tbuckley/cabot-search huggingface dataset:
Cutaneous mosaicism: right before our eyes
Authors: Jorge Frank, Rudolf Happle
Journal: Journal of Clinical Investigation (2007)

Autosomal recessive cutaneous disorders, including various types of epidermolysis bullosa (EB), usually manifest shortly after birth. The clinical course of these diseases is often characterized by severe complications, limited therapeutic options, and a poor prognosis. A study by Pasmooij et al. reported in this issue of the JCI unravels the molecular mechanisms by which germline mutations in non-Herlitz junctional EB can be corrected in vivo by multiple spontaneously occurring somatic mutational events, a phenomenon known as revertant mosaicism (see the related article beginning on page 1240). These insights open new avenues of thinking for the design of future gene therapy strategies for skin diseases.
Genetic Diversity in Melanoma
Authors: Paul S. Meltzer
Journal: New England Journal of Medicine (2005)

As with other cancers, the process of the transformation of normal melanocytes into malignant melanoma requires the acquisition of genomic abnormalities. Although progress in the search for the targets of genetic aberration in cancer has been stunning in many respects, the clinical effect of this work has been limited. But it is clear that tracking down the genetic changes in cancer is no mere academic exercise; rather, it has proved to be a powerful approach to the selection of therapeutic targets. Progress in the treatment of chronic myelogenous leukemia, gastrointestinal stromal tumor, and some lung cancers can be directly linked . . .
Cimetidine-Induced Impotence and Breast Changes in Patients with Gastric Hypersecretory States
Authors: Robert T. Jensen, Martin J. Collen, Stephen J. Pandol, Hector D. Allende, Jean-Pierre Raufman, Bruce M. Bissonnette, Wallace C. Duncan, Patricia L. Durgin, J. Christian Gillin, Jerry D. Gardner
Journal: New England Journal of Medicine (1983)

Cimetidine has been shown to be an effective drug for healing peptic ulcers and for preventing their recurrence.1 In most clinical trials cimetidine has been associated with few side effects of clinical importance. Early toxicologic studies with cimetidine, however, showed a decrease in the weight of the prostate and seminal vesicles in rats and dogs,2 , 3 suggesting the presence of antiandrogen activity. Later studies demonstrated that cimetidine could inhibit the binding of dihydrotestosterone to androgen receptors in the prostates of rats and the kidneys of mice.3 4 5 6 Subsequently, the occurrence of gynecomastia,7 8 9 10 especially in pathologic hypersecretory states,7 , 11 , 12 and occasional cases of impotence . . .
The Treatment of Bilharzia Disease
Authors: P. Sonsino
Journal: BMJ (1885)

The coincidence that, both in the case related above and in De Haen's case, the patient was periodically subject to abdominal pains, associated in the first with a constricting sensation, in the second with tympanites, may be noted as, perhaps; indicating that the intestine had not unfrequently slipped into the opening before the fatal incarceration took place.I am indebted to MIr. T.
Repetitive organic dust exposure in vitro impairs macrophage differentiation and function
Authors: Jill A. Poole, Neil E. Alexis, Conrad Parks, Amy K. MacInnes, Martha J. Gentry-Nielsen, Paul D. Fey, Lennart Larsson, Diane Allen-Gipson, Susanna G. Von Essen, Debra J. Romberger
Journal: Journal of Allergy and Clinical Immunology (2008)
Predictive Value of Angiotensin II Antagonists in Renovascular Hypertension
Authors: Fetnat M. Fouad
Journal: JAMA (1983)

An angiotensin II antagonist, sarcosine-1, threonine-8 angiotensin II ( [Sar1, Thr8] A II), was infused preoperatively in 14 patients with renal artery stenosis. Postoperative graft patency was documented by renal flow scan in 13 patients. One of these required antihypertensive therapy immediately after surgery, while the other 12 had a significant BP reduction in the first postoperative week (141 +/- 3.7 to 110 +/- 1.6 mm Hg). With longer follow-up, six patients remained normotensive (group 1), while the other six had "residual hypertension" (group 2). There was no significant difference between the two groups as regards age, preoperative BP level, plasma renin activity, blood volume, or response to [Sar1, Thr8] A II. In contrast, clinical signs were most helpful in predicting response to surgery. "Cured" patients had shorter duration of hypertension (less than one year) than patients with residual hypertension, and less impairment of renal excretory function; three patients in group 2 but none in group 1 had a history of malignant hypertension. The decision to operate remains a multifactorial evaluation and cannot be based on results of any single test alone.
UK chancellor hints at cutbacks in NHS IT programme
Authors: M. Cross
Journal: BMJ (2009)

