tbuckley/cabot-search huggingface dataset:
The effect of myosin light chain 2 dephosphorylation on Ca-sensitivity of force is enhanced in failing human hearts
Authors: J VANDERVELDEN, Z PAPP, N BOONTJE, R ZAREMBA, J DEJONG, P JANSSEN, G HASENFUSS, G STIENEN
Journal: Cardiovascular Research (2003)

Phosphorylation of the myosin light chain 2 (MLC-2) isoform expressed as a percentage of total MLC-2 was decreased in failing (21.1+/-2.0%) compared to donor (31.9+/-4.8%) hearts. To assess the functional implications of this change, we compared the effects of MLC-2 dephosphorylation on force development in failing and non-failing (donor) human hearts.Cooperative effects in isometric force and rate of force redevelopment (K(tr)) were studied in single Triton-skinned human cardiomyocytes at various [Ca(2+)] before and after protein phosphatase-1 (PP-1) incubation.Maximum force and K(tr) values did not differ between failing and donor hearts, but Ca(2+)-sensitivity of force (pCa(50)) was significantly higher in failing myocardium (Deltap Ca(50)=0.17). K(tr) decreased with decreasing [Ca(2+)], although this decrease was less in failing than in donor hearts. Incubation of the myocytes with PP-1 (0.5 U/ml; 60 min) decreased pCa(50) to a larger extent in failing (0.20 pCa units) than in donor cardiomyocytes (0.10 pCa units). A decrease in absolute K(tr) values was found after PP-1 in failing and donor myocytes, while the shape of the K(tr)-Ca(2+) relationships remained unaltered.Surprisingly, the contractile response to MLC-2 dephosphorylation is enhanced in failing hearts, despite the reduced level of basal MLC-2 phosphorylation. The enhanced response to MLC-2 dephosphorylation in failing myocytes might result from differences in basal phosphorylation of other thin and thick filament proteins between donor and failing hearts. Regulation of Ca(2+)-sensitivity via MLC-2 phosphorylation may be a potential compensatory mechanism to reverse the detrimental effects of increased Ca(2+)-sensitivity and impaired Ca(2+)-handling on diastolic function in human heart failure.
Cholestatic hepatitis with marked thrombocytopenia
Authors: M Hartleb
Journal: Gut (2006)

A 54 year old woman was admitted because of abnormal liver laboratory tests (serum bilirubin 3.0 mg/dl, alanine aminotransferase 492 U/l, aspartate aminotransferase 186 U/l, alkaline phosphatase 199 U/l, and gamma glutamyl transferase (GGT) 154 U/l), associated with normosideric anaemia (haemoglobin 9.0 g/dl, …
Body Size and Prostate Cancer: A 20-Year Follow-up Study Among 135006 Swedish Construction Workers
Authors: S.-O. Andersson, A. Wolk, R. Bergstrom, H.-O. Adami, G. Engholm, A. Englund, O. Nyren
Journal: JNCI Journal of the National Cancer Institute (1997)

