tbuckley/cabot-search huggingface dataset:
Immune complex nephritis complicating miliary tuberculosis.
Authors: J H Shribman, J B Eastwood, J Uff
Journal: BMJ (1983)

blurred vision, other anticholinergic effects, or headache.Nausea persisted for three days after the overdose but had not been mentioned during treatment.This case provides further evidence of the safety of zimeldine in overdose.[Sales of zimeldine in all countries were discontinued by Astra Pharma- ceuticals in September 1983 because of the company's concern about reports of serious neurological side effects including the Guillain Barre syndrome.]
117 S-adenosylmethionine protects mice against acute liver failure
Authors: M MARR, A MORALES, C GARCIARUIZ, J FERNANDEZCHECA
Journal: Hepatology (2003)

Simvastatin (SIM), a HMG-CoA reductase inhibitor, has therapeutic effects that are not limited to cholesterol reduction. In this study, we investigated the change in the cell surface area and protein content of cultured rat cardiomyocytes on exposure to cardiotrophin-1 (CT-1), a cytokine involved in the growth and survival of cardiac cells, plus SIM, and thus confirmed that SIM ameliorated cardiomyocyte hypertrophy induced by CT-1. We also showed that SIM attenuated cardiac hypertrophy in rats with pressure overload due to abdominal aortic constriction by measuring such parameters as systolic blood pressure, ratio of heart weight to body weight and ratio of left ventricular weight to body weight in rats as well as cross-sectional area of cardiomyocytes. Western blot analysis indicated that the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway was involved in the mechanisms underlying the in vitro and in vivo inhibitory effects of SIM on cardiac hypertrophy. Moreover, the effect of SIM amelioration on CT-1-induced cultured cardiomyocyte hypertrophy might be related to the change in angiotensinogen (AGT) mRNA expression, as evidenced by RT-PCR analysis, and the subsequent alteration in angiotensin II (Ang II) levels. The results of our study provide further evidence that SIM, like other HMG-CoA reductase inhibitors, is a promising drug for prevention and treatment of cardiac hypertrophy.
Mild hyperhomocysteinemia in adult patients with sickle cell disease: A common finding unrelated to folate and cobalamin status
Authors: Meekoo Dhar, Rita Bellevue, Shabneet Brar, Ralph Carmel
Journal: American Journal of Hematology (2004)

Homocysteine has associations with both vitamin insufficiency and vascular complications, and its status is therefore of interest in sickle cell disease (SCD). However, information is limited, especially in adults. We studied plasma total homocysteine (tHcy) and three of its major modifiers, cobalamin, folate, and creatinine, in 90 adult patients with SCD and 76 control subjects. The patients had higher tHcy levels than did controls (P = 0.03) and had elevated tHcy more often (20% vs. 3%, P = 0.0005). None of the hyperhomocysteinemic patients had low cobalamin or folate levels; on the contrary, patients with SCD had high folate levels more often than control subjects (32% vs. 7%; P < 0.0001). Although serum creatinine values were lower in SCD patients than in control subjects (P = 0.03), high levels also tended to occur more often (8% vs. 1%; P = 0.054). Most importantly, creatinine levels correlated significantly with tHcy (P < 0.0001) and logistic regression analyses showed creatinine to be the only significant predictor of high tHcy levels in SCD (P = 0.01). Our results show that hyperhomocysteinemia affects 20% of adults with SCD despite routine folate supplementation and is independent of folate and cobalamin status. Creatinine was the major identifiable influence on tHcy, but renal insufficiency explained only 4 of the 18 elevated tHcy levels. Longitudinal studies will be needed to determine whether the frequent hyperhomocysteinemia of SCD influences the vascular complications in SCD. If reducing tHcy becomes advisable, then interventions other than folate therapy will be needed.
The Patchwork Mouse
Authors: Philip C. Anderson
Journal: JAMA (1976)

