tbuckley/cabot-search huggingface dataset:
Novel cycle changes in scalp hair are caused by etretinate therapy
Authors: J. BERTH-JONES, P.E HUTCHINSON
Journal: British Journal of Dermatology (1995)

The scalp hair of 15 patients, who were treated with etretinate for at least 6 months, was investigated, with the aims of confirming the previously described reduction in the duration of anagen and establishing the mechanism of etretinate alopecia. An increase in hair shedding rate and an increase in plucked telogen count, both of which continued for 6 months of treatment, were found, whereas there was no significant increase in the proportion of new, or regrowing, anagen hairs in a cut sample (NAH). The sustained decrease in the duration of anagen was confirmed, and it was further shown that this decrease was progressive. This would appear to be the main cause of the observed increased shedding associated with etretinate treatment. In relation to the mechanism of the alopecia, it was concluded that an arrest at the onset of anagen and a follicular anchorage defect in telogen were causes. The evidence for an arrest at the onset of anagen was a failure of NAH to rise on treatment, and a large increase in NAH on stopping treatment. The evidence for a follicular anchorage defect was a rise in shed rate very early in treatment, and an observed shed rate greater than expected, on the basis of plucked telogen results, later in treatment. These pathogenic mechanisms have never been described previously in drug-induced alopecia, or in the majority of hair disorders in general. However, it would seem highly unlikely that these mechanisms are exclusive to etretinate therapy.
Drug makers end free lunches
Authors: Fred Charatan
Journal: BMJ (2007)

<h3>BACKGROUND AND PURPOSE:</h3> Fetal imaging is crucial in the evaluation of open neural tube defects. The identification of intraventricular hemorrhage prenatally has unclear clinical implications. We aimed to explore fetal imaging findings in open neural tube defects and evaluate associations between intraventricular hemorrhage with prenatal and postnatal hindbrain herniation, postnatal intraventricular hemorrhage, and ventricular shunt placement. <h3>MATERIALS AND METHODS:</h3> After institutional review board approval, open neural tube defect cases evaluated by prenatal sonography between January 1, 2013 and April 24, 2018 were enrolled (<i>n</i> = 504). The presence of intraventricular hemorrhage and gray matter heterotopia by both prenatal sonography and MR imaging studies was used for classification. Cases of intraventricular hemorrhage had intraventricular hemorrhage without gray matter heterotopia (<i>n</i> = 33) and controls had neither intraventricular hemorrhage nor gray matter heterotopia (<i>n</i> = 229). A total of 135 subjects with findings of gray matter heterotopia were excluded. Outcomes were compared with regression analyses. <h3>RESULTS:</h3> Prenatal and postnatal hindbrain herniation and postnatal intraventricular hemorrhage were more frequent in cases of prenatal intraventricular hemorrhage compared with controls (97% versus 79%, 50% versus 25%, and 63% versus 12%, respectively). Increased third ventricular diameter, specifically &gt;1 mm, predicted hindbrain herniation (OR = 3.7 [95% CI, 1.5–11]) independent of lateral ventricular size and prenatal intraventricular hemorrhage. Fetal closure (<i>n</i> = 86) was independently protective against postnatal hindbrain herniation (OR = 0.04 [95% CI, 0.01–0.15]) and postnatal intraventricular hemorrhage (OR = 0.2 [95% CI, 0.02–0.98]). Prenatal intraventricular hemorrhage was not associated with ventricular shunt placement. <h3>CONCLUSIONS:</h3> Intraventricular hemorrhage is relatively common in the prenatal evaluation of open neural tube defects. Hindbrain herniation is more common in cases of intraventricular hemorrhage, but in association with increased third ventricular size. Fetal closure reverses hindbrain herniation and decreases the rate of intraventricular hemorrhage postnatally, regardless of the presence of prenatal intraventricular hemorrhage.
A somatic component to myocardial infarction
Authors: K S Channer
Journal: BMJ (1985)

The question of measuring blood cholesterol values for assessing risk in individuals will continue to be debated.What is certain is that blood cholesterol concentrations in British men are high and constitute a considerable risk for ischaemic heart disease.The high risk approach in the United States and Great Britain would appear to have severe limitations.Given the present distribution of blood cholesterol concentrations in British men, nothing short of a population approach is likely to be effective, and even that would have to be applied from childhood if it is to have much effect.
A study of local immunity in psoriasis
Authors: ANA RAMIREZ-BOSCA, L. MARTINEZ-OJEDA, FRANCISCA VALCUENDE-CAVERO, A. CASTELLS-RODELLAS
Journal: British Journal of Dermatology (1988)

