed tumour-specific immunological memory.

Prognostic value of carcinoembryonic antigen level in patients with colorectal cancer liver metastasis treated with percutaneous microwave ablation under ultrasound guidance

PubMed Central

Peng, Shaoyong; Huang, Pinzhu; Yu, Huichuan; Wen, Yanlin; Luo, Yanxin; Wang, Xiaolin; Zhou, Jiaming; Qin, Si; Li, Tuoyang; Chen, Yao; Liu, Guangjian; Huang, Meijin

2018-01-01

Abstract Thermal ablation is an alternative treatment for colorectal cancer liver metastasis (CRLM). However, prognostic factors in patients with CRLM who have undergone microwave ablation (MWA) have not been clearly defined. Therefore, this study aimed to analyze the risk factors associated with early recurrence in patients with CRLM treated with MWA. Herein, we retrospectively analyzed data for 140 patients with CRLM who underwent MWA from 2013 to 2015 in our institution. Patients were grouped by median pretreatment carcinoembryonic antigen (CEA) level into the high CEA level (>3.7 ng/mL) group and low CEA level (≤3.7 ng/mL) group. Variables that might affect overall survival were subjected to univariable and multivariable Cox regression analysis. Our results showed a median progression-free survival (PFS) and median liver progression-free survival (LPFS) of 9 and 11.5 months, respectively, for the 99 CRLM patients analyzed. Both the median PFS duration (7.5 vs. 12.0 months; hazard ratio [HR]: 1.852; 95% confidence interval [CI]: 1.131–3.034; P = .014) and LPFS duration (7.5 vs 14.0 months; HR: 2.117; 95% CI: 1.247–3.593; P = .005) were significantly shorter in the high CEA level group than in the low level group. In multivariable analysis, high CEA level, >3 tumors, and positive node status for the primary tumor were independent factors for PFS, with corrected HRs of 2.11 (95% CI: 1.257–3.555; P = .005), 2.450 (95% CI: 1.420–4.226; P = .001), and 2.265 (95% CI: 1.304–3.935; P = .004), respectively. However, age, tumor size, regional lymph node were not associated with LPFS. CEA level could be a valuable prognostic factor for early recurrence in patients with CRLM after MWA irrespective of the presence of early local recurrence in the liver or disease progression. PMID:29517661

Radiocurability by Targeting Tumor Necrosis Factor-{alpha} Using a Bispecific Antibody in Carcinoembryonic Antigen Transgenic Mice

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

Larbouret, Christel; Robert, Bruno; Linard, Christine

2007-11-15

Purpose: Tumor necrosis factor-{alpha} (TNF-{alpha}) enhances radiotherapy (RT) killing of tumor cells in vitro and in vivo. To overcome systemic side effects, we used a bispecific antibody (BsAb) directed against carcinoembryonic antigen (CEA) and TNF-{alpha} to target this cytokine in a CEA-expressing colon carcinoma. We report the evaluation of this strategy in immunocompetent CEA-transgenic mice. Methods and Materials: The murine CEA-transfected colon carcinoma MC-38 was used for all experiments. In vitro, clonogenic assays were performed after RT alone, TNF-{alpha} alone, and RT plus TNF-{alpha}. In vivo, the mice were randomly assigned to treatment groups: control, TNF-{alpha}, BsAb, BsAb plus TNF-{alpha},more » RT, RT plus TNF-{alpha}, and RT plus BsAb plus TNF-{alpha}. Measurements of endogenous TNF-{alpha} mRNA levels and evaluation of necrosis (histologic evaluation) were assessed per treatment group. Results: In vitro, combined RT plus TNF-{alpha} resulted in a significant decrease in the survival fraction at 2 Gy compared with RT alone (p < 0.00001). In vivo, we observed a complete response in 5 (50%) of 10, 2 (20%) of 10, 2 (18.2%) of 11, and 0 (0%) of 12 treated mice in the RT plus BsAb plus TNF-{alpha}, RT plus TNF-{alpha}, RT alone, and control groups, respectively. This difference was statistically significant when TNF-{alpha} was targeted with the BsAb (p = 0.03). The addition of exogenous TNF-{alpha} to RT significantly increased the endogenous TNF-{alpha} mRNA level, particularly when TNF-{alpha} was targeted with BsAb (p < 0.01). The percentages of necrotic area were significantly augmented in the RT plus BsAb plus TNF-{alpha} group. Conclusion: These results suggest that targeting TNF-{alpha} with the BsAb provokes RT curability in a CEA-expressing digestive tumor syngenic model and could be considered as a solid rationale for clinical trials.« less

Selection of tumor antigens as targets for immune attack using immunohistochemistry: protein antigens.

PubMed

Zhang, S; Zhang, H S; Cordon-Cardo, C; Ragupathi, G; Livingston, P O

1998-11-01

The relative expression of mucin antigens MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC7 and glycoprotein antigens KSA, carcinoembryonic antigen, prostate-specific membrane antigen (PSMA), HER-2/neu, and human chorionic gonadotropin-beta on different cancers and normal tissues is difficult to determine from available reports. We have compared the distribution of these antigens by immunohistology on a broad range of malignant and normal tissues. MUC1 expression was most intense in cancers of breast, lung, ovarian, and endometrial origin; MUC2 was most intense in cancers of colon and prostate origin; and MUC5AC was most intense in cancers of breast and gastric origin. MUC4 was intensely expressed in 50% of cancers of colon and pancreas origin, and MUC3, MUC5B, and MUC7 were expressed in a variety of epithelial cancers, but not so intensely. KSA was intensely and uniformly expressed on all epithelial cancers; carcinoembryonic antigen was expressed in most cancers of breast, lung, colon, pancreas, and gastric origin; and PSMA was expressed only in cancers of prostate origin. Human chorionic gonadotropin-beta was expressed on the majority of sarcomas and cancers of breast, lung, and pancreas origin, although intense staining was not seen. Staining on normal tissues was restricted to one or many normal epithelial tissues ranging from MUC3, MUC4, and PSMA, which were expressed only on epithelia of pancreas, stomach, and prostate origin, respectively, to MUC1 and KSA, which were expressed on most normal epithelia. Expression was restricted to the secretory borders of these epithelia while stroma and other normal tissues were completely negative. These results plus the results of the two previous papers (S. Zhang et al, Int. J. Cancer, 73: 42-49, 1997; S. Zhang et al., Int. J. Cancer, 73: 50-56, 1997) in this series provide the basis for selection of multiple cell surface antigens as targets for antibody-mediated attack against these cancers.

Processing of carcinoembryonic antigen by Kupffer cells: recognition of a penta-peptide sequence.

PubMed

Gangopadhyay, A; Thomas, P

1996-10-01

Carcinoembryonic antigen (CEA) binds to an 80-kDa cell surface receptor on Kupffer cells via the peptide sequence PELPK (residues 108-112) located at the hinge region between the N and Al immunoglobulin-like domains. This study is aimed at analyzing the specificity of the peptide binding, determining biodistribution of 80-kDa receptor, and processing of CEA by this receptor. We synthesized a number of bovine serum albumin (BSA) derivatives carrying PELPK and related sequences. A series of peptides (YPELPK, YPDLPK, YPDLPR, and YPELGK) were conjugated to bovine serum albumin using N-hydroxysuccinimidyl-4-azidobenzoate. When 125I peptide conjugates, CEA, and BSA were injected intravenously into rats CEA and the PELPK-albumin conjugate were cleared rapidly. The other peptide conjugates and BSA cleared at a much slower rate. Activity of 125I-labeled CEA and PELPK-albumin conjugate per gram of tissue was highest for the liver and spleen. Clearance of 125I-CEA was inhibited by the presence of higher concentrations of the PELPK-albumin conjugate. With isolated rat Kupffer cells, only CEA and the PELPK-albumin conjugate were bound and internalized in vitro and CEA binding was inhibited by higher concentrations of the PELPK-albumin conjugate. Similarly, binding of the PELPK-albumin conjugate was inhibited by the presence of unlabeled CEA. Use of a heterobifunctional cross linking agent demonstrated reaction of the PELPK-albumin with an 80-kDa protein on the Kupffer cell surface by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). This semisynthetic ligand (PELPK-albumin) allows us to examine the function of the 80-kDa receptor without interference due to other properties of CEA including its ability to bind lectins and to cause homotypic aggregation of cells. The consequences of CEA binding to the 80-kDa receptor may have implications in the development of hepatic metastasis from colorectal cancer.

Medically unexplained symptoms, somatisation disorder and hypochondriasis: course and prognosis. A systematic review.

PubMed

olde Hartman, Tim C; Borghuis, Machteld S; Lucassen, Peter L B J; van de Laar, Floris A; Speckens, Anne E; van Weel, Chris

2009-05-01

To study the course of medically unexplained symptoms (MUS), somatisation disorder, and hypochondriasis, and related prognostic factors. Knowledge of prognostic factors in patients presenting persistent MUS might improve our understanding of the naturalistic course and the identification of patients with a high risk of a chronic course. A comprehensive search of Medline, PsycInfo, CINAHL, and EMBASE was performed to select studies focusing on patients with MUS, somatisation disorder, and hypochondriasis, and assessing prognostic factors. Studies focusing on patients with single-symptom unexplained disorder or distinctive functional somatic syndromes were excluded. A best-evidence synthesis for the interpretation of results was used. Only six studies on MUS, six studies on hypochondriasis, and one study on abridged somatisation could be included. Approximately 50% to 75% of the patients with MUS improve, whereas 10% to 30% of patients with MUS deteriorate. In patients with hypochondriasis, recovery rates vary between 30% and 50%. In studies on MUS and hypochondriasis, we found some evidence that the number of somatic symptoms at baseline influences the course of these conditions. Furthermore, the seriousness of the condition at baseline seemed to influence the prognosis. Comorbid anxiety and depression do not seem to predict the course of hypochondriasis. Due to the limited numbers of studies and their high heterogeneity, there is a lack of rigorous empirical evidence to identify relevant prognostic factors in patients presenting persistent MUS. However, it seems that a more serious condition at baseline is associated with a worse outcome.

Psychosocial correlates, psychological distress, and quality of life in patients with medically unexplained symptoms: a primary care study in Karachi, Pakistan.

PubMed

Husain, Muhammad Ishrat; Chaudhry, Nasim; Morris, Julie; Zafar, Shehla Naeem; Jaffery, Farhat; Rahman, Raza; Duddu, Venu; Husain, Nusrat

2015-01-01

To examine the psychosocial correlates and association of psychological distress and quality of life (QOL) in patients with medically unexplained symptoms (MUS) compared to those with medically explained symptoms (MES) in a primary care setting in Karachi, Pakistan. A cross-sectional study of 472 patients attending GP clinics between March and August 2009 in Karachi. Participants completed questionnaires to assess demographic details, somatic symptoms, anxiety, depression, and QOL. The patients' GP recorded whether the presenting complaint was medically unexplained or medically explained. MUS subjects in our study were more educated, had better social support and fewer financial problems, were less depressed and had a better QOL than subjects who had medically explained symptoms (non-MUS). Both groups (MUS and non-MUS) were comparable in terms of anxiety and number of somatic symptoms, but non-MUS subjects were more depressed than the MUS group. In a regression analysis, the number of somatic symptoms and lower levels of anxiety predicted poorer QOL in this sample. Whether these symptoms were medically explained (or not) did not seem to contribute significantly to the QOL. Our findings confirm that even in the developing world, patients with MUS are common among primary care attendees. However, patients with MUS in urban Karachi, Pakistan may differ from Western MUS subjects in the role of stress, support, and anxiety in their presentation, and may be reflective of a conceptually different group of difficulties. © 2015, The Author(s).

Stress and recurrent miscarriage.

PubMed

Craig, M

2001-09-01

Our current understanding into the role of stress in unexplained recurrent miscarriages comes from two different research strategies. The majority of research has examined the role of psychological support within this patient population. This support has been provided in a number of ways ranging from weekly interviews with a psychiatrist or gynaecologist and or visual re-assurance in the form of ultrasound scans. A comparison of psychological support with an absence of such intervention has found differences in successful pregnancy outcome varying from as great as 84 versus 26%, respectively. It has been assumed that psychological support reduces the miscarriage rate by reducing “stress”within this patient population. In addition it provides indirect support for a role of stress in the aetiology of unexplained recurrent miscarriage. Other studies have attempted to directly assess the effect of personality characteristics on miscarriage rate; these studies have yielded conflicting results.The mechanism by which stress may be causal in the aetiology of unexplained recurrent miscarriage has not been examined in humans. Animal studies, however, have found that psychological distress can alter immune parameters that may be intricately involved with implantation. These parameters include an elevation of the “abortive” cytokine TNF-a and a reduction in the “anti-abortive” cytokine TGF-P2. Cells that are involved in the release of TNF-a at the feto-maternal interface include T cells, macrophages and mast cells.Mechanisms through which stress may act on these cells are explored and an integrated model is postulated.

Cytoarchitectural and functional abnormalities of the inferior colliculus in sudden unexplained perinatal death.

PubMed

Lavezzi, Anna M; Pusiol, Teresa; Matturri, Luigi

2015-02-01

The inferior colliculus is a mesencephalic structure endowed with serotonergic fibers that plays an important role in the processing of acoustic information. The implication of the neuromodulator serotonin also in the aetiology of sudden unexplained fetal and infant death syndromes and the demonstration in these pathologies of developmental alterations of the superior olivary complex (SOC), a group of pontine nuclei likewise involved in hearing, prompted us to investigate whether the inferior colliculus may somehow contribute to the pathogenetic mechanism of unexplained perinatal death. Therefore, we performed in a wide set of fetuses and infants, aged from 33 gestational weeks to 7 postnatal months and died of both known and unknown cause, an in-depth anatomopathological analysis of the brainstem, particularly of the midbrain. Peculiar neuroanatomical and functional abnormalities of the inferior colliculus, such as hypoplasia/structural disarrangement and immunonegativity or poor positivity of serotonin, were exclusively found in sudden death victims, and not in controls. In addition, these alterations were frequently related to dysgenesis of connected structures, precisely the raphé nuclei and the superior olivary complex, and to nicotine absorption in pregnancy. We propose, on the basis of these results, the involvement of the inferior colliculus in more important functions than those related to hearing, as breathing and, more extensively, all the vital activities, and then in pathological conditions underlying a sudden death in vulnerable periods of the autonomic nervous system development, particularly associated to harmful risk factors as cigarette smoking.

Primary care consultations about medically unexplained symptoms: how do patients indicate what they want?

PubMed

Salmon, Peter; Ring, Adele; Humphris, Gerry M; Davies, John C; Dowrick, Christopher F

2009-04-01

Patients with medically unexplained physical symptoms (MUS) are often thought to deny psychological needs when they consult general practitioners (GPs) and to request somatic intervention instead. We tested predictions from the contrasting theory that they are transparent in communicating their psychological and other needs. To test predictions that what patients tell GPs when they consult about MUS is related transparently to their desire for (1) emotional support, (2) symptom explanation and (3) somatic intervention. Prospective naturalistic study. Before consultation, patients indicated what they wanted from it using a self-report questionnaire measuring patients' desire for: emotional support, explanation and reassurance, and physical investigation and treatment. Their speech during consultation was audio-recorded, transcribed and coded utterance-by-utterance. Multilevel regression analysis tested relationships between what patients sought and what they said. Patients (N = 326) consulting 33 GPs about symptoms that the GPs designated as MUS. Patients who wanted emotional support spoke more about psychosocial problems, including psychosocial causes of symptoms and their need for psychosocial help. Patients who wanted explanation and reassurance suggested more physical explanations, including diseases, but did not overtly request explanation. Patients' wish for somatic intervention was associated only with their talk about details of such interventions and not with their requests for them. In general, patients with medically unexplained symptoms provide many cues to their desire for emotional support. They are more indirect or guarded in communicating their desire for explanation and somatic intervention.

Relationship among nausea, anxiety, and orthostatic symptoms in pediatric patients with chronic unexplained nausea.

PubMed

Tarbell, Sally E; Shaltout, Hossam A; Wagoner, Ashley L; Diz, Debra I; Fortunato, John E

2014-08-01

This study evaluated the relationship among nausea, anxiety, and orthostatic symptoms in pediatric patients with chronic unexplained nausea. We enrolled 48 patients (36 females) aged 15 ± 2 years. Patients completed the Nausea Profile, State-Trait Anxiety Inventory for Children and underwent 70° head upright tilt testing (HUT) to assess for orthostatic intolerance (OI) and measure heart rate variability (HRV). We found nausea to be significantly associated with trait anxiety, including total nausea score (r = 0.71, p < 0.01) and 3 subscales: somatic (r = 0.64, p < 0.01), gastrointestinal (r = 0.48, p = 0.01), and emotional (r = 0.74, p < 0.01). Nausea was positively associated with state anxiety, total nausea (r = 0.55, p < 0.01), somatic (r = 0.48, p < .01), gastrointestinal (r = .30, p < .05), and emotional (r = .64, p < .01) subscales. Within 10 min of HUT, 27 patients tested normal and 21 demonstrated OI. After 45 min of HUT, only 13 patients (27%) remained normal. Nausea reported on the Nausea Profile before HUT was associated with OI measured at 10 min of tilt (nausea total r = 0.35, p < 0.05; nausea emotional subscale r = 0.40, p < 0.01) and lower HRV at 10 min of HUT (F = 6.39, p = 0.01). We conclude that nausea is associated with both anxiety symptoms and OI. The finding of decreased HRV suggests an underlying problem in autonomic nervous system function in children and adolescents with chronic unexplained nausea.

Molecular autopsy of sudden unexplained deaths reveals genetic predispositions for cardiac diseases among young forensic cases.

