tbuckley/cabot-search huggingface dataset:
Paced ventricular electrogram fractionation and sudden death in hypertrophic cardiomyopathy and other non-coronary heart diseases
Authors: R Saumarez
Journal: Cardiovascular Research (2000)

Time for primary review 25 days. 

The prediction of sudden arrhythmic death (SCD) in patients with non-coronary heart disease has become increasingly important because of the need to select high risk patients who require prophylactic implantable cardioverter-defibrillators (ICD). Hypertrophic cardiomyopathy (HCM) is an important cause of SCD, and while it is clear that ICDs are effective in aborting SCD due to ventricular fibrillation [1–3], there is no generally accepted method of risk stratification to allow large-scale, selective ICD implantation in such patients [4]. This article reviews the various trials which have been performed to predict SCD in patients with HCM. Then an emerging technique which was initially developed for HCM, paced electrogram fractionation analysis (PEFA), is reviewed. This technique is based on detection of the substrate for VF and has promise in identifying high risk patients with HCM and other non-coronary heart diseases which cause SCD. Finally, preliminary results obtained in man and animal models are compared suggesting that PEFA may be used to interpret electrophysiological data from humans at risk of SCD in the context of animal experiments.

A useful ‘test’ for predicting SCD must have high enough accuracy to persuade physicians to treat their patients either with or without ICDs on the basis of its results. The definition of a good test depends on the perceived risk/benefit ratio of ICDs in HCM and so the minimum required predictive accuracy of the test will vary amongst physicians. As there is no consensus on the criteria for ICD implantation, we hope to achieve a positive predictive accuracy (PPA) of 0.3 so that three out of every ten patients implanted with an ICD would develop VF.

The relatively low SCD rate in HCM causes problems in designing a trial to establish the SCD rate or the PPA of a … 

* Corresponding author. Tel.: +44-1480-830-541, ext. 4189; fax: +44-1480-831-819
Urea space and total body water measurements by stable isotopes in patients with acute renal failure
Authors: T. Alp Ikizler, M. Tugrul Sezer, Paul J. Flakoll, Sree Hariachar, N. Suren Kanagasundaram, Nancy Gritter, Stephanie Knights, Yu Shyr, Emil Paganini, Raymond M. Hakim, None Jonathan Himmelfarb for the PICARD Study Group
Journal: Kidney International (2004)
Hemodynamic effects of labetalol, an alpha and beta adrenergic blocking agent, in hypertensive subjects.
Authors: J Mehta, J N Cohn
Journal: Circulation (1977)

Labetalol was administered to six hypertensive subjects in increasing doses for seven days. A decrease in both supine and standing arterial pressure and heart rate was observed with no change in cardiac output and few side effects. Exercise tolerance was unaltered by the drug, but the heart rate and arterial pressure response to exercise were significantly blunted. The infusion rate of isoproterenol required to produce tachycardia was increased sevenfold by 800 mg/day labetalol and tenfold by 1600 mg/day. More than twice the control dose of phenylephrine was required during labetalol therapy to produce a rise in diastolic arterial pressure reflex tachycardia to amyl nitrite-induced hypotension was attenuated. These studies indingina pectoris.
Opportunities for Research in General Practice
Authors: R. Platt
Journal: BMJ (1953)