Attempts to revive confidence in the £13bn (€14.3bn; $21.3bn) effort to computerise the NHS in England were thrown into disarray this week when the chancellor of the exchequer, Alistair Darling, singled out the programme as a prime candidate for spending cuts. 

In a BBC television interview on Sunday, in advance of the prebudget report due this week, Mr Darling described the programme as “not essential for the front line” and “something we do not need to go ahead with just now.”

Opposition politicians welcomed the statement. However, the BMA and NHS management bodies warned against cutting back the upgrade of information technology systems in use by NHS organisations. …
Heterogeneous mutations in the SLC3A1 and SLC7A9 genes in Chinese patients with cystinuria
Authors: Y.-P. Yuen, C.-W. Lam, C.-K. Lai, S-F Tong, P.-S. Li, S. Tam, E.Y-W. Kwan, S.-Y. Chan, W.-K. Tsang, K.-Y. Chan, W.-L. Mak, C.-W. Cheng, Y.-W. Chan
Journal: Kidney International (2005)
Elisha Kent Kane, Physician and Explorer
Authors: Henry H. Fertig
Journal: New England Journal of Medicine (1953)

THE name of Elisha Kent Kane is one of which all Americans can be proud, and from his life physicians in particular can gain lasting inspiration. His great-grandmother received training as a surgeon in London in 1749 and, after coming to the colonies, did much to alleviate the suffering of the American prisoners in the Philadelphia prison during the British occupation. Kane was born in Philadelphia on February 3, 1820. As a youth, "he manifested no extraordinary love of learning," and rebelled against the systematic method of study in the schools. At the age of sixteen, when he was attempting . . .
Our Art, Our Heritage
Authors: Eugene L. Vickery
Journal: JAMA (1983)

THE ABILITY of revered old-time physicians to heal was very real. Of course they lacked our modern resources and they, with their patients, faced devastating failures in treatment of conditions now readily controlled. They knew, to their glory, how to mobilize the best of the patient's own strength, the desire and ability to recover. We think few of their medications were effective; some may have been deleterious, and some of their procedures, if we go back far enough, seem ill-advised. Now we want all the assurance possible that everything we do or use is beneficial. We generally give almost blind obeisance to double- or triple-blind studies of clinical effectiveness. We dutifully shudder at the thought that we might have anything in common with primitive medicine men or modern semieducated flamboyant healers. Yet, somehow, we realize that there is more to the care and healing of people than science presently provides.
The measurement of gastric transmucosal potential difference through a gastroduodenoscope.
Authors: K M Cochran, R I Russell
Journal: Gut (1973)

The existence of a gastric transmucosal electrical potential difference has been recognized for many years.Goodman (1942) claimed that changes in the .electricalpotential difference across the gastric mucosa may be of value in the differential diagnosis of gastric disorders.Ingram (1953) confirmed much of this work and Andersson and Grossman (1966) showed that the difference in gastric and duodenal electrical potential difference was of value in accuratelydemarcatingtheduodenal-gastric junction.Until 1970 most workers used skin as the site of the reference electrode.Geall, Code, McIlrath, and Summerskill, (1970a), however, showed that the use
ALUMINIUM THROAT SWABS
Authors: L. Grant
Journal: BMJ (1922)

The accompanying diagram shows the daily case incidence tlhroughout this epi.demic,under thle two headings: those admitted to the sanator.ium (black continuous line), and tlhose ill in their respective boarding lhouses (dotted line); so tllat to obtain the number of cases under treatment on any given day it is ncessaxry tQ add togethertlke sum total of bothi groups.Tlhegeneral results -may be briefly.suimmarized in tabular form, and tle following statistics, siowing the perceutage of
Segmental Tuberculosis of the Colon Diagnosed by Colonoscopy
Authors: E. Medina, E. Orti, A. Tomé, F. Quiles, P. Canelles, A. Mertinez
Journal: Endoscopy (1990)