PubMed

Hellenthal, Nicole; Gaertner-Rommel, Anna; Klauke, Bärbel; Paluszkiewicz, Lech; Stuhr, Markus; Kerner, Thoralf; Farr, Martin; Püschel, Klaus; Milting, Hendrik

2017-11-01

Coronary artery disease accounts for the majority of sudden cardiac deaths (SCD) in the older population whereas cardiomyopathies and arrhythmogenic abnormalities predominate in younger SCD victims (<35 years) with a significant genetic component. The elucidation of the pathogenetic cause of death might be relevant for the prevention of further deaths within affected families. Aim of this study was to determine the portion of underlying genetic heart diseases among unexplained putative SCD cases from a large German forensic department. We included 10 forensic cases of sudden unexplained death (SUD) victims aged 19-40 years, who died by SCD due to forensic autopsy. DNA was analysed by next generation panel sequencing of 174 candidate genes for channelopathies and cardiomyopathies. Cardiological examinations, genetic counselling, and subsequent genetic testing were offered to all affected families. We identified within 1 year 10 cases of SUD among 172 forensic cases. Evidence for a genetic disposition was found in 8 of 10 (80%) cases, with pathogenic mutations in 3 and variants of uncertain significance in 5 of SCD cases. Subsequent selective screening of family members revealed two additional mutation carriers. The study provides strong evidence that molecular genetics improves the post mortem diagnosis of fatal genetic heart diseases among SUD victims. Molecular genetics should be integrated in forensic and pathological routine practice. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Unexplained hepatitis following halothane.

PubMed Central

Walton, B; Simpson, B R; Strunin, L; Doniach, D; Perrin, J; Appleyard, A J

1976-01-01

Full clinical and laboratory details of 203 patients with postoperative jaundice were submitted to a panel of hepatologists. All patients whose jaundice may have had an identifiable cause were excluded, which left 76 patients with unexplained hepatitis following halothane anaesthesia (UHFH). Hepatitis in 95% of these cases followed multiple exposure to halothane, with repeated exposure within four weeks in 55% of cases. Twenty-nine patients were obese, 52 were aged 41-70, and 53 were women. Thirteen patients died in acute hepatic failure. Rapid onset of jaundice after anaesthesia, male sex, and obesity in either sex were poor prognostic signs. Of the clinical stigmata of hypersensitivity, only eosinophilia was impressive. The UHFH group had a much greater incidence of liver kidney microsomal (LKM) and thyroid antibodies and autoimmune complement fixation than those patients whose jaundice related to identifiable factors. Thirteen of the 19 patients with LKM antibodies also had thyroid antibodies. In six patients retested two to three years later LKM antibodies had disappeared, although thyroid antibodies persisted. Rapidly repeated exposure to halothane may cause hepatitis, but such a complication is probably rare. Possibly obese women with a tendency to organ-specific autoimmunity may be more at risk. Nevertheless, the comparative risks of rapidly repeated halothane or non-halothane anaesthesia cannot be determined from the present data. If alternative satisfactory agents are available halothane should be avoided in patients with unexplained hepatitis after previous exposure, although in three to five patients with UHFH who were re-exposed to halothane jaundice did not recur. PMID:1268612

Enteroviruses as major cause of microbiologically unexplained acute respiratory tract infections in hospitalized pediatric patients.

PubMed

Renois, Fanny; Lévêque, Nicolas; Deliège, Pierre-Guillaume; Fichel, Caroline; Bouin, Alexis; Abely, Michel; N'guyen, Yohan; Andréoletti, Laurent

2013-06-01

To assess the etiological role and the clinical characteristics of HRV and HEV infections in pediatric patients hospitalized for acute respiratory tract infections (ARTIs). RT-qPCR assays and molecular sequencing methods were used to identify HRV and HEV strains in nasopharyngeal aspirates of 309 hospitalized pediatric patients with microbiologically unexplained ARTIs and in 210 hospitalized pediatric patients without respiratory symptoms from September 2009 to June 2010 in France. Among the 309 ARTI cases, 15 HEV and 172 HRV strains were identified whereas only 1 HEV and 37 HRV strains were observed in control patients (187 vs. 38: P < 10(-3)). HRV strains were identified in 150 of the 164 lower ARTIs whereas HEV strains were identified in only 14 of these cases. Among bronchiolitis and asthma exacerbation cases (n = 133), HEV infected cases were older (Median age (months) 36 vs. 11, P = 0.003) and were more frequently associated with a respiratory distress (P = 0.01) and a need for oxygen supply at the time of admission (P = 0.01) than cases infected by HRV strains. HRV and HEV strains were identified as potential etiological causes of 60.5% of microbiologically unexplained ARTIs diagnosed in hospitalized pediatric cases. A higher clinical severity was observed in HEV infected bronchiolitis or asthma exacerbation cases in comparison to HRV infected cases. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Management of the first in vitro fertilization cycle for unexplained infertility: a cost-effectiveness analysis of split in vitro fertilization-intracytoplasmic sperm injection

PubMed Central

Vitek, Wendy S.; Galárraga, Omar; Klatsky, Peter C.; Robins, Jared C.; Carson, Sandra A.; Blazar, Andrew S.

2015-01-01

Objective To determine the cost-effectiveness of split IVF-intracytoplasmic sperm injection (ICSI) for the treatment of couples with unexplained infertility. Design Adaptive decision model. Setting Academic infertility clinic. Patient(s) A total of 154 couples undergoing a split IVF-ICSI cycle and a computer-simulated cohort of women <35 years old with unexplained infertility undergoing IVF. Intervention(s) Modeling insemination method in the first IVF cycle as all IVF, split IVF-ICSI, or all ICSI, and adapting treatment based on fertilization outcomes. Main Outcome Measure(s) Live birth rate, incremental cost-effectiveness ratio (ICER). Result(s) In a single cycle, all IVF is preferred as the ICER of split IVF-ICSI or all ICSI ($58,766) does not justify the increased live birth rate (3%). If two cycles are needed, split IVF/ICSI is preferred as the increased cumulative live birth rate (3.3%) is gained at an ICER of $29,666. Conclusion(s) In a single cycle, all IVF was preferred as the increased live birth rate with split IVF-ICSI and all ICSI was not justified by the increased cost per live birth. If two IVF cycles are needed, however, split IVF/ICSI becomes the preferred approach, as a result of the higher cumulative live birth rate compared with all IVF and the lesser cost per live birth compared with all ICSI. PMID:23876534

Management of the first in vitro fertilization cycle for unexplained infertility: a cost-effectiveness analysis of split in vitro fertilization-intracytoplasmic sperm injection.

PubMed

Vitek, Wendy S; Galárraga, Omar; Klatsky, Peter C; Robins, Jared C; Carson, Sandra A; Blazar, Andrew S

2013-11-01

To determine the cost-effectiveness of split IVF-intracytoplasmic sperm injection (ICSI) for the treatment of couples with unexplained infertility. Adaptive decision model. Academic infertility clinic. A total of 154 couples undergoing a split IVF-ICSI cycle and a computer-simulated cohort of women <35 years old with unexplained infertility undergoing IVF. Modeling insemination method in the first IVF cycle as all IVF, split IVF-ICSI, or all ICSI, and adapting treatment based on fertilization outcomes. Live birth rate, incremental cost-effectiveness ratio (ICER). In a single cycle, all IVF is preferred as the ICER of split IVF-ICSI or all ICSI ($58,766) does not justify the increased live birth rate (3%). If two cycles are needed, split IVF/ICSI is preferred as the increased cumulative live birth rate (3.3%) is gained at an ICER of $29,666. In a single cycle, all IVF was preferred as the increased live birth rate with split IVF-ICSI and all ICSI was not justified by the increased cost per live birth. If two IVF cycles are needed, however, split IVF/ICSI becomes the preferred approach, as a result of the higher cumulative live birth rate compared with all IVF and the lesser cost per live birth compared with all ICSI. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Cytoarchitectural and Functional Abnormalities of the Inferior Colliculus in Sudden Unexplained Perinatal Death

PubMed Central

Lavezzi, Anna M.; Pusiol, Teresa; Matturri, Luigi

2015-01-01

Abstract The inferior colliculus is a mesencephalic structure endowed with serotonergic fibers that plays an important role in the processing of acoustic information. The implication of the neuromodulator serotonin also in the aetiology of sudden unexplained fetal and infant death syndromes and the demonstration in these pathologies of developmental alterations of the superior olivary complex (SOC), a group of pontine nuclei likewise involved in hearing, prompted us to investigate whether the inferior colliculus may somehow contribute to the pathogenetic mechanism of unexplained perinatal death. Therefore, we performed in a wide set of fetuses and infants, aged from 33 gestational weeks to 7 postnatal months and died of both known and unknown cause, an in-depth anatomopathological analysis of the brainstem, particularly of the midbrain. Peculiar neuroanatomical and functional abnormalities of the inferior colliculus, such as hypoplasia/structural disarrangement and immunonegativity or poor positivity of serotonin, were exclusively found in sudden death victims, and not in controls. In addition, these alterations were frequently related to dysgenesis of connected structures, precisely the raphé nuclei and the superior olivary complex, and to nicotine absorption in pregnancy. We propose, on the basis of these results, the involvement of the inferior colliculus in more important functions than those related to hearing, as breathing and, more extensively, all the vital activities, and then in pathological conditions underlying a sudden death in vulnerable periods of the autonomic nervous system development, particularly associated to harmful risk factors as cigarette smoking. PMID:25674737

Lord Byron's death: a case of late malarial relapse?

PubMed

Tsiamis, Costas; Piperaki, Evangelia Theophano; Kalantzis, George; Poulakou Rebelakou, Effie; Tompros, Nikolaos; Thalassinou, Eleni; Spilipoulou, Chara; Tsakris, Athanassios

2015-09-01

The study examines the pathological circumstances related to Byron's death, the primary issue being malaria. Lord Byron died during the Greek War of Independence against the Ottoman Empire, in Messolonghi on 19 April 1824. Byron's medical profile consists of recurrent onsets of fever, which gave rise to the issue of malaria relapses. According to Byron's letters he reported crises of fever in Greece (1810), Malta (1811), Italy (1817-1819) and England. Evidence from Byron's autopsy, specifically the absence of hepatosplenomegaly, does not support a hypothetical diagnosis of malaria. Nonetheless, the relapsing fevers cannot be ignored and the same applies to the possibility of malaria relapse or re-infection in line with the endemic nature of the Messolonghi area. Our research on the chronologies of Byron's reported fevers found that new attacks occurred at intervals of 540 days on average. Moreover, the most outstanding feature of Plasmodium vivax and Plasmodium ovale is their ability to form dormant forms of hypnozoites in the liver which, when reactivated (110-777 days), cause true relapses of clinical disease. Of course, an ex post facto diagnosis is under debate, because the diagnosis is not clinical but microscopic. Byron's example raises alarm over a current medical problem, i.e. the diagnosis of unexplained fevers, and the need for a detailed travel or immigration history, which will include malaria in the differential diagnosis.

Exploring the source of the mid-level hump for intensity discrimination in quiet and the effects of noisea)

PubMed Central

Roverud, Elin; Strickland, Elizabeth A.

2015-01-01

Intensity discrimination Weber fractions (WFs) measured for short, high-frequency tones in quiet are larger at mid levels than at lower or higher levels. The source of this “mid-level hump” is a matter of debate. One theory is that the mid-level hump reflects basilar-membrane compression, and that WFs decrease at higher levels due to spread-of-excitation cues. To test this theory, Experiment 1 measured the mid-level hump and growth-of-masking functions to estimate the basilar membrane input/output (I/O) function in the same listeners. Results showed the initial rise in WFs could be accounted for by the change in I/O function slope, but there was additional unexplained variability in WFs. Previously, Plack [(1998). J. Acoust. Soc. Am. 103(5), 2530–2538] showed that long-duration notched noise (NN) presented with the tone reduced the mid-level hump even with a temporal gap in the NN. Plack concluded the results were consistent with central profile analysis. However, simultaneous, forward, and backward NN were not examined separately, which may independently test peripheral and central mechanisms of the NN. Experiment 2 measured WFs at the mid-level hump in the presence of NN and narrowband noise of different durations and temporal positions relative to the tone. Results varied across subjects, but were consistent with more peripheral mechanisms. PMID:25786945

Novel artificial optical annular structures in the high latitude ionosphere over EISCAT

NASA Astrophysics Data System (ADS)

Kosch, M. J.; Rietveld, M. T.; Senior, A.; McCrea, I. W.; Kavanagh, A. J.; Isham, B.; Honary, F.

2004-06-01

The EISCAT low-gain HF facility has been used repeatedly to produce artificially stimulated optical emissions in the F-layer ionosphere over northern Scandinavia. On 12 November 2001, the high-gain HF facility was used for the first time. The pump beam zenith angle was moved in 3° steps along the north-south meridian from 3°N to 15°S, with one pump cycle per position. Only when pumping in the 9°S position were annular optical structures produced quite unexpectedly. The annuli were approximately centred on the pump beam but outside the -3 dB locus. The optical signature appears to form a cylinder, which was magnetic field-aligned, rising above the pump wave reflection altitude. The annulus always collapsed into the well-known optical blobs after ~60 s, whilst descending many km in altitude. All other pump beam directions produced optical blobs only. The EISCAT UHF radar, which was scanning from 3° to 15°S zenith angle, shows that enhanced ion-line backscatter persisted throughout the pump on period and followed the morphology of the optical signature. These observations provide the first experimental evidence that Langmuir turbulence can accelerate electrons sufficiently to produce the optical emissions at high latitudes. Why the optical annulus forms, and for only one zenith angle, remains unexplained.

An association between pulmonary Mycobacterium avium-intracellulare complex infections and biomarkers of Th2-type inflammation.

PubMed

Pfeffer, Paul E; Hopkins, Susan; Cropley, Ian; Lowe, David M; Lipman, Marc

2017-05-15

The rising incidence of pulmonary Mycobacterium avium-intracellulare complex (MAI) infection is unexplained but parallels the growing world-wide epidemic of allergic disease. We hypothesized an association between pulmonary MAI infection and Th2-type immune responses as seen in allergy. Biomarkers of patient Th2-type immune responses (peripheral blood eosinophil counts and serum IgE levels) were compared between patients with positive pulmonary samples for tuberculosis and non-tuberculous mycobacterial (NTM) infection. A further comparison of clinical characteristics, including respiratory co-morbidities, and biomarkers, was conducted between patients culturing MAI NTM and those culturing NTM other than MAI. Patients culturing NTM from pulmonary samples had significantly higher peripheral blood eosinophil levels than those culturing Mycobacterium tuberculosis. Furthermore, patients culturing MAI compared to those culturing NTM other than MAI had higher eosinophil counts (mean 0.29x10 9 /L vs 0.15x10 9 /L, p = 0.010) and IgE levels (geometric mean 138kU/L vs 47kU/L, p = 0.021). However there was no significant difference in the frequency of asthma between the two NTM groups. There is an association between biomarkers of Th2-type immune responses and pulmonary MAI. Prospective and translational research could identify the direction of causation; and so determine whether our finding may be utilized within future management strategies for MAI.

Evaluation of a New Cardiac Pacemaker

ClinicalTrials.gov

2013-06-25

Atrial Fibrillation With 2 or 3° AV or Bifascicular Bundle Branch (BBB) Block; Normal Sinus Rhythm With 2 or 3° AV or BBB Block; Sinus Bradycardia With Infrequent Pauses or Unexplained Syncope With EP Findings

Statistical analysis of tire treadwear data

DOT National Transportation Integrated Search

1985-03-01

This report describes the results of a statistical analysis of the treadwear : variability of radial tires subjected to the Uniform Tire Quality Grading (UTQG) : standard. Because unexplained variability in the treadwear portion of the standard : cou...

Simulated microgravity does not alter epithelial cell adhesion to matrix and other molecules

NASA Technical Reports Server (NTRS)

Jessup, J. M.; Brown, K.; Ishii, S.; Ford, R.; Goodwin, T. J.; Spaulding, G.

1994-01-01

Microgravity has advantages for the cultivation of tissues with high fidelity; however, tissue formation requires cellular recognition and adhesion. We tested the hypothesis that simulated microgravity does not affect cell adhesion. Human colorectal carcinoma cells were cultured in the NASA Rotating Wall Vessel (RWV) under low shear stress with randomization of the gravity vector that simulates microgravity. After 6 - 7 days, cells were assayed for binding to various substrates and compared to cells grown in standard tissue culture flasks and static suspension cultures. The RWV cultures bound as well to basement membrane proteins and to Carcinoembryonic Antigen (CEA), an intercellular adhesion molecule, as control cultures did. Thus, microgravity does not alter epithelial cell adhesion and may be useful for tissue engineering.

A novel bispecific antibody, S-Fab, induces potent cancer cell killing.

PubMed

Li, Li; He, Ping; Zhou, Changhua; Jing, Li; Dong, Bin; Chen, Siqi; Zhang, Ning; Liu, Yawei; Miao, Ji; Wang, Zhong; Li, Qing

2015-01-01

Bispecific antibodies that engage immune cells to kill cancer cells have been actively studied in cancer immunotherapy. In this study, we present a novel bispecific format, S-Fab, fabricated by linking a single-domain anti-carcinoembryonic antigen VHH to a conventional anti-CD3 Fab. In contrast to most bispecific antibodies, the S-Fab bispecific antibody can be efficiently expressed and purified from bacteria. The purified S-Fab is stable in serum and is able to recruit T cells to drive potent cancer cell killing. In xenograft models, the S-Fab antibody suppresses tumor growth in the presence of human immune cells. Our study suggested that the bispecific S-Fab format can be applied to a wide range of immunotherapies.

Cell membrane antigen-antibody complex dissociation by the widely used glycine-HCL method: an unreliable procedure for studying antibody internalization.

