tbuckley/cabot-search huggingface dataset:
Online medical genetics resources: a UK perspective
Authors: A. Stewart
Journal: BMJ (2001)

Health professionals, patients, and the general public need authoritative, up to date information on genetics to enable them to understand and apply advances in this discipline. The immediacy and accessibility of the world wide web make it the perfect vehicle for this information. Identifying high quality resources tailored to the requirements of particular users among the vast number of sites is not easy. We have compiled a list of useful web resources from the perspective of users based in the United Kingdom.

#### Summary points

Several websites provide information for geneticists on genetic disease, genetic services, and professional training

Two UK sites act as gateways to information on specific diseases and support groups, suitable for patients and their carers

Public health professionals and policymakers are well served by sites maintained by the Department of Health and the NHS

Good web based information on genetics for general practitioners and non-geneticist clinicians is lacking

Ethical, legal, and social issues in genetics are covered in sites maintained by national and international regulatory bodies in bioethics

We selected sites on the basis of those used most often by our colleagues in different specialist areas of genetics. This article represents a consensus of their views. Sites are grouped by their major user communities; there is overlap, but the contents of the site give a good indication of those with wider relevance. We have also included both national and international online resources for bioethics.

OMIM—Online Mendelian Inheritance in Man (www.ncbi.nlm.nih.gov/Omim) is the “Bible” for all geneticists. The site contains constantly updated information on over 12 000 genetic diseases, their symptoms, inheritance patterns, and associated genetic loci (where known). It is easy to search and is now linked to the National Center for Biotechnology Information's “Entrez” system, so that it can be queried in the same way as other resources …
Restoration of a tumorigenic phenotype by beta 2-microglobulin transfection to EL-4 mutant cells.
Authors: R Glas, K Sturmhöfel, G J Hämmerling, K Kärre, H G Ljunggren
Journal: The Journal of Experimental Medicine (1992)

It has frequently been suggested that loss of beta 2-microglobulin (beta 2m) in tumor cells may lead to malignant progression due to escape from immunological recognition. Here, we directly tested the role of beta 2m expression in tumorigenicity. A beta 2 m loss mutant (C4.4-25-), selected from the murine lymphoma EL-4, showed a marked reduction in tumorigenicity as compared with EL-4 in normal C57B1/6 (B6) mice. The reduced tumorigenicity was directly related to beta 2 m expression. Transfection of an intact murine beta 2m gene markedly increased the tumorigenic potential. The reduced tumorigenicity of C4.4-25- compared with beta 2m transfected cells was observed also in athymic B6 nu/nu mice, but was abolished in B6 mice depleted of natural killer (NK) 1.1-positive cells. These results show that restoration of beta 2m expression can promote tumorigenicity and demonstrate for the first time that induction of major histocompatibility complex class I expression by transfection can lead to escape from NK cells in vivo.
Safety of the anti-IGF-1R antibody CP-751,871 in combination with exemestane in patients with advanced breast cancer.
Authors: PD Ryan, P Neven, LY Dirix, CH Barrios, WH Miller, D Fenton, MF Abraham, L Paccagnella, A Gualberto, PE Goss
Journal: Cancer Research (2009)

Abstract Abstract #2136 Background: Aromatase inhibitors (AIs) are established first-line treatment for postmenopausal estrogen receptor (ER)+ metastatic breast cancer. However, not all patients benefit from AIs and those whose tumors initially respond eventually relapse. One hypothesized mechanism for tumor insensitivity to hormonal agents seems to be cross-talk between the ER pathway and other growth factor signaling pathways, in particular the insulin-like growth factor receptor type 1 (IGF-1R). In xenograft breast cancer models, CP-751,871 administration increased tumor growth inhibition induced by tamoxifen. Thus our trial addresses the effect of combining AI with an IGF-1R antagonist.&amp;#x2028; Methods: A phase II, multicenter, randomized, two-arm, comparative, two-stage trial to determine PFS of CP-751,871, a fully human IgG2 monoclonal antibody targeting IGF-1R, in combination with exemestane versus exemestane alone as first-line treatment in patients with hormone receptor positive, advanced breast cancer. Secondary endpoints include clinical benefit (CR, PR, or SD ≥6 months), safety/tolerability and PK. Patients included in the study are post menopausal, ≥18 years with locally advanced/metastatic breast cancer (stage IIIB or IV), ECOG PS 0–2, and adequate hematological, biochemical, and cardiac functions. CP-751,871 is given by intravenous infusion at a dose of 20 mg/kg every 21 days while 25 mg exemestane was given p.o. daily.&amp;#x2028; Results: To date 37 patients have been dosed with CP-751,871 plus exemestane. Median age is 60.5 years (range 34–84). Patients received a median of 9.5 treatment cycles (range 1–22). One GR 4 CP-751,871-related AE (hoarse voice) was reported, which resolved after 3 days without intervention. GR 3 CP-751,871-related toxicities included 8.1% hyperglycemia (n=3), 8.1% GGT elevation (n=3), 5.4% allergic reaction (n=2), 5.4% hearing loss (n=2), 5.4% weight loss (n=2), and 2.7% anorexia (n=1). GR 2 CP-751,871-related AEs &amp;gt;10% were headaches, muscle cramps, and nail changes. Both hyperglycemia and hypersensitivity reactions were manageable (with oral hypoglycemic drug/insulin and antihistamine), while GGT elevation seems to be reversible.&amp;#x2028; Conclusions: CP-751,871 in combination with exemestane is well tolerated. The most frequent GR 3 side effects are either well managed with medications or appear to be reversible. Therefore, CP-751,871, due to its safety profile, is a good targeted agent to combine with standard hormonal therapy. The stage I portion of the study to determine efficacy and toxicity is ongoing. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2136.
Respiratory Morbidity in Office Workers in a Water-Damaged Building
Authors: Jean M. Cox-Ganser, Sandra K. White, Rebecca Jones, Ken Hilsbos, Eileen Storey, Paul L. Enright, Carol Y. Rao, Kathleen Kreiss
Journal: Environmental Health Perspectives (2005)

