tbuckley/cabot-search huggingface dataset:
Comparative Outcomes Study of Metformin Intervention Versus Conventional Approach The COSMIC Approach Study
Authors: Dennis R. Cryer, Savian P. Nicholas, David H. Henry, Donna J. Mills, Bruce V. Stadel
Journal: Diabetes Care (2005)

OBJECTIVE—Metformin was approved by the Food and Drug Administration in 1995 subject to the conduct of a randomized trial to evaluate the risk of lactic acidosis or other serious adverse events (SAEs) with this agent, under usual care conditions. RESEARCH DESIGN AND METHODS—The Comparative Outcomes Study of Metformin Intervention versus Conventional (COSMIC) Approach Study was a randomized, open-label, active-comparator, parallel-group, 1-year trial in type 2 diabetic patients suboptimally controlled on diet or sulfonylurea. Patients received metformin (n = 7,227) or other usual care treatments (n = 1,505). The primary end point was the incidence of SAEs, death, and hospitalization. RESULTS—SAEs occurred in 10.3% (95% CI 9.6–11.1%) of the metformin group and in 11.0% (9.5–12.7%) of the usual care group (P = 0.431). Lactic acidosis did not occur. All-cause mortality (1.1% [0.9–1.4%] vs. 1.3% [0.8–2.0%], P = 0.596) and hospitalization (9.4% [8.8–10.1%] vs. 10.4% [8.9–12.1%], P = 0.229) were similar between groups. CONCLUSIONS—The incidence of SAEs was similar between groups. Lactic acidosis was not observed. Metformin may be safely prescribed for type 2 diabetes if contraindications and warnings are respected. This study demonstrates the utility of large, simple trials for risk evaluation of treatments for common diseases.
Characterization of a hepatitis B and hepatitis delta virus receptor binding site
Authors: Matthias Engelke, Kerry Mills, Stefan Seitz, Petra Simon, Philippe Gripon, Martina Schnölzer, Stephan Urban
Journal: Hepatology (2006)

Insights into the early infection events of the human hepatitis B (HBV) and hepatitis delta virus (HDV) have been limited because of the lack of a cell culture system supporting the full replication cycle for these important pathogens. The human hepatoma cell line HepaRG allows the experimental induction of a differentiated state, thereby gaining susceptibility toward HBV and HDV infection. We recently identified HBV envelope protein–derived lipopeptides comprising amino acids 2 though 48 of the preS-domain of the L-surface protein, which block infection already at picomolar concentrations. To map the responsible sequence for the peptides' activity we describe an Escherichia coli expression system that permits myristoylation and investigated recombinant HBVpreS-GST fusion proteins with deletion- and point-mutations for their ability to prevent HBV and HDV infection. We found that (1) a myristoylated HBVpreS/2-48-GST fusion protein efficiently interferes with HBV infection of HepaRG cells; (2) deletions and point mutations in the highly conserved preS1 sequence between amino acids 11 through 21 result in the loss of infection inhibition activity; (3) hepatitis B viruses carrying single amino acid exchanges within this region lose infectivity; and (4) HDV infection of HepaRG cells can be inhibited by myristoylated HBVpreS peptides with the same specificity. In conclusion, HBV and HDV use at least one common step to enter hepatocytes and require a highly conserved preS1-sequence within the L-protein. This step is exceptionally sensitive toward inactivation by acylated HBVpreS1 peptides, which therefore represent a novel group of entry inhibitors that could be used for the treatment of hepatitis B and D. (HEPATOLOGY 2006;43:750–760.)
Legislative Harassment of Physicians and Researchers
Authors: Neil L. Chayet
Journal: New England Journal of Medicine (1971)

One of the most costly aspects of the problem of drug abuse is that measures designed to control this problem frequently miss the mark and rather than limiting illicit traffic in and use of abused dangerous drugs, they have their major impact on the legitimate practitioner of medicine and researcher.The most blatant example to date is found in an attempted recodification of the drug laws of Massachusetts, which, if passed, would constitute the most destructive and restrictive statute in the United States in the area of research and medical practice. The bill provides that researchers must file protocols with . . .
Late presentation of primary pulmonary lymphangiectasis.
Authors: S S Wagenaar, J Swierenga, C A Wagenvoort
Journal: Thorax (1978)