Obesity is associated with endocrine changes (e.g., increased estrogen and decreased testosterone in the blood) that have been implicated in the cause of prostate cancer and, therefore, an association between body weight and the risk of developing prostate cancer would be expected. However, because of bias or low statistical power in previous epidemiologic studies, associations between anthropometric measurements (height and weight), body mass index (BMI), and the risk of prostate cancer may have been inadvertently overlooked.We performed a large, retrospective cohort study among Swedish construction workers to evaluate possible associations of adult weight, height, BMI, and lean body mass (LBM) by age at entry in the study with the incidence and mortality rate of prostate cancer.We analyzed data that had been compiled in a computerized central register on a cohort of approximately 135000 male construction workers. Information on height and weight had been collected with the use of a comprehensive questionnaire filled out by nurses at the time of enrollment in the cohort, from 1971 through 1975. Complete follow-up was achieved through 1991 by means of record linkage to the Swedish National Cancer Register, the Death Register, and the Migration Register. A total of 2368 incident cases and 708 deaths from prostate cancer occurred in the cohort during a follow-up period averaging 18 years. We used only information obtained at the index visit from 1971 through 1975 to determine age-adjusted rate ratios (RRs) in a Poisson-based multiplicative multivariate model with age and the relevant exposure variable (e.g., weight, height, BMI, and LBM) as independent variables.All anthropometric measurements were positively associated with the risk of prostate cancer and were more strongly related to mortality than to incidence. The excess risk of death from prostate cancer was statistically significant in all BMI categories above the reference category: RR = 1.40 (95% confidence interval [CI] = 1.09-1.81) in the highest category compared with the lowest (P for trend = .04). For height and LBM, the excess risk in the highest compared with the lowest categories was somewhat less pronounced: RR = 1.28 (95% CI = 1.02-1.60) and RR = 1.26 (95% CI = 1.02-1.57), respectively. Statistically significant linear dose-response relationships were also found with the incidence of prostate cancer, with the exception of BMI (P for trend = .10).Our large cohort study indicates that various aspects of body size are related to the risk of prostate cancer and that future studies are needed to study the role of body size and prostate cancer.
Pre-Load Stress Echocardiography for Predicting the Prognosis in Mild Heart Failure
Authors: Hirotsugu Yamada, Kenya Kusunose, Susumu Nishio, Mika Bando, Junko Hotchi, Shuji Hayashi, Takayuki Ise, Shusuke Yagi, Koji Yamaguchi, Takashi Iwase, Takeshi Soeki, Tetsuzo Wakatsuki, Masataka Sata
Journal: JACC. Cardiovascular imaging (2014)
Endogenous adenosine restrains renin release in conscious rats.
Authors: C J Kuan, J N Wells, E K Jackson
Journal: Circulation Research (1990)

The purpose of this study was to test the hypothesis that endogenous adenosine functions to restrain the renin release response to pharmacological and pathophysiological stimuli. To achieve this objective, we examined the effects of an adenosine receptor antagonist, 1,3-dipropyl-8-(p-sulfophenyl)xanthine (DPSPX), on the renin release response induced by acute administration of hydralazine or by chronic clipping of the left renal artery (renovascular hypertensive rats). In conscious, unrestrained rats, DPSPX significantly increased plasma renin activity (PRA) in control rats, in rats treated with hydralazine, and in renovascular hypertensive rats. The effect of DPSPX on PRA was significantly greater in rats treated with hydralazine or in renovascular hypertensive rats compared with control rats. DPSPX did not influence arterial blood pressure in any group, did not affect the measurement of PRA, and did not alter the elimination of renin activity from the circulation. Additional experiments were performed in the in situ autoperfused kidney so that the effects of DPSPX on renal hemodynamics and renal excretory function could be assessed. In this experimental model, DPSPX also increased PRA in hydralazine-treated rats and in renovascular hypertensive rats without affecting arterial pressure, renal blood flow, or sodium excretion. In a final set of studies in conscious, unrestrained rats, adenosine deaminase increased PRA in a dose-dependent manner in hydralazine-treated rats and significantly increased the slope of the relation between PRA and the depressor response to hydralazine. We conclude: 1) Although the kidney has both A1 and A2 adenosine receptors mediating inhibitory and stimulatory actions, respectively, on renin release, the dominant effect of endogenous adenosine on renin release is inhibitory. 2) Even under basal physiological conditions, endogenous adenosine tonically inhibits renin release. 3) This inhibitory effect is augmented whenever the renin-angiotensin system is stimulated regardless of the approach used to activate renin release. 4) Endogenous adenosine negatively modulates renin release by a direct effect on juxtaglomerular cells.
Bone marrow transplants from peripheral blood
Authors: T L Holyoake, I M Franklin
Journal: BMJ (1994)

Treating malignant disease with very high dose chemotherapy, often with total body irradiation, has become established during the past decade, particularly for lymphomas and leukaemias. Reinfusion of some of the patient's bone marrow (collected before high dose chemotherapy) has improved the outcome of these very intensive regimens. These autologous bone marrow transplants (autografts) entail about four weeks' pancytopenia,1 and despite improvements in supportive care this procedure is associated with substantial morbidity and a 5–10% mortality, mainly due to myelosuppression.

Normal bone marrow contains enough undifferentiated stem cells to allow long term reconstitution (engraftment), but it seems to lack those more committed progenitors that would lead to engraftment within two or three weeks. In the past few years it has become possible to collect such committed progenitor and stem cells not from wihin the bone marrow cavity but from peripheral blood. The use of peripheral blood stem cells as autografts has changed much of haematological practice and will transform medical oncology within the next few years.