We conducted a study on building-related respiratory disease and associated social impact in an office building with water incursions in the northeastern United States. An initial questionnaire had 67% participation (888/1,327). Compared with the U.S. adult population, prevalence ratios were 2.2-2.5 for wheezing, lifetime asthma, and current asthma, 3.3 for adult-onset asthma, and 3.4 for symptoms improving away from work (p < 0.05). Two-thirds (66/103) of the adult-onset asthma arose after occupancy, with an incidence rate of 1.9/1,000 person-years before building occupancy and 14.5/1,000 person-years after building occupancy. We conducted a second survey on 140 respiratory cases, 63 subjects with fewer symptoms, and 44 comparison subjects. Health-related quality of life decreased with increasing severity of respiratory symptoms and in those with work-related symptoms. Symptom status was not associated with job satisfaction or how often jobs required hard work. Respiratory health problems accounted for one-third of sick leave, and respiratory cases with work-related symptoms had more respiratory sick days than those without work-related symptoms (9.4 vs. 2.4 days/year; p < 0.01). Abnormal lung function and/or breathing medication use was found in 67% of respiratory cases, in 38% of participants with fewer symptoms, and in 11% of the comparison group (p < 0.01), with similar results in never-smokers. Postoccupancy-onset asthma was associated with less atopy than preoccupancy-onset asthma. Occupancy of the water-damaged building was associated with onset and exacerbation of respiratory conditions, confirmed by objective medical tests. The morbidity and lost work time burdened both employees and employers.
Serological Assessment of Rubella During Pregnancy
Authors: J. E. Banatvala, J. M. Best, J. Bertrand, N. A. Bowern, S. M. Hudson
Journal: BMJ (1970)

In 45 patients with rubella-like illnesses during pregnancy serological tests showed that the clinical diagnosis had been accurate in only 20. Since only 16 of these patients had presented for laboratory investigations within a week of the onset of symptoms, the value of haemagglutination-inhibition tests was considerably reduced; the diagnosis in these cases was confirmed by complement-fixation and rubella-specific IgM tests.Of 172 patients exposed to a rubella-like illness, only 17 were seronegative; 105 sought advice within two weeks of exposure, and therefore the haemagglutination-inhibition antibody tests were useful in determining immunity. Since the clinical diagnosis of rubella was proved incorrect in a number of cases, these pregnancies were saved. Hence both doctors and patients should report both exposure to and rubella-like illnesses as early as possible, so that laboratory investigations may be carried out without delay.
POEMS syndrome: 2011 update on diagnosis, risk‐stratification, and management
Authors: Angela Dispenzieri
Journal: American Journal of Hematology (2011)

Abstract Disease overview POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. Diagnoses are often delayed because the syndrome is rare and can be mistaken for other neurologic disorders, most commonly chronic inflammatory demyelinating polyradiculoneuropathy. POEMS syndrome should be distinguished from the Castleman disease variant of POEMS syndrome, which has no clonal PCD and typically little to no peripheral neuropathy but has several of the minor diagnostic criteria for POEMS syndrome. Diagnosis: The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria. Risk stratification: Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. The number of clinical criteria is not prognostic, but the extent of the plasma cell disorder is. Those patients with an iliac crest bone marrow biopsy that does not reveal a plasma cell clone are candidates for local radiation therapy; those with a more extensive or disseminated clone will be candidates for systemic therapy. Risk‐adapted therapy: For those patients with a dominant sclerotic plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3 to 6 months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. The benefit of anti‐VEGF antibodies is conflicting. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes. Am. J. Hematol. 86:592–601, 2011. © 2011 Wiley‐Liss, Inc.
Chekhov's Doctors
Authors: Jack Coulehan
Journal: JAMA (1997)

