tbuckley/cabot-search huggingface dataset:
Acute hepatotoxicity of ethylene and halogenated ethylenes after PCB pretreatment
Authors: Rory B. Conolly, Rudolph J. Jaeger
Journal: Environmental Health Perspectives (1977)

Previous studies from our laboratory have shown that ethylene, vinyl fluoride monomer (VFM), vinyl chloride monomer (VCM), and vinyl bromide monomer (VBM) are all acutely hepatotoxic in rats pretreated with polychlorinated biphenyl (PCB). The time course of hepatic injury development after exposure and several parameters, environmental and chemical, affecting this toxicity were evaluated in the work reported here. Liver injury, as measured by serum alanine-α-ketoglutarate transaminase (SAKT) or sorbitol dehydrogenase (SDH), develops progressively over a 24-hr period following a 4-hr inhalation exposure of PCB-pretreated rats to ethylene or VCM. Environmental temperature during exposure to VCM does not affect hepatotoxicity or mortality below 30.3°C. At 33.8°C, however, mortality and SAKT are dramatically increased. Overnight fasting, which depletes hepatic glutathione (GSH) of PCB-pretreated rats before exposure to ethylene or VCM, significantly increases the hepatotoxicity of these compounds as measured by SDH. The combined effects of fasting and of trichloropropane epoxide (TCPE), an inhibitor of epoxide hydrase (EH), were also examined. TCPE treatment of fasted PCB-pretreated rats immediately before exposure was synergistic in increasing the acute toxicity of ethylene and VCM. TCPE increased mortality in fed or fasted rats exposed to VFM, but there was no effect of fasting alone. Both fasting and TCPE increased the sensitivity of PCB-pretreated rats to VBM, but there was not a clearly synergistic effect of fasting plus TCPE. These data suggest that the acute toxicity of these compounds is mediated through epoxide intermediates.
Nutritional status as marker for disease activity and severity predicting mortality in patients with systemic sclerosis
Authors: Lijana Krause, Mike O Becker, Claudia S Brueckner, Christina-Julia Bellinghausen, Corinna Becker, Udo Schneider, Thomas Haeupl, Katharina Hanke, Karin Hensel-Wiegel, Heidrun Ebert, Sabine Ziemer, Ulf-Müller Ladner, Matthias Pirlich, Gerd R Burmester, Gabriela Riemekasten
Journal: Annals of the Rheumatic Diseases (2010)

Objective To assess and analyse nutritional status in patients with systemic sclerosis (SSc) and identify possible associations with clinical symptoms and its prognostic value. Methods Body mass index (BMI) and parameters of bioelectrical impedance analysis (BIA) were assessed in 124 patients with SSc and 295 healthy donors and matched for sex, age and BMI for comparisons. In patients with SSc, BMI and BIA values were compared with clinical symptoms in a cross-sectional study. In a prospective open analysis, survival and changes in the nutritional status and energy uptake induced by nutritional treatment were evaluated. Results Patients with SSc had reduced phase angle (PhA) values, body cell mass (BCM), percentages of cells, increased extracellular mass (ECM) and ECM/BCM values compared with healthy donors. Malnutrition was best reflected by the PhA values. Of the patients with SSc, 69 (55.7%) had malnutrition that was associated with severe disease and activity. As assessed by multivariate analysis, low predicted forced vital capacity and high N-terminal(NT)-proBNP values discriminated best between good and bad nutritional status. Among different clinical parameters, low PhA values were the best predictors for SSc-related mortality. BMI values were not related to disease symptoms or mortality. Fifty per cent of patients with SSc had a lower energy uptake related to their energy requirement, 19.8% related to their basal metabolism. Nutritional treatment improved the patients' nutritional status. Conclusions In patients with SSc, malnutrition is common and not identified by BMI. BIA parameters reflect disease severity and provide best predictors for patient survival. Therefore, an assessment of nutritional status should be performed in patients with SSc.
<i>Torulopsis glabrata</i>Fungemia during Prolonged Intravenous Alimentation Therapy
Authors: Roberto J. Rodrigues, Hiromi Shinya, William I. Wolff, Donald Puttlitz
Journal: New England Journal of Medicine (1971)

