tbuckley/cabot-search huggingface dataset:
Skin biopsy: a new tool for diagnosing peripheral neuropathy
Authors: Giuseppe Lauria, Raffaella Lombardi
Journal: BMJ (2007)

The prevalence of peripheral neuropathy is about 2% in the general population, but it rises to 12% and 17% in people with one or two recognised risk factors.1 Diabetes is one such risk factor and the most common cause of this disorder—about half of patients who have had diabetes for 25 years have peripheral neuropathy. The early symptoms of diabetic neuropathy and other peripheral neuropathies are due to degeneration of small somatic nerve fibres, which may remain the only nerves involved.2 However, “small fibre neuropathy” may not be detected by traditional physical, neurophysiological, and neuropathological tests. In the past decade, skin biopsy has become a popular method for investigating small nerve fibres.3 It allows general practitioners and non-specialists—such as diabetologists and specialists in orthopaedics—to diagnose neuropathy (thereby avoiding delayed or incorrect diagnosis), to investigate its aetiology, and to focus treatment, in particular for neuropathic pain.

We searched the Medline database using combinations of the terms “skin biopsy”, “cutaneous nerve fibres”, “intraepidermal nerve fibres”, “neuropathy”, “painful neuropathy”, and “pain”. We also included evidence provided by the recent guidelines of the European Federation of the Neurological Societies.3

Small fibre neuropathy can be associated with common metabolic disorders (such as diabetes and hyperlipidaemia), immune mediated conditions (such as Sjogren's syndrome, sarcoidosis, and coeliac disease), drug toxicity (such as that caused by antineoplastic drugs and antiretroviral drugs), and viral infections (such as HIV). It can be a feature of hereditary diseases (such as familial amyloidosis and Fabry's disease), or it may be idiopathic.

In the absence of known systemic disease, the diagnosis of small fibre neuropathy may not be easy. Pain or burning (or both) in the feet are prominent symptoms, and may be worse at night. Some patients report that contact with warm or cold water elicits discomfort or …
Low birth weight and residential proximity to PCB-contaminated waste sites.
Authors: Akerke Baibergenova, Rustam Kudyakov, Michael Zdeb, David O Carpenter
Journal: Environmental Health Perspectives (2003)

Previous investigations have shown that women exposed to polychlorinated biphenyls (PCBs) are at increased risk of giving birth to an infant with low birth weight (< 2,500 g), and that this relationship is stronger for male than for female infants. We have tested the hypothesis that residents in a zip code that contains a PCB hazardous waste site or abuts a body of water contaminated with PCBs are at increased risk of giving birth to a low-birth-weight baby. We used the birth registry of the New York State Vital Statistics to identify all births between 1994 and 2000 in New York State except for New York City. This registry provides information on the infant, mother, and father together with the zip code of the mother's residence. The 865 state Superfund sites, the 86 National Priority List sites, and the six Areas of Concern in New York were characterized regarding whether or not they contain PCBs as a major contaminant. We identified 187 zip codes containing or abutting PCB-contaminated sites, and these zip codes were the residences of 24.5% of the 945,077 births. The birth weight in the PCB zip codes was on average 21.6 g less than in other zip codes (p < 0.001). Because there are many other risk factors for low birth weight, we have adjusted for these using a logistic regression model for these confounders. After adjusting for sex of the infant, mother's age, race, weight, height, education, income, marital status, and smoking, there was still a statistically significant 6% increased risk of giving birth to a male infant of low birth weight. These observations support the hypothesis that living in a zip code near a PCB-contaminated site poses a risk of exposure and giving birth to an infant of low birth weight.
Exertional dyspnoea and syncope
Authors: J. M. Tarkin, A. Kelion, T. Mittal, M. C. Dalby
Journal: BMJ (2012)

A 64 year old man presented with a two year history of exertional dyspnoea, which improved with rest. He reported laboured breathing after walking for about 10 minutes on the flat or after climbing one flight of stairs. He had no chest pain or other symptoms. His medical history included hypertension and pulmonary embolism. He was a retired mechanical engineer with no family history of cardiac disease and was a non-smoker.

On examination, his pulse was 60 beats/min and blood pressure 130/80 mm Hg. His jugular venous pressure was not raised, his heart sounds were normal, and he had no peripheral oedema. Electrocardiography showed sinus rhythm, with low voltage complexes in the limb leads, poor R wave progression, and no evidence of left ventricular hypertrophy. Chest radiography showed clear lung fields and increased cardiothoracic ratio.

