tbuckley/cabot-search huggingface dataset:
Ethnic Differences in the Relationship Between Insulin Sensitivity and Insulin Response
Authors: Keiichi Kodama, Damon Tojjar, Satoru Yamada, Kyoko Toda, Chirag J. Patel, Atul J. Butte
Journal: Diabetes Care (2013)

OBJECTIVE Human blood glucose levels have likely evolved toward their current point of stability over hundreds of thousands of years. The robust population stability of this trait is called canalization. It has been represented by a hyperbolic function of two variables: insulin sensitivity and insulin response. Environmental changes due to global migration may have pushed some human subpopulations to different points of stability. We hypothesized that there may be ethnic differences in the optimal states in the relationship between insulin sensitivity and insulin response. RESEARCH DESIGN AND METHODS We identified studies that measured the insulin sensitivity index (SI) and acute insulin response to glucose (AIRg) in three major ethnic groups: Africans, Caucasians, and East Asians. We identified 74 study cohorts comprising 3,813 individuals (19 African cohorts, 31 Caucasian, and 24 East Asian). We calculated the hyperbolic relationship using the mean values of SI and AIRg in the healthy cohorts with normal glucose tolerance. RESULTS We found that Caucasian subpopulations were located around the middle point of the hyperbola, while African and East Asian subpopulations are located around unstable extreme points, where a small change in one variable is associated with a large nonlinear change in the other variable. CONCLUSIONS Our findings suggest that the genetic background of Africans and East Asians makes them more and differentially susceptible to diabetes than Caucasians. This ethnic stratification could be implicated in the different natural courses of diabetes onset.
Council sets up inquiry into closure of London surgery with 4700 patients
Authors: T. Foot
Journal: BMJ (2012)

An inquiry into the sudden closure of a general practice in north London earlier this year that left thousands of patients temporarily without a GP is opening at Camden Town Hall, north London, on 10 May.

The Camden Road Practice, in Camden Town, had 4700 patients when its closure was announced in February. About 2700 have since registered with other practices, but the remaining 2000 are being allocated by the local health authority, NHS North Central London, to other practices, in some cases a considerable distance from their home.

The inquiry is to be chaired by the Camden Labour councillor Angela Mason, and a report will be filed to Camden borough council’s health scrutiny committee in June.

The Camden Road Practice was run as a GP partnership until 2008, when the Camden Primary Care Trust decided …
The effect of low-dose atorvastatin on circulating monocyte chemoattractant protein–1 in patients with type 2 diabetes complicated by hyperlipidemia
Authors: Kohzo Takebayashi, Sachiko Matsumoto, Sadao Wakabayashi, Yoshihisa Inukai, Rika Matsutomo, Yoshimasa Aso, Toshihiko Inukai
Journal: Metabolism (2005)
The demonstration of alternating contractile state in pulsus alternans
Authors: R. Joe Noble, Donald O. Nutter
Journal: Journal of Clinical Investigation (1970)

Pulsus alternans was induced in 11 anesthetized, open-chest dogs by rapid atrial pacing, and the left ventricular filling characteristics and length-tension-velocity relationship of alternating beats were compared. The end-diastolic circumferences (cire) of the strong beats were slightly, but significantly, increased over the weak beats (7.3 > 6.9 cm, P < 0.01), confirming that diastolic filling does alternate in pulsus alternans. This alternation in initial fiber length seemed to result from an alternation in the prior end-systolic length, rather than from an alternation in diastolic filling time or compliance. There was also no difference in end-diastolic tension as measured by an isometric strain gauge suggesting no difference in contractile element relaxation before weak and strong beats. THE CONTRACTILE STATE OF THE STRONG BEATS WAS CONSISTENTLY GREATER THAN THAT OF THE WEAK BEATS WHEN CONTRACTILITY WAS DEFINED IN TERMS OF: (a) V(max) (3.13 > 2.53 circ/sec, P < 0.01); and (b) the velocity of circumferential fiber shortening (0.84 > 0.39 circ/sec, P < 0.001) and developed tension (82.5 > 74 g/cm, P < 0.01) at isolength. The length-tension-velocity relationship of the left ventricle also varied between strong and weak beats when: (a) the maximum velocity of contractile element shortening at least common tension (1.68 > 1.28 circ/sec, P < 0.05); and (b) the velocity of circumferential fiber shortening (0.81 > 0.39 circ/sec, P < 0.001) at maximum developed tension were examined. Analysis of the length-tension-velocity characteristics of sequential beats at the onset of alternans in three dogs suggests that an alternation in contractility initiates alternans, with secondary alternations in ventricular filling. Cross-clamping of the aorta in three other dogs essentially eliminated the alternating changes in end-diastolic length and pressure, while the resultant isovolumic contractions continued to demonstrate clear evidence of pulsus alternans in the ventricular systolic pressure, suggesting the persistance of an alternating contractile state. The evidence suggests that an important mechanism in the production and propagation of pulsus alternans, as produced in the intact canine ventricle by rapid pacing, is a beat-to-beat alternation in contractile state with secondary alternations in ventricular filling.
Better Writing Anyone?
Authors: Lester S. King
Journal: JAMA (1978)