<h3>Objective:</h3> Assess efficacy and safety of incobotulinumtoxinA in lower-limb (LL) or combined LL/upper-limb (LL/UL) spasticity in children and adolescents with cerebral palsy (CP). <h3>Background:</h3> Spasticity is the most prominent movement disorder in children with CP. <h3>Design/Methods:</h3> Two phase III studies; a lead-in prospective, double-blind, randomized study (TIM) followed by an open-label, non-controlled study (TIMO). TIM had three parallel dose groups (4 U/kg body weight (BW), 12 U/kg BW, 16 U/kg BW); subjects were randomized in a 1:1:2 ratio and received 2 double-blind injection cycles. In TIMO, subjects who had completed TIM, or newly recruited treatment-naïve or pre-treated subjects, received 4 injection cycles with the highest dose of TIM. The primary endpoints of TIM were change from baseline in Ashworth Scale (AS) of the plantar flexors (PF) score at Week 4 of Cycle 1, and the Investigator’s Global Impression of Change of Plantar Flexor Spasticity Scale (GICS-PF) score at Week 4 of Cycle 1. TIMO was focused on safety, and did not have primary efficacy endpoints. <h3>Results:</h3> In TIM, all 3 dose groups experienced a statistically significant improvement in AS-PF score 4 weeks post-injection versus baseline. In TIMO, cumulative improvements in AS scores for the PF, knee flexors and thigh adductors were observed from TIM baseline to 4 weeks post-injection. Investigator’s GICS-PF scores indicated a positive response to treatment in all dose groups 4 weeks post-injection in TIM Cycle 1 and improvements were maintained in all treatment groups in Cycle 2. Respective clinical assessments also confirmed consistent improvement in LL and UL spasticity at Week 4 in all TIMO injection cycles. Both studies had good overall safety profiles. <h3>Conclusions:</h3> IncobotulinumtoxinA at total doses up to 16–20 U/kg is effective and well tolerated for the multi-level, multi-pattern treatment of LL/UL spasticity due to CP in children and adolescents. <b>Disclosure:</b> Dr. Dabrowski has nothing to disclose. Dr. Chambers has nothing to disclose. Dr. Heinen has nothing to disclose. Dr. Kanovsky has nothing to disclose. Dr. Schroeder has nothing to disclose. Dr. Graham has nothing to disclose. Dr. Banach has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz. Dr. Banach has received research support from Merz, Ipsen, Kedrion, Shire, Allergan. Dr. Dersch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz Pharmaceuticals GmBH. Dr. Geister has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz Pharmaceuticals GmBH. Dr. Martinez-Torres has nothing to disclose. Dr. Pulte has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Merz Pharmaceuticals GmBH. Dr. Gaebler-Spira has nothing to disclose.
Minilaparoscopy-Guided Spleen Biopsy in Systemic Disease with Splenomegaly of Unknown Origin
Authors: U. Denzer, I. Helmreich-Becker, P. R. Galle, A. W. Lohse
Journal: Endoscopy (2002)

With the advent of a minimally invasive laparoscopy technique, the advantages of diagnostic laparoscopy are being rediscovered. We report here on four patients with systemic disease of unknown origin and splenomegaly, in whom minilaparoscopy-guided splenic biopsy yielded a definitive diagnosis. Four patients with unclear systemic disease were studied using diagnostic minilaparoscopy and guided spleen biopsy, after failure of diagnostic work-up. Minilaparoscopic spleen biopsy revealed the diagnosis of a B-cell non-Hodgkin's lymphoma in two cases. In one patient, who had a history of Still's disease, the spleen biopsy showed granulocytic infiltration in the spleen typical of an acute episode of Still's disease. One patient with a known immunodeficiency syndrome (stage C III) showed multiple hypodense lesions in the spleen. Biopsy allowed a diagnosis of mycobacterial infection, with identification of Mycobacterium tuberculosis. No major complications occurred in any of the four cases; post-biopsy bleeding was observed in three of the four, but was easily managed by argon plasma coagulation or application of fibrin glue, or both. We recommend the use of spleen biopsy as a diagnostic tool in splenopathy of unknown origin if previous diagnostic methods have failed to yield a definitive diagnosis.
Angiogenesis Is Impaired by Hypercholesterolemia
Authors: James J. Jang, Hoai-Ky V. Ho, Helen H. Kwan, Luis F. Fajardo, John P. Cooke
Journal: Circulation (2000)

Many angiogenic factors require endothelium-derived nitric oxide (NO) to exert their effects. Recently, an endogenous competitive antagonist of NO synthase has been characterized: asymmetric dimethylarginine (ADMA). Elevated plasma levels of ADMA reduce NO synthesis in hypercholesterolemia. Accordingly, we hypothesized that hypercholesterolemia impairs angiogenesis by an ADMA-dependent mechanism.Angiogenesis was assessed with the use of a disk angiogenesis system implanted subcutaneously in normal (E(+)) mice or apolipoprotein (apo)E-deficient hypercholesterolemic (E(-)) mice. After 2 weeks, the disks were removed, and the fibrovascular growth area was used as an index of angiogenesis. Basal and fibroblast growth factor-stimulated angiogenesis was impaired in E(-) mice, associated with an elevation in plasma ADMA. Oral administration of L-arginine reversed the impairment of angiogenesis in E(-) mice. By contrast, oral administration of L-nitroarginine (an exogenous antagonist of NO synthase) reduced angiogenesis. When added directly to the disk, ADMA dose-dependently inhibited basal and fibroblast growth factor-induced angiogenesis, an effect that was reversed by oral administration of L-arginine.The derangement of the NO synthase pathway that occurs in hypercholesterolemia is associated with an impairment of angiogenesis. The lipid-induced impairment of angiogenesis can be reversed by oral administration of L-arginine and can be mimicked in normocholesterolemic animals by administration of an NO synthase antagonist. The data are consistent with the hypothesis that ADMA is an endogenous inhibitor of angiogenesis.
A UNIVERSITY PRESIDENT LOOKS AT MEDICAL EDUCATION
Authors: Deane W. Malott
Journal: JAMA (1960)