Pulmonary lymphangiectasis can occur either as a primary change or secondary to chronic congestion. Primary lymphangiectasis is generally considered to occur exclusively in young children. This report describes three male patients, aged 13, 16, and 19 years, in whom the changes are limited to one lobe or to two lobes and the mediastinum. So far as could be ascertained these patients are the oldest reported. Lymphangiectasis should be considered in the clinical differential diagnosis of "pulmonary cysts" in children and young adults.
Incidence of coronary heart disease in a health authority in London: review of a community register
Authors: Steven J Sutcliffe, Kevin F Fox, David A Wood, Angela Sutcliffe, Kathryn Stock, Melissa Wright, Fawaz Akhras, Ed Langford
Journal: BMJ (2003)

Strategies to reduce deaths from coronary heart disease need to take into account clinical presentation of the disease.1–4 We used a coronary heart register to examine non-fatal and fatal presentations of the disease in a health authority in outer London.

Bromley Health Authority employs 151 general practitioners with a total of 295 584 patients on their lists. The Bromley coronary register prospectively identified all incidences of coronary heart disease in people aged 16–74 from September 1996 to August 1997 for men and from September 1996 to May 1998 for women.

The health authority invited general practitioners to refer new cases of suspected exertional angina to a daily “rapid access” clinic for patients with chest pain at Bromley …
Long term risk for hypertension, renal impairment, and cardiovascular disease after gastroenteritis from drinking water contaminated with Escherichia coli O157:H7: a prospective cohort study
Authors: W. F. Clark, J. M. Sontrop, J. J. Macnab, M. Salvadori, L. Moist, R. Suri, A. X. Garg
Journal: BMJ (2010)

<b>Objectives</b> To evaluate the risk for hypertension, renal impairment, and cardiovascular disease within eight years of gastroenteritis from drinking water contaminated with <i>Escherichia coli</i> O157:H7 and <i>Campylobacter</i>. <b>Design</b> A prospective cohort study. <b>Setting </b>Walkerton, Ontario, Canada. <b>Participants</b> 1977 adult participants in the Walkerton Health Study recruited between 2002 and 2005 after an outbreak of gastroenteritis in May 2000, when a municipal water system was contaminated, with no pre-outbreak history of outcome measures. <b>Outcome measures</b> Information was collected annually via survey, physical examination, and laboratory assessment. Primary measures were acute gastroenteritis (diarrhoeal illness lasting &gt;3 days, bloody diarrhoea, or &gt;3 loose stools/day), hypertension (blood pressure ≥140/90 mm Hg), and renal impairment (microalbuminuria or estimated glomerular filtration rate &lt;60 ml/min/1.73 m<sup>2</sup>). Self reported physician diagnosis of cardiovascular disease (myocardial infarction, stroke, or congestive heart failure) was a secondary outcome. <b>Results</b> Acute gastroenteritis at the time of the outbreak was reported by 1067 (54%) of participants. Incident hypertension was detected in 697 (35%) (294 (32%) of group not exposed to acute gastroenteritis <i>v</i> 403 (38%) of exposed group). While 572 (29%) had at least one indicator of renal impairment (266 (29%) of unexposed <i>v</i> 306 (29%) of exposed), only 30 (1.5%) had both (8 (0.9%) of unexposed <i>v</i> 22 (2.1%) of exposed). Cardiovascular disease was reported by 33/1749 (1.9%). The adjusted hazard ratios for hypertension and cardiovascular disease after acute gastroenteritis were 1.33 (95% confidence interval 1.14 to 1.54) and 2.13 (1.03 to 4.43) respectively. The adjusted hazard ratio for the presence of either indicator of renal impairment was 1.15 (0.97 to 1.35) and was 3.41 (1.51 to 7.71) for the presence of both. <b>Conclusion</b> Gastroenteritis from drinking water contaminated with <i>E coli</i> O157:H7 and <i>Campylobacter </i>was associated with an increased risk for hypertension, renal impairment, and self reported cardiovascular disease. Annual monitoring of blood pressure and periodic monitoring of renal function may be warranted for individuals who experience <i>E coli</i> O157:H7 gastroenteritis.
Abstract 2672: Early evaluation of response to Vemurafenib treatment with FDG PET/CT in patients with metastatic melanoma.
Authors: Luigi Aloj, Corradina Caracò, Francesca Di Gennaro, Antonio M. Grimaldi, Ester Simeone, Marcello Curvietto, Corrado Caracò, Nicola Mozzillo, Valter Torri, Paolo A. Ascierto, Secondo Lastoria
Journal: Cancer Research (2013)