PubMed

Tsaltas, G; Ford, C H

1993-02-01

Methods following the process of binding and internalization of antibodies to cell surface antigens have often employed low pH isoosmolar buffers in order to dissociate surface antigen-antibody complexes. One of the most widely used buffers is a 0.05 M glycine-HCL buffer pH 2.8. Since the efficacy of action of this buffer was critical to a series of internalization experiments employing monoclonal antibodies (Mabs) to carcinoembryonic antigen (CEA) expressing cancer cell lines in this laboratory, we tested its performance in a number of different assays. Our results indicate that this buffer only partially dissociates antigen-antibody bonds and therefore can introduce major inaccuracies in internalization experiments.

IVF with planned single-embryo transfer versus IUI with ovarian stimulation in couples with unexplained subfertility: an economic analysis.

PubMed

van Rumste, Minouche M E; Custers, Inge M; van Wely, Madelon; Koks, Carolien A; van Weering, Hans G I; Beckers, Nicole G M; Scheffer, Gabrielle J; Broekmans, Frank J M; Hompes, Peter G A; Mochtar, Monique H; van der Veen, Fulco; Mol, Ben W J

2014-03-01

Couples with unexplained subfertility are often treated with intrauterine insemination (IUI) with ovarian stimulation, which carries the risk of multiple pregnancies. An explorative randomized controlled trial was performed comparing one cycle of IVF with elective single-embryo transfer (eSET) versus three cycles of IUI-ovarian stimulation in couples with unexplained subfertility and a poor prognosis for natural conception, to assess the economic burden of the treatment modalities. The main outcome measures were ongoing pregnancy rates and costs. This study randomly assigned 58 couples to IVF-eSET and 58 couples to IUI-ovarian stimulation. The ongoing pregnancy rates were 24% in with IVF-eSET versus 21% with IUI-ovarian stimulation, with two and three multiple pregnancies, respectively. The mean cost per included couple was significantly different: €2781 with IVF-eSET and €1876 with IUI-ovarian stimulation (P<0.01). The additional costs per ongoing pregnancy were €2456 for IVF-eSET. In couples with unexplained subfertility, one cycle of IVF-eSET cost an additional €900 per couple compared with three cycles of IUI-ovarian stimulation, for no increase in ongoing pregnancy rates or decrease in multiple pregnancies. When IVF-eSET results in higher ongoing pregnancy rates, IVF would be the preferred treatment. Couples that have been trying to conceive unsuccessfully are often treated with intrauterine insemination (IUI) and medication to improve egg production (ovarian stimulation). This treatment carries the risk of multiple pregnancies like twins. We performed an explorative study among those couples that had a poor prognosis for natural conception. One cycle of IVF with transfer of one selected embryo (elective single-embryo transfer, eSET) was compared with three cycles of IUI-ovarian stimulation. The aim of this study was to assess the economic burden of both treatments. The Main outcome measures were number of good pregnancies above 12weeks and costs. We randomly assigned 58 couples to IVF-eSET and 58 couples to IUI-ovarian stimulation. The ongoing pregnancy rates were comparable: 24% with IVF-eSET versus 21% with IUI-ovarian stimulation. There were two multiple pregnancies with IVF-eSET and three multiple pregnancies with IUI-ovarian stimulation. The mean cost per included couple was significantly different, €2781 with IVF-eSET and €1876 with IUI-ovarian stimulation. The additional costs per ongoing pregnancy were €2456 for IVF-eSET. In couples with unexplained subfertility, one cycle of IVF-eSET costed an additional €900 per couple compared to three cycles of IUI-ovarian stimulation, for no increase in ongoing pregnancy rates or decrease in multiple pregnancies. We conclude that IUI-ovarian stimulation is the preferred treatment to start with. When IVF-eSET results in a higher ongoing pregnancy rate (>38%), IVF would be the preferred treatment. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Welding in airplane construction

NASA Technical Reports Server (NTRS)

Rechtlich, A; Schrenk, M

1928-01-01

The present article attempts to explain the principles for the production of a perfect weld and to throw light on the unexplained problems. Moreover, it is intended to elucidate the possibilities of testing the strength and reliability of welded parts.

Rapid clinical deterioration in an individual with Down syndrome.

PubMed

Jacobs, Julia; Schwartz, Alison; McDougle, Christopher J; Skotko, Brian G

2016-07-01

A small percentage of adolescents and young adults with Down syndrome experience a rapid and unexplained deterioration in cognitive, adaptive, and behavioral functioning. Currently, there is no standardized work-up available to evaluate these patients or treat them. Their decline typically involves intellectual deterioration, a loss of skills of daily living, and prominent behavioral changes. Certain cases follow significant life events such as completion of secondary school with friends who proceed on to college or employment beyond the individual with DS. Others develop this condition seemingly unprovoked. Increased attention in the medical community to clinical deterioration in adolescents and young adults with Down syndrome could provide a framework for improved diagnosis, evaluation, and treatment. This report presents a young adult male with Down syndrome who experienced severe and unexplained clinical deterioration, highlighting specific challenges in the systematic evaluation and treatment of these patients. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Current and emerging indications for implantable cardiac monitors.

PubMed

Giada, Franco; Bertaglia, Emanuele; Reimers, Bernhard; Noventa, Donatella; Raviele, Antonio

2012-09-01

Implantable cardiac monitors (ICMs) continuously monitor the patient's electrocardiogram and perform real-time analysis of the heart rhythm, for up to 36 months. The current clinical use of ICMs involves the evaluation of transitory symptoms of possible arrhythmic origin, such as unexplained syncope and palpitations. Moreover, ICMs can also be used for the evaluation of difficult cases of epilepsy and unexplained falls, though current indications for their application in these sectors are less clearly defined. Finally, the ability of new-generation ICMs to automatically record arrhythmic episodes suggests that these devices could also be used to study asymptomatic arrhythmias, and thus could be proposed for the long-term evaluation of the total (symptomatic and asymptomatic) arrhythmic burden in patients at risk of arrhythmic events. In particular, ICMs may have an emerging role in the management of patients with atrial fibrillation and in those at risk of ventricular arrhythmias. ©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

Prospective Analysis on the Effect of Botanical Medicine (Tribulus terrestris) on Serum Testosterone Level and Semen Parameters in Males with Unexplained Infertility.

PubMed

Roaiah, Mohamed Farid; Elkhayat, Yasser Ibrahim; Saleh, Sameh Fayek GamalEl Din; Abd El Salam, Mohamed Ahmed

2016-06-23

We evaluated the role of Tribulus terrestris in males with unexplained infertility and its effect on serum testosterone and semen parameters. Thirty randomized male patients presenting to Andrology outpatient clinic complaining of idiopathic infertility were selected. They were given Tribulus terrestris (750 mg) in three divided doses for three months. The effect of Tribulus terrestris on serum testosterone (total and free) and luteinizing hormone (LH), as well as its impact on semen parameters in those patients, was studied. No statistically significant difference was observed in the levels of testosterone (total and free) and LH and semen parameters (sperm concentration or motility, or abnormal forms) before and after the treatment. In addition, no statistically significant correlations were observed between testosterone (free and total) and LH and semen parameters before and after the treatment. Tribulus terrestris was ineffective in the treatment of idiopathic infertility.

[Anemia in the elderly].

PubMed

Maerevoet, M; Sattar, L; Bron, D; Gulbis, B; Pepersack, T

2014-09-01

Anaemia is a problem that affects almost 10% over 65 years and 20% over 85 years. There is no physiological anaemia in the elderly. Any anaemia expresses the existence of a pathological process, regardless of its severity. Anaemia in the elderly is always associated with a poor prognosis that is in terms of mortality, morbidity and risk of fragility. The diagnostic approach to anemia in the elderly is the same as in younger individual. There are many causes of anaemia; anaemia balance is a complex diagnostic process. Most anaemias are due to a deficiency, chronic inflammation or comorbidity. However, in the elderly, the etiology of anaemia is often multifactorial. In a number of cases remain unexplained anaemia. In a number of cases, anemia remain unexplained. Treatment of anaemia is the treatment of the cause, but specific therapeutic aspects to the elderly should be considered, as among other martial substitution or use of erythropoietin (EPO).

Unexplained severe illness possibly associated with consumption of Kombucha tea--Iowa, 1995.

PubMed

1995-12-08

Kombucha tea is a popular health beverage made by incubating the Kombucha mushroom in sweet black tea. Although advocates of Kombucha tea have attributed many therapeutic effects to the drink (1-3), its beneficial and/or adverse effects have not been determined scientifically. During April 1995, cases of unexplained severe illness (including one death) occurred in two persons in a rural town in northwestern Iowa who had been drinking Kombucha tea daily for approximately 2 months. Based on the findings of a preliminary investigation by the Iowa Department of Public Health (IDPH), on April 10 IDPH issued a news release recommending that persons refrain from drinking Kombucha tea until the role of the tea in the two cases of illness had been evaluated fully. This report summarizes the investigation of these cases by the IDPH, CDC, and the Food and Drug Administration (FDA).

Covert video monitoring in the assessment of medically unexplained symptoms in children.

PubMed

Wallace, Dustin P; Sim, Leslie A; Harrison, Tracy E; Bruce, Barbara K; Harbeck-Weber, Cynthia

2012-04-01

Diagnosis of medically unexplained symptoms (MUS) occurs after thorough evaluations have failed to identify a physiological cause for symptoms. However, families and providers may wonder if something has been missed, leading to reduced confidence in behavioral treatment. Confidence may be improved through the use of technology such as covert video monitoring to better assess functioning across settings. A 12-year-old male presented with progressive neurological decline, precipitated by chronic pain. After thorough evaluation and the failure of standard treatments (medical, rehabilitative, and psychological) covert video monitoring revealed that the patient demonstrated greater abilities when alone in his room. Negative reinforcement was used to initiate recovery, accompanied by positive reinforcement and a rehabilitative approach. Covert video monitoring assisted in three subsequent cases over the following 3 years. In certain complex cases, video monitoring can inform the assessment and treatment of MUS. Discussion includes ethical and practical considerations.

Profound metabolic acidosis and oxoprolinuria in an adult.

PubMed

Hodgman, Michael J; Horn, James F; Stork, Christine M; Marraffa, Jeanna M; Holland, Michael G; Cantor, Richard; Carmel, Patti M

2007-09-01

Profound metabolic acidosis in critically ill adults sometimes remains unexplained despite extensive evaluation. A 58-year-old female presented in a confused state to the emergency department; she had been confused for several days. Laboratory evaluation revealed a high anion gap metabolic acidosis and modestly elevated acetaminophen level. Lactic acid was only modestly elevated. There was no evidence of ketoacids, salicylate, methanol, or ethylene glycol. A urine sample submitted on day 1 of hospitalization revealed a markedly elevated level of 5-oxoproline. Originally described in children with an inherited defect of glutathione synthetase, 5-oxoproline is an unusual cause of metabolic acidosis. More recently this disturbance has been recognized in critically ill adults without a recognized inherited metabolic disorder. In most of these cases there has been the concomitant use of acetaminophen. Any causal relationship between acetaminophen and this disturbance is speculative. In critically ill adults with unexplained metabolic acidosis, 5-Oxoproline should be considered in the differential.

Anxiety and depressive symptoms and anxiety sensitivity in youngsters with noncardiac chest pain and benign heart murmurs.

PubMed

Lipsitz, Joshua D; Masia-Warner, Carrie; Apfel, Howard; Marans, Zvi; Hellstern, Beth; Forand, Nicholas; Levenbraun, Yosef; Fyer, Abby J

2004-12-01

Chest pain in children and adolescents is rarely associated with cardiac disease. We sought to examine psychological symptoms in youngsters with medically unexplained chest pain. We hypothesized that children and adolescents with medically unexplained chest pain would have high rates of anxiety and depressive symptoms. We assessed 65 youngsters with noncardiac chest pain (NCCP) and 45 comparison youngsters with benign heart murmurs using self-report measures of anxiety and depressive symptoms and anxiety sensitivity. Compared with the asymptomatic benign-murmur group, youngsters with NCCP had higher levels of some anxiety symptoms and anxiety sensitivity. Differences on depressive symptoms were not significant. Though preliminary, results suggest that youngsters with chest pain may experience increased levels of some psychological symptoms. Future studies of noncardiac chest pain in youngsters should include larger samples and comprehensive diagnostic assessments as well as long-term follow-up evaluations.

Pancytopenia in a surgical patient, a rare presentation of hyperthyroidism.

PubMed

Jha, Prabhat; Singh, Yogendra Prasad; Ghimire, Bikal; Jha, Binit Kumar

2014-12-15

Pancytopenia is a rare complication of hyperthyroidism. Various mechanisms have been described such as immunological, bone marrow suppression. The possibility of hyperthyroidism should be considered in patients with unexplained pancytopenia. There are many case reports showing the association between hyperthyroidism and pancytopenia. All of these reports show association between Graves disease and pancytopenia but our case shows association between Multinodular goitre and pancytopenia. Besides it is uncommon to find such association in a surgical patient. This case report describes a 62 yr old hindu female with splenic injury and pancytopenia. On further investigations the patient was found to have hyperthyroidism. Though the definite mechanism regarding the association of pancytopenia with hyperthyroidism isn't clear, various cases have been described in the literature. This case shows the diagnostic dilemma that can occur in patients with pancytopenia. Any patient with unexplained pancytopenia should undergo thyroid function tests to rule out hyperthyroidism.

Female Infertility and Serum Auto-antibodies: a Systematic Review.

PubMed

Deroux, Alban; Dumestre-Perard, Chantal; Dunand-Faure, Camille; Bouillet, Laurence; Hoffmann, Pascale

2017-08-01

On average, 10 % of infertile couples have unexplained infertility. Auto-immune disease (systemic lupus erythematosus, anti-phospholipid syndrome) accounts for a part of these cases. In the last 20 years, aspecific auto-immunity, defined as positivity of auto-antibodies in blood sample without clinical or biological criteria for defined diseases, has been evoked in a subpopulation of infertile women. A systematic review was performed (PUBMED) using the MESH search terms "infertility" and "auto-immunity" or "reproductive technique" or "assisted reproduction" or "in vitro fertilization" and "auto-immunity." We retained clinical and physiopathological studies that were applicable to the clinician in assuming joint management of both infertility associated with serum auto-antibodies in women. Thyroid auto-immunity which affects thyroid function could be a cause of infertility; even in euthyroidia, the presence of anti-thyroperoxydase antibodies and/or thyroglobulin are related to infertility. The presence of anti-phospholipid (APL) and/or anti-nuclear (ANA) antibodies seems to be more frequent in the population of infertile women; serum auto-antibodies are associated with early ovarian failure, itself responsible for fertility disorders. However, there exist few publications on this topic. The methods of dosage, as well as the clinical criteria of unexplained infertility deserve to be standardized to allow a precise response to the question of the role of serum auto-antibodies in these women. The direct pathogenesis of this auto-immunity is unknown, but therapeutic immunomodulators, prescribed on a case-by-case basis, could favor pregnancy even in cases of unexplained primary or secondary infertility.

Extension of the Peters–Belson method to estimate health disparities among multiple groups using logistic regression with survey data

PubMed Central

Li, Y.; Graubard, B. I.; Huang, P.; Gastwirth, J. L.

2015-01-01

Determining the extent of a disparity, if any, between groups of people, for example, race or gender, is of interest in many fields, including public health for medical treatment and prevention of disease. An observed difference in the mean outcome between an advantaged group (AG) and disadvantaged group (DG) can be due to differences in the distribution of relevant covariates. The Peters–Belson (PB) method fits a regression model with covariates to the AG to predict, for each DG member, their outcome measure as if they had been from the AG. The difference between the mean predicted and the mean observed outcomes of DG members is the (unexplained) disparity of interest. We focus on applying the PB method to estimate the disparity based on binary/multinomial/proportional odds logistic regression models using data collected from complex surveys with more than one DG. Estimators of the unexplained disparity, an analytic variance–covariance estimator that is based on the Taylor linearization variance–covariance estimation method, as well as a Wald test for testing a joint null hypothesis of zero for unexplained disparities between two or more minority groups and a majority group, are provided. Simulation studies with data selected from simple random sampling and cluster sampling, as well as the analyses of disparity in body mass index in the National Health and Nutrition Examination Survey 1999–2004, are conducted. Empirical results indicate that the Taylor linearization variance–covariance estimation is accurate and that the proposed Wald test maintains the nominal level. PMID:25382235

Skin test reactivity to female sex hormones in women with primary unexplained recurrent pregnancy loss.

PubMed

Ellaithy, Mohamed I; Fathi, Hesham M; Farres, Mohamed N; Taha, Marwa S

2013-09-01

The objective was to examine the hypothesis that primary unexplained recurrent pregnancy loss might be associated with an inappropriate immunologically mediated response to progesterone and/or estrogen. This prospective study included 47 women with two or more documented consecutive early pregnancy losses of unknown etiology, and no previous history of deliveries. Intradermal skin testing was performed in the luteal phase of the cycle (days 16-20) using estradiol benzoate, progesterone, and a placebo of refined sesame oil. Immediate (20 min) and late (24h and 1 week) skin test readings for all cases were compared with those of 12 parous women of comparable age with no history of spontaneous miscarriages, premenstrual disorders, pregnancy, or sex hormone-related allergic or autoimmune diseases. Main outcome measure was skin test reactivity to estradiol and/or progesterone. Immediate skin test reactivity to both hormones was observed among half of the cases at 20 min. A papule after 24h, which persisted for up to 1 week, was observed among 32 (68.1%) and 34 (72.3%) cases at the sites of estrogen and progesterone injection, respectively. 55.3% of cases had combined skin test reactivity to both estradiol and progesterone at 1 week. All women in the control group showed absence of skin test reactivity for both estradiol and progesterone at 20 min, 24h, and 1 week. None of the subjects in either group showed skin test reactivity to placebo. There is an association between primary unexplained recurrent pregnancy loss and skin test reactivity to female sex hormones. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Costs of unstructured investigation of unexplained syncope: insights from a micro-costing analysis of the observational PICTURE registry.