We have studied biopsies of lesional skin with monoclonal and polyclonal antibodies to determine the nature of the infiltrate in different forms of psoriasis. In guttate psoriasis the number of Langerhans cells (LC) was not increased and CD8+ cells predominated, however, most CD4+ cells were activated. In erythrodermal psoriasis some CDI+ cells were found in the dermis although CD8+ cells predominated and were activated. In palmo-plantar psoriasis LC were found in the epidermis and superficial dermis and CD4+ cells were more numerous than CD8+ cells, some in turn expressing HLA-DR. In flexural psoriasis the LC formed clusters in the epidermis, and activated CD4+ cells predominated. In psoriasis vulgaris CD4+ cells predominated over CD8+ although the latter were activated. Our observations tend to support Valdimarsson's hypothesis on the immune basis of psoriasis, but we believe that two cycles coexist in psoriasis--one inflammatory and the other immunological--and that interaction between these leads to epidermal hyperproliferation.
Effect of Rimonabant, a Cannabinoid-1 Receptor Blocker, on Weight and Cardiometabolic Risk Factors in Overweight or Obese Patients
Authors: F. Xavier Pi-Sunyer, Louis J. Aronne, Hassan M. Heshmati, Jeanne Devin, Julio Rosenstock, for the RIO-North America Study Group
Journal: JAMA (2006)

Rimonabant, a selective cannabinoid-1 receptor blocker, may reduce body weight and improve cardiometabolic risk factors in patients who are overweight or obese.To compare the efficacy and safety of rimonabant with placebo each in conjunction with diet and exercise for sustained changes in weight and cardiometabolic risk factors over 2 years.Randomized, double-blind, placebo-controlled trial of 3045 obese (body mass index > or =30) or overweight (body mass index >27 and treated or untreated hypertension or dyslipidemia) adult patients at 64 US and 8 Canadian clinical research centers from August 2001 to April 2004.After a 4-week single-blind placebo plus diet (600 kcal/d deficit) run-in period, patients were randomized to receive placebo, 5 mg/d of rimonabant, or 20 mg/d of rimonabant for 1 year. Rimonabant-treated patients were rerandomized to receive placebo or continued to receive the same rimonabant dose while the placebo group continued to receive placebo during year 2.Body weight change over year 1 and prevention of weight regain during year 2. Additional efficacy measures included changes in waist circumference, plasma lipid levels, and other cardiometabolic risk factors.At year 1, the completion rate was 309 (51%) patients in the placebo group, 620 (51%) patients in the 5 mg of rimonabant group, and 673 (55%) patients in the 20 mg of rimonabant group. Compared with the placebo group, the 20 mg of rimonabant group produced greater mean (SEM) reductions in weight (-6.3 [0.2] kg vs -1.6 [0.2] kg; P<.001), waist circumference (-6.1 [0.2] cm vs -2.5 [0.3] cm; P<.001), and level of triglycerides (percentage change, -5.3 [1.2] vs 7.9 [2.0]; P<.001) and a greater increase in level of high-density lipoprotein cholesterol (percentage change, 12.6 [0.5] vs 5.4 [0.7]; P<.001). Patients who were switched from the 20 mg of rimonabant group to the placebo group during year 2 experienced weight regain while those who continued to receive 20 mg of rimonabant maintained their weight loss and favorable changes in cardiometabolic risk factors. Use of different imputation methods to account for the high rate of dropouts in all 3 groups yielded similar results. Rimonabant was generally well tolerated; the most common drug-related adverse event was nausea (11.2% for the 20 mg of rimonabant group vs 5.8% for the placebo group).In this multicenter trial, treatment with 20 mg/d of rimonabant plus diet for 2 years promoted modest but sustained reductions in weight and waist circumference and favorable changes in cardiometabolic risk factors. However, the trial was limited by a high drop-out rate and longer-term effects of the drug require further study. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00029861.
Retroviral-mediated expression of recombinant Fancc enhances the repopulating ability of Fancc−/−hematopoietic stem cells and decreases the risk of clonal evolution
Authors: Laura S. Haneline, Xiaxin Li, Samantha L. M. Ciccone, Ping Hong, Yanzhu Yang, Hal E. Broxmeyer, Suk-Hee Lee, Attilio Orazi, Edward F. Srour, D. Wade Clapp
Journal: Blood (2003)