Until 1984, the stem cell content of either bone marrow or peripheral blood could be estimated only indirectly by in vitro colony forming assays. Since then a monoclonal antibody, now …
Crusaders for Fitness: The History of American Health Reformers
Authors: Richard Wightman
Journal: JAMA (1983)

Historians have recently devoted much attention to the social history of medicine, and James Whorton has made a valuable addition to that literature.<i>Crusaders for Fitness</i>is a lively survey of health reformers from the Jacksonian to the Progessive periods—from Sylvester Graham, the prophet of bran bread in the 1830s, to John Harvey Kellogg and Bernarr Macfadden, progressive proponents of dietary efficiency and physical culture, respectively. Whorton demonstrates convincingly that health reform cannot be reduced to health faddism, to fanciful schemes concocted by pseudoscientific publicists. Even the most farfetched remedies must be understood as serious efforts by middle-class Americans to take control of their own health—a "democratic" impulse with deep roots in Protestant American culture. It was an impulse against which the medical profession had to do protracted battle in its attempt to rationalize and monopolize the provision of health care. The main problem with the book is that in
Successful treatment of persistent erythroid aplasia caused by parvovirus B19 infection in a patient with common variable immunodeficiency with low-dose immunoglobulin
Authors: Tatsuya Chuhjo, Shinji Nakao, Tamotsu Matsuda
Journal: American Journal of Hematology (1999)

Parvovirus B19 causes persistent erythroid aplasia in immunocompromised hosts. From April through July 1996, we encountered five adult patients presenting with reticulocytopenia and fever caused by parvovirus B19 infection. The reticulocyte count of four patients with normal immunity recovered within two weeks after the onset of fever. However, in the one remaining patient with common variable immunodeficiency (CVI), reticulocytopenia, and other symptoms including fever and the elevation of lactate dehydrogenase (LDH) levels persisted beyond 16 days of onset. Although the DNA of parvovirus B19 was detected in the peripheral blood of the CVI patient, neither immunoglobulin Ig-G nor Ig-M antibodies specific to the virus were detectable. We administered 50 mg/kg of Ig to the CVI patient for six days. The reticulocyte count recovered promptly on the sixth day of the treatment and parvovirus B19 DNA was not detectable 30 days after therapy. This indicates that although patients with CVI may be susceptible to persistent erythroid aplasia during an endemic of parvovirus B19, the complication can be treated successfully with relatively low-dose Ig.
An inbred line of transgenic mice expressing an internally deleted gene for type II procollagen (COL2A1). Young mice have a variable phenotype of a chondrodysplasia and older mice have osteoarthritic changes in joints.
Authors: H J Helminen, K Kiraly, A Pelttari, M I Tammi, P Vandenberg, R Pereira, R Dhulipala, J S Khillan, L Ala-Kokko, E L Hume
Journal: Journal of Clinical Investigation (1993)

Studies were carried out on a line of transgenic mice that expressed an internally deleted COL2A1 gene and developed a phenotype resembling human chondrodysplasias (Vandenberg et al. 1991. Proc. Natl. Acad. Sci. USA. 88:7640-7644. Marked differences in phenotype were observed with propagation of the mutated gene in an inbred strain of mice in that approximately 15% of the transgenic mice had a cleft palate and a lethal phenotype, whereas the remaining mice were difficult to distinguish from normal littermates. 1-d- and 3-mo-old transgenic mice that were viable showed microscopic signs of chondrodysplasia with reduced amounts of collagen fibrils in the cartilage matrix, dilatation of the rough surfaced endoplasmic reticulum in the chondrocytes, and decrease of optical path difference in polarized light microscopy. The transgenic mice also showed signs of disturbed growth as evidenced by lower body weight, lower length and weight of the femur, decreased bone collagen, decreased bone mineral, and decreased resistance of bone to breakage. Comparisons of mice ranging in age from 1 d to 15 mo demonstrated that there was decreasing evidence of a chondrodysplasia as the mice grew older. Instead, the most striking feature in the 15-mo-old mice were degenerative changes of articular cartilage similar to osteoarthritis.
Elevated Homocysteine Is Associated With Reduced Regional Left Ventricular Function
Authors: Khurram Nasir, Michael Tsai, Boaz D. Rosen, Veronica Fernandes, David A. Bluemke, Aaron R. Folsom, João A.C. Lima
Journal: Circulation (2007)