FUNGAL infections, rare in surgical patients, may follow prolonged antimicrobial therapy or may occur when systemic resistance factors are depleted. Saprophytic fungi, consistently present in the environment, can produce clinical infections that have been described as "opportunistic."1 , 2 Recently, the frequency of such infections has increased strikingly. More uncommon species are emerging as etiologic agents in severe and sometimes fatal infections.A case of Torulopsis glabrata fungemia occurred in a patient with cancer while she was receiving radiation therapy and parenteral alimentation. The source of infection was the indwelling subclavian catheter. A review of the literature reveals only five reported cases . . .
Drug discovery in jeopardy
Authors: Pedro Cuatrecasas
Journal: Journal of Clinical Investigation (2006)

Despite striking advances in the biomedical sciences, the flow of new drugs has slowed to a trickle, impairing therapeutic advances as well as the commercial success of drug companies. Reduced productivity in the drug industry is caused mainly by corporate policies that discourage innovation. This is compounded by various consequences of mega-mergers, the obsession for blockbuster drugs, the shift of control of research from scientists to marketers, the need for fast sales growth, and the discontinuation of development compounds for nontechnical reasons. Lessons from the past indicate that these problems can be overcome, and herein, new and improved directions for drug discovery are suggested.
Visualization of a Malignant Pericardial Effusion with Tc-99m-EHDP
Authors: VIRGILIO A. VALDEZ, JEROME G. JACOBSTEIN
Journal: Clinical Nuclear Medicine (1980)

Increased accumulation of radioactivity in a pericardial effusion was observed on a routine bone scan in a patient with known primary breast and lung carcinomas. A dynamic flow study and echocardiography confirmed the presence of the effusion. Microscopic examination of the pericardial fluid revealed the presence of malignant cells.
Qualitative research in health care: Assessing quality in qualitative research
Authors: N. Mays
Journal: BMJ (2000)

This is the first in a series of three articles 

In the past decade, qualitative methods have become more commonplace in areas such as health services research and health technology assessment, and there has been a corresponding rise in the reporting of qualitative research studies in medical and related journals.1 Interest in these methods and their wider exposure in health research has led to necessary scrutiny of qualitative research. Researchers from other traditions are increasingly concerned to understand qualitative methods and, most importantly, to examine the claims researchers make about the findings obtained from these methods.

The status of all forms of research depends on the quality of the methods used. In qualitative research, concern about assessing quality has manifested itself recently in the proliferation of guidelines for doing and judging qualitative work.2–5 Users and funders of research have had an important role in developing these guidelines as they become increasingly familiar with qualitative methods, but require some means of assessing their quality and of distinguishing “good” and “poor” quality research. However, the issue of “quality” in qualitative research is part of a much larger and contested debate about the nature of the knowledge produced by qualitative research, whether its quality can legitimately be judged, and, if so, how. This paper cannot do full justice to this wider epistemological debate. Rather it outlines two views of how qualitative methods might be judged and argues that qualitative research can be assessed according to two broad criteria: validity and relevance.

#### Summary points

Qualitative methods are now widely used and increasingly accepted in health research, but quality in qualitative research is a mystery to many health services researchers

There is considerable debate over the nature of the knowledge produced by such methods and how such research should be judged

Antirealists argue …
Coffee Consumption and Risk for Type 2 Diabetes Mellitus
Authors: Eduardo Salazar-Martinez, Walter C. Willett, Alberto Ascherio, JoAnn E. Manson, Michael F. Leitzmann, Meir J. Stampfer, Frank B. Hu
Journal: Annals of Internal Medicine (2004)

