tbuckley/cabot-search huggingface dataset:
Maximal rates of activation in electrically stimulated swine carotid media.
Authors: H A Singer, R A Murphy
Journal: Circulation Research (1987)

The kinetics of crossbridge phosphorylation and cellular activation rates in arterial smooth muscle are unknown, and the response rates are usually limited by agonist diffusion rates. In this study, electrical field stimulation (10-20 V AC, 60 Hz) was used to activate strips of swine carotid artery smooth muscle. Pretreatment with 0.5 microM phenoxybenzamine (PBZ) for 30 minutes significantly inhibited field stimulated stress due to norepinephrine released from adrenergic nerves. Addition of 1-10 mM tetraethylammonium ion (TEA) to PBZ-pretreated tissues allowed direct stimulation of muscle cells and significantly potentiated the response to field stimulation. Activation in field stimulated tissues pretreated with PBZ and TEA was strongly inhibited by the Ca2+-channel antagonist verapamil (0.5 microM for 15 minutes). Activation was rapid with myosin light chain (MLC)-phosphorylation values rising to greater than 50% of total MLC, with a half-time of approximately 1 second. Stress and stiffness development was biphasic and lagged with an estimated half-time for the first phase of 3 seconds. Stress and stiffness continued to slowly rise after 5 seconds of stimulation, while MLC phosphorylation declined significantly between 5 and 10 seconds to a nearly constant value of 35-40% for up to 60 seconds. Unloaded shortening velocity was maximal (0.067 Lo/sec) at the earliest time point examined (0.5 second), prior to significant stress development and at submaximal phosphorylation. Significant decreases in unloaded shortening velocity were observed after 10 seconds. These results show that the kinetics of phosphorylation and dephosphorylation and the rates of activation are very rapid in this arterial smooth muscle.
Type a Behavior and Mortality from Coronary Heart Disease
Authors: David R. Ragland, Richard J. Brand
Journal: New England Journal of Medicine (1988)

The relation of behavior (Type A or Type B) to the morbidity and mortality of coronary heart disease (CHD) is still debated. We studied the survival of 257 male patients with CHD from the initial, 8.5-year phase of the Western Collaborative Group Study to see whether behavior type — as assessed by a structured interview before the CHD event — was related to subsequent CHD mortality. Behavior type was not related to mortality in 26 patients who died within 24 hours of the coronary event. However, of the 231 patients who survived for 24 hours, the mortality rate associated with CHD among 160 Type A patients studied during an average 12.7 years was 19.1 per 1000 person-years. This was unexpectedly lower than the corresponding rate of 31.7 among 71 Type B patients who were followed for an average of 11.5 years (P = 0.04). In a proportional-hazards survival analysis, which controlled for variable follow-up time, the type of initial coronary event, and traditional risk variables, the relative CHD-associated mortality rate among Type A as compared with Type B patients was 0.58 (P = 0.03; 95 percent confidence interval, 0.35 to 0.96). The lower mortality among Type A subjects occurred in both younger and older subgroups but was more pronounced in patients whose initial diagnosis was symptomatic myocardial infarction rather than silent myocardial infarction or angina pectoris. This apparent advantage associated with Type A behavior is surprising and needs confirmation, but the results do indicate that patients with CHD and a Type A behavior pattern are not at increased risk for subsequent CHD mortality. (N Engl J Med 1988; 318:65–9.)
Changes of sex hormone levels in patients with hepatitis B virus-related postnecrotic cirrhosis: Relationship to the severity of portal hypertension
Authors: Yuan-Jen Wang, Shou-Dong Lee, Han-Chieh Lin, Hsiao-Chung Hsia, Fa-Yauh Lee, Yang-Te Tsai, Kwang-Juei Lo
Journal: Journal of Hepatology (1993)
Prevention of PKG1α oxidation augments cardioprotection in the stressed heart
Authors: Taishi Nakamura, Mark J. Ranek, Dong I. Lee, Virginia Shalkey Hahn, Choel Kim, Philip Eaton, David A. Kass
Journal: Journal of Clinical Investigation (2015)