Fanconi anemia (FA) is a chromosomal instability disorder characterized by a progressive bone marrow (BM) failure and an increased incidence of myeloid leukemias. Children with FA are currently being enrolled in clinical trials to evaluate the safety of retroviral-mediated gene transfer. Previously, we used Fancc(-/-) mice to show that Fancc(-/-) hematopoietic stem cells (HSCs) have a profound defect in repopulating ability. Here, we examined whether retroviral-mediated gene transfer of recombinant Fancc (rFancc) would restore the repopulating ability of Fancc(-/-) HSC to wild-type levels. Fancc(-/-) HSCs transduced with a retrovirus encoding rFancc exhibited a repopulating ability that approached wild-type levels. Interestingly, approximately 30% of primary recipients (7 of 22) transplanted with uncorrected Fancc(-/-) cells developed a range of hematopoietic abnormalities including pancytopenia and BM hypoplasia similar to individuals with FA. Hematopoietic abnormalities were detected in only 1 of 22 mice transplanted with Fancc(-/-) cells transduced with a retrovirus encoding rFancc. Moreover, several mice with hematopoietic defects had progenitors that displayed a marked resistance to IFN-gamma, TNF-alpha, and MIP-1alpha compared to both Fancc(-/-) progenitors, which are uniquely hypersensitive to these cytokines, and wild-type progenitors. These data are analogous to studies using progenitors from patients with myelodysplasia and provide functional support for clonal evolution in these mice. Collectively, these data show that gene transfer can enhance HSC repopulating ability and suppresses the tendency for clonal evolution. These studies also reveal potential detrimental effects of ex vivo manipulation for untransduced Fancc(-/-) HSCs.
861. Recombinant Adeno_Associated Virus Vector Mediated Gene Therapy of Adenosine Deaminase Deficiency in a Mouse Model
Authors: Jennifer M. Crawford, Teh-sheng Chan, Lillian L. Chan
Journal: Molecular Therapy (2006)

Clinical trials for adenosine deaminase deficiency associated_severe combined immunodeficiency (ADA_SCID) have been ongoing for nearly two decades, yet unequivocal success has not been achieved. The use of inadequate delivery systems with severe side_effects and lack of an animal model have limited progress. Recently, our lab has generated a developmentally regulated ADA knockout mouse to study the pathogenesis of ADA_SCID and test therapies in vivo. As in afflicted humans, ADA deficient mice are devoid of B and T cells and experience pulmonary insufficiency.
Literature and Medicine
Authors: Stanley Weintraub
Journal: JAMA (1989)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Coagulation factor Xa stimulates platelet-derived growth factor release and mitogenesis in cultured vascular smooth muscle cells of rat.
Authors: F N Ko, Y C Yang, S C Huang, J T Ou
Journal: Journal of Clinical Investigation (1996)

The mitogenic effect of activated coagulation factor X (factor Xa) was examined in cultured aortic smooth muscle cells (VSMC) from Wistar-Kyoto rats (WKY). Factor Xa stimulated DNA synthesis and cell growth in VSMC, not through the phospholipase C-protein kinase C pathway because increase of inositol monophosphate (IP) accumulation and intracellular Ca2+ concentration was not observed, but probably via the PDGF receptor tyrosine kinase pathway since the pathway's components, Ras, Raf-1, MAPK (both 42 and 44 kD), and the transcription factors, c-Fos and c-Jun, were activated. These appeared to be effected by the serine protease activity of factor Xa, since in the presence of serine protease inhibitors such as PMSF, leupeptin, benzamidine, TAP anticoagulant, and TLCK, the latter three being specific inhibitors of the factor Xa, active site, the effects were completely blocked. Anti-factor Xa mAb, 5224, which specifically negated the activity of factor Xa, also inhibited completely the mitogenic effect of factor Xa, but not that of thrombin. Addition of PDGF did not affect the effect of factor Xa, which, however, was inhibited by anti-PDGF-AB antibody. This observation and the activation of PDGF receptor tyrosine kinase pathway suggested that the factor Xa might exert its effect via PDGF-like function. Direct measurement confirmed that factor Xa stimulated the release of PDGF from VSMC. Factor Xa, therefore, exerts serine protease activity on VSMC, causing somehow the release of PDGF, that in turn acts on the PDGF receptor tyrosine kinase; the pathway is then turned on, leading eventually to DNA synthesis and cell proliferation.
Hormonal and Metabolic Effects of a Pancreatic Endocrine Graft
Authors: DAVID E. R. SUTHERLAND
Journal: Annals of Internal Medicine (1981)