PubMed

Edvardsson, Nils; Wolff, Claudia; Tsintzos, Stelios; Rieger, Guido; Linker, Nicholas J

2015-07-01

The observational PICTURE (Place of Reveal In the Care pathway and Treatment of patients with Unexplained Recurrent Syncope) registry enrolled 570 patients with unexplained syncope, documented their care pathway and the various tests they underwent before the insertion of an implantable loop recorder (ILR). The aims were to describe the extent and cost of diagnostic tests performed before the implant. Actual costs of 17 predefined diagnostic tests were characterized based on a combination of data from PICTURE and a micro-costing study performed at a medium-sized UK university hospital in the UK. The median cost of diagnostic tests per patient was £1114 (95% CI £995-£1233). As many patients received more than the median number of tests, the mean expenditure per patient was higher with £1613 (95% CI £1494-£1732), and for 10% of the patients the cost exceeded £3539. Tests were frequently repeated, and early use of specific and expensive tests was common. In the 12% of patients with types of tests entirely within the recommendations for an initial evaluation before ILR implant, the mean cost was £710. Important opportunities to reduce test-related costs before an ILR implant were identified, e.g. by more appropriate use of tests recommended in the initial evaluation, by decreasing repetition of tests, and by avoiding early use of specialized and expensive tests. A structured multidisciplinary approach would be the best model to achieve an optimal outcome. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

[Diagnosis of a case with Williams-Beuren syndrome with nephrocalcinosis using chromosome microarray analysis].

PubMed

Jin, S J; Liu, M; Long, W J; Luo, X P

2016-12-02

Objective: To explore the clinical phenotypes and the genetic cause for a boy with unexplained growth retardation, nephrocalcinosis, auditory anomalies and multi-organ/system developmental disorders. Method: Routine G-banding and chromosome microarray analysis were applied to a child with unexplained growth retardation, nephrocalcinosis, auditory anomalies and multi-organ/system developmental disorders treated in the Department of Pediatrics of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in September 2015 and his parents to conduct the chromosomal karyotype analysis and the whole genome scanning. Deleted genes were searched in the Decipher and NCBI databases, and their relationships with the clinical phenotypes were analyzed. Result: A six-month-old boy was refered to us because of unexplained growth retardation and feeding intolerance.The affected child presented with abnormal manifestation such as special face, umbilical hernia, growth retardation, hypothyroidism, congenital heart disease, right ear sensorineural deafness, hypercalcemia and nephrocalcinosis. The child's karyotype was 46, XY, 16qh + , and his parents' karyotypes were normal. Chromosome microarray analysis revealed a 1 436 kb deletion on the 7q11.23(72701098_74136633) region of the child. This region included 23 protein-coding genes, which were reported to be corresponding to Williams-Beuren syndrome and its certain clinical phenotypes. His parents' results of chromosome microarray analysis were normal. Conclusion: A boy with characteristic manifestation of Williams-Beuren syndrome and rare nephrocalcinosis was diagnosed using chromosome microarray analysis. The deletion on the 7q11.23 might be related to the clinical phenotypes of Williams-Beuren syndrome, yet further studies are needed.

Application of chromosome microarray analysis in patients with unexplained developmental delay/intellectual disability in South China.

PubMed

Wang, Rongyue; Lei, Tingying; Fu, Fang; Li, Ru; Jing, Xiangyi; Yang, Xin; Liu, Juan; Li, Dongzhi; Liao, Can

2018-03-26

Chromosome microarray analysis (CMA) is currently the first-tier diagnostic assay for the evaluation of developmental delay (DD) and intellectual disability (ID) with unknown etiology. Here, we present our clinical experience in implementing whole-genome high-resolution single nucleotide polymorphism (SNP) arrays to investigate 489 patients with unexplained DD/ID in whom standard karyotyping analyses showed normal karyotypes. This study aimed to assess the usefulness of CMA for clinical diagnostic testing in the Chinese population. A total of 489 children were classified into three groups: isolated DD/ID (n = 358), DD/ID with epilepsy (n = 49), and DD/ID with other structural anomalies (n = 82). We identified 126 cases (25.8%, 126/489) of pathogenic copy number variants (CNVs) by CMA, including 89 (24.9%, 89/358) with isolated DD/ID, 13 (26.5%, 13/49) with DD/ID with epilepsy, and 24 (29.3%, 24/82) with DD/ID with other structural anomalies. Among the 126 cases of pathogenic CNVs, 79 cases were identified as microdeletion/microduplication syndromes, among which 76 cases were classified as common syndromes, and 3 cases were classified as rare syndromes, including 15q24 microdeletion syndrome, Xq28 microduplication syndrome and Lowe syndrome. Additionally, there were forty-seven cases of non-syndromic pathogenic CNVs. The ABAT, FTSJ1, DYNC1H1, and SETBP1 genes were identified as DD/ID candidate genes. Our findings suggest the necessity of CMA as a routine diagnostic test for unexplained DD/ID in South China. Copyright © 2018. Published by Elsevier B.V.

Relationships between equine airway reactivity measured by flowmetric plethysmography and specific indicators of airway inflammation in horses with suspected inflammatory airway disease.

PubMed

Wichtel, M; Gomez, D; Burton, S; Wichtel, J; Hoffman, A

2016-07-01

Agreement between airway reactivity measured by flowmetric plethysmography and histamine bronchoprovocation, and lower airway inflammation measured by bronchoalveolar lavage (BAL) cytology, has not been studied in horses with suspected inflammatory airway disease (IAD). We tested the hypothesis that airway reactivity is associated with BAL cytology in horses presenting for unexplained poor performance and/or chronic cough. Prospective clinical study. Forty-five horses, predominantly young Standardbred racehorses, presenting for unexplained poor performance or chronic cough, underwent endoscopic evaluation, tracheal wash, flowmetric plethysmography with histamine bronchoprovocation and BAL. Histamine response was measured by calculating PC35, the concentration of nebulised histamine eliciting an increase in Δflow of 35%. In this population, there was no significant correlation between histamine response and cell populations in BAL cytology. When airway hyperreactivity (AHR) was defined as ≥35% increase in Δflow at a histamine concentration of <6 mg/ml, 24 of the 45 horses (53%) were determined to have AHR. Thirty-three (73%) had either abnormal BAL cytology or AHR, and were diagnosed with IAD on this basis. Of horses diagnosed with IAD, 9 (27%) had an abnormal BAL, 11 (33%) had AHR and 13 (39%) had both. Airway reactivity and BAL cytology did not show concordance in this population of horses presenting for unexplained poor performance and/or chronic cough. Failure to include tests of airway reactivity may lead to underdiagnosis of IAD in young Standardbred racehorses that present with clinical signs suggestive of IAD. © 2015 EVJ Ltd.

Ten questions about terminology for children with unexplained language problems

PubMed Central

Bishop, D V M

2014-01-01

Background In domains other than language, there is fairly consistent diagnostic terminology to refer to children's developmental difficulties. For instance, the terms ‘dyslexia’, ‘attention deficit hyperactivity disorder’ and ‘autistic spectrum disorder’ are used for difficulties with reading, attention or social cognition, respectively. There is no agreed label, however, for children with unexplained language problems. Aims To consider whether we need labels for unexplained language problems in children, and if so, what terminology is appropriate. Main Contribution There are both advantages and disadvantages to labels, but they are important to ensure children receive services, and to increase our knowledge of the nature and causes of such problems. A survey of labels in current use found 132 different terms, 33 of which had 600 or more returns on Google Scholar between 1994 and 2013. Many of these labels were too general to be useful. Of the remainder, the term ‘specific language impairment’ was the most commonly used. Conclusions The current mayhem in diagnostic labels is unsustainable; it causes confusion and impedes research progress and access to appropriate services. We need to achieve consensus on diagnostic criteria and terminology. The DSM-5 term ‘language disorder’ is problematic because it identifies too wide a range of conditions on an internet search. One solution is to retain specific language impairment, with the understanding that ‘specific’ means idiopathic (i.e., of unknown origin) rather than implying there are no other problems beyond language. Other options are the terms ‘primary language impairment’, ‘developmental language disorder’ or ‘language learning impairment’. PMID:25142090

Grazing livestock are exposed to terrestrial cyanobacteria.

PubMed

McGorum, Bruce C; Pirie, R Scott; Glendinning, Laura; McLachlan, Gerry; Metcalf, James S; Banack, Sandra A; Cox, Paul A; Codd, Geoffrey A

2015-02-25

While toxins from aquatic cyanobacteria are a well-recognised cause of disease in birds and animals, exposure of grazing livestock to terrestrial cyanobacteria has not been described. This study identified terrestrial cyanobacteria, predominantly Phormidium spp., in the biofilm of plants from most livestock fields investigated. Lower numbers of other cyanobacteria, microalgae and fungi were present on many plants. Cyanobacterial 16S rDNA, predominantly from Phormidium spp., was detected in all samples tested, including 6 plant washings, 1 soil sample and ileal contents from 2 grazing horses. Further work was performed to test the hypothesis that ingestion of cyanotoxins contributes to the pathogenesis of some currently unexplained diseases of grazing horses, including equine grass sickness (EGS), equine motor neuron disease (EMND) and hepatopathy. Phormidium population density was significantly higher on EGS fields than on control fields. The cyanobacterial neurotoxic amino acid 2,4-diaminobutyric acid (DAB) was detected in plant washings from EGS fields, but worst case scenario estimations suggested the dose would be insufficient to cause disease. Neither DAB nor the cyanobacterial neurotoxins β-N-methylamino-L-alanine and N-(2-aminoethyl) glycine were detected in neural tissue from 6 EGS horses, 2 EMND horses and 7 control horses. Phormidium was present in low numbers on plants where horses had unexplained hepatopathy. This study did not yield evidence linking known cyanotoxins with disease in grazing horses. However, further study is warranted to identify and quantify toxins produced by cyanobacteria on livestock fields, and determine whether, under appropriate conditions, known or unknown cyanotoxins contribute to currently unexplained diseases in grazing livestock.

Awareness of cancer symptoms and anticipated patient interval for healthcare seeking. A comparative study of Denmark and Sweden.

PubMed

Hvidberg, Line; Lagerlund, Magdalena; Pedersen, Anette F; Hajdarevic, Senada; Tishelman, Carol; Vedsted, Peter

2016-07-01

Background Recent epidemiologic data show that Denmark has considerably poorer survival from common cancers than Sweden. This may be related to a lower awareness of cancer symptoms and longer patient intervals in Denmark than in Sweden. The aims of this study were to: 1) compare population awareness of three possible symptoms of cancer (unexplained lump or swelling, unexplained bleeding and persistent cough or hoarseness); 2) compare anticipated patient interval when noticing any breast changes, rectal bleeding and persistent cough; and 3) examine whether potential differences were noticeable in particular age groups or at particular levels of education in a Danish and Swedish population sample. Method Data were derived from Module 2 of the International Cancer Benchmarking Partnership. Telephone interviews using the Awareness and Beliefs about Cancer measure were conducted in 2011 among 3000 adults in Denmark and 3070 adults in Sweden. Results Danish respondents reported a higher awareness of two of three symptoms (i.e. unexplained lump or swelling and persistent cough or hoarseness) and a shorter anticipated patient interval for two of three symptoms studied (i.e. any breast changes and rectal bleeding) than Swedish respondents. Differences in symptom awareness and anticipated patient interval between these countries were most pronounced in highly educated respondents. Conclusion Somewhat paradoxically, the highest awareness of symptoms of cancer and the shortest anticipated patient intervals were found in Denmark, where cancer survival is lower than in Sweden. Thus, it appears that these differences in symptom awareness and anticipated patient interval do not help explain the cancer survival disparity between Denmark and Sweden.

Intra-articular co-infection by Borrelia burgdorferi and Chlamydia trachomatis

PubMed Central

Putschky, N; Schnarr, S; Wollenhaupt, J; Zeidler, H; Kuipers, J

2001-01-01

OBJECTIVE—Chlamydia trachomatis and Borrelia burgdorferi infections are frequently the cause of unexplained oligoarthritis, as shown by identification of bacteria specific DNA in joint material from patients with reactive arthritis, Lyme arthritis, and undifferentiated oligoarthritis. The aim of this study was to determine whether the two organisms occur simultaneously in joint material from patients with arthritis.
METHODS—Seventy six patients with unexplained arthritis were prospectively studied. Synovial fluid was obtained from all patients and examined for DNA from C trachomatis and B burgdorferi using specific polymerase chain reaction (PCR) protocols. Data concerning prior genitourinary infection or a history of tick bite were recorded and serum antibodies to C trachomatis and B burgdorferi were determined.
RESULTS—Six patients (8%) had DNA from both C trachomatis and B burgdorferi in the same synovial fluid specimen (mean leucocyte count 11.925/mm3, 65% granulocytes). These patients (four men, two women; mean age 33.7 years) all had oligoarthritis of the knee, ankle, or both (mean disease duration 11.3 months). From the history and serological examination, four patients had some evidence of actual or previous infection with one or other of the bacteria, while the other two patients had a positive serological test for Chlamydia only.
CONCLUSIONS—DNA from two different microorganisms which are known to be triggering agents for arthritis may be present simultaneously in joint material from patients with unexplained oligoarthritis. This finding raises the question as to whether, in such cases, one or both bacteria contribute to the pathogenesis of the disease or whether they are only innocent bystanders.

 PMID:11350854

Investigating unexplained fatigue in general practice with a particular focus on CFS/ME.

PubMed

Bansal, Amolak S

2016-07-19

Unexplained fatigue is not infrequent in the community. It presents a number of challenges to the primary care physician and particularly if the clinical examination and routine investigations are normal. However, while fatigue is a feature of many common illnesses, it is the main problem in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). This is a poorly understood condition that is accompanied by several additional symptoms which suggest a subtle multisystem dysfunction. Not infrequently it is complicated by sleep disturbance and alterations in attention, memory and mood.Specialised services for the diagnosis and management of CFS/ME are markedly deficient in the UK and indeed in virtually all countries around the world. However, unexplained fatigue and CFS/ME may be confidently diagnosed on the basis of specific clinical criteria combined with the normality of routine blood tests. The latter include those that assess inflammation, autoimmunity, endocrine dysfunction and gluten sensitivity. Early diagnosis and intervention in general practice will do much to reduce patient anxiety, encourage improvement and prevent expensive unnecessary investigations.There is presently an on-going debate as to the precise criteria that best confirms CFS/ME to the exclusion of other medical and psychiatric/psychological causes of chronic fatigue. There is also some disagreement as to best means of investigating and managing this very challenging condition. Uncertainty here can contribute to patient stress which in some individuals can perpetuate and aggravate symptoms. A simple clinical scoring system and a short list of routine investigations should help discriminate CFS/ME from other causes of continued fatigue.

Costs of unstructured investigation of unexplained syncope: insights from a micro-costing analysis of the observational PICTURE registry

PubMed Central

Edvardsson, Nils; Wolff, Claudia; Tsintzos, Stelios; Rieger, Guido; Linker, Nicholas J.

2015-01-01

Aims The observational PICTURE (Place of Reveal In the Care pathway and Treatment of patients with Unexplained Recurrent Syncope) registry enrolled 570 patients with unexplained syncope, documented their care pathway and the various tests they underwent before the insertion of an implantable loop recorder (ILR). The aims were to describe the extent and cost of diagnostic tests performed before the implant. Methods and results Actual costs of 17 predefined diagnostic tests were characterized based on a combination of data from PICTURE and a micro-costing study performed at a medium-sized UK university hospital in the UK. The median cost of diagnostic tests per patient was £1114 (95% CI £995–£1233). As many patients received more than the median number of tests, the mean expenditure per patient was higher with £1613 (95% CI £1494–£1732), and for 10% of the patients the cost exceeded £3539. Tests were frequently repeated, and early use of specific and expensive tests was common. In the 12% of patients with types of tests entirely within the recommendations for an initial evaluation before ILR implant, the mean cost was £710. Conclusion Important opportunities to reduce test-related costs before an ILR implant were identified, e.g. by more appropriate use of tests recommended in the initial evaluation, by decreasing repetition of tests, and by avoiding early use of specialized and expensive tests. A structured multidisciplinary approach would be the best model to achieve an optimal outcome. PMID:25759408

Cardiovascular function in women with recurrent miscarriage, pre-eclampsia and/or intrauterine growth restriction.

PubMed

Mahendru, Amita A; Everett, Thomas R; McEniery, Carmel M; Wilkinson, Ian B; Lees, Christoph C

2013-03-01

To investigate prepregnancy cardiovascular function and risk factors in women with previous pregnancy complications. Thirty-four women with previous normal pregnancy (controls), 26 with unexplained recurrent miscarriage (RM) and 14 with pre-eclampsia (PE) and/or intrauterine growth restriction (IUGR), planning to conceive were recruited. Brachial and central blood pressures (BP), cardiac output (CO), peripheral vascular resistance (PVR), aortic stiffness, blood biochemistry and platelet aggregation were assessed. Women with previous PE/IUGR had higher brachial diastolic BP (78 ± 9 vs 71 ± 7 mmHg; p = 0.03), central systolic BP (107 ± 10 vs 99 ± 8 mmHg; p = 0.03), mean arterial pressure (92 ± 10 vs 84 ± 8 mmHg; p = 0.01) and PVR (1499 ± 300 vs 1250 ± 220 dynes.s(-1) cm(-5); p = 0.005), than the controls. No differences were observed in either cardiovascular function or blood biochemistry in women with unexplained RM compared with the controls. Women with previous PE/IUGR though not with RM had a stronger family history of cardiovascular disease (CVD) than controls. Women with previous PE and/or IUGR had higher BP and PVR compared with controls, which may predispose them to CVD later in life. However, in the absence of underlying vascular pathology, women with unexplained RM did not have abnormal cardiovascular function. Prepregnancy period provides an opportunity to identify cardiovascular risks in relation to previous obstetric history.