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
Conjugal Histoplasmosis
Authors: MORTON SILLS
Journal: Annals of Internal Medicine (1973)

Six months after having primary pulmonary histoplasmosis, a young man developed progressive dissemination enhanced by steroid therapy, which had been given because the initial illness was diagnosed as sarcoidosis. Subsequently, he venerally transmitted his infection to his wife. Man-to-man transmission of histoplasmosis has not been previously reported, to our knowledge.
US panel calls for sweeping changes to funding of graduate medical education
Authors: M. McCarthy
Journal: BMJ (2014)

The US system for funding physician training should be overhauled to ensure that it produces a workforce better matched to the nation’s needs, says a new report from the Institute of Medicine.1

Currently, US taxpayers provide $15bn (£8.9bn; €11.2bn) a year, primarily through Medicare, to pay for postgraduate medical training. Most of that money goes to teaching hospitals, with few strings attached. “This funding is essentially guaranteed—regardless of whether the funded programs reflect local, regional, or national healthcare priorities,” the 21 member panel wrote.

This has resulted in a physician workforce with too many specialists and too few doctors who were prepared to work in primary care or in underserved communities, the panel said. It added that hospital based training left many physicians unprepared to practice in the ambulatory care settings …
Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart Study
Authors: Chin-Chi Kuo, Barbara V. Howard, Jason G. Umans, Matthew O. Gribble, Lyle G. Best, Kevin A. Francesconi, Walter Goessler, Elisa Lee, Eliseo Guallar, Ana Navas-Acien
Journal: Diabetes Care (2015)

OBJECTIVE Little is known about arsenic metabolism in diabetes development. We investigated the prospective associations of low-moderate arsenic exposure and arsenic metabolism with diabetes incidence in the Strong Heart Study. RESEARCH DESIGN AND METHODS A total of 1,694 diabetes-free participants aged 45–75 years were recruited in 1989–1991 and followed through 1998–1999. We used the proportions of urine inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) over their sum (expressed as iAs%, MMA%, and DMA%) as the biomarkers of arsenic metabolism. Diabetes was defined as fasting glucose ≥126 mg/dL, 2-h glucose ≥200 mg/dL, self-reported diabetes history, or self-reported use of antidiabetic medications. RESULTS Over 11,263.2 person-years of follow-up, 396 participants developed diabetes. Using the leave-one-out approach to model the dynamics of arsenic metabolism, we found that lower MMA% was associated with higher diabetes incidence. The hazard ratios (95% CI) of diabetes incidence for a 5% increase in MMA% were 0.77 (0.63–0.93) and 0.82 (0.73–0.92) when iAs% and DMA%, respectively, were left out of the model. DMA% was associated with higher diabetes incidence only when MMA% decreased (left out of the model) but not when iAs% decreased. iAs% was also associated with higher diabetes incidence when MMA% decreased. The association between MMA% and diabetes incidence was similar by age, sex, study site, obesity, and urine iAs concentrations. CONCLUSIONS Arsenic metabolism, particularly lower MMA%, was prospectively associated with increased incidence of diabetes. Research is needed to evaluate whether arsenic metabolism is related to diabetes incidence per se or through its close connections with one-carbon metabolism.
Thyroxine Binding Globulin and Thyroid Function Tests in Patients with Hepatocellular Carcinoma
Authors: John W. Kalk, Michael C. Kew, Mervyn D. Danilewitz, Frederick Jacks, Andre L. Van Der Walt, Joseph Levin
Journal: Hepatology (1982)

To determine the prevalence of elevated serum concentrations of thyroxine binding globulin (TBG) in patients with hepatocellular carcinoma (HCC) and the influence of the associated cirrhosis, TBG was measured in 39 patients with HCC, 22 with and 17 without cirrhosis, in 20 patients with cryptogenic macronodular cirrhosis but without HCC, and in 40 matched controls. The mean serum TBG concentration in the patients was 34.5 ± 17.7 μg per ml, compared to 21.4 ± 6.8 μg per ml in controls and 20.5 ± 6.3 μg per ml in cirrhosis without HCC (p &lt; 0.01). The presence or absence of cirrhosis in the HCC patients did not significantly influence the frequency with which elevated TBG levels were found; levels were normal in every subject with cirrhosis and no HCC. The mean thyroxine (T 4 ): TBG ratio was 5.58 ± 1.78 in controls and was reduced in HCC patients with both elevated (3.33 ± 0.80, p &lt; 0.001) and normal TBG values (4.39 ± 1.90, p &lt; 0.05), and in cirrhotics without HCC (4.29 ± 1.01, p &lt; 0.01). T 4 and TBG concentrations correlated significantly in controls, in HCC patients with elevated TBG, and in the cirrhotics without HCC. It is concluded that in patients with HCC (i) TBG levels may be elevated both in the presence or absence of cirrhosis; (ii) there is reduced binding of T 4 TBG, and (iii) a low T 4 :TBG ratio excludes the diagnosis of hyperthyroidism in the presence of high T 4 levels. TBG levels are normal in patients with cryptogenic macronodular cirrhosis without HCC.
Gastrointestinal endoscopy: infection and disinfection.
Authors: H J O'Connor, A T Axon
Journal: Gut (1983)