Abstract Targeted therapy against the V600 mutated form of BRAF is a proven effective therapy for melanoma. Reduction of FDG accumulation on PET/CT studies occurs very rapidly in responding patients. This exploratory study aims to correlate early changes in FDG uptake patterns with treatment outcome in patients undergoing Vemurafenib treatment. Patients treated at our institution were evaluated with PET-CT at baseline and at day 7, 14 and 28 from the start of therapy. Maximal Standardized Uptake Value (SUVmax) and Total Lesion Glycolysis (TLG, mean SUV x lesion volume) were recorded and compared for single lesions in the 4 studies. Patients were then monitored for clinical, laboratory and imaging signs of progression and results correlated to the early PET/CT findings. Fifteen patients have been studied. A total of 87 lesions are available for comparative evaluation. A greater than 30% reduction in SUVmax compared to baseline was seen in 69 lesions at day 7, 76 at day 14 and 75 at day 28. Nineteen lesions showed a greater than 20% increase in FDG uptake between day 14 and 28. Similar results were found when comparing TLG values. Quantitative and visual analysis of PET/CT studies identified 5 patients showing signs of metabolic progression between day 14 and 28 likely indicating early signs of treatment resistance. Three of these patients showed signs of disease progression by other means within 4 months from the beginning of treatment while 2 are still in treatment with 3 months follow-up. Of the 10 patients not showing metabolic signs of progression at day 28, four have progressed between 2 and 9 months from the beginning of treatment, while the remaining 6 are still in treatment and progression free with 2 to 12 months of follow-up. In conclusion, our preliminary results suggest that PET/CT may be a powerful surrogate marker of treatment response to vemurafenib. Sequential monitoring of targeted therapy with PET/CT may be useful in early identification of treatment resistance, aid in tailoring alternative strategies and deserves further investigation. Citation Format: Luigi Aloj, Corradina Caracò, Francesca Di Gennaro, Antonio M. Grimaldi, Ester Simeone, Marcello Curvietto, Corrado Caracò, Nicola Mozzillo, Valter Torri, Paolo A. Ascierto, Secondo Lastoria. Early evaluation of response to Vemurafenib treatment with FDG PET/CT in patients with metastatic melanoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2672. doi:10.1158/1538-7445.AM2013-2672
Experts criticise new German law for favouring drug companies
Authors: A. Tuffs
Journal: BMJ (2010)

A new law on approving drugs for reimbursement by German insurance companies currently being debated in parliament could put the safety of patients at risk, experts have warned. 

The law would substantially weaken the role of the German Institute for Quality and Efficiency in Health Care (IQWiG), the German equivalent of the UK National Institute for Health and Clinical Excellence, and lead to inefficient and dangerous drugs being approved, say experts. 

An amendment to the law proposed by the governing coalition of the Christian Democrats and the liberal Free Democratic Party says that all new …
MPs call for investigation into how psychiatric patients are being detained
Authors: M. Gould
Journal: BMJ (2013)

Psychiatrists facing a desperate shortage of beds are sectioning patients so that they can get hospital care, say MPs who are calling for urgent government reviews of mental health services.

In its report on the effects of the 2007 Mental Health Act, the House of Commons Health Committee heard evidence that many psychiatric wards are still desperately short of beds, with some 15% operating at over 100% occupancy.

The committee concluded, “It is now acknowledged that there appears to be an inverse relationship between the number of available beds and rates of detention.”

Stephen Dorrell, the committee’s chairman, and a former health secretary, said that patients’ basic rights were being “violated.” He called for a government investigation into whether voluntary patients were being sectioned to get a bed, adding, “It is never acceptable for patients …
ACUTE PARTIAL ENTEROCELE.
Authors: FRANK A. STAHL
Journal: JAMA (1897)

Herniæ involving only a portion of the circumference of the bowel, and usually spoken of as Littre's herniæ, are of two forms: One is a diverticular hernia, a hernia where a diverticulum of the bowel forms the contents of the hernial sac; the other is the partial intestinal wall hernia, partial, lateral enterocele (<i>enterocele partialis seu lateralis seu hemiperipherica</i>), where only a segment of the free margin of the bowel forms the contents of the hernial sac. Partial intestinal wall herniæ occur in two forms: The acute partial enterocele, where the hernia is of sudden origin and without adhesions; the chronic partial enterocele, where the hernia is of slow origin and usually with adhesions; that the acute form occurs is denied. Clinical experience alone can refute this denial, and the material is not lacking that will constitute the necessary burden of proof to establish the fact that acute partial enterocele
Transluminal angioplasty in experimental atherosclerosis. Analysis for embolization using an in vivo perfusion system.
Authors: T A Sanborn, D P Faxon, D Waugh, D M Small, C Haudenschild, S B Gottsman, T J Ryan
Journal: Circulation (1982)