We describe the case of a woman with rectorhagia and rectal tenesmus. Colonoscopy revealed a 3-4 cm-long ulcerated lesion with a reduced colon lumen 35 cm from the anus, and multiple biopsies were obtained from the ulcerated region, but histopathology was non-specific. Biopsy culture was positive for M. tuberculosis. Anti-tuberculous chemotherapy was initiated on the diagnosis of segmental tuberculosis of the colon. Subsequent evolution was favorable, both clinically and endoscopically. Emphasis is placed on the importance of colonoscopy and biopsy in the diagnosis of tuberculosis of the colon.
Mycophenolate Mofetil for the Treatment of Takayasu Arteritis: Report of Three Cases
Authors: Erica Daina, Arrigo Schieppati, Giuseppe Remuzzi
Journal: Annals of Internal Medicine (1999)

Background: Takayasu arteritis is a rare form of chronic inflammatory disease of the large arterial vessels. Some patients do not respond to steroids or immunosuppressant drugs. Objective: To evaluate the effect of mycophenolate mofetil in patients with severe Takayasu arteritis. Design: Case series. Setting: Clinical Research Center for Rare Diseases in Bergamo, Italy. Patients: Three patients with Takayasu arteritis. Intervention: Mycophenolate mofetil (2 g/d) given orally in two divided doses. Measurements: Clinical evaluation and assessment of leukocyte counts were done weekly. Vascular lesions were assessed by using Doppler ultrasonography. Results: All patients showed clinical benefit, and two resumed work after months of inactivity. Patients were also able to taper and discontinue steroid use. Mycophenolate mofetil was well tolerated, and no signs of toxicity were observed. Conclusions: Mycophenolate mofetil may be an alternative to steroids and cytotoxic agents in patients with Takayasu arteritis. Before results of controlled trials become available, mycophenolate mofetil should be considered only for patients who do not improve or stabilize with conventional therapy.
The need for water quality criteria for frogs.
Authors: R Boyer, C E Grue
Journal: Environmental Health Perspectives (1995)

Amphibians are considered reliable indicators of environmental quality. In the western United States, a general decline of frog populations parallels an apparent worldwide decline. The factors thought to be contributing to declines in frog populations include habitat loss, introduction of exotic species, overexploitation, disease, climate change, and decreasing water quality. With respect to water quality, agroecosystems use 80-90% of the water resources in the western United States, frequently resulting in highly eutrophic conditions. Recent investigations suggest that these eutrophic conditions (elevated pH, water temperature, and un-ionized ammonia) may be associated with frog embryo mortality or malformations. However, water quality criteria for frogs and other amphibians do not currently exist. Here, we briefly review data that support the need to develop water quality parameters for frogs in agroecosystems and other habitats.
Herschell Kenneth Weinbren
Authors: M. Weinbren
Journal: BMJ (2010)

Professor Herschell Kenneth Weinbren MD FRCPath died aged 87 on 19 May 2010. He was professor of histopathology at the Royal Postgraduate Medical School at Hammersmith Hospital until his retirement in 1988, a prominent student leader at university, and a researcher of talent.

Born in 1923 in Cape Town, South Africa, he graduated from Witwatersrand University in Johannesburg, where he was …
Points: Treating the discharging ear
Authors: G. G Browning
Journal: BMJ (1988)

gresses more rapidly in this group is in dispute.Although we are unlikely to find premalignant disease in the sexually active girls under 16, we think that cytological screening is useful to educate them about the need for regular cervical smears.These patients are likely to have many sexual partners, have a high prevalence of sexually trans- mitted diseases (770/o-A J Robinson, unpublished data), and be at high risk of developing cervical intraepithelial neoplasia.
Recent developments: Breast cancer
Authors: Monica Morrow, William Gradishar
Journal: BMJ (2002)

As our understanding of the biology of breast cancer continues to improve, treatment of the disease continues to change. Although the ultimate goal of treatment remains improved survival, increasing emphasis is now put on less morbid treatments and improving quality of life. Prevention remains a major focus, particularly in women at high risk of developing breast cancer because of mutations in susceptibility genes. In this article, we review the current prevention strategies in carriers of BRCA1 and BRCA2 mutations, data on sentinel node biopsy for axillary staging, and trials of new endocrine treatments for advanced breast cancer.
Paracetamol: is all the concern valid?
Authors: Evan S Schwarz, Michael E Mullins
Journal: Annals of the Rheumatic Diseases (2015)