The past decade has seen the development of an array of complex flexible fibreoptic instruments for gastrointestinal (GI) endoscopy, and an increasing use of these for diagnostic and therapeutic purposes. It has been recognised more recently that the use of contaminated endoscopic equipment can lead to serious and occasionally fatal infections. Infection with a wide variety of micro-organisms has been reported following oesophago-gastroduodenoscopy (OGD) and endoscopic retrograde cholangio-pancreatography (ERCP).
Costs and benefits of a community special care baby service
Authors: J. M Couriel, P. Davies
Journal: BMJ (1988)

Between January 1981 and December 1986 3829 low birthweight (less than 2500 g) infants and 1980 other high risk infants were cared for at home after they were discharged from hospital by a specialist neonatal nursing service. Of the infants who were referred to this service, 720 (12%) weighed under 2000 g and 1919 (33%) under 2250 g at the time of discharge home. The infants were visited by the community neonatal sisters on an average of 11 occasions, but the number of visits varied from six to over 100 depending on the needs of the child and parents. There was close liaison with other community and hospital staff. Two hundred and thirty (4%) referred infants were readmitted to hospital while under the care of the specialist nursing service. In 1985 the cost of the service was pounds 127,000, or pounds 123 for each infant referred. Providing this specialist support at home allowed much earlier discharge of low birthweight infants from hospital. When compared with the cost of providing continuing inpatient neonatal care earlier discharge was estimated to have saved roughly pounds 250,000 in 1985. Low birthweight infants have an increased risk of serious illness or death that extends beyond the neonatal period. Many are born to young and socially disadvantaged parents who can benefit from expert guidance and support at home. A community neonatal nursing service has advantages for high risk infants and their parents, is cost effective, and allows more efficient use of limited hospital resources.
Emergency department evaluation of the febrile traveler
Authors: David C. Pigott
Journal: Journal of Infection (2006)

The emergency department evaluation of the febrile traveler presents the emergency physician with a set of unique and often challenging circumstances. In addition to evaluating and managing the usual array of community-acquired infections, the clinician must be prepared to diagnose and treat a host of uncommon and potentially life-threatening pathogens. This diseases range from widespread tropical diseases such as malaria to the more exotic and lethal viral hemorrhagic fevers. A thoughtful approach guided by geographic patterns of illness offers a reliable method for determining the most likely sources of fever in the returned traveler as well as a focused diagnostic and treatment strategy.
Reflux disease and Barrett’s esophagus
Authors: J. Abrams, C. Lightdale
Journal: Endoscopy (2008)

Despite the high prevalence of gastroesophageal reflux disease (GERD) and, to a lesser degree, Barrett’s esophagus in the Western world, there are still many unknowns with regard to the epidemiology, natural history, and appropriate treatments for these conditions. There is a significant amount of ongoing research into endoscopic treatment modalities in an attempt to reduce the need for medical therapy for GERD. Meanwhile, the underlying biology of Barrett’s carcinogenesis is incompletely understood, as is the ideal treatment for Barrett’s esophagus and advanced neoplasia.
Metabolic Effects of Dietary Sucrose in Type II Diabetic Subjects
Authors: John P Bantle, Joyce E Swanson, William Thomas, Dawn C Laine
Journal: Diabetes Care (1993)

Objective— To assess in diabetic subjects the effects of dietary sucrose on glycemia and lipemia. Research Design and Methods— Twelve type II diabetic subjects consumed, in random order, two isocaloric, 55% carbohydrate study diets for 28 days. In one diet, 19% of energy was derived from sucrose. In the other diet, &amp;lt;3% of energy was derived from sucrose, and carbohydrate energy came primarily from starch. Both study diets were composed of common foods. All meals were prepared in a metabolic kitchen where foods were weighed during meal preparation. Results— No significant differences were noted between the study diets at any time point in mean plasma glucose. At day 28, mean plasma glucose values for the sucrose diet were 9.6 ± 0.5 mM and for the starch diet were 9.4 ± 0.6 mM (P = 0.63). Also, no significant differences were observed between the study diets in urine glucose, fasting serum total, HDL, or LDL cholesterol; fasting serum TG; or peak postprandial serum TG. Conclusions— A high sucrose diet did not adversely affect glycemia or lipemia in type II diabetic subjects.