We used polarized light microscopy and thin-layer chromatography to determine whether embolization of atherosclerotic material occurs after transluminal angioplasty. The experimental model consisted of an in vivo perfusion system of the atherosclerotic rabbit left iliac artery. Of eight rabbits that underwent successful angioplasty, four had angiographic evidence of dissection and three showed aneurysm formation. Histologic studies demonstrated fracture of the intimal plaque, dissection, and stretching of the noninvolved portion of the vessel. Perfusate analysis revealed no detectable cholesterol by thin-layer chromatography in six of eight rabbits. In two rabbits, a very small amount of cholesterol was measured, which was totally accounted for by hemorrhage into the perfusate rather than from cholesterol in the plaque. No evidence of arterial wall embolic debris could be detected by polarized light microscopy in seven rabbits, but lipid debris from the plaque was found in the perfusate of one rabbit that had excessive arterial trauma. We conclude that the major mechanism of successful transluminal angioplasty in this experimental model is intimal fracture combined with stretching of a noninvolved portion of the vessel. Furthermore, embolization of atheromatous lipid debris was an uncommon event related to arterial trauma during catheter placement rather than transluminal angioplasty itself.
MEDICAL PROGRESS.Read by Title in the Section of Medicine and Physiology, at the Forty-Second Annual Meeting of the American Medical Association, held at Washington, D. C., May, 1891.
Authors: C. R. EARLEY
Journal: JAMA (1891)

My time is so limited that I can only make a very slight review of the practice of medicine, showing the progress made during so many years. The present time can boast of great progress; yet we have much to regret as to the failures to come up to the standard of olden times in many respects. We should look well to this. Medicine has its history, its philosophy, its politics, its literature, of which the world at large knows nothing. It has its arts and occupations; it has its organizations and institutions, and dissentions, not always amenable to logic or to the learning of the schools. In ethics, traditions and superstitions it dates anterior to the Church. Being in use before the civil law, is it any wonder that the members of our profession, drawn together by such ties, should unite as a brotherhood? Such has ever
Risk assessment of relapse in Swiss participants of BIG 1-98 with grade 2 early breast cancer by gene expression profiling using RNA from formalin-fixed, paraffin embedded (FFPE) tissue.
Authors: S Aebi, J Antonov, V Popovici, M Delorenzi, A Giobbie-Hurder, G Viale, B Thürlimann, H Altermatt, R Jaggi
Journal: Cancer Research (2009)

Abstract Abstract #1073 BIG 1-98 is a randomized controlled clinical trial for postmenopausal patients with early, estrogen and/or progesterone receptor (ER/PgR) positive breast cancer. It compares adjuvant therapy with 5 years of tamoxifen (T) or letrozole (L), two years of T followed by 3 years of L (T→L) or vice versa (L→T). L improved disease free survival (DFS) over T by 18% (hazard ratio 0.82, JCO 2007;25:486ff). Switzerland contributed 598/8010 patients. The patient and tumor characteristics of Swiss patients was similar to the entire BIG 1-98 population. The purpose of this study was to test a prognostic score in RNA derived from FFPE tissues.&amp;#x2028; Scores representing ER and progesterone receptor (PgR) function, proliferation (PRO14, AURKA/STK15, BIRC5/SURV, CCNB1, CCNB2, CCNE2, CDC2, ENPF, KIF20A, MKI67, MYBL2, ORC6L, PRC1, SPAG5, TOP2A), and HER-2 were built from multiple genes for each score. Genes were selected according to an analysis of publicly available cDNA array databases. In a prior set of 82 pairs of breast cancer samples the Pearson correlation coefficients of the scores between fresh frozen and FFPE tissues were at least 0.94. Cut-offs for ER and HER-2 scores were defined as the antimodes of fitted bimodal Gaussian distributions; the ER and HER-2 scores closely agreed with immunohistochemical (IHC) data (kappa(ER)=0.868, kappa(HER-2)=0.836).&amp;#x2028; FFPE tissues were available from 437 Swiss BIG 1-98 patients. RNA of sufficient quantity and quality was extracted from 388 blocks (89%). Forty-seven genes were quantified by QRTPCR on TaqMan Low Density Arrays (TLDAs) as reported previously (Proc AACR 2008, Abstract 974).&amp;#x2028; The PRO14 score was positively correlated with the histological grade. PRO14 scores greater than the median and PGR scores lower than the median were associated with shorter DFS. In patients with grade 2 tumors, PRO14 scores were significant predictors of DFS in univariate Cox regression analyses. Multivariate analyses will be presented. Our findings are in agreement with an analysis of fresh frozen tissues of Belgian participants in BIG 1-98 (European Breast Cancer Conference 2008, Abstract 481).We show that RNA can be extracted from FFPE in sufficient quantity and quality to be used in QRTPCR using TLDAs. This opens the possibility of using FFPE tumor banks from controlled clinical trials for the investigation of gene expression patterns. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1073.
Serotonin Induces Temporally and Mechanistically Distinct Phases of Persistent PKA Activity in Aplysia Sensory Neurons
Authors: Uli Müller, Thomas J Carew
Journal: Neuron (1998)