Over two years ago, selected New York science writers were summoned to a big story concerning the new director of Memorial Sloan-Kettering Cancer Center, Dr Robert Good, whose protege had falsified some highly touted research concerning graft immunology. The protege, William Summerlin, was suspended during a review of his case and then dismissed with a year's salary paid. Throughout the affair, center stage was accorded to Dr Good who, an innovative Minnesotan, was coming into the highly political New York research community and the desirable directorship at Memorial Sloan-Kettering. Readers may be disappointed that this book does not set forth new key issues from this brief, awkward incident after two years of study; validate some conclusion about biomedical ethics; or suggest some elegant way to prevent such falsifications of research data. The analysis is thorough, concerning only the small scandal at Memorial Sloan-Kettering. Hixson explores the differences between a single,
Hospital merger is jeopardised by private provider's objections
Authors: D. Cohen, G. Iacobucci
Journal: BMJ (2013)

The new competition arrangements in the NHS in England are a “bonanza for lawyers and consultants” and could lead to scandals, the deputy chairman of the healthcare regulator Monitor has warned.

The statement from Stephen Thornton came ahead of a proposed merger of two NHS hospital trusts in the south of England that doctors fear may be derailed by competition law and by opposition from private providers. The final ruling is due next month.

The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust and Poole Hospital Foundation NHS Trust, which first proposed merging in 2011, said that the move was essential to ensure the sustainability of services in the area and would be of clinical and financial benefit.

But, despite support from local GPs and consultants, the move has been provisionally blocked by the Competition Commission on the grounds that it would reduce patients’ choice.

The merger proposal is thought to have cost millions of pounds in fees. “I wince at the money that should instead have been spent on patient care. We are heading for some scandals here,” Thornton said.

Local doctors are understood to be angry at the decision and at opposition from a …
The Fifteen Minute Hour: Applied Psychotherapy for the Primary Care Physician
Authors: Roberta Wallace
Journal: JAMA (1991)

This little book contributes to the implementation of several critical paradigmatic shifts already under way in health care. Not the least among these is the recognition that patients bring to the physician not only their illness, but also a resource system and capacity that can be used to enhance their own health. The book shows how the physician can mobilize the patient's resources to alleviate medical symptoms more rapidly and reduce frustratingly repetitive office visits. The process can occur very quickly within the patient-physician visit; hence, "The Fifteen Minute Hour." Stuart and Liebermann provide empirical data from several studies on the relationship between mental health, immune system responses, and illness to support their assertion that positive mental health potentiates physical wellbeing. They endorse the contemporary view that the role of the primary care giver is to reengage the healthy self——to support people under stress to focus on adaptive defenses and
A SPORADIC CASE OF TYPHUS FEVER
Authors: Harold Hastings Newman
Journal: JAMA (1913)

At the meeting of the Association of American Physicians, in Washington, May 6, 1913, Dr. John F. Anderson,<sup>1</sup>Director Hygienic Laboratory, United States Public Health Service, called the attention of the medical profession to the existence of typhus fever in Boston and New York. He expressed the opinion that typhus fever was unrecognized in other large American cities and stated, "the possibility should ever be borne in mind that it may acquire virulence and epidemic prevalence." On account of the preceding statements, I report the following case of typhus fever. <h3>Patient.</h3> —A. C., a girl aged 12, of Bohemian parentage, had attended school in Baltimore, at the House of the Good Shepherd, from December, 1912, till March, 1913. She had lived on a farm in the District
IN VITRO-INITIATED SECONDARY ANTI-HAPTEN RESPONSE
Authors: Wesley W. Bullock, Marvin B. Rittenberg
Journal: The Journal of Experimental Medicine (1970)

Decreasing antigen in vivo may preferentially stimulate cells with the potential for synthesis of high-affinity antibody through activation of surface receptors with similarly high affinity. This selection should result in cells with increased sensitivity to lower antigen concentrations, cells with greater avidity for antigen. We have followed the in vivo changes in anti-TNP memory-cell sensitivity by initiating the secondary anti-hapten response in vitro. This response was determined by anti-TNP plaque assay. The results indicate that cell populations with increased sensitivity for antigen continue to emerge with time after priming and that this sensitivity may increase 1000-fold in a 4 month period. Increased sensitivity to stimulation by antigen is concomitant with suppression by higher, previously stimulatory doses as in high zone immune tolerance. The data support the hypothesis that memory cells of high avidity result from the selective pressure of diminishing in vivo antigen concentration.
Enhancement of fibrinolysis in vitro by ultrasound.
Authors: C W Francis, P T Onundarson, E L Carstensen, A Blinc, R S Meltzer, K Schwarz, V J Marder
Journal: Journal of Clinical Investigation (1992)