A new modification of pancreas transplant technique, the vascularized segmental intraperitoneal graft without duct ligation, has provided reversal of insulin-dependent (type I) diabetes mellitus for as long as 2 years of comfortable life. Although the risks associated with immunosuppression remain high (two of the 12 patients have died of early postoperative infection), selected data are presented from six cases to show the following striking hormonal and metabolic results after transplantation and withdrawal of insulin: restoration of normal beta cell function as shown by 24-hour urine C-peptide excretion and acutely responsive serum insulin, restoration of normal suppressibility of plasma glucagon, elimination of ketosis and negative nitrogen balance, normal fasting plasma glucose and glycosylated hemoglobin, and normal or near-normal glucose tolerance. These results provide a standard for current explorations of new ways of treating insulin-dependent diabetes.
Screening for Adrenal Antibodies in Children With Type 1 Diabetes and Autoimmune Thyroid Disease
Authors: Seth D. Marks, Rose Girgis, Robert M. Couch
Journal: Diabetes Care (2003)

Type 1 diabetes is associated with other autoimmune diseases. Many diabetes centers routinely screen patients with type 1 diabetes for autoimmune thyroid disease (ATD). The presence of two autoimmune diseases raises the possibility of polyendocrine autoimmune disease. The association of autoimmune adrenal insufficiency, or Addison’s disease, with type 1 diabetes is described in case reports dating back more than a century (1,2). Studies have illustrated shared HLA alleles (DQA1*0501, for example) among patients with type 1 diabetes, ATD, and Addison’s disease (3,4). Pancreatic islet cell antibodies have been detected in 6.2% of patients with Addison’s disease (5). Yet, it is unclear whether patients with type 1 diabetes should be routinely screened for …
A Computational Model to Predict the Effects of Class I Anti-Arrhythmic Drugs on Ventricular Rhythms
Authors: Jonathan D. Moreno, Z. Iris Zhu, Pei-Chi Yang, John R. Bankston, Mao-Tsuen Jeng, Chaoyi Kang, Lianguo Wang, Jason D. Bayer, David J. Christini, Natalia A. Trayanova, Crystal M. Ripplinger, Robert S. Kass, Colleen E. Clancy
Journal: Science Translational Medicine (2011)

Two- and three-dimensional models of cardiac excitability based on sodium channel kinetics can predict the adverse effects of class I anti-arrhythmic drugs.
Fine doctors and fallen bishops
Authors: I. Robertson
Journal: BMJ (1996)

There's an awful lot of them about these days—morals I mean. We've had a lot of them from the leaders of the main political parties in Britain. And ex-Roman Catholic Bishop Roddy Wright could have done with some of his ex-lover's morals before selling his story to the News of the World. His ex-mistress tore up his cheque for £2000 and gave her story to the BBC rather than to the chequebook waving tabloid newspapers. That's about as close to the moral high ground as I've seen among this bunch.

I confess to a deep suspicion of those from whom the word moral escapes their lips …
Lancets and libel
Authors: W. Moore
Journal: BMJ (2010)

Whether exposing quackery in complementary medicine or challenging malpractice in orthodox medicine, journalists have always needed thick skins and nerves of steel—though deep pockets are sometimes useful too. But, in navigating Britain’s repressive libel laws, modern medical hacks can always turn for inspiration to Thomas Wakley.

Trained in surgery at St Thomas’s and Guy’s Hospitals in London, Wakley (1795-1862) was disillusioned by the nepotism and bungling that he witnessed. Cutting short his career as a general practitioner to turn poacher, in 1823 he founded the Lancet in a mission to end the “mystery of concealment” in medicine. Noting that a lancet was both “an arched window …
Both Dietary Fish-Oil Supplementation and Aspirin Fail to Inhibit Atherosclerosis in Long-term Vein Bypass Grafts in Moderately Hypercholesterolemic Nonhuman Primates
Authors: Lawrence E. Boerboom, Gordon N. Olinger, G. Hossein Almassi, Victor A. Skrinska
Journal: Circulation (1997)