The cAMP signaling cascade has been implicated in several stages of memory formation. We have examined activation of this cascade by serotonin (5-HT) in the sensory neurons of Aplysia. We find that different patterns of 5-HT exposure induce three distinct modes of PKA activation. First, a single 5 min pulse induces transient (5 min) PKA activation that requires neither transcription nor translation. Second, 4–5 pulses induce intermediate-term persistent activation (3 hr duration) that requires translation but not transcription. Third, 5 pulses of 5-HT, as well as continuous (90 min) exposure, induce long-term persistent activation 20 hr later, which requires both transcription and translation. Thus, in the sensory neurons, different patterns of 5-HT give rise to three independent phases of PKA activation that differ in their induction requirements, their temporal profiles, and their molecular mechanisms.
TREATMENT OF SUPERFICIAL INJURIES AND BURNS OF THE HAND
Authors: HARVEY S. ALLEN
Journal: JAMA (1941)

Superficial injuries of the hand may be divided for purposes of discussion of treatment into those which are sharply lacerated and those which are the result of a crushing or avulsing injury. This discussion applies to the injury to soft tissue involving only the skin and the subcutaneous tissues of the hand.  The purpose of treatment of any wound is to convert it from an open wound to a closed one as early as possible so as to prevent the occurrence of infection or any delay in healing. Wounds seen within six or eight hours from the time of injury may be safely converted into a closed wound provided they have not been tampered with, as by injudicious attempts to control hemorrhage. After eight hours one feels that the wound has progressed beyond the state of simple contamination to one of actual infection and that it is unwise to close
Inflammation and infection in cystic fibrosis - hen or egg?
Authors: N. Høiby
Journal: European Respiratory Journal (2001)

The noninflammatory defence of the lungs consists of: 1) the primary noninflammatory, nonspecific defence mechanisms, such as the mucociliary escalator, coughing, alveolar macrophages, defensins and surfactant; and 2) the secondary noninflammatory, specific defence mechanisms, such as secretory immunoglobulin A (S-IgA) 1. The action of these defence mechanisms is silent and very effective in normal subjects, and their activity does not give rise to any symptoms. No tissue damage is mediated through these defence mechanisms. Congenital defects of the primary noninflammatory defence mechanisms comprise cystic fibrosis (CF) (mucus) 2 and ciliary dyskinesia syndrome (cilia). These defects lead to secondary acute or chronic bacterial infections and recruitment of the primary inflammatory defence mechanisms of the lungs, such as polymorphonuclear (PMN) leukocytes, and the secondary inflammatory defence mechanisms of the lungs, such as immunoglobulin G (IgG). The activity of the inflammatory defence mechanisms may lead to successful killing of the offending pathogens, but in addition may give rise to local and systemic symptoms of inflammation such as fever, tissue damage and impaired function. If the …
Scrotal gangrene after male sterilization.
Authors: J P Pryor, A J Yates-Bell, D A Packham
Journal: BMJ (1971)

protective car design proceeds at three levels which are dis- tinct and approached in the following order-research, stan- dardization, enforcement.Whatever research evidence is used to formulate standards for protective car design that may ultimately be enforced, it seems clear that a fourth level of procedure is essential-namely, continual resrch into the actual crash performance of cars that have the new and devel- oping protective designs and devices, so that the maximum degree of protection of occupants may be achieved.We are indebted to Mr. Henry Proctor for Fig. 3.