Background: In small, short-term studies, acute administration of caffeine decreases insulin sensitivity and impairs glucose tolerance. Objective: To examine the long-term relationship between consumption of coffee and other caffeinated beverages and incidence of type 2 diabetes mellitus. Design: Prospective cohort study. Setting: The Nurses' Health Study and Health Professionals' Follow-up Study. Participants: The authors followed 41 934 men from 1986 to 1998 and 84 276 women from 1980 to 1998. These participants did not have diabetes, cancer, or cardiovascular disease at baseline. Measurements: Coffee consumption was assessed every 2 to 4 years through validated questionnaires. Results: The authors documented 1333 new cases of type 2 diabetes in men and 4085 new cases in women. The authors found an inverse association between coffee intake and type 2 diabetes after adjustment for age, body mass index, and other risk factors. The multivariate relative risks for diabetes according to regular coffee consumption categories (0, <1, 1 to 3, 4 to 5, or ≥ 6 cups per day) in men were 1.00, 0.98, 0.93, 0.71, and 0.46 (95% CI, 0.26 to 0.82; P = 0.007 for trend), respectively. The corresponding multivariate relative risks in women were 1.00, 1.16, 0.99, 0.70, and 0.71 (CI, 0.56 to 0.89; P < 0.001 for trend), respectively. For decaffeinated coffee, the multivariate relative risks comparing persons who drank 4 cups or more per day with nondrinkers were 0.74 (CI, 0.48 to 1.12) for men and 0.85 (CI, 0.61 to 1.17) for women. Total caffeine intake from coffee and other sources was associated with a statistically significantly lower risk for diabetes in both men and women. Conclusions: These data suggest that long-term coffee consumption is associated with a statistically significantly lower risk for type 2 diabetes.
Hidradenitis suppurativa. A plea for early operative treatment
Authors: D. M. Shaughnessy
Journal: JAMA (1972)

Hidradenitis suppurativa has often been misdiagnosed in most patients, leading to delays in management and, too often, improper treatment. When the involved areas are as clean as possible, all of the diseased apocrine gland tissue should be excised and grafted primarily. Histories of two patients demonstrate the problems involved and the end results of proper therapy.
What is apoptosis, and why is it important?
Authors: A. G Renehan
Journal: BMJ (2001)

Philosophers have spent many centuries searching for the meaning of life, but in recent decades cell biologists have become even more fascinated by the meaning of death. Apoptosis describes the orchestrated collapse of a cell characterised by membrane blebbing, cell shrinkage, condensation of chromatin, and fragmentation of DNA followed by rapid engulfment of the corpse by neighbouring cells. It is distinguished from death by necrosis by the absence of an associated inflammatory response. These observations were made by Kerr et al as early as 1972,1 but their importance was underestimated for many years. Today, however, apoptosis is implicated in biological processes ranging from embryogenesis to ageing, from normal tissue homoeostasis to many human diseases, and it has become one of the hottest fields of biomedical research.

#### Summary points

Apoptosis is a genetically regulated form of cell death

It has a role in biological processes, including embryogenesis, ageing, and many diseases

The molecular mechanisms involved in death signals, genetic regulation, activation of effectors have been identified

Many existing treatments (such as non-steroidal anti-inflammatories and anticancer treatments) act through apoptosis

New treatments aimed at modifying apoptosis are being developed and are likely to be used to manage common diseases in the next decade

The term apoptosis is often used interchangeably with programmed cell death. In the strictest sense, programmed cell death may …
Prime minister’s office denies plans to withhold treatment from people with unhealthy lifestyles
Authors: Caroline White
Journal: BMJ (2008)

<h3>ABSTRACT</h3> In mice, IFNγ-producing γδ T cells that express the co-stimulatory molecule, CD27, play a critical role in host defence and anti-tumour immunity. However, their phenotypic diversity, composition in peripheral and secondary lymphoid organs, similarity to αβ T cells as well as homology with human γδ T cells is poorly understood. Here, using single cell RNA sequencing, we show that CD27<sup>+</sup> γδ T cells consist of two major clusters, which are distinguished by expression of Ly6C. We demonstrate that CD27<sup>+</sup>Ly6C<sup>—</sup> γδ T cells exhibit a naïve T cell-like phenotype, whereas CD27<sup>+</sup>Ly6C<sup>+</sup> γδ T cells display a memory-like phenotype, produce several NK cell-related and cytotoxic molecules and are highly similar to both mouse CD8<sup>+</sup> T cells and mature human γδ T cells. In a breast cancer mouse model, depletion of CD27<sup>+</sup> γδ T cells failed to affect tumour growth, but these cells could be coerced into killing cancer cells after expansion <i>ex vivo</i>. These results identify novel subsets of γδ T cells in mice that are comparable to human γδ T cells, opening new opportunities for γδ T cell-based cancer immunotherapy research.
Murine pancreatic beta-cells express H-2K and H-2D but not Ia antigens.
Authors: D Faustman, V Hauptfeld, J M Davie, P E Lacy, D C Shreffler
Journal: The Journal of Experimental Medicine (1980)