ABSTRACT Medical editors, however much they may disagree on scientific, social, or economic problems, will agree on one point: papers submitted for publication are, with few exceptions, badly written. The need for better medical writing is a perennial complaint: but what to do about it?One remedy is a book designed for self-study. Almost every year, publishers will bring out one or more volumes of this type, often helpful if used earnestly and critically. The two most recent such books, by Dirckx and by Bernstein, are reviewed in this issue of JAMA (p 767). A second resource for improvement is the workshop or short course in writing. Occasionally in the past, a one-day course in writing was given in association with local or national medical meetings. But the large number of participants, the brevity of the course (you cannot form good habits in a single day), the desire to cover too
Abstract 3259: Evaluation of the aromatase inhibition potential of standardized grape extract
Authors: Janet E. Olson, Summer V. Allen, Vera J. Suman, Tanya L. Hoskin, Celine M. Vachon, James N. Ingle
Journal: Cancer Research (2014)

Abstract OBJECTIVE: To determine the role of grape extract as a potential aromatase inhibitor by testing of plasma hormone levels. PROCEDURE: A six-week study was conducted involving postmenopausal women during which 94 grams of grape extract was consumed in addition to their usual diet. Plasma hormones were measured before and after treatment. RESULTS: Of the 18 women involved in the study, average age and BMI were 61.4 years and 24.4, respectively. For the hormone levels studied, the following median (IQR) percent change from baseline to 6 weeks values were found: estradiol +11.8% (-34.4%,+44.2%), p = 0.42; estrone +3.4% (-15.7%,+12.9%), p = 0.64; estrone sulfate +5.3% (-19.9%,+56.3%), p = 0.35; testosterone -1.5% (-14.7%,+10.7%), p = 0.97; androstenedione +12.6% (-17.1%, +49.1%), p = 0.15. The hormone levels did not significantly change between baseline and six weeks. Further, the changes that were observed did not tend to go in the hypothesized direction (estrogens and conjugates increased slightly, testosterone decreased slightly). Only androstenedione showed a trend toward change in the hypothesized direction. CONCLUSION: In this study, there was no evidence that plasma hormone levels are altered by 6 weeks of daily consumption of 94 grams of grape extract powder. Citation Format: Janet E. Olson, Summer V. Allen, Vera J. Suman, Tanya L. Hoskin, Celine M. Vachon, James N. Ingle. Evaluation of the aromatase inhibition potential of standardized grape extract. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3259. doi:10.1158/1538-7445.AM2014-3259
Fatal congenital thrombotic thrombocytopenic purpura with apparent ADAMTS13 inhibitor: in vitro inhibition of ADAMTS13 activity by hemoglobin
Authors: Jan-Dirk Studt, Johanna A. Kremer Hovinga, Gerhard Antoine, Martin Hermann, Manfred Rieger, Friedrich Scheiflinger, Bernhard Lämmle
Journal: Blood (2004)
The Brighton resuscitation ambulances: a continuing experiment in prehospital care by ambulance staff.
Authors: R S Briggs, P M Brown, M E Crabb, T J Cox, H W Ead, R A Hawkes, P W Jequier, D P Southall, R Grainger, J H Williams, D A Chamberlain
Journal: BMJ (1976)