Studying Unexplained Veteran Illnesses at the APS

ScienceCinema

Schmidt, Millicent

2018-02-14

Researchers from Stony Brook University come to Argonne's Advanced Photon Source to study the potential underlying causes for an unusual increased incidence of pulmonary disease in U.S. soldiers returning from military service in the Middle East and Afghanistan.

Colour Perception in ADHD

ERIC Educational Resources Information Center

Banaschewski, Tobias; Ruppert, Sinje; Tannock, Rosemary; Albrecht, Bjorn; Becker, Andreas; Uebel, Henrik; Sergeant, Joseph A.; Rothenberger, Aribert

2006-01-01

Attention-deficit/hyperactivity disorder (ADHD) is associated with unexplained impairments on speeded naming of coloured stimuli. These deficits may reflect hypofunctioning retinal dopaminergic mechanisms impairing particularly blue-yellow colour discrimination. Colour perception and rapid colour naming ability were investigated in 14 children…

The Metabolic Basis of Cystinosis

DTIC Science & Technology

1981-05-12

glucose, amino acids and other organic acids appear. The present- ing symptoms of the disease— polyuria , polydipsia and recurrent unexplained fevers are... polyuria and polydypsia which results make children with the disease extremely susceptible to dehydration. This vulnerability to dehydration explains

A study on phthalate metabolites, bisphenol A and nonylphenol in the urine of Chinese women with unexplained recurrent spontaneous abortion

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

Peng, Fanli

Humans are widely exposed to phthalates, bisphenol A and nonylphenol owing to the ubiquitous use of these chemicals in consumer products. Increasing attention has been paid to exposure to phthalates, bisphenol A and nonylphenol because of their potential adverse effects on human fertility. A validated method was developed to investigate the three classes of environmental estrogen, mentioned above, in the urine of Chinese women of Nanjing area with unexplained recurrent spontaneous abortion. Solid-phase extraction coupled with ultra performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) was used. In this method, amounts of bisphenol A (BPA), nonylphenol (NP) and four phthalate metabolites, mono-n-butylmore » phthalate (MBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP) and mono-2-ethylhexyl phthalate (MEHP), along with their isotope labeled internal standards, were measured using UPLC-MS/MS operated in negative electrospray ionization multiple reaction monitoring mode. The limits of detection were 0.3 ng/mL for the four phthalate metabolites, and 0.5 ng/mL for bisphenol A and nonylphenol. For women with unexplained recurrent spontaneous abortion, the mean concentrations of MBP, MiBP, MBzP, MEHP, BPA and 4-n-NP were 6.52±6.04, 5.51±4.19, 0.53±0.42, 10.12±4.16, 7.13±7.42, 0.41±0.49 ng/mL (mean±SD), respectively. For the control group, the mean concentrations of the corresponding analytes were 4.15±3.57, 2.96±3.30, 0.46±0.49, 6.50±2.81, 4.43±2.23,0.48±0.43 ng/mL (mean±SD), respectively. Levels of MiBP and MEHP were significantly different between the two groups, using Wilcoxon rank sum tests. This method can be applied in epidemiological studies to explore the association between exposure to environmental estrogens and relevant adverse outcomes. - Highlights: • Studied on the exposure level of six analytes in Chinese women with unexplained recurrent spontaneous abortion. • Differences in MEHP and MiBP urine levels were found between case and control groups. • A robust UPLC-MS/MS method was established for detecting phthalate monoesters, bisphenol A and nonylphenol. • An excellent solid-phase extraction method was established for urine.« less

Double Stranded Sperm DNA Breaks, Measured by Comet Assay, Are Associated with Unexplained Recurrent Miscarriage in Couples without a Female Factor

PubMed Central

Ribas-Maynou, Jordi; García-Peiró, Agustín; Fernandez-Encinas, Alba; Amengual, Maria José; Prada, Elena; Cortés, Pilar; Navarro, Joaquima; Benet, Jordi

2012-01-01

It is known that sperm samples from recurrent pregnancy loss (RPL) couples have an increase in their sperm DNA fragmentation (SDF), but no studies have been performed in order to identify differences between single stranded SDF (ssSDF) and double stranded SDF (dsSDF) in these patients. This could be relevant because the type of DNA damage could have different effects. Semen samples were classified attending their clinical status: 25 fertile donors and 20 RPL patients with at least two unexplained first trimester miscarriages. SDF was analysed using alkaline and neutral Comet assay, SCD test and pulsed-field gel electrophoresis (PFGE), and ROC analysis including data from 105 more infertile patients (n = 150) was performed to establish predictive threshold values. SDF for alkaline and neutral Comet, and the SCD test was analysed in these categories of individuals. Data revealed the presence of two subgroups within fertile donors. The values obtained were 21.10±9.13, 23.35±10.45 and 12.31±4.31, respectively, for fertile donors with low values for both ssSDF and dsSDF; 27.86±12.64, 80.69±12.67 and 12.43±5.22, for fertile donors with low ssSDF and high dsSDF; and 33.61±15.50, 84.64±11.28 and 19.28±6.05, for unexplained RPL patients, also showing a low ssSDF and high dsSDF profile. This latter profile was seen in 85% of unexplained RPL and 33% of fertile donors, suggesting that it may be associated to a male risk factor for undergoing RPL. ROC analysis regarding recurrent miscarriage set the cut-off value at 77.50% of dsDNA SDF. PFGE for low ssSDF and high dsSDF profile samples and positive controls treated with DNase, to induce dsDNA breaks, showed a more intense band of about 48 kb, which fits the toroid model of DNA compaction in sperm, pointing out that some nuclease activity may be affecting their sperm DNA in RPL patients. This work identifies a very specific SDF profile related to the paternal risk of having RPL. PMID:23028579

The INeS study: prevention of multiple pregnancies: a randomised controlled trial comparing IUI COH versus IVF e SET versus MNC IVF in couples with unexplained or mild male subfertility.

PubMed

Bensdorp, Alexandra J; Slappendel, Els; Koks, Carolien; Oosterhuis, Jur; Hoek, Annemieke; Hompes, Peter; Broekmans, Frank; Verhoeve, Harold; de Bruin, Jan Peter; van Weert, Janne Meije; Traas, Maaike; Maas, Jacques; Beckers, Nicole; Repping, Sjoerd; Mol, Ben W; van der Veen, Fulco; van Wely, Madelon

2009-12-18

Multiple pregnancies are high risk pregnancies with higher chances of maternal and neonatal mortality and morbidity. In the past decades the number of multiple pregnancies has increased. This trend is partly due to the fact that women start family planning at an increased age, but also due to the increased use of ART.Couples with unexplained or mild male subfertility generally receive intrauterine insemination IUI with controlled hormonal stimulation (IUI COH). The cumulative pregnancy rate is 40%, with a 10% multiple pregnancy rate.This study aims to reveal whether alternative treatments such as IVF elective Single Embryo Transfer (IVF e SET) or Modified Natural Cycle IVF (MNC IVF) can reduce the number of multiple pregnancy rates, but uphold similar pregnancy rates as IUI COH in couples with mild male or unexplained subfertility. Secondly, the aim is to perform a cost effective analyses and assess treatment preference of these couples. We plan a multicentre randomised controlled clinical trial in the Netherlands comparing six cycles of intra-uterine insemination with controlled ovarian hyperstimulation or six cycles of Modified Natural Cycle (MNC) IVF or three cycles with IVF-elective Single Embryo Transfer (eSET) plus cryo-cycles within a time frame of 12 months.Couples with unexplained subfertility or mild male subfertility and a poor prognosis for treatment independent pregnancy will be included. Women with anovulatory cycles, severe endometriosis, double sided tubal pathology or serious endocrine illness will be excluded.Our primary outcome is the birth of a healthy singleton. Secondary outcomes are multiple pregnancy, treatment costs, and patient experiences in each treatment arm. The analysis will be performed according tot the intention to treat principle. We will test for non-inferiority of the three arms with respect to live birth. As we accept a 12.5% loss in pregnancy rate in one of the two IVF arms to prevent multiple pregnancies, we need 200 couples per arm (600 couples in total). Determining the safest and most cost-effective treatment will ensure optimal chances of pregnancy for subfertile couples with substantially diminished perinatal and maternal complications. Should patients find the most cost-effective treatment acceptable or even preferable, this could imply the need for a world wide shift in the primary treatment. Current Controlled Trials ISRCTN 52843371.

Holocene Sea-Levels from Greenland to Antarctica: A Pole-to-Pole Transect of Sea Level History

NASA Astrophysics Data System (ADS)

Horton, Benjamin; Peltier, William; Roy, Keven; Ashe, Erica; Shaw, Tim; Engelhart, Simon; Khan, Nicole; Kopp, Robert; Simkins, Lauren; Vacchi, Matteo; Woodroffe, Sarah

2017-04-01

The Holocene is the most recent period during which natural temperature variability predominates and, therefore, provides an important paleo perspective for understanding the climate:sea-level relationship prior to anthropogenic modification of the climate system. But our understanding of Holocene sea level is limited by a lack of a standard protocol that incorporates full consideration of vertical and temporal uncertainty for each sea-level index point. We have compiled a Holocene RSL database of 3000 validated sea-level index points from Greenland, North American Atlantic coast, Caribbean, South American Atlantic coast and Antarctica. The databases were collated using a formalized and consistent methodology to facilitate the development and comparison of regional RSL records. The database also includes information relevant to sediment compaction, and modelling of both modern-day and paleotidal ranges. We develop a spatio-temporal empirical hierarchical model to compare regional RSL histories and estimate rates of change. Holocene RSL history from near-field regions (e.g., Antarctica, Greenland and Canada) reveal a complex pattern of RSL fall from a maximum marine limit due to the net effect of eustatic sea-level rise and glacio-isostatic uplift with rates of RSL fall as great as 70 ± 5 m/ka (East Hudson Bay). Intermediate field regions (e.g., North American mid-Atlantic coast) display variable rates of RSL rise from the cumulative effect of eustatic and isostatic factors. Fast rates of RSL rise (up to 10 ± 4m/ka; New Jersey) are found in the early Holocene in regions near the center of forebulge collapse. Far-field RSL records (South American Atlantic coast) exhibit a mid-Holocene highstand, the timing and magnitude of which varies between 8 and 4 ka and <1 and 6 m, respectively. We compare RSL histories with the predictions from two recent models of the Glacial Isostatic Adjustment (GIA) process, namely the ICE-6GC (VM5a) model of Peltier et al. (2015) and the ICE-7G_NA (VM7) model of Roy and Peltier (2017 in press). Although the fit of these models to the wide range of inferred RSL histories along the pole-to-pole transect is very high quality, unexplained signals are identified in several restricted regions upon which work is continuing. It is remarkable that a spherically symmetric model of the internal viscoelastic structure is able to reconcile the wide range of RSL signals observed.

Unexplained Weight Loss

MedlinePlus

... weight is affected by your calorie intake, activity level, overall health, age, nutrient absorption, and economic and social factors. If you're losing weight without trying and you're concerned about it, consult your doctor — as a rule of thumb, losing more than 5 ...

The preparation of ethylenediamine-modified fluorescent carbon dots and their use in imaging of cells.

PubMed

Dong, Wei; Zhou, Siqi; Dong, Yan; Wang, Jingwen; Ge, Xin; Sui, Lili

2015-09-01

In this work, fluorescent carbon dots (CDs) were synthesized using a hydrothermal method with glucose as the carbon source and were surface-modified with ethylenediamine. The properties of as-prepared CDs were analyzed by transmission electron microscopy (TEM), Fourier transform infrared (FTIR), ultraviolet-visible light (UV/vis) absorption and fluorescent spectra. Furthermore, CDs conjugated with mouse anti-(human carcinoembryonic antigen) (CEA) monoclonal antibody were successful employed in the biolabeling and fluorescent imaging of human gastric carcinoma cells. In addition, the cytotoxicity of CDs was also tested using human gastric carcinoma cells. There was no apparent cytotoxicity on human gastric carcinoma cells. These results suggest the potential application of the as-prepared CDs in bioimaging and related fields. Copyright © 2015 John Wiley & Sons, Ltd.

Application of boronated anti-CEA immunoliposome to tumour cell growth inhibition in in vitro boron neutron capture therapy model.

PubMed Central

Yanagië, H.; Tomita, T.; Kobayashi, H.; Fujii, Y.; Takahashi, T.; Hasumi, K.; Nariuchi, H.; Sekiguchi, M.

1991-01-01

An immunoliposome containing a 10B-compound has been examined as a selective drug delivery system in boron neutron-capture therapy. Liposomes, conjugated with monoclonal antibodies specific for carcinoembryonic antigen (CEA) were shown to bind selectively to cells bearing CEA on their surface. The immunoliposomes attached to tumour cells suppressed growth in vitro upon thermal neutron irradiation and suppression was dependent upon the concentration of the 10B-compound in the liposomes and on the density of antibody conjugated to the liposomes. The results suggest that immunoliposomes containing the 10B-compound could act as a selective and efficient carrier of 10B atoms to target tumour cells in boron neutron-capture therapy. Images Figure 1 PMID:2021537

Biomarkers in pancreatic adenocarcinoma: current perspectives.

PubMed

Swords, Douglas S; Firpo, Matthew A; Scaife, Courtney L; Mulvihill, Sean J

2016-01-01

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC.

Biomarkers in pancreatic adenocarcinoma: current perspectives

PubMed Central

Swords, Douglas S; Firpo, Matthew A; Scaife, Courtney L; Mulvihill, Sean J

2016-01-01

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC. PMID:28003762

Study of pharmaceutical industrial problems

NASA Technical Reports Server (NTRS)

Pincus, J. H.

1979-01-01

The growth of a human colon carcinoma cell line (SK-CO-1) and its production of carcinoembryonic antigen (CEA) in monolayer culture and on single layers of glass beads in unit gravity were evaluated. The limitations of using a microsphere-cell growth system in unit gravity were identified and how these may be overcome in space was considered. The project had the following tasks: (1) growth of cultured human colon carcinoma cells on a monolayer and CEA production; (2) evaluation of CEA production and release by SK-CO-1 cells grown on glass beads; (3) evaluation of other microcarriers for growing SK-CO-1 cells and determination of the minimum amount of culture medium needed for cell growth; and (4) growth of SK-CO-1 cells on collagen monolayers and CEA production.

Space Shuttle Project

NASA Image and Video Library

1998-03-24

The roman candle effect as seen in this picture represents the testing of a solid rocket booster (SRB) for unexplained corrosion conditions (EUCC) which have occurred on the nozzles of redesigned solid rocket motors (RSRM). The motor being tested in this photo is a 48 M-NASA motor.

Anomalies.

ERIC Educational Resources Information Center

Online-Offline, 1999

1999-01-01

This theme issue on anomalies includes Web sites, CD-ROMs and software, videos, books, and additional resources for elementary and junior high school students. Pertinent activities are suggested, and sidebars discuss UFOs, animal anomalies, and anomalies from nature; and resources covering unexplained phenonmenas like crop circles, Easter Island,…

Unusual Transmission of Plasmodium falciparum, Bordeaux, France, 2009

PubMed Central

Vareil, Marc-Olivier; Tandonnet, Olivier; Chemoul, Audrey; Bogreau, Hervé; Saint-Léger, Mélanie; Micheau, Maguy; Millet, Pascal; Koeck, Jean-Louis; Boyer, Alexandre; Rogier, Christophe

2011-01-01

Plasmodium falciparum malaria is usually transmitted by mosquitoes. We report 2 cases in France transmitted by other modes: occupational blood exposure and blood transfusion. Even where malaria is not endemic, it should be considered as a cause of unexplained acute fever. PMID:21291597

Placental telomere shortening in stillbirth: a sign of premature senescence?

PubMed

Ferrari, Francesca; Facchinetti, Fabio; Saade, George; Menon, Ramkumar

2016-01-01

The objective of this study is to investigate placental telomere shortening in unexplained stillbirths (SBs) as an indication of premature senescence. Placentas were collected from 42 unexplained SB (>22 weeks), 43 term and 15 preterm live births, at the Policlinico Hospital of Modena (Italy). DNA extracted from placentae was studied for telomere length by real time PCR. Standard curves were generated for telomere lengths from single copy gene amplifications using a reference DNA. The telomere length for each sample was derived based on the ratio of telomere length between the sample and single copy gene standard (T/S ratio). The mean ratio of placental telomere in term live births was 5.181 ± 3.841. A twofold decrease in telomere length was seen in SBs (over all 2.455 ± 1.239; p < 0.001). For early SBs (above 34 weeks), the T/S was 2.8884 ± 1.224 and for late SBs, the T/S was 2.207 ± 1.201, both lower than term live births (both p < 0.01). T/S remained lower both in small for gestational age-SB (2.639 ± 1.619) and appropriate for gestational age-SB (2.653 ± 1.335) with no difference between these subgroups (p = ns). T/S was lower in SB compared with spontaneous preterm births (PTBs) (6.382 ± 5.525; p < 0.01), whereas SBs telomere length were similar to those of preterm premature rupture of membranes (pPROM) (3.296 ± 3.599; p = ns). Substantial reduction in telomere length in SBs is indicative of placental senescence. These data provide mechanistic insights that premature aging may lead to placental dysfunction as an initiator of fetal demise in unexplained SBs.

Attributions of cancer 'alarm' symptoms in a community sample.