The cGMP-dependent protein kinase-1α (PKG1α) transduces NO and natriuretic peptide signaling; therefore, PKG1α activation can benefit the failing heart. Disease modifiers such as oxidative stress may depress the efficacy of PKG1α pathway activation and underlie variable clinical results. PKG1α can also be directly oxidized, forming a disulfide bond between homodimer subunits at cysteine 42 to enhance oxidant-stimulated vasorelaxation; however, the impact of PKG1α oxidation on myocardial regulation is unknown. Here, we demonstrated that PKG1α is oxidized in both patients with heart disease and in rodent disease models. Moreover, this oxidation contributed to adverse heart remodeling following sustained pressure overload or Gq agonist stimulation. Compared with control hearts and myocytes, those expressing a redox-dead protein (PKG1α(C42S)) better adapted to cardiac stresses at functional, histological, and molecular levels. Redox-dependent changes in PKG1α altered intracellular translocation, with the activated, oxidized form solely located in the cytosol, whereas reduced PKG1α(C42S) translocated to and remained at the outer plasma membrane. This altered PKG1α localization enhanced suppression of transient receptor potential channel 6 (TRPC6), thereby potentiating antihypertrophic signaling. Together, these results demonstrate that myocardial PKG1α oxidation prevents a beneficial response to pathological stress, may explain variable responses to PKG1α pathway stimulation in heart disease, and indicate that maintaining PKG1α in its reduced form may optimize its intrinsic cardioprotective properties.
Geographic Medicine for the Practitioner
Authors: Jerry D. Smilack
Journal: JAMA (1986)

Most physicians in the United States and the other developed countries of the world rarely encounter "tropical diseases," a phrase that brings to mind exotic parasitic and viral diseases that include leishmaniasis, hemorrhagic fever, and echinococcosis. This book, however, reminds us that we are never more than a few hours away from these, as well as many more-common infections acquired in no-longer-remote areas of the world. With this compact volume, Warren and Mahmoud introduce us to geographic medicine, with a strong emphasis on what is clinically relevant to the American physician. The reader can readily turn to chapters on more than a score of subjects ranging from African or American trypanosomiasis to yellow fever. The authors concisely describe each disease's causative microorganisms, epidemiology, clinical presentations, diagnosis, and treatment. Algorithms highlight and summarize textual information and provide a bird's-eye overview usually not available in weightier texts. The emphasis here is on
Leucocyte migration-inhibition in systemic lupus erythematosus.
Authors: P Hughes, S Holt, N.R Rowell
Journal: Annals of the Rheumatic Diseases (1974)

The method used was the micro-modification devised by Federlin and others (1971). 30ml. venous blood were anticoagulated by defibrination, and the erythrocytes then sedimented by adding 5 ml. of 'Plasmagel' (Laboratoire copyright.
Upregulation of tumor necrosis factor-alpha gene by Epstein-Barr virus and activation of macrophages in Epstein-Barr virus-infected T cells in the pathogenesis of hemophagocytic syndrome.
Authors: J D Lay, C J Tsao, J Y Chen, M E Kadin, I J Su
Journal: Journal of Clinical Investigation (1997)

A potentially fatal hemophagocytic syndrome has been noted in patients with malignant lymphomas, particularly in EBV-infected T cell lymphoma. Cytokines, such as interferon-gamma (IFN-gamma), TNF-alpha, and IL-1alpha, are elevated in patients' sera. To verify whether infection of T cells by EBV will upregulate specific cytokine genes and subsequently activate macrophages leading to hemophagocytic syndrome, we studied the transcripts of TNF-alpha, IFN-gamma, and IL-1alpha in EBV-infected and EBV-negative lymphoma tissues. By reverse transcription PCR analysis, transcripts of TNF-alpha were detected in 8 (57%) of 14 EBV-infected T cell lymphomas, higher than that detected in EBV-negative T cell lymphoma (one of six, 17%), EBV-positive B cell lymphoma (two of five, 40%) and EBV-negative B cell lymphomas (one of seven, 14%). Transcripts of IFN-gamma were consistently detected in T cell lymphoma and occasionally in B cell lymphoma, but were independent of EBV status. IL-1alpha expression was not detectable in any category. Consistent with these in vivo observations, in vitro EBV infection of T cell lymphoma lines caused upregulation of TNF-alpha gene, and increased secretion of TNF-alpha, but not IFN-gamma or IL-1alpha. Expression of TNF-alpha, IFN-gamma, and IL-1alpha was not changed by EBV infection of B cell lymphoma lines. To identify the specific cytokine(s) responsible for macrophage activation, culture supernatants from EBV-infected T cells were cocultured with a monocytic cell line U937 for 24 h. Enhanced phagocytosis and secretion of TNF-alpha, IFN-gamma, and IL-1alpha by U937 cells were observed, and could be inhibited to a large extent by anti-TNF-alpha (70%), less effectively by anti-IFN-gamma (31%), but almost completely by the combination of anti-TNF-alpha and anti-IFN-gamma (85%). Taken together, the in vivo and in vitro observations suggest that infection of T cells by EBV selectively upregulates the TNF-alpha expression which, in combination with IFN-gamma and probably other cytokines, can activate macrophages. This study not only highlights a probable pathogenesis for virus-associated hemophagocytic syndrome, but also suggests that anti-TNF-alpha will have therapeutic potential in the context of their fatal syndrome.
Current therapy 1963; latest approved methods of treatment for the practicing physician.
Authors: Mildred L. Geiger
Journal: JAMA (1963)