An elevated homocysteine (Hcy) level has been reported to be a risk factor for the development of congestive heart failure in individuals free of myocardial infarction. In this study, we aim to investigate the relationship between Hcy levels and regional left ventricular function in an asymptomatic population.Regional peak systolic midwall circumferential strains were calculated from 1178 tagged magnetic resonance imaging studies in participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Left ventricular regions were defined by coronary territories (left anterior descending, left circumflex, right coronary artery). For the 1178 study participants (66+/-10 years of age, 58% males), the median (interquartile range) of Hcy was 9.1 (9.0 to 9.3). After adjustment for traditional risk factors, race, height, weight, left ventricular end-diastolic mass/volume, serum creatinine, and measures of atherosclerosis, reduced regional myocardial circumferential shortening across sex-specific quartiles of plasma Hcy in the left anterior descending (P=0.038) and left circumflex (P=0.009) regions persisted, which indicated an important association of reduced function with elevated Hcy. Multiple linear regression analyses confirmed that circumferential systolic dysfunction was associated with log transformed Hcy levels in the left anterior descending (P=0.004) and left circumflex (P=0.0002) regions. In the fully adjusted model, the odds ratio for left ventricular strains below the 10th percentile with 1 SD increases in log-transformed Hcy was 1.33 (95% confidence interval, 1.04 to 1.70; P=0.022) for the left anterior descending, 1.28 (95% confidence interval, 1.00 to 1.64; P=0.046) for the left circumflex, and 1.32 (95% confidence interval, 1.03 to 1.69; P=0.025) for the right coronary artery region.In this asymptomatic population, an elevated Hcy level is associated with reduced regional left ventricular systolic function detected by tagged magnetic resonance imaging.
Reinstitutionalisation in mental health care
Authors: S. Priebe
Journal: BMJ (2003)

Since the 1950s mental health care in most industrialised countries has been characterised by deinstitutionalisation, with national reforms varying in their pace, fashion, and exact results. 1 2 The development of comprehensive community mental health care is widely regarded as not yet complete. In England the national service framework and NHS Plan aim at establishing new community based services—for example, for home treatment, assertive outreach, and early intervention. Yet despite the apparent evidence of ongoing deinstitutionalisation, we argue that a new era in mental health care has already started—reinstitutionalisation. It is displaying a synonymous pattern across Europe, as with deinstitutionalisation, but this time it has been occurring largely unnoticed by the scientific community and unscrutinised by politicians and the media.

What are the signs of reinstitutionalisation? Firstly, the number of forensic beds is rising, in the United Kingdom, with dramatic increases in the private sector. Plans to increase this number further are in hand. Secure units are extremely costly, with no evidence …
Unity in Medicine
Authors: Norman A. Welch
Journal: JAMA (1964)

I ACCEPT the office of President of the American Medical Association with gratitude and humility. I am aware of the responsibilities of my new position, and I pledge all of the dedication at my command in discharging these responsibilities. We are particularly honored by the presence of those who share this platform with us this evening. Here we have the presidents, or their appointed representatives, of the major medical specialty organizations in the United States. I believe it would be safe to say that this occasion is the first time in the history of organized medicine that the presidents of so many medical specialty organizations have assembled together. I want to express my personal thanks to each of them for their presence. This occasion is historic for all of medicine. As I pondered over what contribution I might make as President of the American Medical Association, I was mindful of
Laparoscopic Diagnosis of Peritoneal Serous Papillary Carcinoma
Authors: M. Trauner, M. Klimpfinger, R. E. Stauber, F. Schreiber, H. Stöger, G. J. Krejs
Journal: Endoscopy (1995)