PubMed

Whitaker, Katriina L; Scott, Suzanne E; Winstanley, Kelly; Macleod, Una; Wardle, Jane

2014-01-01

Attribution of early cancer symptoms to a non-serious cause may lead to longer diagnostic intervals. We investigated attributions of potential cancer 'alarm' and non-alarm symptoms experienced in everyday life in a community sample of adults, without mention of a cancer context. A questionnaire was mailed to 4858 adults (≥50 years old, no cancer diagnosis) through primary care, asking about symptom experiences in the past 3 months. The word cancer was not mentioned. Target 'alarm' symptoms, publicised by Cancer Research UK, were embedded in a longer symptom list. For each symptom experienced, respondents were asked for their attribution ('what do you think caused it'), concern about seriousness ('not at all' to 'extremely'), and help-seeking ('did you contact a doctor about it': Yes/No). The response rate was 35% (n = 1724). Over half the respondents (915/1724; 53%) had experienced an 'alarm' symptom, and 20 (2%) cited cancer as a possible cause. Cancer attributions were highest for 'unexplained lump'; 7% (6/87). Cancer attributions were lowest for 'unexplained weight loss' (0/47). A higher proportion (375/1638; 23%) were concerned their symptom might be 'serious', ranging from 12% (13/112) for change in a mole to 41% (100/247) for unexplained pain. Just over half had contacted their doctor about their symptom (59%), although this varied by symptom. Alarm symptoms were appraised as more serious than non-alarm symptoms, and were more likely to trigger help-seeking. Consistent with retrospective reports from cancer patients, 'alarm' symptoms experienced in daily life were rarely attributed to cancer. These results have implications for understanding how people appraise and act on symptoms that could be early warning signs of cancer.

The black box in somatization: unexplained physical symptoms, culture, and narratives of trauma.

PubMed

Waitzkin, H; Magaña, H

1997-09-01

Stimulated by our clinical work with patients who manifest unexplained "somatoform" symptoms in the primary care setting, this article addresses a theoretical black box in our understanding of somatization: how does culture mediate severe stress to produce symptoms that cannot be explained by the presence of physical illness? Despite various problems in his explanation of hysteria, Freud broke new ground by emphasizing narratives of traumatic experiences in the development and treatment of unexplained physical symptoms. Except in anthropologically oriented cultural psychiatry, contemporary psychiatry has traveled away from a focus on narrative in the study of somatization. On the other hand, recent interest in narrative has spread across many intellectual disciplines, including the humanities and literary criticism, psychology, history, anthropology, and sociology. We operationally define narratives as attempts at storytelling that portray the interrelationships among physical symptoms and the psychologic, social, or cultural context of these symptoms. Regarding somatization and trauma, we focus on the ways that narrative integrates the cultural context with traumatic life events. In explaining the black box, we postulate that extreme stress (torture, rape, witnessing deaths of relatives, forced migration, etc.) is processed psychologically as a terrible, largely incoherent narrative of events too awful to hold in consciousness. Culture patterns the psychologic and somatic expression of the terrible narrative. Methodologically, we have developed some techniques for eliciting narratives of severe stress and somatic symptoms, which we illustrate with observations from an ongoing research project. In designing interventions to improve the care of somatizing patients, we are focusing on the creation of social situations where patients may feel empowered to express more coherent narratives of their prior traumatic experiences.

Obstetric outcomes of recurrent pregnancy loss patients diagnosed wıth inherited thrombophilia.

PubMed

Karadağ, C; Yoldemir, T; Karadağ, S D; İnan, C; Dolgun, Z N; Aslanova, L

2017-08-01

Recurrent pregnancy loss (RPL) is defined by two or more failed pregnancies. The relation between RPL and inherited thrombophilia requires anticoagulant therapy during pregnancy. However the obstetric outcomes have not been well defined in these RPL patients diagnosed with inherited thrombophilia, who have been given anticoagulant therapy. To investigate the obstetric outcomes in pregnant women with RPL who are given low molecular weight heparin (LMWH) and low-dose aspirin due to diagnosis of inherited thrombophilia. A hundred and eight RPL women were diagnosed with inherited thrombophilia, and 98 women were diagnosed with unexplained RPL. The patients with inherited thrombophilia were given LMWH and low-dose aspirin. Unexplained RPL patients were not given any medicine. The obstetric outcomes of participants were noted. In thrombophilic group, the live-birth levels were significantly higher [90 (83%) vs 67 (68%) p < 0.05], and the miscarriage levels were significantly lower than that in the control group [14 (13%) vs 27 (28%) p < 0.01]. The number of patients with preeclampsia was significantly higher in the thrombophilic group [16 (15%) vs 6 (6%) p < 0.05]. The number of preterm births was significantly higher than that of the controls [25 (23%) vs 10 (10%) p < 0.05]. The median gestation age of delivery was 35 weeks for thrombophilic patients and 38 weeks for controls (p < 0.05). The RPL patients diagnosed with inherited thrombophilia and who were given LMWH with low-dose aspirin had higher live-birth rates and lower miscarriage rates than those in the unexplained RPL patients. Increased risk of preeclampsia is seen in RPL patients with inherited thrombophilia despite thrombophilia prophylaxis.

Lead intoxication due to ayurvedic medications as a cause of abdominal pain in adults.

PubMed

Mehta, Varun; Midha, Vandana; Mahajan, Ramit; Narang, Vikram; Wander, Praneet; Sood, Ridhi; Sood, Ajit

2017-02-01

Though a majority of cases of lead intoxication come from occupational exposures, traditional and folk remedies have also been reported to contain toxic amounts of lead. We present a large series of patients with lead poisoning due to intake of Ayurvedic medicines, all of whom presented with unexplained abdominal pain. This was a retrospective, observational case series from a tertiary care center in India. The charts of patients who underwent blood lead level (BLL) testing as a part of workup for unexplained abdominal pain between 2005 and 2013 were reviewed. The patients with lead intoxication (BLLs >25 μg/dl) were identified and demographics, history, possible risk factors, clinical presentation and investigations were reviewed. Treatment details, duration, time to symptomatic recovery, laboratory follow-up and adverse events during therapy were recorded. BLLs were tested in 786 patients with unexplained abdominal pain and high levels were identified in 75 (9.5%) patients, of which a majority (73 patients, 9.3%) had history of Ayurvedic medication intake and only two had occupational exposure. Five randomly chosen Ayurvedic medications were analyzed and lead levels were impermissibly high (14-34,950 ppm) in all of them. Besides pain in abdomen, other presenting complaints were constipation, hypertension, neurological symptoms and acute kidney injury. Anemia and abnormal liver biochemical tests were observed in all the 73 patients. Discontinuing the Ayurvedic medicines and chelation with d-penicillamine led to improvement in symptoms and reduction in BLLs in all patients within 3-4 months. The patients presenting with severe recurrent abdominal pain, anemia and history of use of Ayurvedic medicines should be evaluated for lead toxicity. Early diagnosis in such cases can prevent unnecessary investigations and interventions, and permits early commencement of the treatment.

Response to parenteral iron therapy distinguish unexplained refractory iron deficiency anemia from iron-refractory iron deficiency anemia.

PubMed

Akin, M; Sarbay, H; Guler, S; Balci, Y I; Polat, A

2016-04-01

We evaluated that response to parenteral iron therapy could be helpful in distinguishing the types of iron deficiency anemia. This study analyzed responses to IV iron sucrose therapy of 15 children with unexplained refractory iron deficiency anemia (URIDA). We compared the results at diagnosis, 6 weeks and 6 months after the therapy. Results were compared with responses of 11 patients' results with iron-refractory iron deficiency anemia (IRIDA) from our previous study. Six weeks after the start of treatment, ferritin, MCV, MCH and Hb values were in normal range in 10 patients. The increase in Hb, MCH, MCV, and ferritin values ranged 2.6-3.5 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. In five patients, Hb, MCH, and MCV mean (range) values [11.2 g/dL (11-12.2), 24.5 pg (24-25.6), and 67 fL (65-70)] were nearly normal but ferritin mean (range) values [9.8 ng/mL (8-11)] were below normal. Six weeks after the start of treatment, Hb, MCH, MCV and ferritin values of patients with IRIDA were increased. The increase in Hb, MCH, MCV, and ferritin values ranged 0.8-2.7 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. IRIDA is only partially responsive to parenteral iron supplementation. In conclusion, this study demonstrated that the response to intravenous iron therapy for the URIDA cases improved blood parameters more effectively than hereditary IRIDA. Response to parenteral iron therapy would be helpful to distinguish unexplained refractory IDA from hereditary IRIDA for clinicians who do not have access to hepcidin or TMPRS6 mutation analysis. © 2016 John Wiley & Sons Ltd.

Diagnostic Yield and Economic Assessment of a Diagnostic Protocol With Systematic Use of an External Loop Recorder for Patients With Palpitations.

PubMed

Francisco-Pascual, Jaume; Santos-Ortega, Alba; Roca-Luque, Ivo; Rivas-Gándara, Nuria; Pérez-Rodón, Jordi; Milà-Pascual, Laia; García-Dorado, David; Moya-Mitjans, Àngel

2018-05-24

To assess the diagnostic yield and cost-effectiveness of a diagnostic protocol based on the systematic use of latest-generation external loop recorders (ELRs) compared with the classic diagnostic strategy for patients with recurrent unexplained palpitations. Two cohorts of consecutive patients referred for diagnosis of unexplained palpitations to the outpatient clinic of the arrhythmia unit were compared: a prospective cohort after the implementation of a new diagnostic protocol based on the systematic use of ELRs, and another, retrospective, cohort before the implementation of the protocol. The cost of diagnosis was calculated based on the number of complementary examinations, visits to outpatient clinics, or emergency department visits required to reach a diagnosis, and its costs according the prices published for the local health system. One hundred and forty-nine patients were included (91 in the ELR group, 58 in the control group). The diagnostic yield was higher in the ELR group (79 [86.8%] definitive diagnoses in the ELR group vs 12 [20.7%] in the control group, P < .001). The cost per diagnosis was €375.13 in the ELR group and €5184.75 in the control group (P < .001). The cost-effectiveness study revealed that the systematic use of ELR resulted in a cost reduction of €11.30 for each percentage point of increase in diagnosis yield. In patients with recurrent unexplained palpitations, evaluation by means of a study protocol that considers the systematic use of a latest-generation ELR increases diagnostic yield while reducing the cost per diagnosis. Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Aetiological diagnosis of male sex ambiguity: a collaborative study.

PubMed

Morel, Yves; Rey, Rodolfo; Teinturier, Cécile; Nicolino, Marc; Michel-Calemard, Laurence; Mowszowicz, Irène; Jaubert, Francis; Fellous, Marc; Chaussain, Jean-Louis; Chatelain, Pierre; David, Michel; Nihoul-Fékété, Claire; Forest, Maguelone G; Josso, Nathalie

2002-01-01

A collaborative study, supported by the Biomed2 Programme of the European Community, was initiated to optimise the aetiological diagnosis in genetic or gonadal males with intersex disorders, a total of 67 patients with external sexual ambiguity, testicular tissue and/or a XY karyotype. In patients with gonadal dysgenesis or true hermaphroditism, the incidence of vaginal development was 100%, a uterus was present in 60%; uni or bilateral cryptorchidism was seen in nearly all cases of testicular dysgenesis (99%) but in only 57% of true hermaphrodites. Mean serum levels of anti-mullerian hormone and of serum testosterone response to chorionic gonadotropin stimulation were significantly decreased in both conditions, by comparison with patients with unexplained male pseudohermaphroditism or partial androgen insensitivity (PAIS). Mutations in the androgen receptor, 90% within exons 2-8, were detected in patients with PAIS. Clinically, a vaginal pouch was present in 90%, cryptorchidism in 36%. In 52% of cases, no diagnosis could be reached, despite an exhaustive clinical and laboratory work-up, including routine sequencing of exons 2-8 of the androgen receptor. By comparison with PAIS, unexplained male pseudohermaphroditism was characterised by a lower incidence of vaginal pouch (55%) and cryptorchidism (22%) but a high incidence of prematurity/intrauterine growth retardation (30%) or mild malformations (14%). reaching an aetiological diagnosis in cases of male intersex is difficult because of the variability of individual cases. Hormonal tests may help to discriminate between partial androgen insensitivity and gonadal dysgenesis/true hermaphroditism but are of less use for differentiating from unexplained male pseudohermaphroditism. Sequencing of exons 2-8 of the androgen receptor after study of testosterone precursors following human chorionic gonadotrophin stimulation is recommended when gonadal dysgenesis and true hermaphroditism can be excluded.

Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction

PubMed Central

2011-01-01

Background It has been well documented that pre-eclampsia and unexplained fetal growth restriction (FGR) have a common etiological background, but little is known about their linkage at the molecular level. The aim of this study was to further investigate the mechanisms underlying pre-eclampsia and unexplained FGR. Methods We analyzed differentially expressed genes in placental tissue from severe pre-eclamptic pregnancies (n = 8) and normotensive pregnancies with or (n = 8) without FGR (n = 8) using a microarray method. Results A subset of the FGR samples showed a high correlation coefficient overall in the microarray data from the pre-eclampsia samples. Many genes that are known to be up-regulated in pre-eclampsia are also up-regulated in FGR, including the anti-angiogenic factors, FLT1 and ENG, believed to be associated with the onset of maternal symptoms of pre-eclampsia. A total of 62 genes were found to be differentially expressed in both disorders. However, gene set enrichment analysis for these differentially expressed genes further revealed higher expression of TP53-downstream genes in pre-eclampsia compared with FGR. TP53-downstream apoptosis-related genes, such as BCL6 and BAX, were found to be significantly more up-regulated in pre-eclampsia than in FGR, although the caspases are expressed at equivalent levels. Conclusions Our current data indicate a common pathophysiology for FGR and pre-eclampsia, leading to an up-regulation of placental anti-angiogenic factors. However, our findings also suggest that it may possibly be the excretion of these factors into the maternal circulation through the TP53-mediated early-stage apoptosis of trophoblasts that leads to the maternal symptoms of pre-eclampsia. PMID:21810232

Lower frequency of the HLA-G UTR-4 haplotype in women with unexplained recurrent miscarriage.

PubMed

Meuleman, T; Drabbels, J; van Lith, J M M; Dekkers, O M; Rozemuller, E; Cretu-Stancu, M; Claas, F H J; Bloemenkamp, K W M; Eikmans, M

2018-04-01

HLA-G expressed by trophoblasts at the fetal-maternal interface and its soluble form have immunomodulatory effects. HLA-G expression depends on the combination of DNA polymorphisms. We hypothesized that combinations of specific single nucleotide polymorphisms (SNPs) in the 3'untranslated region (3'UTR) of HLA-G play a role in unexplained recurrent miscarriage. In a case control design, 100 cases with at least three unexplained consecutive miscarriages prior to the 20th week of gestation were included. Cases were at time of the third miscarriage younger than 36 years, and they conceived all their pregnancies from the same partner. The control group included 89 women with an uneventful pregnancy. The association of HLA-G 3'UTR SNPs and specific HLA-G haplotype with recurrent miscarriage was studied with logistic regression. Odds ratios (OR) and 95% confidence intervals (95% CI) were reported. Individual SNPs were not significantly associated with recurrent miscarriage after correction for multiple comparisons. However, the presence of the UTR-4 haplotype, which included +3003C, was significantly lower in women with recurrent miscarriage (OR 0.4, 95% CI 0.2-0.8, p = 0.015). In conclusion, this is the first study to perform a comprehensive analysis of HLA-G SNPs and HLA-G haplotypes in a well-defined group of women with recurrent miscarriage and women with uneventful pregnancy. The UTR-4 haplotype was less frequently observed in women with recurrent miscarriage, suggesting an immunoregulatory role of this haplotype for continuation of the pregnancy without complications. Thus, association of HLA-G with recurrent miscarriage is not related to single polymorphisms in the 3'UTR, but is rather dependent on haplotypes. Copyright © 2018 Elsevier B.V. All rights reserved.

Modeling Efficacy of Bevacizumab Treatment for Metastatic Colon Cancer

PubMed Central

Islam, Rezwan; Chyou, Po-Huang; Burmester, James K

2013-01-01

Purpose: Bevacizumab, an FDA-approved adjuvant treatment for metastatic colon cancer, has extended survival for many patients. However, factors predicting response to treatment remain undefined. Patients and Methods: Relevant clinical and environmental data were abstracted from medical records of 149 evaluable patients treated with bevacizumab for metastatic colon cancer at a multi-specialty clinic. Tumor response was calculated from radiologic reports using Response Evaluation Criteria in Solid Tumors (RECIST) criteria and verified by oncologist review. Patients with at least one occurrence of complete or partial response or stable disease were classified as responders; those exhibiting progressive disease were classified as non-responders. Results: Univariate analysis demonstrated that blood in stool (P<0.05), unexplained weight loss (P<0.05), primary colon cancer site (P<0.05), chemotherapy treatment of primary tumor site (P<0.05), and adenocarcinoma versus adenoma subtype (P<0.05) was associated with tumor responsiveness. Factors remaining statistically significant following multivariate modeling included adenocarcinoma as tumor cell type versus other adenocarcinoma subtypes (OR=6.35, 95% CI: 1.08-37.18), chemotherapy treatment applied to primary tumor (OR= 0.07, 95% CI: 0.0-0.76,), tumor localization to cecal/ascending colon (OR=0.061, 95% CI: 0.006-0.588,), and unexplained weight loss (OR=0.1, 95% CI: 0.02-0.56,). Chemotherapy treatment of primary tumor, unexplained weight loss, and cecal/ascending localization of the tumor were associated with poorer outcomes. Adenocarcinoma as cell type compared to other adenocarcinoma subtypes was associated with better response to bevacizumab treatment. Conclusion: Results suggest that response to bevacizumab therapy may be predicted by modeling clinical factors including symptomology on presentation, tumor location and type, and initial response to chemotherapy. PMID:23678369

Multiple unexplained fractures in infants and child physical abuse.