Direct microcytotoxicity testing and absorption analyses were employed to determine whether H-2K, H-2D, and Ia antigens are present on murine islet of Langerhans cells. Products of the H-2K and H-2D loci were found on beta-cells from three different mouse strains, but I-region (Ia) antigens were not detected. The absence of Ia gene products from islet cells may be of importance in explaining the survival of islet allografts across major histocompatibility barriers.
On Proving Therapeutic Effectiveness in Acute Pancreatitis
Authors: Eddy D. Palmer
Journal: JAMA (1974)

Clinicians are likely to agree that among abdominal diseases none displays a diversity of clinical features to equal that of acute pancreatitis. Both the subjective and objective spectrums are so broad that the clinician, however experienced, regularly hesitates to make the diagnosis on the clinical manifestations alone. He prefers to await laboratory confirmation by demonstration of increased circulating amylase and lipase activity. (see communication by Katz et al on p 47). As a consequence, acute pancreatitis is a particularly interesting disease on the ward and a most difficult one to handle in an investigational setting. Assessment of the precise usefulness of any one of the several therapeutic moves ordinarily employed for management of the acute stage becomes almost impossible.  The present-day therapeutic potpourri for acute pancreatitis has become standard because each of its components makes sense when one considers what we know of the disease's pathophysiology. Thus, we know there
Prevention of Russian Influenza by Amantadine
Authors: Arnold S. Monto, Robert A. Gunn, Mark G. Bandyk, Christopher L. King
Journal: JAMA (1979)

We tested the effectiveness of amantadine hydrochloride in prevention of illness and infection caused by Russian (h1n1) influenza. The trial lasted seven weeks and was double-blind and placebo controlled. The dosage used was 200 mg daily. Efficacy in prevention of serologically confirmed clinical influenza was 70.7%. Efficacy in prevention of infection, symptomatic or asymptomatic, was 39.4%. Side effects seen were all mild, began within two days of the start of the trial, and terminated rapidly on cessation of prophylaxis. The withdrawal rate attributable to use of amantadine was 6.2%. Those who continued to receive prophylaxis for the remainder of the trial did not exhibit excess side effects. It is concluded that amantadine is safe and effective in prophylaxis of H1N1 strains, as has been shown previously for other subtypes of A influenza.
RENAL CALCULUS.UNUSUAL SIZE, VOLUNTARILY EXPELLED.
Authors: W. H. AXTELL
Journal: JAMA (1905)

<h3>Patient.</h3> —Mrs. A., aged 22, married, with one child 14 months old, is anemic, has had no illness since childhood, but suffers from dysmenorrhea, which she has had since the beginning of menstruation. <h3>History of Illness.</h3> —The latter part of November, 1904, she had a severe attack of cramps, which lasted three or four days, the exact cause or nature of which was not determined. Two weeks previous to the present attack she had a similar attack, severe in character. The present illness began suddenly Jan. 7, 1905, with a sharp, spasmodic, colicky pain in the right side, with nausea and vomiting. January 8, the pain became so excruciating that she fell in collapse. I found her in a condition of profound shock. She was pulseless at the wrist and the heart sounds were very indistinct; temperature, 95.8, skin moist with cold, clammy perspiration; semi-delirious. Three-quarters of a grain of morphin given hypodermically gave very little relief. She was removed to the hospital. <h3>Examination.</h3> —January 9, examination revealed pronounced tympanitis, with tenderness on pressure on right side, extending from the margin of the rib to the right groin; the pain radiated from a point over the right kidney toward the bladder. The point of greatest tenderness and distension was in the region of the right kidney and of the gall bladder. The great distension of the abdomen and the severe pain made a
Action potential alternans and irregular dynamics in quinidine-intoxicated ventricular muscle cells. Implications for ventricular proarrhythmia.
Authors: H S Karagueuzian, S S Khan, K Hong, Y Kobayashi, T Denton, W J Mandel, G A Diamond
Journal: Circulation (1993)