Transthoracic echocardiography with harmonic adjustment showed grossly thickened myocardium with a “speckled” appearance, impaired long axis left ventricular function with an ejection fraction of 53%, thickened mitral and tricuspid valve leaflets, and evidence of diastolic impairment. We performed computed tomography to investigate differential diagnoses of breathlessness, including coronary artery disease and chronic pulmonary embolism. Computed tomography showed unobstructive mild calcification of the left anterior descending artery and no evidence of pulmonary embolism. The patient collapsed after being given metoprolol as part of the computed tomography imaging protocol. An electrocardiogram taken after initial resuscitation showed atrial flutter with 3:1 block. Cardiac magnetic resonance imaging confirmed myocardial thickening seen on previous imaging and showed circumferential transmural delayed enhancement of the left ventricle and to a lesser extent the right ventricle.



### 1 What is the most likely underlying diagnosis?

#### Short answer

Cardiac amyloidosis.

#### Long answer

Cardiac amyloidosis is caused …
Biocompatibility studies of anionic collagen membranes with different degree of glutaraldehyde cross-linking
Authors: Gilberto Goissis, Elcio Marcantonio, Rosemary Adriana Chierici Marcantônio, Rafael Carlos Comelli Lia, Daniela C.J. Cancian, Wanda Maria de Carvalho
Journal: Biomaterials (1999)
Role of two recently cloned rat liver GSH transporters in the ubiquitous transport of GSH in mammalian cells.
Authors: S C Lu, W M Sun, J Yi, M Ookhtens, G Sze, N Kaplowitz
Journal: Journal of Clinical Investigation (1996)

Recently our laboratory has cloned both the rat canalicular and sinusoidal GSH transporters (RcGshT and RsGshT, respectively; Yi, J., S. Lu, J. Fernandez-Checa, and N. Kaplowitz. 1994. J. Clin. Invest. 93:1841-1845; and 1995. Proc. Natl. Acad. Sci. USA. 92:1495-1499). The current work characterized GSH transport and the expression of these two GSH transporters in various mammalian cell lines. The average cell GSH levels (nmol/10(6) cells) were 25, 22, 32, 13, and 13 in HepG2, HeLa, CaCo-2, MDCK, and Cos-1 cells, respectively. GSH efflux was temperature dependent and averaged 0.018, 0.018, 0.012, 0.007, and 0.019 nmol/10(6) cells/min from HepG2, HeLa, CaCo-2, MDCK, and Cos-1 cells, respectively. Dithiothreitol (DTT), which stimulates rat sinusoidal GSH efflux, stimulated GSH efflux only in HepG2 and HeLa cells which was partially reversed by subsequent cystine treatment. GSH uptake (1 mM plus 35S-GSH) was temperature dependent, linear up to 45 min, and Na+-independent with average rates of 1.12, 0.91, 0.45, and 0.45 nmol/10(6) cells/30 min for HepG2, HeLa, CaCo-2, MDCK, and Cos-1 cells, respectively. BSP-GSH (2mM), which cis-inhibits sinusoidal GSH uptake in rat liver and HepG2 cells, inhibited GSH uptake only in HeLa cells. mRNA and polypeptide of RcGshT are expressed in all cells whereas those of RsGshT are expressed only in HepG2 and HeLa cells. In conclusion, bidirectional GSH transport, mediated by the "canalicular" GSH transporter, is ubiquitous in mammalian cells. Sinusoidal GSH transporter expression is more restricted, being present in HepG2 and HeLa cells. DTT and BSP-GSH affect GSH transport only in cells expressing the sinusoidal transporter confirming their selective action on this transporter.
Horizon: Thalidomide: A Second Chance?
Authors: Vittal Katikireddi
Journal: BMJ (2004)

BBC 2, 12 February at 9 pm Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Few, if any, drugs have achieved the notoriety of thalidomide. Serendipitously discovered in 1954, thalidomide caused congenital birth defects in thousands of children, and has been one of the most cautionary tales in the history of medicine. But has its age of redemption come? Could it be the “new wonder drug” that many researchers hope? This episode of the BBC science documentary series Horizon introduced us to Dr Chase Peterson. Dr Peterson, the programme explained, is a man who should be dead: he has the blood cancer multiple myeloma, which is usually lethal in between two and five years. After conventional treatment (chemotherapy and bone marrow transplantation) had failed, Dr Peterson tried an experimental drug that he hoped would get … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Abstract 1038: Defining the mechanism by which melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24)-induced autophagy switches to apoptosis in prostate cancer cells
Authors: Sujit K. Bhutia, Rupesh Dash, Belal Azab, Swadesh Das, Zhao-zhong Su, Seok-Geun Lee, Steven Grant, Paul Dent, David T. Curiel, Devanand Sarkar, Paul B. Fisher
Journal: Cancer Research (2010)