PubMed

Cannell, John Jacob; Holick, Michael F

2018-01-01

When an infant presents with X-rays showing multiple unexplained fractures in various stages of healing (MUFVSH), the child is usually diagnosed with child abuse based on criteria of the Academy of Pediatrics' Committee on Child Abuse and Neglect (AAPCCAAN). Almost always, the infant is subsequently removed from the home and civil or criminal proceeding commence. It may be that healing infantile rickets or other poorly understood metabolic bone disorders of infancy are responsible for these x-rays. Activated vitamin D is a seco-steroid hormone, whose mechanism of action is genetic regulation. Lack of it can result in musculoskeletal defects known as rickets. Low calcium can also cause rickets. However, it is clear that experts for the state believe that the x-rays in these cases are so definitive as to be pathognomonic for child abuse. Therefore, if the caregivers deny abusing their infants, experts following American Academy of Pediatric's Committee on Child Abuse and Neglect. guidelines are essentially claiming that x-rays showing multiple unexplained fractures in various stages of healing are lie detector tests. However, it is not widely appreciated that the gold standard for the diagnosis of rickets is a bone biopsy, not x-rays, as radiologists miss biopsy proven rickets 80% of the time; that is, 4 out of 5 infants with rickets will have normal x-rays. In this article we provide reports of two cases and their outcomes. We discuss information about healing infantile rickets and an example of common sense medical conclusions in these cases. This information could lead to a significant reduction in the number of innocent parents having their infant removed or sent to prison. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Randomized Trial of Progesterone in Women with Recurrent Miscarriages.

PubMed

Coomarasamy, Arri; Williams, Helen; Truchanowicz, Ewa; Seed, Paul T; Small, Rachel; Quenby, Siobhan; Gupta, Pratima; Dawood, Feroza; Koot, Yvonne E M; Bender Atik, Ruth; Bloemenkamp, Kitty W M; Brady, Rebecca; Briley, Annette L; Cavallaro, Rebecca; Cheong, Ying C; Chu, Justin J; Eapen, Abey; Ewies, Ayman; Hoek, Annemieke; Kaaijk, Eugenie M; Koks, Carolien A M; Li, Tin-Chiu; MacLean, Marjory; Mol, Ben W; Moore, Judith; Ross, Jackie A; Sharpe, Lisa; Stewart, Jane; Vaithilingam, Nirmala; Farquharson, Roy G; Kilby, Mark D; Khalaf, Yacoub; Goddijn, Mariette; Regan, Lesley; Rai, Rajendra

2015-11-26

Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain. We conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice-daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation. A total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, -4.0 to 9.0). There were no significant between-group differences in the rate of adverse events. Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (Funded by the United Kingdom National Institute of Health Research; PROMISE Current Controlled Trials number, ISRCTN92644181.).

The effect of swim-up and gradient sperm preparation techniques on deoxyribonucleic acid (DNA) fragmentation in subfertile patients.

PubMed

Oguz, Yuksel; Guler, Ismail; Erdem, Ahmet; Mutlu, Mehmet Firat; Gumuslu, Seyhan; Oktem, Mesut; Bozkurt, Nuray; Erdem, Mehmet

2018-03-23

To compare the effect of two different sperm preparation techniques, including swim-up and gradient methods on sperm deoxyribonucleic acid (DNA) fragmentation status of semen samples from unexplained and mild male factor subfertile patients undergoing intrauterine insemination (IUI). A prospective randomized study was conducted in 65 subfertile patients, including 34 unexplained and 31 male factor infertility to compare basal and post-procedure DNA fragmentation rates in swim-up and gradient techniques. Sperm DNA fragmentation rates were evaluated by a sperm chromatin dispersion (SCD) test in two portions of each sample of semen that was prepared with either swim-up or gradient techniques. Sperm motility and morphology were also assessed based on WHO 2010 criteria. Swim-up but not gradient method yielded a statistically significant reduction in the DNA fragmented sperm rate after preparation as compared to basal rates, in the semen samples of both unexplained (41.85 ± 22.04 vs. 28.58 ± 21.93, p < 0.001 for swim-up; and 41.85 ± 22.04 vs. 38.79 ± 22.30, p = 0.160 for gradient) and mild male factor (46.61 ± 19.38 vs. 30.32 ± 18.20, p < 0.001 for swim-up and 46.61 ± 19.38 vs. 44.03 ± 20.87, p = 0.470 for gradient) subgroups. Swim-up method significantly reduces sperm DNA fragmentation rates and may have some prognostic value on intrauterine insemination in patients with decreased sperm DNA integrity.

Low-level APC mutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases.

PubMed

Spier, Isabel; Drichel, Dmitriy; Kerick, Martin; Kirfel, Jutta; Horpaopan, Sukanya; Laner, Andreas; Holzapfel, Stefanie; Peters, Sophia; Adam, Ronja; Zhao, Bixiao; Becker, Tim; Lifton, Richard P; Perner, Sven; Hoffmann, Per; Kristiansen, Glen; Timmermann, Bernd; Nöthen, Markus M; Holinski-Feder, Elke; Schweiger, Michal R; Aretz, Stefan

2016-03-01

In 30-50% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, or POLE or POLD1, causing polymerase-proofreading-associated polyposis can be identified, although a hereditary aetiology is likely. This study aimed to explore the impact of APC mutational mosaicism in unexplained polyposis. To comprehensively screen for somatic low-level APC mosaicism, high-coverage next-generation sequencing of the APC gene was performed using DNA from leucocytes and a total of 53 colorectal tumours from 20 unrelated patients with unexplained sporadic adenomatous polyposis. APC mosaicism was assumed if the same loss-of-function APC mutation was present in ≥ 2 anatomically separated colorectal adenomas/carcinomas per patient. All mutations were validated using diverse methods. In 25% (5/20) of patients, somatic mosaicism of a pathogenic APC mutation was identified as underlying cause of the disease. In 2/5 cases, the mosaic level in leucocyte DNA was slightly below the sensitivity threshold of Sanger sequencing; while in 3/5 cases, the allelic fraction was either very low (0.1-1%) or no mutations were detectable. The majority of mosaic mutations were located outside the somatic mutation cluster region of the gene. The present data indicate a high prevalence of pathogenic mosaic APC mutations below the detection thresholds of routine diagnostics in adenomatous polyposis, even if high-coverage sequencing of leucocyte DNA alone is taken into account. This has important implications for both routine work-up and strategies to identify new causative genes in this patient group. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Attributions of Cancer ‘Alarm’ Symptoms in a Community Sample

PubMed Central

Whitaker, Katriina L.; Scott, Suzanne E.; Winstanley, Kelly; Macleod, Una; Wardle, Jane

2014-01-01

Background Attribution of early cancer symptoms to a non-serious cause may lead to longer diagnostic intervals. We investigated attributions of potential cancer ‘alarm’ and non-alarm symptoms experienced in everyday life in a community sample of adults, without mention of a cancer context. Methods A questionnaire was mailed to 4858 adults (≥50 years old, no cancer diagnosis) through primary care, asking about symptom experiences in the past 3 months. The word cancer was not mentioned. Target 'alarm' symptoms, publicised by Cancer Research UK, were embedded in a longer symptom list. For each symptom experienced, respondents were asked for their attribution (‘what do you think caused it'), concern about seriousness (‘not at all’ to ‘extremely’), and help-seeking (‘did you contact a doctor about it’: Yes/No). Results The response rate was 35% (n = 1724). Over half the respondents (915/1724; 53%) had experienced an ‘alarm’ symptom, and 20 (2%) cited cancer as a possible cause. Cancer attributions were highest for ‘unexplained lump’; 7% (6/87). Cancer attributions were lowest for ‘unexplained weight loss’ (0/47). A higher proportion (375/1638; 23%) were concerned their symptom might be ‘serious’, ranging from 12% (13/112) for change in a mole to 41% (100/247) for unexplained pain. Just over half had contacted their doctor about their symptom (59%), although this varied by symptom. Alarm symptoms were appraised as more serious than non-alarm symptoms, and were more likely to trigger help-seeking. Conclusions Consistent with retrospective reports from cancer patients, ‘alarm’ symptoms experienced in daily life were rarely attributed to cancer. These results have implications for understanding how people appraise and act on symptoms that could be early warning signs of cancer. PMID:25461959

Negotiating explanations: doctor-patient communication with patients with medically unexplained symptoms-a qualitative analysis.

PubMed

den Boeft, Madelon; Huisman, Daniëlle; Morton, LaKrista; Lucassen, Peter; van der Wouden, Johannes C; Westerman, Marjan J; van der Horst, Henriëtte E; Burton, Christopher D

2017-02-01

Patients with medically unexplained physical symptoms (MUPS) seek explanations for their symptoms, but often find general practitioners (GPs) unable to deliver these. Different methods of explaining MUPS have been proposed. Little is known about how communication evolves around these explanations. To examine the dialogue between GPs and patients related to explanations in a community-based clinic for MUPS. We categorized dialogue types and dialogue outcomes. Patients were ≥18 years with inclusion criteria for moderate MUPS: ≥2 referrals to specialists, ≥1 functional syndrome/symptoms, ≥10 on the Patient Health Questionnaire-15 and GP's judgement that symptoms were unexplained. We analysed transcripts of 112 audio-recorded consultations (39 patients and 5 GPs) from two studies on the Symptoms Clinic Intervention, a consultation intervention for MUPS in primary care. We used constant comparative analysis to code and classify dialogue types and outcomes. We extracted 115 explanation sequences. We identified four dialogue types, differing in the extent to which the GP or patient controlled the dialogue. We categorized eight outcomes of the sequences, ranging from acceptance to rejection by the patient. The most common outcome was holding (conversation suspended in an unresolved state), followed by acceptance. Few explanations were rejected by the patient. Co-created explanations by patient and GP were most likely to be accepted. We developed a classification of dialogue types and outcomes in relation to explanations offered by GPs for MUPS patients. While it requires further validation, it provides a framework, which can be used for teaching, evaluation of practice and research. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The effect of unions on the distribution of wages of hospital-employed registered nurses in the United States.

PubMed

Spetz, Joanne; Ash, Michael; Konstantinidis, Charalampos; Herrera, Carolina

2011-01-01

We estimate the impact of unionisation on the wage structure of hospital-employed registered nurses in the USA. We examine whether unions have an effect on wage differences associated with race, gender, immigration status, education and experience, as well as whether there is less unexplained wage variation among unionised nurses. In the past decade, there has been resurgence in union activity in the health care industry in the USA, particularly in hospitals. Numerous studies have found that unions are associated with higher wages. Unions may also affect the structure of wages paid to workers, by compressing the wage structure and reducing unexplained variation in wages. Cross-sectional analysis of pooled secondary data from the United States Current Population Survey, 2003-2006. Multivariate regression analysis of factors that predict wages, with models derived from labour economics. There are no wage differences associated with gender, race or immigration status among unionised nurses, but there are wage penalties for black and immigrant nurses in the non-union sector. For the most part, the pay structures of the union and non-union sectors do not significantly differ. The wage penalty associated with diploma education for non-union nurses disappears among unionised nurses. Unionised nurses receive a lower return to experience, although the difference is not statistically significant. There is no evidence that unexplained variation in wages is lower among unionised nurses. While in theory unions may rationalise wage-setting and reduce wage dispersion, we found no evidence to support this hypothesis. The primary effect of hospital unions is to raise wages. Unionisation does not appear to have other important wage effects among hospital-employed nurses. © 2010 Blackwell Publishing Ltd.

PREDICTING A THIRD PLANET IN THE KEPLER-47 CIRCUMBINARY SYSTEM

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

Hinse, Tobias C.; Haghighipour, Nader; Kostov, Veselin B.

2015-01-20

We have studied the possibility that a third circumbinary planet in the Kepler-47 planetary system is the source of the single unexplained transiting event reported during the discovery of these planets. We applied the MEGNO technique to identify regions in the phase space where a third planet can maintain quasi-periodic orbits, and assessed the long-term stability of the three-planet system by integrating the entire five bodies (binary + planets) for 10 Myr. We identified several stable regions between the two known planets as well as a region beyond the orbit of Kepler-47c where the orbit of the third planet could bemore » stable. To constrain the orbit of this planet, we used the measured duration of the unexplained transit event (∼4.15 hr) and compared that with the transit duration of the third planet in an ensemble of stable orbits. To remove the degeneracy among the orbits with similar transit durations, we considered the planet to be in a circular orbit and calculated its period analytically. The latter places an upper limit of 424 days on the orbital period of the third planet. Our analysis suggests that if the unexplained transit event detected during the discovery of the Kepler-47 circumbinary system is due to a planetary object, this planet will be in a low eccentricity orbit with a semi-major axis smaller than 1.24 AU. Further constraining of the mass and orbital elements of this planet requires a re-analysis of the entire currently available data, including those obtained post-announcement of the discovery of this system. We present details of our methodology and discuss the implication of the results.« less

Disability, distress and unemployment in neurology outpatients with symptoms 'unexplained by organic disease'.

PubMed

Carson, A; Stone, J; Hibberd, C; Murray, G; Duncan, R; Coleman, R; Warlow, C; Roberts, R; Pelosi, A; Cavanagh, J; Matthews, K; Goldbeck, R; Hansen, C; Sharpe, M

2011-07-01

To determine the disability, distress and employment status of new neurology outpatients with physical symptoms unexplained by organic disease and to compare them with patients with symptoms explained by organic disease. As part of a cohort study (the Scottish Neurological Symptoms Study) neurologists rated the extent to which each new patient's symptoms were explained by organic disease. Patients whose symptoms were rated as 'not at all' or only 'somewhat' explained by disease were considered cases, and those whose symptoms were 'largely' or 'completely' explained by disease were considered controls. All patients completed self-ratings of disability, health status (Medical Outcomes Study Short Form 12-Item Scale (SF-12)) and emotional distress (Hospital Anxiety and Depression Scale) and also reported their employment and state financial benefit status. 3781 patients were recruited: 1144 (30%) cases and 2637 (70%) controls. Cases had worse physical health status (SF-12 score 42 vs 44; difference in means 1.7 (95% CI -2.5 to 0.9)) and worse mental health status (SF-12 score 43 vs 47; difference in means -3.5 (95% CI -4.3 to to 2.7)). Unemployment was similar in cases and controls (50% vs 50%) but cases were more likely not to be working for health reasons (54% vs 37% of the 50% not working; OR 2.0 (95% CI 1.6 to 2.4)) and also more likely to be receiving disability-related state financial benefits (27% vs 22%; (OR 1.3, 95% CI 1.1 to 1.6)). New neurology patients with symptoms unexplained by organic disease have more disability-, distress- and disability-related state financial benefits than patients with symptoms explained by disease.

Subfertility in Women With Rheumatoid Arthritis and the Outcome of Fertility Assessments.

PubMed

Brouwer, Jenny; Fleurbaaij, Rosalie; Hazes, Johanna M W; Dolhain, Radboud J E M; Laven, Joop S E

2017-08-01

Subfertility is frequently encountered among female rheumatoid arthritis (RA) patients and has been associated with disease activity and antirheumatic drugs. However, little is known about the results of the fertility assessments in these women. Our aim was to study the outcome of fertility assessments in subfertile women with RA. A cross-sectional study was performed in a nationwide cohort of female RA patients who were pregnant or trying to conceive between 2002 and 2010 (Pregnancy-Induced Amelioration of Rheumatoid Arthritis Study). Patients who had given consent for future contact (n = 260) received a questionnaire on reproductive history, fertility examinations, and fertility treatments. Medical files were obtained from attending gynecologists. A completed questionnaire was returned by 178 women (68%), of whom 96% had ended their efforts to conceive. Eighty-two subjects (46%) had at least 1 subfertile episode, and for 61 women a diagnosis for subfertility was available. Unexplained subfertility (48%) and anovulation (28%) were the most common gynecologic diagnoses, and both occurred more often in RA patients than reported in the general population. Women with unexplained subfertility more often used nonsteroidal antiinflammatory drugs (NSAIDs) during the periconceptional period. Seventeen percent of all pregnancies were conceived after fertility treatments. Fertility treatments had equal or higher pregnancy rates in RA compared to other subfertile populations. Unexplained subfertility is more often diagnosed in subfertile female RA patients than in the general population, and is related to periconceptional NSAID use. Despite the higher incidence of subfertility in women with RA, the outcome of fertility treatments in these women appears favorable. © 2016 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Surgical lung biopsy in patients with hematological malignancy or hematopoietic stem cell transplantation and unexplained pulmonary infiltrates: improved outcome with specific diagnosis.

PubMed

Zihlif, Mamoon; Khanchandani, Geeta; Ahmed, Huma P; Soubani, Ayman O

2005-02-01

Using a retrospective review of medical records, we sought the findings of surgical lung biopsy (SLB) in patients with hematological malignancy or hematopoietic stem cell transplantation (HSCT) and unexplained pulmonary infiltrates and to determine the impact of this procedure on management and outcome of these patients. Sixty-two patients who underwent SLB were evaluated; 31 patients had underlying hematological malignancy and 31 patients were HSCT recipients; 58% of whom underwent allogeneic HSCT. Thirty-three patients (53%) had focal infiltrates on chest CT scan while 29 (47%) had diffuse infiltrates. Thirteen patients were mechanically ventilated prior to SLB, and 27 (43%) were neutropenic. There were 66 diagnoses in the 62 patients, 44 (67%) were specific and 22 (33%) were nonspecific. The most common specific diagnoses were infection (29%), malignancy (27%), and inflammatory conditions (11%). Aspergillosis was the most common diagnosis of all biopsies (21%). SLB led to a change in therapy in 40% of patients and was associated with complications in 7 patients (11%). Specific diagnosis was more likely to lead to a change in therapy (48% vs. 27%, P = 0.06) and was associated with a lower mortality when compared to a nonspecific finding (30% vs. 59%, P = 0.02). Nonspecific diagnosis, on the other hand, was seen more in patients on mechanical ventilation prior to SLB compared to those off mechanical ventilation (69% vs. 27%, P = 0.02). SLB provides a specific diagnosis in the majority of patients with hematologic malignancy or HSCT recipients and unexplained pulmonary infiltrates. Specific diagnosis is more likely to lead to a change in therapy and is associated with a better outcome. Copyright 2005 Wiley-Liss, Inc.

The medico-legal investigation of sudden, unexpected and/or unexplained infant deaths in South Africa: where are we--and where are we going?