This is the 15th annual edition of a book which, by now, must be considered a standard reference source.<i>Current Therapy</i>is designed to provide up-to-date, authoritative, and concise information on methods of treatment for most diseases encountered in everyday medical practice. To accomplish this, almost 300 distinguished clinicians have contributed articles describing the therapy they prefer for a particular disease. The articles, while sufficiently detailed to permit discussion of new advances as well as time-tested regimens, are limited to therapy only. Thus, discussions of pathogenesis, diagnosis, or prognosis are absent or minimal. Obviously, the basic treatment of certain diseases does not vary much from year to year. However, even without startling new discoveries in a particular disease area, there can be differences in approach and variations in technique of therapy among different physicians. Sometimes these differences are relatively minor, as in choice of a drug among several effective agents
Complete Vagotomy and its Consequences: Follow-up of 146 Patients
Authors: C. G. Clark, J. G. Murray, I. M. Slessor, J. H. Wyllie
Journal: BMJ (1964)

Division of all vagal branches to the stomach may be important in the treatment of duodenal ulcer. As long ago as 1947 Dragstedt and his colleagues pointed out that if a branch of the vagus is inadvertently missed at operation there may be reactivation of the whole of the glandular apparatus, return of high acid secretion, and consequent recurrence of ulc?ration ; more recently Murray (1962a) discussed the mechanism of return of nervous activity. In 1958 B?rge and Vane introduced a method of testing for completeness of vagal section at the time of operation, and Clark and Murray (1963) investigated the usefulness of the test in 100 patients. This report is con cerned with a follow-up from two to five years after operation in which  complete vagotomy  was carried out. In all cases the drainage procedure was gastro-enterostomy. An attempt has been made to answer a number of questions. Does complete vagotomy confer an immunity from recurrence of ulc?ration ? How does morbidity after complete vagotomy compare with that after incomplete nerve section and after partial gastrectomy ?
Signaling via the anti-CD30 mAb SGN-30 sensitizes Hodgkin's disease cells to conventional chemotherapeutics
Authors: C G Cerveny, C-L Law, R S McCormick, J S Lenox, K J Hamblett, L E Westendorf, A K Yamane, J M Petroziello, J A Francisco, A F Wahl
Journal: Leukemia (2005)
Clinical and Angiographic Effects of Chronic Calcium Channel Blocker Therapy Continued Beyond First Postoperative Year in Patients With Radial Artery Grafts
Authors: Mario Gaudino, Franco Glieca, Nicola Luciani, Francesco Alessandrini, Gianfederico Possati
Journal: Circulation (2001)

This study was conceived to elucidate the clinical and angiographic effects of chronic calcium channel blocker therapy (CCCBT) continued after the first postoperative year in patients in whom the radial artery (RA) was used for myocardial revascularization.Patients who received RA grafts at our institution and who at 1 year had no scintigraphic evidence of ischemia in the RA territory or angiographic evidence of RA malfunction (n=120) were randomly assigned to continue (n=63) or suspend (n=57) the CCCBT with diltiazem (120 mg/d). After 5 years, all patients were reassessed clinically and by stress myocardial scintigraphy, and 87 of them (45 from the continued group that continued CCCBT and 42 from the group that suspended CCCBT) were restudied angiographically. No differences regarding either the clinical and scintigraphic results or the RA angiographic status were demonstrated between the 2 groups.After the first postoperative year, the continuation of CCCBT does not affect RA graft patency or clinical and scintigraphic results.
Bone-specific delivery and sustained release of diclofenac, a non-steroidal anti-inflammatory drug, via bisphosphonic prodrug based on the Osteotropic Drug Delivery System (ODDS)
Authors: Hideki Hirabayashi, Toshiya Takahashi, Jiro Fujisaki, Taro Masunaga, Sachio Sato, Jun Hiroi, Yuji Tokunaga, Sumihisa Kimura, Takehisa Hata
Journal: Journal of Controlled Release (2001)
The Predisposition to Obesity and Diabetes in Offspring of Diabetic Mothers
Authors: Dana Dabelea
Journal: Diabetes Care (2007)