Abstract Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24), a unique member of the IL-10 gene family, displays a broad range of antitumor properties including cancer-specific induction of apoptosis, inhibition of tumor angiogenesis, and modulation of an anti-tumor immune response. Apoptosis induction by mda-7/IL-24, when delivered by an adenovirus (Ad. mda-7), involves an endoplasmic reticulum (ER) stress response and generation of ceramides. Additionally, Ad. mda-7 promotes autophagy in certain cancer cell types. In the present study, we document that Ad-mda-7-induced ER stress and ceramide generation result in induction of autophagy in prostate cancer cells, without affecting normal human prostate epithelial cells, via the canonical autophagic pathway, involving Beclin-1, atg5 and hVps34. Autophagy is evident until 24 h post Ad. mda-7-infection and then switches to apoptosis at 48 h. Inhibition of autophagy by 3-methyladenosine (3-MA) significantly increases Ad. mda-7-induced apoptosis suggesting that autophagy might first be initiated as a cytoprotective mechanism in prostate cancer cells. Inhibition of apoptosis by overexpression of anti-apoptotic proteins Bcl-2 or Bcl-xL increases autophagy upon Ad. mda-7 infection. During the apoptotic phase, MDA-7/IL-24 protein physically interacts with Beclin-1 and this interaction might inhibit Beclin-1 function culminating in apoptosis. Conversely, Ad. mda-7 infection leads to calpain-mediated cleavage of ATG5 protein that might also facilitate a biochemical switch from autophagy to apoptosis. Our present studies reveal novel aspects of interplay between autophagy and apoptosis that underlie the cytotoxic action of mda-7/IL-24 in prostate cancer cells. These new insights into mda-7/IL-24 action provide interesting leads for developing innovative combinatorial approaches for prostate cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1038.
Inhibition of tumor angiogenesis in vivo by a monoclonal antibody targeted to domain 5 of high molecular weight kininogen
Authors: James S. Song, Irma M. Sainz, Stephen C. Cosenza, Irma Isordia-Salas, Abdel Bior, Harlan N. Bradford, Yan-Lin Guo, Robin A. Pixley, E. Premkumar Reddy, Robert W. Colman
Journal: Blood (2004)
Erythroblastosis Foetalis and Breast-feeding
Authors: C. C. Bowley, I. Dunsford
Journal: BMJ (1947)

proposed investigation of fatal cases of influenza referred to in the paper on p. 994 of this issue of the Journal, I would like to invite the co-operation of practitioners.Would any practitioner who is interested in the subject and who might in the future be able to supply clinical details of fatal illnesses notified by him as being due to influenza please write to me at the address given below.-I am, etc.,
Scleroderma 'en coup de sabre'.
Authors: J David, J Wilson, P Woo
Journal: Annals of the Rheumatic Diseases (1991)

A case of scleroderma 9en coup de sabre9 presenting with uveitis, predominantly posterior, and intractable grand mal seizures is described. The histopathology specimens and neuroradiology investigations reaffirm the clinical impression that inflammation is not solely confined to the skin in this form of linear scleroderma.
Treatment of the premenstrual syndrome by subcutaneous estradiol implants and cyclical oral norethisterone: placebo controlled study.
Authors: A L Magos, M Brincat, J W Studd
Journal: BMJ (1986)