Paracetamol: is all the concern valid?Given the widespread use and availability of paracetamol, we appreciate the ongoing need to evaluate its safety.However the review by Roberts et al 1 appears to be one in a string of recent articles drawing dubious or misleading conclusions regarding the safety of paracetamol. 2 3We question these conclusions about the safety of taking properly dosed paracetamol.The alternatives for chronic pain, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, carry risks of significant morbidity and mortality. 4 5 In the systematic review, the authors only included cohort studies.While cohorts can be valuable when studying the risk of long-term adverse events from an exposure, they can also introduce significant bias due to multiple other uncontrolled variables.While the included studies did attempt to adjust for confounders, half of the studies did not adjust for NSAIDs and what was adjusted for varied between studies.As such, paracetamol use may be a marker for other medical conditions, which caused the need for regular paracetamol use as well as complications such as cardiovascular, renal and gastrointestinal disease.The authors suggest a dose-response relationship between the amount of acetaminophen ingested and the adverse events as proof of a correlation between the two.An alternative interpretation is that sicker patients were more likely to use more paracetamol than NSAIDs or opioids.This association becomes even more dubious when included studies relied upon self-report to determine the amount of paracetamol ingested.In addition, the inclusion criteria widely varied between the different studies, including four that only included women, one that only included men, and one study that only included patients with chronic kidney disease.As such, the inclusion of all of the studies in a single meta-analysis may not be appropriate.The authors also intentionally left out case-control studies.We question their rationale for doing so as case-control studies may have been better suited to relate any adverse event to the use of acetaminophen, assuming the cases and controls were appropriately matched.The quality of evidence included was also poor.We commend the authors for using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to assess the quality of the outcomes of the included studies.Unfortunately, all of the studied outcomes were scored 'very low,' the lowest rating possible using GRADE.Even the bestconducted meta-analysis will suffer if the quality of data is poor as 'garbage in equals garbage out.'While the topic is worth studying and important, we wonder what, if any, useful conclusions these data provide.
Nocturnal Oxygen Desaturation in Patients With Sickle Cell Anemia
Authors: Milton B. Scharf
Journal: JAMA (1983)

The sleep of two patients with sickle cell disease was punctuated by periods with notably reduced arterial O<sub>2</sub>saturation despite simultaneous normal respiratory rates. The O<sub>2</sub>levels returned to baseline during intermittent wakefulness. Gas exchange patterns during sleep may contribute to the morbidity of sickle cell disease. (<i>JAMA</i>1983;249:1753-1755)
Identification of a hemagglutinin-specific idiotype associated with reovirus recognition shared by lymphoid and neural cells.
Authors: J T Nepom, H L Weiner, M A Dichter, M Tardieu, D R Spriggs, C F Gramm, M L Powers, B N Fields, M I Greene
Journal: The Journal of Experimental Medicine (1982)

A xenogeneic antiserum raised to antireovirus immunoglobulin was used to define an idiotypic determinant present on antibodies to reovirus type 3 hemagglutinin. The same idiotype was identified on nonimmune lymphoid cells and on neuronal cells that specifically bind the hemagglutinin of type 3 reovirus. This idiotypic determinant, called Id3, is shared by (a) a monoclonal antibody to the neutralization site of hemagglutinin from type 3 reovirus; (b) BALB/c serum antibodies to the hemagglutinin of reovirus type 3; (c) R1.1, a murine thymoma cell line that binds reovirus type 3; (d) primary cultures of murine neuronal cells. The presence of an idiotype shared by antihemagglutinin antibodies and by structures on nonlymphoid cells suggests a general relationship between disparate receptors that recognize a common determinant. Furthermore, this suggests a novel approach for the study of viral receptor interactions and for analysis of mechanisms of autoimmune responses.
Candidate Performance Measures for Screening for, Assessing, and Treating Unhealthy Substance Use in Hospitals: Advocacy or Evidence-Based Practice?
Authors: Richard Saitz
Journal: Annals of Internal Medicine (2010)