The hypothesis of fuel-mediated teratogenesis (1) proposes that intrauterine exposure to an excess of fuels (for example, glucose) causes permanent fetal changes. In pregnancies complicated by diabetes, this would lead to malformations, greater birth weight, and an increased risk of developing type 2 diabetes in later life. Recently, obesity in the offspring has been included as an outcome in pregnancies complicated by diabetes. The hypothesis is now widely accepted, although the relatively few studies that have examined the question are poorly comparable and focus almost exclusively on growth and glucose regulation.

This article reviews the evidence that intrauterine exposure to maternal diabetes conveys high risks for obesity and type 2 diabetes in the offspring, in addition to genetic predisposition, and regardless of maternal diabetes type. It also discusses potential mediators as well as possible public health consequences of fuel-mediated teratogenesis driven by maternal hyperglycemia in utero.

Development in a diabetic intrauterine environment results in excess fetal growth. While maternal glucose freely crosses the placenta, maternal insulin does not (1). The developing fetal pancreas responds to this increased glucose load by producing additional insulin, which in turn, acts as a fetal growth hormone promoting growth and adiposity (1). Only two studies have prospectively examined the role of exposure to diabetes in utero on childhood growth, later obesity, and risk for type 2 diabetes in the offspring: the Pima Indian Study and the Diabetes in Pregnancy Study at Northwestern University in Chicago.

### Growth and risk for obesity

Researchers at the Diabetes in Pregnancy Center at Northwestern University in Chicago have reported excessive growth in a multiethnic population of offspring of women with diabetes during pregnancy, including both gestational diabetes mellitus (GDM) and insulin-treated preexistent diabetes (2). Children were examined at birth, at age 6 months, and annually to age 8 years. The symmetry index (an obesity index …
Renal Tubular Acidosis After Kidney Transplantation
Authors: D. R. WILSON
Journal: Annals of Internal Medicine (1973)

Thirty-two patients whose renal allografts have been functioning for 1 to 3 years have been followed and repeatedly tested for urine acidification. In the first 1 to 2 months after transplantation a variety of defects—distal renal tubular acidosis (complete or incomplete), proximal bicarbonate-wasting renal tubular acidosis, or reduced ammonia excretion—were seen; these may be related to factors such as secondary hyperparathyroidism, malnutrition, acute tubular necrosis, and acute rejection. Long-term studies indicated that proximal renal tubular acidosis and reduced ammonia excretion usually disappeared. Distal renal tubular acidosis (incomplete), however, was associated with the features of chronic rejection (proteinuria, hypertension, decreased creatinine clearance) and was present in 43% of patients followed for 1 to 3 years. Distal renal tubular acidosis in long-standing renal allografts is probably the result of immunologic mechanisms and may be the functional equivalent of the interstitial infiltrate and fibrosis that are present in kidneys affected by chronic rejection.
Liver Dysfunction with Mestranol but not with Norethynodrel in a Patient with Enovid®-Induced Jaundice
Authors: ERNEST URBAN
Journal: Annals of Internal Medicine (1968)