The effect of ultrasound on the rate of fibrinolysis has been investigated using an in vitro system. Plasma or blood clots containing a trace label of 125I fibrin were suspended in plasma containing plasminogen activator and intermittently exposed to continuous wave 1-MHz ultrasound at intensities up to 8 W/cm2. Plasma clot lysis at 1 h with 1 microgram/ml recombinant tissue plasminogen activator (rt-PA) was 12.8 +/- 1.2% without ultrasound and was significantly (P = 0.0001) increased by exposure to ultrasound with greater lysis at 1 W/cm2 (18.0 +/- 1.4%), 2 W/cm2 (19.3 +/- 0.7%), 4 W/cm2 (22.8 +/- 1.8%), and 8 W/cm2 (58.7 +/- 7.1%). Significant increases in lysis were also seen with urokinase at ultrasound intensities of 2 W/cm2 and above. Exposure of clots to ultrasound in the absence of plasminogen activator did not increase lysis. Ultrasound exposure resulted in a marked reduction in the rt-PA concentration required to achieve an equivalent degree of lysis to that seen without ultrasound. For example, 15% lysis occurred in 1 h at 1 microgram/ml rt-PA without ultrasound or with 0.2 microgram/ml with ultrasound, a five-fold reduction in concentration. Ultrasound at 1 W/cm2 and above also potentiated lysis of retracted whole blood clots mediated by rt-PA or urokinase. The maximum temperature increase of plasma clots exposed to 4 W/cm2 ultrasound was only 1.7 degrees C, which could not explain the enhancement of fibrinolysis. Ultrasound exposure did not cause mechanical fragmentation of the clot into sedimentable fragments, nor did it alter the sizes of plasmic derivatives as demonstrated by SDS polyacrylamide gel electrophoresis. We conclude that ultrasound at 1 MHz potentiates enzymatic fibrinolysis by a nonthermal mechanism at energies that can potentially be applied and tolerated in vivo to accelerate therapeutic fibrinolysis.
A Global Theme Issue on Emerging and Reemerging Global Microbial Threats-Reply
Authors: James M. Hughes
Journal: JAMA (1996)

In Reply.  —The comments by Dr Plaut illustrate the complacency about infectious diseases that has developed over the past 30 years in the United States and in many other developed countries. Such complacency has resulted in the deterioration of the public health system required to detect, respond to, and minimize the impact of infectious diseases as highlighted in a recent Institute of Medicine report on emerging infectious diseases. 1 In fact, infectious diseases are the leading cause of death worldwide and the third leading cause of death in the United States, 2,3 and the threats may be increasing.  Many pathogens, such as Legionella pneumophila, Hantavirus, and Escherichia coli 0157:H7, have been recognized in the past 25 years, and diseases such as salmonellosis, shigellosis, and wild animal rabies have demonstrated a resurgence. In addition, the increasing problem of antimicrobial resistance has resulted in untreatable enterococcal blood-stream infections and dramatic increases in community-acquired
Natural rubber‐latex allergy in patients not intensely exposed
Authors: F. Ruëff, P. Thomas, G. Reißig, B. Przybilla
Journal: Allergy (1998)