This article has been corrected. The original version (PDF) is appended to this article as a supplement. The Joint Commission recently proposed candidate performance measures addressing unhealthy substance use in hospitalized patients. The proposed measures of screening and brief intervention (SBI) assume that interventions that work in one setting (primary care outpatient practice) would work in another (hospital); treatment would have the same benefits for persons identified by screening as for those with symptoms who seek help; treatments that work for persons less severely affected by substance use would also work for those with more severe illness; and an approach that works for nondependent, unhealthy alcohol use would work for drug use. However, these assumptions extrapolate evidence of the effectiveness of SBI for primary care outpatients with nondependent, unhealthy alcohol use to the inpatient setting, persons with dependence, and other substances. Although quality of care for unhealthy substance use in all medical settings needs to improve, the evidence base for SBI in the hospital is too limited for the implementation of performance measures assessing this care.
Binding specificity of antiidiotypic autoantibodies to anti-DNA antibodies in humans.
Authors: T Sasaki, T Muryoi, O Takai, E Tamate, H Saito, K Yoshinaga
Journal: Journal of Clinical Investigation (1988)

Human antiidiotypic antibodies to anti-DNA antibodies can be separated into at least two categories based on their binding to anti-DNA, antiidiotypic antibodies, and antigens. One type was found mainly in inactive stage of SLE. The antiidiotypic antibodies appear to be directed towards idiotype (Id) determinants in the antigen-binding sites of anti-DNA antibodies. Antibody from patient T.K. acted like a mirror image of anti-single-stranded DNA antibodies, O-81, as determined by a competitive inhibition RIA. Antibodies from patient S.U. also seemed to be Ab 2 beta and Ab 2 gamma to anti-double-stranded(ds) DNA antibodies, NE-1. Most of normal subjects, on the other hand, had antibodies that bound to the human monoclonal anti-ds DNA antibodies, NE-1, NE-13, 7F4, and O-81. The Id-anti-Id interaction was not inhibited by the addition of DNA. Thus, normal subjects had Ab2 alpha activity that recognizes Id determinants in the framework region common among anti-DNA antibodies, whereas antiidiotypic antibodies in most SLE sera appear to show Ab 2 beta and Ab 2 gamma activity. The results provide evidence that the Id network system regulates immunological tolerance to DNA in humans.
Pharmacokinetics and Repolarization Effects of Intravenous and Transdermal Granisetron
Authors: Jay W. Mason, Daniel S. Selness, Thomas E. Moon, Bridget O'Mahony, Peter Donachie, Julian Howell
Journal: Clinical Cancer Research (2012)

The need for greater clarity about the effects of 5-HT(3) receptor antagonists on cardiac repolarization is apparent in the changing product labeling across this therapeutic class. This study assessed the repolarization effects of granisetron, a 5-HT(3) receptor antagonist antiemetic, administered intravenously and by a granisetron transdermal system (GTDS).In a parallel four-arm study, healthy subjects were randomized to receive intravenous granisetron, GTDS, placebo, or oral moxifloxacin (active control). The primary endpoint was difference in change from baseline in mean Fridericia-corrected QT interval (QTcF) between GTDS and placebo (ddQTcF) on days 3 and 5.A total of 240 subjects were enrolled, 60 in each group. Adequate sensitivity for detection of QTc change was shown by a 5.75 ms lower bound of the 90% confidence interval (CI) for moxifloxacin versus placebo at 2 hours postdose on day 3. Day 3 ddQTcF values varied between 0.2 and 1.9 ms for GTDS (maximum upper bound of 90% CI, 6.88 ms), between -1.2 and 1.6 ms for i.v. granisetron (maximum upper bound of 90% CI, 5.86 ms), and between -3.4 and 4.7 ms for moxifloxacin (maximum upper bound of 90% CI, 13.45 ms). Day 5 findings were similar. Pharmacokinetic-ddQTcF modeling showed a minimally positive slope of 0.157 ms/(ng/mL), but a very low correlation (r = 0.090).GTDS was not associated with statistically or clinically significant effects on QTcF or other electrocardiographic variables. This study provides useful clarification on the effect of granisetron delivered by GTDS on cardiac repolarization.