Peritoneal serous papillary carcinoma is a rare primary tumor of the peritoneum. We report here a case diagnosed by laparoscopy, and summarize the clinicopathological features previously reported in patients with this tumor. Laparoscopy was performed in a 66-year-old woman with high-protein ascites and a three-month history of lower abdominal pain. Macroscopically, the parietal and visceral peritoneum was studded with prominent white nodules up to 5 mm in diameter. Multiple biopsies revealed a tubulopapillary serous adenocarcinoma. After exclusion of metastatic peritoneal carcinomatosis (especially ovarian cancer) and malignant mesothelioma, the diagnosis of peritoneal serous papillary carcinoma was established. The patient was placed on chemotherapy (first-line: 5-fluorouracil, adriamycin, and mitomycin C; second-line: paclitaxel). She died 22 months after diagnosis. The present case is also remarkable for the coexistence of granulomatous peritonitis overshadowing the malignant nature of the process. This case report emphasizes the importance of laparoscopy with multiple biopsies in the workup of undetermined exudative ascites.
TCT-105 Device-to-Annulus Pre-deployment Angle by Intraoperative Transesophageal Echocardiography Predicts Paravalvular Regurgitation following Transcatheter Aortic Valve Replacement
Authors: Leo Marcoff, Omar K. Khalique, Susheel Kodali, Mathew Williams, Tamim Nazif, Jean-Michel Paradis, Isaac George, Martin Leon, Rebecca Hahn
Journal: Journal of the American College of Cardiology (2013)
EHPnet: Green Halloween
Authors: Erin E. Dooley
Journal: Environmental Health Perspectives (2008)

Strong Signal for Cell Phone EffectsWith 3 billion cell phone users worldwide and more than 260 million in the United States alone-among them 46% of U.S. children aged 8-12, according to Nielsen Mobile figures released 10 September 2008human exposure to low-energy radiation in the 800-to 2,000-megahertz range is at an all-time high.The most recent attempt to systematically review the epidemiologic evidence for increased risk of brain tumors related to cell phone use indicates that repercussions from this global experiment are coming to light.In a meta-analysis published in the May 2008 issue of the International Journal of Oncology, Swedish researchers found significant associations between longterm cell phone use and brain tumor risk."We found that cell phone use is linked to gliomas [malignant brain tumors] and acoustic neuromas [benign tumors of the brain's auditory nerve] and are showing up after only ten years," says lead author Lennart Hardell, an oncologist and cancer epidemiologist at University Hospital in Örebro, Sweden.Specifically, for studies that included at least 10 years of exposure, there was a doubling in the risk of gliomas for ipsilateral (same-side) but not contralateral (opposite-side) exposures to the head (as reflected by which hand the subject typically used to hold his/her cell phone).A 2.4-fold increase in risk was seen for acoustic neuromas due to ipsilateral exposures, whereas no increased risk occurred for meningiomas (tumors that occur in the membranes covering the brain and spinal cord)."Clearly we need more studies of longterm cell phone usage to better assess the cancer risks," says coauthor Michael Carlberg.Cell phones have been in mainstream usage for only a decade or so, and yet radiation-induced brain tumors normally take about 10-15 years to develop, according to the American Cancer Society.Hardell's research team was itself the source of several studies included in the meta-analysis.In the October 2006 issue of the World Journal of Surgical Oncology, the investigators reported a 70% increased risk of grade III-IV astrocytomas (highly aggressive brain tumors) for analog cell phone users.This same study found a nearly 4-fold increase in risk for acoustic neuromas after 15 years of exposure to analog cell phones.
European commission proposes new laws to halt decline in number of clinical trials
Authors: R. Watson
Journal: BMJ (2012)

The European Commission has proposed new legislation to remove some of the regulatory burdens on clinical trials in the European Union.1

The legislation will replace rules that have been in place since 2001 and aims to encourage the development of new treatments.

Current procedures have been criticised by patients, researchers, and the drug industry for being excessively bureaucratic. National authorities across the EU have also applied them in different ways. The result has been a sharp decline in the number of clinical trials being conducted in the EU: from 5000 in 2007 to 3800 last year. 

Introducing …
Visual-Motor Function of the Primate Superior Colliculus
Authors: R H Wurtz, J E Albano
Journal: Annual Review of Neuroscience (1980)

(Ada­ mlik 1870). But it has only recently been possible to study the relation of single cell activity within this structure to both movement and vision. This cellular approach, along with new anatomical, physiological, and behavioral methods, has enabled the investigation of the machinery whereby the visual stimulus initiates motor movement. It is these advances that we concentrate on in this review. We emphasize the primate superior colliculus because most of the work relating to movement has been done in the rhesus monkey, Macaca mulatta. At the same time we draw on work done on the cat and tree shrew to supplement areas as yet unexplored in the monkey, although many interesting facets of work on these and other species are not considered. Other recent reviews have considered many of these other aspects (Sprague et al 1970, Gordon 1975, Sprague 1972,