Immediate‐type allergy to natural rubber latex (NRL) is common in highly exposed groups, particularly in health‐care workers and patients with spina bifida. The occurrence of NRL allergy was investigated in subjects not belonging to such risk groups. A total of 493 patients presenting with various diseases for allergologic evaluation was studied. A questionnaire‐based history was taken, skin prick tests with NRL milk and common aeroallergens were done, and NRL‐specific serum IgE antibodies were measured. A total of 317 subjects (64.3%) was atopic. There were skin prick test reactions to NRL in 80 (16.2%) and NRL‐specific IgE in the serum in 79 (16.0%) subjects; both were found in 25 patients (5.1%). Altogether, NRL sensitization was found in 134 patients (27.2%). By history and/or challenge tests. 13 subjects (2.6%) were diagnosed as having clinically relevant NRL allergy. In five of these, anaphylactic reactions had occurred during dental procedures, and in four during general anesthesia; 10 subjects reported immediate‐type reactions to NRL products in daily life. AU patients with clinically relevant NRL allergy had a skin prick test reaction to NRL milk (sensitivity 100%). Nine had specific IgE antibodies in the serum (sensitivity 69.2%); respective specificity was 86.0% or 85.4%. Nine of the 13 patients (69.2%) with NRL allergy were atopic. Despite exclusion of those at risk, many patients had clinically relevant allergy to NRL, and many of these had had severe reactions. NRL allergy is an important health issue also beyond the known risk groups.
NovoSol Basal: pharmacokinetics of a novel soluble long acting insulin analogue.
Authors: S. Jorgensen, A. Vaag, L. Langkjaer, P. Hougaard, J. Markussen
Journal: BMJ (1989)

OBJECTIVE--To determine the courses of absorption and the interindividual and intraindividual variations in absorption of iodine-125 labelled Ultratard HM and NovoSol Basal injected subcutaneously. DESIGN--Open randomised crossover study. Each patient was tested during two study periods of five days each, during which he or she received a subcutaneous injection of either 125I-NovoSol Basal or 125I-Ultratard HM on four consecutive days. The aim was to detect a reduction in intraindividual standard deviation by a factor of two with a probability 0.95, taking 0.05 as the level of significance. This required 24 degrees of freedom and led to the choice of four courses in each of eight patients. SETTING--Referrals to the diabetes research centre in Hvidøre, Copenhagen. PATIENTS--Eight insulin dependent (type I) diabetics with low or undetectable C peptide concentrations who were receiving a multiple insulin injection regimen. One patient withdrew immediately after recruitment. INTERVENTIONS--After an overnight fast patients received 96 nmol (16 IU insulin) of either 125I-NovoSol Basal or 125I-Ultratard HM injected subcutaneously into the thigh. To ensure that the insulin entered the subcutaneous fat at the same depth, ultrasonography was performed on each patient before the first injection. A different injection site on the thigh was used each day for four days in order to facilitate monitoring of the disappearance of four different depots in each patient. MAIN OUTCOME MEASURE--Residual activity at the injection site was measured roughly every two hours throughout the day. No radioactivity measurements were performed overnight (10 pm till 8 am). The residual radioactivity after the injection on the first day (upper right thigh) was recorded for five days, that after the injection on the second day (upper left thigh) for four days, after the injection on the third day (lower right thigh) for three days, and after the last injection (lower left thigh) for two days. RESULTS--NovoSol Basal was absorbed according to first order kinetics with a mean t50% of 35.3 (SEM 1.4) hours; Ultratard HM was absorbed after a lag phase and the corresponding t50% was 25.5 (2.5) hours. The intraindividual variations in t50% were significantly smaller with NovoSol Basal than with Ultratard HM (18.4% v 44.5%; p less than 0.001). Interindividual variations, however, were not significantly different (25.2% v 36.9%; p = 0.38). The total variation in t50% was substantially smaller with NovoSol Basal than with Ultratard HM (20.3% v 42.8%). CONCLUSIONS--NovoSol Basal seems to be an appreciable advance over Ultratard HM as a soluble insulin preparation for obtaining reproducible 24 hour insulin concentrations in the blood
Abstract 3555: Anti-tumor activity of CAL-101, a potent selective inhibitor of the p110Δ isoform of PI3K, in models of human glioblastoma
Authors: Adam Kashishian, Sarah Meadows, Bart Steiner, Brian Lannutti
Journal: Cancer Research (2011)