Two ambulances from the existing fleet in Brighton and one in Hove are equipped with portable defibrillator-oscilloscope units. Selected attendants have been trained not only to defibrillate patients but also to perform endotracheal intubation and administer intravenous atropine and lignocaine for carefully defined indications. In the two years up to December 1975 the ambulances responded to 2253 calls which were considered possible emergencies. Retrospective analysis showed that half of these had been for patients with myocardial infarction, coronary insufficiency, or angina. The ambulances took a median time of five minutes to reach a patient. Attempts at resuscitation were made in 207 patients with circulatory arrest, of whom 160 had ventricular fibrillation. Coordinated rhythm was restored at least transiently in 66 patients, and 27 of them survived to leave hospital. Sixteen of the survivors had been in ventricular fibrillation before the arrival of the ambulance. The delay before admission to hospital was reduced: over 50% of patients carried in the ambulances were admitted within two hours of the onset of major symptoms. No extra ambulance staff have been employed for the scheme. The increased load on hospital services has been limited by encouraging a rational admission policy and also by early discharge.
Blood pressures that fall on rechecking
Authors: D T C Barlow
Journal: BMJ (1982)

the investigation of all aged demented patients since the yield of "potentially reversible" causes will certainly be low and the yield of "actually reversible" causes even lower.There are patients of all ages (including aged demented patients) in whom computed tomo- graphy is a valuable procedure, but they will all have to wait a very long time for their scans if we all follow what appears to be Professor Millard's advice and seek computed tomo- graphy scans for all our aged demented patients.
Heterogeneity of IgE response to cefteram pivoxil was noted in 2 patients with cefteram-induced occupational asthma
Authors: Yu-Jin Suh, Young-Mok Lee, Jeung-Hee Choi, Chang-Hee Suh, Dong-Ho Nahm, Hae-Sim Park
Journal: Journal of Allergy and Clinical Immunology (2003)
Partner loyalty is linked to reduced spread of disease in sex workers and in cattle, computational research shows
Authors: N. Hawkes
Journal: BMJ (2015)

Two very different markets—the Italian cattle trade and high class prostitution in Brazil—share common characteristics that may help to control epidemics in their early stages, French and Italian researchers have said in PLoS Computational Biology .1

The authors used data from past cattle movements in Italy and from an online community in Brazil that acts as a TripAdvisor-style website for escorts, to investigate whether past …
Abstract LB-31: Castration induces upregulation of intratumoral androgen biosynthesis and androgen receptor expression in orthotopic VCaP human prostate cancer xenograft model
Authors: Matias Knuuttila, Emrah Yatkin, Jenny Kallio, Saija Savolainen, Teemu Daniel Laajala, Tero Aittokallio, Riikka Oksala, Merja Häkkinen, Pekka Keski-Rahkonen, Seppo Auriola, Matti Poutanen, Sari Mäkelä
Journal: Cancer Research (2014)

Abstract Androgens are key factors involved in the development and progression of prostate cancer (PCa), and the growth of PCa can be suppressed by androgen deprivation therapy (ADT). In a significant proportion of men receiving ADT, PCa progresses to castration-resistant prostate cancer (CRPC), which is a major challenge in the development of efficient therapies. The aim of the study was to characterize the cellular and molecular changes in tumors after ADT (castration), by using orthotopic VCaP human prostate cancer xenograft model. VCaP cells were inoculated in the dorsolateral prostate of immunodeficient mice, and tumor growth was followed by weekly serum PSA measurements. Mice with recurrent tumors after castration were randomized to treatment groups. Serum PSA concentrations showed significant correlation with the tumor volume, confirming that PSA is a reliable indicator of the tumor volume in the orthotopic VCaP xenograft model. Tumor and serum samples were collected and concentrations of androgens were measured by LC-MS/MS. Castration-resistant tumors retained their intratumoral androgen (androstenedione, testosterone, 5α-dihydrotestosterone) concentrations at levels similar to those in tumors growing in intact hosts. Accordingly, castration induced upregulation of enzymes involved in androgen biosynthesis (CYP17A1, AKR1C3 and HSD17B6), as well as expression of full-length androgen receptor (AR) and AR splice variants (AR-V1 and AR-V7). Furthermore, AR target gene expression was maintained in castration-resistant xenografts. AR antagonists, MDV3100 and ARN-509, suppressed the PSA production of castration-resistant tumors, confirming their androgen-dependency. In conclusion, we demonstrated that VCaP xenograft model exhibits the key characteristics of clinical CRPC, thus providing a valuable tool to identify druggable targets and for testing therapeutic strategies targeting AR signaling in CRPC. Citation Format: Matias Knuuttila, Emrah Yatkin, Jenny Kallio, Saija Savolainen, Teemu Daniel Laajala, Tero Aittokallio, Riikka Oksala, Merja Häkkinen, Pekka Keski-Rahkonen, Seppo Auriola, Matti Poutanen, Sari Mäkelä. Castration induces upregulation of intratumoral androgen biosynthesis and androgen receptor expression in orthotopic VCaP human prostate cancer xenograft model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-31. doi:10.1158/1538-7445.AM2014-LB-31
Renal side-effects of cyclosporin A with special reference to autoimmune diseases
Authors: M.J. MIHATSCH, G. THIEL, B. RYFFEL
Journal: British Journal of Dermatology (1990)