PubMed

du Toit-Prinsloo, L; Dempers, J J; Wadee, S A; Saayman, G

2011-03-01

Sudden Infant Death Syndrome (SIDS) has been reported to be the leading cause of death in infants under 1 year of age in many countries. Unfortunately, a paucity of published research data exists in South Africa, with regard to the incidence of and investigation into the circumstances surrounding Sudden Unexplained Deaths in Infants (SUDI) and/or SIDS. Currently, even though most academic centers conform to a protocol consistent with internationally accepted standards, there exists no nationally accepted infant death investigation protocol in South Africa. It is the aim of this study to review the current practice of infant death investigation in two representative but geographically and demographically distinct centers. Retrospective case audit over a five-year period (2000-2004) was conducted at two large medico-legal mortuaries in Pretoria (Gauteng) and Tygerberg (Cape Town). Case files on all infants younger than 1 year of age were reviewed. The outcome measures included number of deaths, demographic details and the nature and final outcome of the post mortem examinations. A total of 512 cases were identified as possible SIDS cases and of these, 171 was classified as SIDS. The study showed marked inter-case and inter-divisional variation in terms of the investigation of infant deaths at the two institutions. It is envisaged that this study will focus attention on the current lack of usable data regarding sudden/unexplained/unexpected infant deaths in South Africa, and aid in the formulation and implementation of a practical (yet internationally accountable) infant death investigation protocol, which could facilitate comparisons with other countries and initiate further structured research in this field.

Estrogen replacement, vascular distensibility, and blood pressures in postmenopausal women.

PubMed

De Meersman, R E; Zion, A S; Giardina, E G; Weir, J P; Lieberman, J S; Downey, J A

1998-05-01

The pathogenesis of blood pressure (BP) rise in aging women remains unexplained, and one of the many incriminating factors may include abnormalities in arteriolar resistance vessels. The aim of this study was to determine the effects of unopposed estrogen on arteriolar distensibility, baroreceptor sensitivity (BRS), BP changes, and rate-pressure product (RPP). We tested the hypotheses that estrogen replacement therapy (ERT) enhances arteriolar distensibility and ameliorates BRS, which leads to decreases in BP and RPP. Postmenopausal women participated in a single-blind crossover study; the participants of this study, after baseline measurements, were randomly assigned to receive estrogen (ERT) or a drug-free treatment with a 6-wk washout period between treatments. The single-blind design was instituted because subjects become unblinded due to physiological changes (i.e., fluid shifts, weight gain, and secretory changes) associated with estrogen intake. However, investigators and technicians involved in data collection and analyses remained blind. After each treatment, subjects performed identical autonomic tests, during which electrocardiograms, beat-by-beat BPs, and respiration were recorded. The area under the dicrotic notch of the BP wave was used as an index of arteriolar distensibility. The magnitude of the reflex bradycardia after a precipitous rise in BP was used to determine BRS. Power spectral analysis of heart rate variability was used to assess autonomic activity. BPs were recorded from resistance vessels in the finger using a beat-by-beat photoplethysmographic device. RPP, a noninvasive marker of myocardial oxygen consumption, was calculated. Repeated-measures analyses of variance revealed a significantly enhanced arteriolar distensibility and BRS after ERT (P < 0.05). A trend of a lower sympathovagal balance at rest was observed after ERT, however, this trend did not reach statistical significance (P = 0.061) compared with the other treatments. The above autonomic changes produced significantly lower systolic and diastolic BP changes and RPPs (P < 0.05) at rest and during isometric exercise. We conclude that short-term unopposed ERT favorably enhances arteriolar distensibility, BRS, and hemodynamic parameters in postmenopausal women. These findings have clinical implications in the goals for treating cardiovascular risk factors in aging women.

GENETIC VARIATION FOR COPPER RESISTANCE IN FATHEAD MINNOW TOXICITY TESTS

EPA Science Inventory

Unexplained variation in the results of aquatic organism toxicity tests is a consistently observed and troubling phenomenon. Possible sources of variation include differences in condition or nutritional status of the population prior to the test, as well as age, density and hand...

Crackdown on Attendance--The Word Is Out.

ERIC Educational Resources Information Center

DuFour, Richard

1983-01-01

Procedures successful for one school in establishing good attendance include phone calls on all unexplained absences, discipline for unexcused absences, incentives for good attendance, charting attendance patterns, and staff coordination for monitoring attendance. Increased state aid, a more positive school climate, and greater student achievement…

Towards a General Model of Temporal Discounting

ERIC Educational Resources Information Center

van den Bos, Wouter; McClure, Samuel M.

2013-01-01

Psychological models of temporal discounting have now successfully displaced classical economic theory due to the simple fact that many common behavior patterns, such as impulsivity, were unexplainable with classic models. However, the now dominant hyperbolic model of discounting is itself becoming increasingly strained. Numerous factors have…

Electron impact contribution to infrared NO emissions in auroral conditions

NASA Astrophysics Data System (ADS)

Campbell, L.; Brunger, M. J.

2007-11-01

Infrared emissions from nitric oxide, other than nightglow, are observed in aurora, principally due to a chemiluminescent reaction between excited nitrogen atoms and oxygen molecules that produces vibrationally excited NO. The rates for this chemiluminescent reaction have recently been revised. Based on new measurements of electron impact vibrational excitation of NO, it has been suggested that electron impact may also be significant in producing auroral NO emissions. We show results of a detailed calculation which predicts the infrared spectrum observed in rocket measurements, using the revised chemiluminescent rates and including electron impact excitation. For emissions from the second vibrational level and above, the shape of the spectrum can be reproduced within the statistical errors of the analysis of the measurements, although there is an unexplained discrepancy in the absolute value of the emissions. The inclusion of electron impact improves the agreement of the shape of the predicted spectrum with the measurements by accounting for part of the previously unexplained peak in emissions from the first vibrational level.

The negotiation of the sick role: general practitioners’ classification of patients with medically unexplained symptoms

PubMed Central

Mik-Meyer, Nanna; Obling, Anne Roelsgaard

2012-01-01

In encounters between general practitioners (GPs) and patients with medically unexplained symptoms (MUS), the negotiation of the sick role is a social process. In this process, GPs not only use traditional biomedical diagnostic tools but also rely on their own opinions and evaluations of a patient’s particular circumstances in deciding whether that patient is legitimately sick. The doctor is thus a gatekeeper of legitimacy. This article presents results from a qualitative interview study conducted in Denmark with GPs concerning their approach to patients with MUS. We employ a symbolic interaction approach that pays special attention to the external validation of the sick role, making GPs’ accounts of such patients particularly relevant. One of the article’s main findings is that GPs’ criteria for judging the legitimacy of claims by those patients that present with MUS are influenced by the extent to which GPs are able to constitute these patients as people with social problems and problematic personality traits. PMID:22384857

Soil mechanics: breaking ground.

PubMed

Einav, Itai

2007-12-15

In soil mechanics, student's models are classified as simple models that teach us unexplained elements of behaviour; an example is the Cam clay constitutive models of critical state soil mechanics (CSSM). 'Engineer's models' are models that elaborate the theory to fit more behavioural trends; this is usually done by adding fitting parameters to the student's models. Can currently unexplained behavioural trends of soil be explained without adding fitting parameters to CSSM models, by developing alternative student's models based on modern theories?Here I apply an alternative theory to CSSM, called 'breakage mechanics', and develop a simple student's model for sand. Its unique and distinctive feature is the use of an energy balance equation that connects grain size reduction to consumption of energy, which enables us to predict how grain size distribution (gsd) evolves-an unprecedented capability in constitutive modelling. With only four parameters, the model is physically clarifying what CSSM cannot for sand: the dependency of yielding and critical state on the initial gsd and void ratio.

Unexplained high thyroid stimulating hormone: a "BIG" problem.

PubMed

Mendoza, Heidi; Connacher, Alan; Srivastava, Rajeev

2009-01-01

Macro-hormones and macro-enzymes are high molecular weight conjugates of hormones or enzymes, respectively, often with immunoglobulins. These are referred to as macromolecular complexes, and may cause artefactually elevated biochemical tests results. Macro enzymes of the most commonly measured serum enzymes have been identified and are recognised as a source of elevated measurements that may cause diagnostic confusion; macro-creatine kinase and macro-amylase are the two better known macro-enzymes in clinical practice. Literature on macro-hormones is largely restricted to macro-prolactin. We present a case of a clinically euthyroid patient, who had persistently elevated thyroid stimulating hormone (TSH) but free thyroxine within the reference limits. She underwent repeated thyroid investigations and thyroid hormone interference studies, until macro-TSH was identified as the most likely cause of unexplained elevated TSH. Following the identification and characterisation of this biochemical abnormality, she is no longer subject to repeated blood tests for assessment of thyroid function; the patient currently remains clinically euthyroid.

Late-onset Pompe disease: what is the prevalence of limb-girdle muscular weakness presentation?

PubMed

Lorenzoni, Paulo José; Kay, Cláudia Suemi Kamoi; Higashi, Nádia Sugano; D'Almeida, Vânia; Werneck, Lineu Cesar; Scola, Rosana Herminia

2018-04-01

Pompe disease is an inherited disease caused by acid alpha-glucosidase (GAA) deficiency. A single center observational study aimed at assessing the prevalence of late-onset Pompe disease in a high-risk Brazilian population, using the dried blood spot test to detect GAA deficiency as a main screening tool. Dried blood spots were collected for GAA activity assay from 24 patients with "unexplained" limb-girdle muscular weakness without vacuolar myopathy in their muscle biopsy. Samples with reduced enzyme activity were also investigated for GAA gene mutations. Of the 24 patients with dried blood spots, one patient (4.2%) showed low GAA enzyme activity (NaG/AaGIA: 40.42; %INH: 87.22%). In this patient, genetic analysis confirmed two heterozygous mutations in the GAA gene (c.-32-13T>G/p.Arg854Ter). Our data confirm that clinicians should look for late-onset Pompe disease in patients whose clinical manifestation is an "unexplained" limb-girdle weakness even without vacuolar myopathy in muscle biopsy.

Professional support requirements and grief interventions for parents bereaved by an unexplained death at different time periods in the grief process.

PubMed

Rudd, Rebecca A; D'Andrea, Livia M

2013-01-01

The purpose of this qualitative phenomenological study examines the support needs and grief interventions professional and bereaved parents believed were helpful during different time periods in the grief process: the first 72 hours, first three to 14 days, and two weeks and beyond. Ten professionals from the following disciplines were interviewed: emergency communications, emergency medical technician, police, fireman, detective, social worker funeral director chaplain, peer support leader, and bereavement organization. Five parents and one grandparent bereaved by Sudden Infant Death Syndrome (SIDS) or Sudden Unexplained Death in Childhood (SUDC) were interviewed. This study identified 13 support need and grief interventions: contact support people, emotional and cognitive regulation, preliminary information on cause of death, time with deceased child, accommodate and advocate, human compassion and support, describe timeline and process, referrals and resources, affordable and easy access to services, communication and follow-up, community experience, professional mental health support, and memorialize. Recommendations are provided on ways to improve services to newly bereaved parents.

The molecular autopsy: an indispensable step following sudden cardiac death in the young?

PubMed Central

Boczek, Nicole J.; Tester, David J.; Ackerman, Michael J.

2013-01-01

Annually thousands of sudden deaths involving young individuals (< 35 years of age) remain unexplained following a complete medicolegal investigation that includes an autopsy. In fact, epidemiological studies have estimated that over half of sudden deaths involving previously healthy young individuals have no morphological abnormalities identifiable at autopsy. Cardiac channelopathies associated with structurally normal hearts such as long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS), leave no evidence to be found at autopsy, leaving investigators to only speculate that a lethal arrhythmia might lie at the heart of a sudden unexplained death (SUD). In cases of autopsy-negative SUD, continued investigation, through the use of a cardiological and genetic evaluation of first- or second-degree relatives and/or a molecular autopsy, may pinpoint the underlying mechanism attributing to the sudden death and allow for the identification of living family members with the pathogenic substrate that renders them vulnerable to an increased risk for cardiac events, including sudden death. PMID:22993115

Prediction of soil stress-strain response incorporates mobilised shear strength envelope of granitic residual soil

NASA Astrophysics Data System (ADS)

Rahman, Abdul Samad Abdul; Noor, Mohd Jamaludin Md; Ahmad, Juhaizad Bin; Sidek, Norbaya

2017-10-01

The concept of effective stress has been the principal concept in characterizing soil volume change behavior in soil mechanics, the settlement models developed using this concept have been empirical in nature. However, there remain certain unexplained soil volume change behaviors that cannot be explained using the effective stress concept, one such behaviour is the inundation settlement. Studies have begun to indicate the inevitable role of shear strength as a critical element to be incorporated in models to unravel the unexplained soil behaviours. One soil volume change model that applies the concept of effective stress and the shear strength interaction is the Rotational Multiple Yield Surface Framework (RMYSF) model. This model has been developed from the soil-strain behavior under anisotropic stress condition. Hence, the RMYSF actually measure the soil actual elasto-plastic response to stress rather than assuming it to be fully elastic or plastic as normally perceived by the industry. The frameworks measures the increase in the mobilize shear strength when the soil undergo anisotropic settlement.

BAD knockout provides metabolic seizure resistance in a genetic model of epilepsy with sudden unexplained death in epilepsy.

PubMed

Foley, Jeannine; Burnham, Veronica; Tedoldi, Meghan; Danial, Nika N; Yellen, Gary

2018-01-01

Metabolic alteration, either through the ketogenic diet (KD) or by genetic alteration of the BAD protein, can produce seizure protection in acute chemoconvulsant models of epilepsy. To assess the seizure-protective role of knocking out (KO) the Bad gene in a chronic epilepsy model, we used the Kcna1 -/- model of epilepsy, which displays progressively increased seizure severity and recapitulates the early death seen in sudden unexplained death in epilepsy (SUDEP). Beginning on postnatal day 24 (P24), we continuously video monitored Kcna1 -/- and Kcna1 -/- Bad -/- double knockout mice to assess survival and seizure severity. We found that Kcna1 -/- Bad -/- mice outlived Kcna1 -/- mice by approximately 2 weeks. Kcna1 -/- Bad -/- mice also spent significantly less time in seizure than Kcna1 -/- mice on P24 and the day of death, showing that BadKO provides seizure resistance in a genetic model of chronic epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Unexplained chest pain in the ED: could it be panic?

PubMed

Foldes-Busque, Guillaume; Marchand, André; Chauny, Jean-Marc; Poitras, Julien; Diodati, Jean; Denis, Isabelle; Lessard, Marie-Josée; Pelland, Marie-Ève; Fleet, Richard

2011-09-01

This study aimed at (1) establishing the prevalence of paniclike anxiety in emergency department (ED) patients with unexplained chest pain (UCP); (2) describing and comparing the sociodemographic, medical, and psychiatric characteristics of UCP patients with and without paniclike anxiety; and (3) measuring the rate of identification of panic in this population. A structured interview, the Anxiety Disorders Interview Schedule for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, was administered to identify paniclike anxiety and evaluate patients' psychiatric status. Anxious and depressive symptoms were evaluated with self-report questionnaires. Medical information was extracted from patients' medical records. The prevalence of paniclike anxiety was 44% (95% CI, 40%-48%) in the sample (n = 771). Psychiatric disorders were more common in panic patients (63.4% vs 20.1%), as were suicidal thoughts (21.3% vs 11.3%). Emergency physician diagnosed only 7.4% of panic cases. Paniclike anxiety is common in ED patients with UCP, and this condition is rarely diagnosed in this population. Copyright © 2011 Elsevier Inc. All rights reserved.

Clinical observation of lymphocyte active immunotherapy in 380 patients with unexplained recurrent spontaneous abortion.

PubMed

Chen, Jian-Ling; Yang, Jian-Ming; Huang, Ya-Zhe; Li, Ying

2016-11-01

This study aims to investigate the clinical curative effect of lymphocyte active immunotherapy (LAI) on unexplained recurrent spontaneous abortion (RSA). A total of 749 RSA patients who received medical service in our hospital from October 2009 to June 2013 were enrolled into this study. These patients were randomly divided into two groups: LAI group (treatment group) and routine progesterone for maintenance tocolysis group (control group). A comparative analysis on the pregnancy outcomes in these two groups was conducted. Abortion rate was significantly lower in the LAI group than in the control group (P<0.05). Furthermore, pregnancy success rates were 89.7% and 32.2% in patients who received LAI and routine progesterone for maintenance tocolysis, respectively, and the difference was statistically significant (P<0.05). Our analysis suggested that LAI can treat RSA effectively and has an excellent clinical effect. Furthermore, the detection of blocking antibodies showed a positive prediction on pregnancy outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

Histological chorioamnionitis is associated with cerebral palsy in preterm neonates.

PubMed

Horvath, Boldizsár; Grasselly, Magda; Bodecs, Tamas; Boncz, Imre; Bodis, József

2012-08-01

To determine the interaction between histological chorioamnionitis and unexplained neonatal cerebral palsy among low birth weight infants. We studied 141 preterm infants below 1500 g delivered between 2000 and 2010. Clinical data, neonatal neuroimaging, laboratory results, the histopathological features of the placenta and gastric smear within the first hour of delivery, were evaluated. Cerebral palsy was detected in 11 out of 141 preterm newborns (7.8%). The incidence of silent histological chorioamnionitis was 33.6% (43 of 128 cases). Chorioamniontis was significantly associated with the risk of unexplained cerebral palsy (p=0.024). There were also significant correlations between maternal genital infections and chorioamnionitis (p=0.005), and between maternal infections and a positive smear of neonatal gastric aspirates (p=0.000). The rate of cesarean section was 67.4% (95 out of 141 deliveries), and elective cesarean section was performed in 68 cases. Intrauterine exposure to maternal infection was associated with a marked increase in the risk of cerebral palsy in preterm infants. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.