Abstract Phosphatidylinositol 3-kinase (PI3K) activation and Akt phosphorylation play a pivotal role in cell proliferation and survival, transducing signals from several cell surface receptors through PI3K isoforms (designated p110α, β, Δ, and γ). Our previous research has elucidated a significant role of the PI3K p110Δ (PI3KΔ) isoform in hematologic malignancies. Aberrant upregulation of the PI3K/Akt pathway is a frequently observed defect in human malignancies, including glioblastoma, but the role of the PI3KΔ isoform, has not been systematically evaluated. Selective inhibition of PI3KΔ with the orally bioavailable investigational drug, CAL-101, offers the potential for targeting PI3KΔ as a therapeutic approach to glioblastoma while avoiding undesirable side effects associated with pan-inhibitors that broadly block PI3K isoforms in multiple cell types. CAL-101 potently inhibits PI3KΔ (with an EC50 of 65 nM in a whole-blood assay) and shows &amp;gt;200-fold selectivity over other Class I PI3K isoforms and no activity against Class II and III PI3K family members or other PI3K-related proteins, including mTOR and DNA-PK. We examined expression levels of PI3KΔ and constitutive pathway activation in a panel of glioma cell lines (LN18, LN229, SF-539, U87MG, U138MG, and U251). PI3KΔ was consistently expressed and was functionally active, inducing high basal levels of phosphorylated-Akt (pAkt) in all tested cell lines. Treatment with CAL-101 decreased p-Akt levels in all cell lines and also reduced phosphorylation of the downstream pathway target, S6. Furthermore, PI3KΔ inhibition with CAL-101 resulted in an accumulation of cells in G1 and a decrease in the S phase population. Consistent with the effects of CAL-101 on G1 cell-cycle arrest, immunoblotting showed a decrease in cyclin D1 levels. In mice bearing U87MG xenografts, in vivo PI3KΔ inhibition resulted in significant anti-tumor effects, delaying time to tumor progression (tumor volume of &amp;gt;1000 mm3) by 30 days (p&amp;lt;0.001). Taken together, these data suggest that PI3KΔ overexpression and heightened functional activity contribute to glioblastoma proliferation, and that selective targeting of PI3KΔ may offer a novel therapeutic approach for patients with central nervous system tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3555. doi:10.1158/1538-7445.AM2011-3555
A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma
Authors: David S. Siegel, Thomas Martin, Michael Wang, Ravi Vij, Andrzej J. Jakubowiak, Sagar Lonial, Suzanne Trudel, Vishal Kukreti, Nizar Bahlis, Melissa Alsina, Asher Chanan-Khan, Francis Buadi, Frederic J. Reu, George Somlo, Jeffrey Zonder, Kevin Song, A. Keith Stewart, Edward Stadtmauer, Lori Kunkel, Sandra Wear, Alvin F. Wong, Robert Z. Orlowski, Sundar Jagannath
Journal: Blood (2012)
Drug Regulation in the United States and the United Kingdom: The Depo-Provera Story
Authors: BARBARA W. RICHARD
Journal: Annals of Internal Medicine (1987)

In 1984, both the United Kingdom and the United States received recommendations from panels of experts specifically convened to consider the merits of Depo-Provera (depot medroxyprogesterone acetate [DMPA]) as a long-term contraceptive agent. This study compares the final reports written by these panels. We explore why, despite access to essentially the same data, the U.K. panel recommended marketing approval but the U.S. Public Board of Inquiry did not. We conclude that differing national policies helped shape the interpretation of the data and thus the divergent outcomes.
Glucocorticoids stimulate rabbit proximal convoluted tubule acidification.
Authors: M Baum, R Quigley
Journal: Journal of Clinical Investigation (1993)

Glucocorticoids have an important role in renal acidification; however, a direct effect of glucocorticoids on proximal convoluted tubule (PCT) acidification has not been directly demonstrated. In the present in vitro microperfusion study PCT from animals receiving dexamethasone (600 micrograms/kg twice daily for 2 d and 2 h before killing) had a significantly higher rate of bicarbonate absorption than did controls (92.0 +/- 13.3 vs 59.9 +/- 3.2 pmol/mm.min, P < 0.01). To examine if glucocorticoids had a direct epithelial action, dexamethasone was added to the bath of PCT perfused in vitro. After 3 h of incubation in paired experiments 10(-6) M and 10(-5) M dexamethasone resulted in an approximately 30% stimulation in the rate of bicarbonate absorption. 10(-7) M dexamethasone and 10(-6) M aldosterone had no effect on bicarbonate absorption. The stimulation of acidification by 10(-5) M dexamethasone was blocked by actinomycin D and cycloheximide. These data are consistent with a direct effect of glucocorticoids on PCT acidification, and this effect is dependent upon protein synthesis.