Cardiac cells display rate-dependent beat-to-beat variations in action-potential duration (APD), action potential amplitude (APA), and excitability during periodic stimulation. We hypothesized that quinidine causes a marked increase in the variability of APD, APA, and excitability of ventricular cells isolated from quinidine-toxic, arrhythmic ventricles.Action potentials were recorded from right ventricular endocardial tissues (2 x 1 cm, < 2 mm thick) isolated from dogs in which ventricular tachycardia and ventricular fibrillation (VT/VF) were induced with intravenous quinidine (80-100 mg/kg) over a 5-hour period in vivo (n = 7). As the basic cycle length (BCL) of stimulation was progressively shortened, rate-dependent variations in APD and APA occurred. The initial dynamic change was alternans of APD and APA that could be either in or out of phase between two cells. The magnitude of alternans was a function of the BCL and the strength of the stimulation current. At critically short BCLs, irregular APD and APA behavior emerged in the quinidine-intoxicated cells. In control cells (n = 16) isolated from three nontreated dogs, APD and APA remained constant at all BCLs tested (2,000-300 msec). Quinidine increased the slope of the APD restitution curve compared with control. The observed quinidine APD restitution curve was fitted with a biexponential equation, and computer simulation using the fitted restitution curve reproduced the aperiodic APD seen in the quinidine toxic cells during periodic stimulation. Thus, the observed irregular APD behavior was predictable from the restitution curve.Quinidine toxicity increases the temporal and spatial variability of APD and APA in the ventricle that may promote the initiation of reentrant VT/VF in vivo. The slope of the APD restitution curve provides a method to quantitate inhomogeneities in repolarization time and could be a useful marker for proarrhythmia.
Reciprocal Regulation of Myocardial microRNAs and Messenger RNA in Human Cardiomyopathy and Reversal of the microRNA Signature by Biomechanical Support
Authors: Scot J. Matkovich, Derek J. Van Booven, Keith A. Youker, Guillermo Torre-Amione, Abhinav Diwan, William H. Eschenbacher, Lisa E. Dorn, Mark A. Watson, Kenneth B. Margulies, Gerald W. Dorn
Journal: Circulation (2009)

Much has been learned about transcriptional control of cardiac gene expression in clinical and experimental congestive heart failure (CHF), but less is known about dynamic regulation of microRNAs (miRs) in CHF and during CHF treatment. We performed comprehensive microarray profiling of miRs and messenger RNAs (mRNAs) in myocardial specimens from human CHF with (n=10) or without (n=17) biomechanical support from left ventricular assist devices in comparison to nonfailing hearts (n=11).Twenty-eight miRs were upregulated >2.0-fold (P<0.001) in CHF, with nearly complete normalization of the heart failure miR signature by left ventricular assist device treatment. In contrast, of 444 mRNAs that were altered by >1.3-fold in failing hearts, only 29 mRNAs normalized by as much as 25% in post-left ventricular assist device hearts. Unsupervised hierarchical clustering of upregulated miRs and mRNAs with nearest centroid analysis and leave-1-out cross-validation revealed that combining the miR and mRNA signatures increased the ability of RNA profiling to serve as a clinical biomarker of diagnostic group and functional class.These results show that miRs are more sensitive than mRNAs to the acute functional status of end-stage heart failure, consistent with important functions for regulated miRs in the myocardial response to stress. Combined miR and mRNA profiling may have superior potential as a diagnostic and prognostic test in end-stage cardiomyopathy.