A patient with Enovid®-induced jaundice was challenged with the estrogen component, mestranol. Pruritus without jaundice developed on the fifth day. There was prolonged elevation of serum alkaline phosphatase, 45-min sulfobromophthalein (BSP) retention, and a marked increase in plasma bile acids. Maximum secretory transport for BSP by the liver was decreased, and storage capacity was increased. Light microscopy of a liver biopsy showed a few very small canalicular plugs of bile. Challenge with the progestational component, norethynodrel, caused fatigue but no other clinical or biochemical abnormality. The natural estrogen, estradiol, 5 mg daily, caused fatigue, headaches, a transient rise in serum glutamic-oxaloacetic transaminase, and elevation of 45-min BSP retention, but serum alkaline phosphatase and bile acid concentration did not change. Smaller doses of estradiol had no effect. Both components of Enovid are C-17 alkylated compounds, but this radical alone was not responsible for the hepatic toxicity in the patient studied. Both mestranol and estradiol have a phenolic A ring as part of their chemical structure, while norethynodrel does not have this configuration. It is postulated that mestranol and estradiol damage a common pathway for biliary excretion.
18F-FDG PET/CT Diagnosis of Vagus Nerve Neurolymphomatosis
Authors: Hailey Hoi Ching Tsang, Elaine Yuen Phin Lee, Marina-Portia Anthony, Pek-Lan Khong
Journal: Clinical Nuclear Medicine (2012)

A 62-year-old woman was in remission from previously treated stage IV diffuse large B-cell lymphoma with cranial involvement. She presented with new-onset hoarseness of voice and choking; MRI of the brain showed disease recurrence in the left cavernous sinus. She was subsequently referred for 18F-FDG PET/CT with contrast for further evaluation of lymphomatous recurrence. 18F-FDG PET/CT not only revealed hypermetabolic activity in the left cavernous sinus correlating to the MRI findings but also showed an interesting manifestation explaining the patient’s hoarseness of voice, being neurolymphomatosis along the left vagus nerve.
Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection
Authors: Christopher B Ford, Philana Ling Lin, Michael R Chase, Rupal R Shah, Oleg Iartchouk, James Galagan, Nilofar Mohaideen, Thomas R Ioerger, James C Sacchettini, Marc Lipsitch, JoAnne L Flynn, Sarah M Fortune
Journal: Nature Genetics (2011)
BMA advises GPs on longer opening hours
Authors: Zosia Kmietowicz
Journal: BMJ (2008)

Graduates from some UK medical schools consistently perform better than others in postgraduate medical exams, says a study published this week.The authors say that their finding supports the introduction of a national licensing examination for doctors.The study retrospectively analysed the performance from 2003 to 2005 of 5827 doctors from 19 UK medical schools in one or more of the three examinations required for membership of the Royal College of Physicians.This is an international postgraduate assessment that is important for career progression and is attempted by about 30% of all UK medical graduates.The research group looked at performance in parts 1 and 2 of the written examination, which are multiple choice assessments, and in part 2 of the practical examination of clinical assessment skills (PACES), which uses real and simulated patients to test clinical examination and communication skills.A further analysis involved data on performance in the part 1 examination over a much longer timeframe, from 1989 to 2002.The results showed that graduates from Oxford, Cambridge, and Newcastle upon Tyne performed significantly better than average in part 1 and part 2 of the written examination (BMC Medicine 2008;6:5).Those from Liverpool, Dundee, Belfast, and Aberdeen showed significantly below average performance.Ninety one per cent of Oxford students, 76% from Cambridge, and 67% from Newcastle passed part 1 at their first attempt, whereas the figures were 32% for Liverpool, 38% for Dundee, 37% for Belfast, and 41% for Aberdeen.The overall relation between medical school and exam performance was highly significant (χ 2 =300, df=6, P<0.001).About 60% of the variance between medical schools was explained by differences in pre-admission qualifications (according to number of points gained, but not subjects taken, in A level examinations or in the Scottish highers).However, the remaining portion of the variance was still significant. Doctors from different schools vary in later postgraduate examsUK NEWS BMA advises GPs on longer opening hours, p 351 World NEWS Inquiry finds scientists collaborated with Nazis, p 353 bmj.comCharity is set up to improve adolescents' health care newS
Roles of midwives and general practitioners in hospital intrapartum care, England and Wales, 1988.
Authors: L F Smith, D Jewell
Journal: BMJ (1991)

registrars.Of those who had had some training, three (23%) thought that it had been less than adequate.Most supervision was done by registrars; some senior house officers, both in the early weeks of the study (10, 26%) and at the end of six months (3, 12%), however reported having had little or no supervision.Asked "How often do you find yourself the responsible doctor in a ward or clinic without back up or support?" 31 (79%) said seldom or never at the first interview and 18 (69%) said seldom or never at the second.Eleven (28%), however, reported at the first interview that they had had to act alone in an emergency and eight (31%) at second.Twenty three (58%) thought that they were inadequately prepared for the work they were expected to do in an obstetrics unit at both the first interview and the subsequent interview.