At therapeutic drug levels, the functional changes which occur are a reduction of glomerular filtration rate and renal plasma flow. At higher doses, morphological changes develop which may result, particularly in severe cases, in acute or chronic renal failure. The threshold for the development of irreversible vascular‐interstitial lesions mainly depends on the increment of serum creatinine, age and drug dosage or drug blood level. Based on the experience with cyclosporin A (CyA), the following recommendations have been made for its clinical use, especially in patients with autoimmune diseases. The initial dose should not exceed 5 mg/kg body weight and the dose should be reduced if blood CyA levels are over 250 ng/ml; in addition, a dose reduction is recommended if serum creatinine values exceed 30% of pre‐treatment values or if other signs of CyA toxicity, such as hepatotoxicity or hypertension, are found. Strict adherence to these suggestions should allow treatment of patients for prolonged periods without irreversible morphological lesions.
Glutathione effects on toxicity and uptake of mercuric chloride and sodium arsenite in rabbit renal cortical slices.
Authors: C A Burton, K Hatlelid, K Divine, D E Carter, Q Fernando, K Brendel, A J Gandolfi
Journal: Environmental Health Perspectives (1995)

The mechanism of renal uptake of nephrotoxic heavy metals such as HgCl2 and NaAsO2 is not clear. The metals are known to react with endogenous sulfhydryls such as glutathione (GSH), so metal-GSH conjugates may be delivered to the kidney. To study this possibility, renal cortical slices from male New Zealand white rabbits were incubated with 10(-4) M HgCl2 or 10(-3) M NaAsO2 +/- stoichiometric amounts (1-3x) of GSH; or synthetic metal-GSH conjugates [10(-4) M Hg(SG)2 or 10(-3) M As(SG)3]. Incubations were performed at 37 degrees C in DME-F12 buffer (95/5 O2/CO2) for 8 hr. Hg(SG)2 reduced slice K+/DNA content, as an indicator of viability, significantly less than HgCl2. As(SG)3 exhibited a 2-hr delay in K+/DNA content reduction compared to NaAsO2. This delay in toxicity was not correlated to changes in uptake. Arsenic and mercury accumulation, determined by proton-induced X-ray emission, were also identical between the metal salts and the metal-GSH conjugates. Exogenous GSH decreased HgCl2 cytotoxicity and was correlated to a decrease in Hg accumulation in the slice. Exogenous GSH had limited if any protective effects against cytotoxicity by NaAsO2 and a decrease in As accumulation was not observed. Complex metal-GSH interactions appear to exist and impact on the uptake and toxicity of these metals.
Abrogation of macrophage migration inhibitory factor decreases West Nile virus lethality by limiting viral neuroinvasion
Authors: Alvaro Arjona, Harald G. Foellmer, Terrence Town, Lin Leng, Courtney McDonald, Tian Wang, Susan J. Wong, Ruth R. Montgomery, Erol Fikrig, Richard Bucala
Journal: Journal of Clinical Investigation (2007)