The hypothesis that the many non-specific changes normally associated with cyclical ovarian activity are the primary aetiological factors in the premenstrual syndrome was tested by suppressing ovulation with subcutaneous oestradiol implants. Sixty eight women with proved premenstrual syndrome were treated under placebo controlled conditions for up to 10 months in a longitudinal study. Active treatment was combined with cyclical oral norethisterone to produce regular withdrawal periods. Symptoms were monitored with daily menstrual distress questionnaires, visual analogue scales, and the 60 item general health questionnaire. Of the 35 women treated with placebo 33 improved, giving an initial placebo response rate of 94%. The placebo effect gradually waned, but the response to the active combination was maintained for the duration of the study. Analysis of the prospective symptom ratings showed a significant superiority of oestradiol implants over placebo after two months for all six symptom clusters in the menstrual distress questionnaire. Changes seen in the retrospective assessments were less significant but the trend was the same. Treatment with oestradiol implants and cyclical progestogen was well tolerated and appears to be both rational and effective for severe cases of the premenstrual syndrome.
Divalent Metal Transporter 1 Regulates Iron-Mediated ROS and Pancreatic β Cell Fate in Response to Cytokines
Authors: Jakob Bondo Hansen, Morten Fog Tonnesen, Andreas Nygaard Madsen, Peter H. Hagedorn, Josefine Friberg, Lars Groth Grunnet, R. Scott Heller, Anja Østergren Nielsen, Joachim Størling, Luc Baeyens, Leeat Anker-Kitai, Klaus Qvortrup, Luc Bouwens, Shimon Efrat, Mogens Aalund, Nancy C. Andrews, Nils Billestrup, Allan E. Karlsen, Birgitte Holst, Flemming Pociot, Thomas Mandrup-Poulsen
Journal: Cell Metabolism (2012)
Drug points: Fixed drug eruption associated with mefenamic acid
Authors: C L Wilson, A Otter
Journal: BMJ (1986)

reported in France and Australia,'2 and 20 Australian subjects said that they used dextromethorphan because they experienced increased perceptual awareness, altered time perception, and visual hallucinations.3We believe that the potential for psychotropic effects of this drug is not fully appreciated and that its abuse may be more widespread than previously recognised.1 Dodds A, Reval E. Toxic psychosis due to dextromethorphan.
Insulin Resistance and Prostate Cancer Risk
Authors: A. W. Hsing, Y.-T. Gao, S. Chua, J. Deng, F. Z. Stanczyk
Journal: JNCI Journal of the National Cancer Institute (2002)

Because high waist-to-hip ratio (WHR) and high serum insulin levels have been reported to be associated with an increased risk of prostate cancer, we assessed the relationship between insulin resistance and prostate cancer risk in Chinese men. We measured fasting serum glucose and insulin levels in 128 case and 306 control subjects and used the homeostasis model assessment to derive indices of insulin sensitivity and resistance. Relative to men in the lowest tertiles, men in the highest tertile of insulin sensitivity had a reduced risk of prostate cancer (odds ratio [OR] = 0.35, 95% confidence interval [CI] = 0.21 to 0.60), but men in the highest tertile of insulin resistance had an increased risk of prostate cancer (OR = 2.78, 95% CI = 1.63 to 4.72). Considering insulin resistance and WHR together, the effect of insulin resistance was apparent in all tertiles of WHR, with men in the highest tertile of insulin resistance and WHR having the highest risk (OR = 8.21, 95% CI = 2.84 to 23.70). The associations between prostate cancer risk and insulin sensitivity or resistance were independent of total caloric intake and serum levels of insulin-like growth factors, sex hormones, and sex hormone-binding globulin. Because of the retrospective design of this study, the role of insulin resistance in prostate cancer needs to be confirmed in prospective studies.
Treatment allocation in trials: stratified randomisation
Authors: P. Sedgwick
Journal: BMJ (2015)

Researchers investigated whether the probiotic Lactobacillus reuteri reduced crying or fussing in infants with colic. A double blind placebo controlled randomised trial was performed. The intervention was oral L reuteri (1×108 colony forming units) given daily for one month. Participants were healthy term breastfed or formula fed infants, aged less than 3 months, who had infant colic. A community based sample of 167 infants was recruited and randomised in a 1:1 ratio to the intervention (n=85) or placebo (n=82). Randomisation was stratified by method of infant feeding (breast fed v formula fed) and age (≤6 weeks v >6 weeks), using a block size of two.1 The primary outcome was daily duration of crying or fussing after one month of follow-up. Secondary outcomes included the infant's sleep duration at seven, 14, and 21 days as well as maternal mental health and family functioning at one and six months. Treatment groups were compared in outcomes using an intention to treat analysis. It was reported that the mean daily duration of crying or fussing fell steadily in both groups. At one month, the probiotic group cried or fussed for 49 minutes longer than the placebo group (95% confidence interval 8 to 90 minutes; P=0.02). There were no significant differences between treatment groups for any of the secondary outcomes. No study related adverse events were reported. The researchers concluded that L reuteri did not benefit breastfed infants or formula fed infants with colic. Which of the following statements, if any, are true?
Computational Medicine: Translating Models to Clinical Care
Authors: Raimond L. Winslow, Natalia Trayanova, Donald Geman, Michael I. Miller
Journal: Science Translational Medicine (2012)