Background Aortocoronary vein bypass grafts are vulnerable to late atherosclerotic occlusion. Conventional platelet inhibitor therapy provides early but not persistent protection against graft failure. Evidence suggests that consumption of marine foods may reduce cardiovascular disease, possibly because of the unique long-chain unsaturated ω-3 fatty acids present in these foods. We hypothesized that dietary fish-oil supplementation would protect against atherosclerosis in vein bypass grafts. Methods and Results Thirty-three moderately hypercholesterolemic cynomolgus macaques were divided into four groups: control, control+aspirin, fish oil, and fish oil+aspirin. Each control group received olive oil as placebo to equalize calorie and fat consumption with that of the fish-oil groups. Both oils were in ethyl ester form, with the fish oil providing 0.88 g/d eicosapentaenoic acid. The aspirin dose was 40 mg/d. Cephalic vein grafts were interposed bilaterally in the carotid arteries and excised for analysis at 4 years. Bleeding time was significantly prolonged in all groups receiving fish oil or aspirin ( P &lt;.05). Plasma cholesterol levels were similar among groups, averaging 6.9±2.4 mmol/L (267±94 mg/dL). The extent of atherosclerosis in vein grafts did not differ among groups as evaluated both by Sudan IV staining of intimal lipid lesions (27±21% of total surface area, P =.89) and analysis of cholesterol content (236±203 nmol/mg, 9.1±7.8 μg/mg, P =.85). Vein graft connective tissue composition was also unaffected by treatment. Conclusions Our findings do not support the use of concentrated dietary fish-oil supplements or aspirin for the prevention of atherosclerosis in long-term vein bypass grafts. Consumption of fish flesh or less refined oil preparations could have effects different from those of the purified fish-oil ethyl esters we used.
IgG4 inhibits peanut-induced basophil and mast cell activation in peanut-tolerant children sensitized to peanut major allergens
Authors: Alexandra F. Santos, Louisa K. James, Henry T. Bahnson, Mohammed H. Shamji, Natália C. Couto-Francisco, Sabita Islam, Sally Houghton, Andrew T. Clark, Alick Stephens, Victor Turcanu, Stephen R. Durham, Hannah J. Gould, Gideon Lack
Journal: Journal of Allergy and Clinical Immunology (2015)

Most children with detectable peanut-specific IgE (P-sIgE) are not allergic to peanut. We addressed 2 non-mutually exclusive hypotheses for the discrepancy between allergy and sensitization: (1) differences in P-sIgE levels between children with peanut allergy (PA) and peanut-sensitized but tolerant (PS) children and (2) the presence of an IgE inhibitor, such as peanut-specific IgG4 (P-sIgG4), in PS patients.Two hundred twenty-eight children (108 patients with PA, 77 PS patients, and 43 nonsensitized nonallergic subjects) were studied. Levels of specific IgE and IgG4 to peanut and its components were determined. IgE-stripped basophils or a mast cell line were used in passive sensitization activation and inhibition assays. Plasma of PS subjects and patients submitted to peanut oral immunotherapy (POIT) were depleted of IgG4 and retested in inhibition assays.Basophils and mast cells sensitized with plasma from patients with PA but not PS patients showed dose-dependent activation in response to peanut. Levels of sIgE to peanut and its components could only partially explain differences in clinical reactivity between patients with PA and PS patients. P-sIgG4 levels (P = .023) and P-sIgG4/P-sIgE (P < .001), Ara h 1-sIgG4/Ara h 1-sIgE (P = .050), Ara h 2-sIgG4/Ara h 2-sIgE (P = .004), and Ara h 3-sIgG4/Ara h 3-sIgE (P = .016) ratios were greater in PS children compared with those in children with PA. Peanut-induced activation was inhibited in the presence of plasma from PS children with detectable P-sIgG4 levels and POIT but not from nonsensitized nonallergic children. Depletion of IgG4 from plasma of children with PS (and POIT) sensitized to Ara h 1 to Ara h 3 partially restored peanut-induced mast cell activation (P = .007).Differences in sIgE levels and allergen specificity could not justify the clinical phenotype in all children with PA and PS children. Blocking IgG4 antibodies provide an additional explanation for the absence of clinical reactivity in PS patients sensitized to major peanut allergens.
CONTRAST-ENHANCED ROTATIONAL ANGIOGRAPHIC C-ARM CT IMAGING OF MYOCARDIAL INFARCTION IN THE INTERVENTIONAL SUITE: OPTIMIZED IMAGING PROTOCOL FOR ACUTE AND CHRONIC INFARCTS
Authors: Erin Girard, Teri Moore, Guenter Lauritsch, Jarrett Rosenberg, Amin Al-Ahmad, Frandics Chan, David Lee, Rebecca Fahrig
Journal: Journal of the American College of Cardiology (2012)
Patient re-training in peritoneal dialysis: Why and when it is needed
Authors: R. Russo, L. Manili, G. Tiraboschi, K. Amar, M. De Luca, E. Alberghini, P. Ghiringhelli, A. De Vecchi, M.T. Porri, G. Marinangeli, R. Rocca, V. Paris, L. Ballerini
Journal: Kidney International (2006)