The flavivirus West Nile virus (WNV) is an emerging pathogen that causes life-threatening encephalitis in susceptible individuals. We investigated the role of the proinflammatory cytokine macrophage migration inhibitory factor (MIF), which is an upstream mediator of innate immunity, in WNV immunopathogenesis. We found that patients suffering from acute WNV infection presented with increased MIF levels in plasma and in cerebrospinal fluid. MIF expression also was induced in WNV-infected mice. Remarkably, abrogation of MIF action by 3 distinct approaches (antibody blockade, small molecule pharmacologic inhibition, and genetic deletion) rendered mice more resistant to WNV lethality. Mif(-/-) mice showed a reduced viral load and inflammatory response in the brain when compared with wild-type mice. Our results also indicate that MIF favors viral neuroinvasion by compromising the integrity of the blood-brain barrier. In conclusion, the data obtained from this study provide direct evidence for the involvement of MIF in viral pathogenesis and suggest that pharmacotherapeutic approaches targeting MIF may hold promise for the treatment of WNV encephalitis.
Diagnosis of Surgical Disease
Authors: Rudolf J. Noer
Journal: JAMA (1969)

Shackelford's<i>Diagnosis of Surgical Disease</i>appears to be, in a sense, a companion work to his invaluable<i>Surgery of the Alimentary Tract</i>published in 1955. This work discusses in considerable detail the diagnostic features of virtually all conditions which a surgeon might encounter. The richness of the author's personal experience is reflected in many chapters which he himself has prepared, but he has unhesitatingly drawn upon the more specialized knowledge of some 22 colleagues for chapters in their particular areas of interest. Volume 1 includes a most extensive consideration of history taking and physical examination, followed by a section of cytopathology and one on radioisotope scanning. The remainder of this volume is devoted to lesions of the nervous system, head and neck, breast, esophagus, and thorax, including heart and lungs. Heart disease in children and in adults is properly considered in separate chapters, written by cardiologists working in these fields.
The plasma membrane of leading pacemaker cells in the rabbit sinus node. A qualitative and quantitative ultrastructural analysis.
Authors: M Masson-Pévet, W K Bleeker, D Gros
Journal: Circulation Research (1979)

We studied the fine structure of the plasma membrane of electrophysiologically identified leading pacemaker cells from the rabbit sinus node, using both ultrathin sections of fixed tissue and replicas of freeze-cleaved material. We found that differences exist between sinus node and working myocardial membranes, but these are only quantitative. The caveolae or sarcolemmal invaginations are present in very large numbers; they increase the surface area of the plasma membrane by about 100%. The small macular nexuses that are present represent 0.2% of the membrane surface area. Nexuses are therefore about 10 times less numerous in leading sinus node cells than in working myocardium cells. A single equivalent electrical representation of the sinus node shows, nevertheless, that an appreciable electrical coupling may be expected.
Variants of Hepatitis B Virus Associated with Fulminant Liver Disease
Authors: David A. Shafritz
Journal: New England Journal of Medicine (1991)

Two elegant articles in this issue of the Journal 1 , 2 describe a fulminant and fatal course of hepatitis in some patients infected with hepatitis B virus (HBV) in whose serum surface antigen (HBsAg) and antibodies to hepatitis B e antigen (anti-HBe) were present, rather than the hepatitis B e antigen (HBeAg) itself. HBeAg is a nonstructural protein of HBV discovered in the early 1970s.3 It is produced during active viral replication and secreted into the serum, but its function remains unknown. Recent studies have shown that the amino acid sequence of the HBeAg protein is largely identical to that of the . . .
Competition and Hospital Costs-Reply
Authors: Jack Zwanziger
Journal: JAMA (1989)

<h3>In Reply.—</h3> Our article addressed the effects of competition on hospital behavior in California following the introduction of selective contracting and the Medicare prospective payment system program. Drs Friedman and Bogue comment on the research reported in our article and on the merits of this type of research in informing policymakers. We will respond to each point in turn. As we understand their point, Drs Friedman and Bogue suggest that the observed cost reductions by hospitals in competitive markets reflect reduced demand rather than hospital competition. They note that increasing HMO enrollment and competition from ambulatorycare providers could be reducing demand for hospital services disproportionately in competitive areas, leading to the observed reductions in costs. Although such processes could account for reductions in total inpatient costs, they do not explain the significantly lower rate of increase in unit costs (both per day and per admission) that we observed in competitive