Because of the inherent complexity of coupled nonlinear biological systems, the development of computational models is necessary for achieving a quantitative understanding of their structure and function in health and disease. Statistical learning is applied to high-dimensional biomolecular data to create models that describe relationships between molecules and networks. Multiscale modeling links networks to cells, organs, and organ systems. Computational approaches are used to characterize anatomic shape and its variations in health and disease. In each case, the purposes of modeling are to capture all that we know about disease and to develop improved therapies tailored to the needs of individuals. We discuss advances in computational medicine, with specific examples in the fields of cancer, diabetes, cardiology, and neurology. Advances in translating these computational methods to the clinic are described, as well as challenges in applying models for improving patient health.
The effect ofN-methyl-N?-nitro-N-nitrosoguanidine on cultured dog gallbladder epithelial cells
Authors: R Malik, S Lee, C E Savard, D Oda, W S Wong, B Y Chan, S P Lee
Journal: Hepatology (1997)

Normal dog gallbladder epithelial cells in long-term culture were used as a model to study the morphologic, genetic, and secretory processes associated with the progression to cancer formation. Dog gallbladder epithelial cells cultured on collagen-coated plates grew into polarized monolayers, could be passaged repeatedly, and showed the typical morphological profile of well-differentiated columnar epithelial cells. After cells were exposed to N -methyl- N ′-nitro- N -nitrosoguanidine (MNNG) at 10 -5 mol/L for 48 hours, the treated cells grew on plastic and could be cloned. Flow cytometry revealed emergence of an aneuploid cell subpopulation. In organotypic culture, treated cells showed a pseudostratified appearance, with cellular and nuclear pleomorphism. Large and hyperchromatic nuclei were present as well as increased mitotic rate. The proteins of MNNG-treated dog gallbladder epithelial cells showed increased phosphorylation of tyrosine residues. Treated cells showed a decrease in mucin secretion in response to prostaglandin E 2 , manifesting an altered pattern of mucin secretion. Transforming growth factor-β failed to inhibit cell proliferation in the MNNG-treated cells compared with the prominent inhibition in normal cells. Together, the data reflected changes representing preliminary steps on the pathway to develop cancer cells. Our results indicate that carcinogenic chemicals can cause measurable chromosomal and cellular modifications to normal biliary epithelial cells in vitro . This model may be useful in understanding the sequential steps in carcinogenesis and affords an opportunity to study chromosomal damage, cytokinetics, changes in molecular genetic markers, and expression, as well as cell biological function during cellular transformation.
Chemotherapeutic Evaluation of Glucarate and N-(4-Hydroxyphenyl)retinamide Alone and in Combination in the Rat Mammary Tumor Model
Authors: H. Abou-Issa, T. E. Webb, J. P. Minton, M. Moeschberger
Journal: JNCI Journal of the National Cancer Institute (1989)

We evaluated calcium glucarate (CGT) and N-(4-hydroxyphenyl)retinamide (HPR) for their effectiveness as anti-tumor agents. For this evaluation, we tested the effects of CGT and HPR given alone or combined in the diet on the growth of established 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors. When given alone, optimal doses of CGT (128.0 mmol/kg in the diet) or HPR (2.0 mmol/kg in the diet) administered daily for 25 days reduced mammary tumor sizes by approximately 15% or 20%, respectively. Suboptimal doses of CGT (64.0 mmol/kg) or HPR (0.75 mmol/kg) administered daily for 25 days only slightly inhibited tumor growth; over the 25-day period, the tumor sizes in rats on the CGT diet and in rats on the HPR diet increased by 55% and 70%, respectively, compared with a 98% increase in tumor sizes in the rats on the control diet. In contrast, the combination of suboptimal doses of CGT (64.0 mmol/kg) and HPR (0.75 mmol/kg) administered daily for 25 days decreased tumor sizes by 33%. These results are statistically significant. They show that CGT and HPR act synergistically. Consequently, lower concentrations of these agents can be used to inhibit mammary tumor development and growth.