An uneasy and highly sensitive equilibrium is perhaps the most a university president can hope to attain in his relationships to his faculty. Charged with full responsibility for the entire operation by his Board of Trustees, in many areas of these responsibilities he is merely symbolic of central authority. Meanwhile, the mantle of academic freedom is thrown more widely around faculty members as an insulative device, to protect them from administrative jurisdiction.  In medical faculties, however, a whole congeries of additional influences arise to affect these administration-faculty relations. There are centrifugal thrusts away from university-oriented procedures and policies, which add to the concern of the university president and his trustees.  There is the growth of the great medical center— a complex of hospitals, research institutes, and training programs of various sorts—with an interrelated administrative hierarchy often so complicated that central authority is impossible to identify. At any rate, the poor
Correlation between Prostate-Specific Antigen Kinetics and Overall Survival in Abiraterone Acetate–Treated Castration-Resistant Prostate Cancer Patients
Authors: Xu S. Xu, Charles J. Ryan, Kim Stuyckens, Matthew R. Smith, Fred Saad, Thomas W. Griffin, Youn C. Park, Margaret K. Yu, An Vermeulen, Italo Poggesi, Partha Nandy
Journal: Clinical Cancer Research (2015)

Abstract Purpose: We constructed a biomarker-survival modeling framework to explore the relationship between prostate-specific antigen (PSA) kinetics and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients following oral administration of 1,000 mg/day of abiraterone acetate (AA). Experimental Design: The PSA-survival modeling framework was based on data from two phase III studies, COU-AA-301 (chemotherapy pretreated, n = 1,184) and COU-AA-302 (chemotherapy naïve, n = 1,081), and included a mixed-effects tumor growth inhibition model and a Cox proportional hazards survival model. Results: The effect of AA on PSA kinetics was significant (P &amp;lt; 0.0001) and comparable between the chemotherapy-naïve and -pretreated patients. PSA kinetics [e.g., PSA nadir, PSA response rate (≥30%, 50%, and 90%), time to PSA progression, PSA doubling time (PSADT)] were highly associated with OS in both populations. The model-based posttreatment PSADT had the strongest association with OS (HR ∼0.9 in both populations). The models could accurately predict survival outcomes. After adjusting for PSA kinetic endpoints, the treatment effect of AA on survival was no longer statistically significant in both studies, and the Prentice criteria of surrogacy were met for the PSA kinetic endpoints. A strong correlation was also observed between PSA and radiographic progression-free survival. Conclusions: The analysis revealed a consistent treatment effect of AA on PSA kinetics and strong associations between PSA kinetics and OS in chemotherapy-pretreated and -naïve patients, thereby providing a rationale to consider PSA kinetics as surrogacy endpoints to indicate clinical benefit in AA-treated patients with mCRPC regardless of chemotherapy treatment. Clin Cancer Res; 21(14); 3170–7. ©2015 AACR.
A 63-Year-Old Man With Multiple Cardiovascular Risk Factors and Poor Adherence to Treatment Plans
Authors: Thomas Bodenheimer
Journal: JAMA (2007)

Mr P has long-standing hypertension, obesity, and diabetes mellitus and has experienced life-threatening cardiovascular events. Mr P is receiving evidence-based clinical care but has adhered to his medical regimen poorly and remains at considerable risk of future catastrophic cardiovascular events. Practicing evidence-based medicine should be a 5-step process: research uncovers the evidence, clinicians learn the evidence, clinicians use the evidence at every visit for every patient, clinicians make sure patients understand the evidence, and clinicians help patients incorporate the evidence into their lives. Research demonstrates, however, that clinicians do not use the evidence at every visit, patients may misunderstand what took place in the visit, and clinicians are not always effective in helping patients incorporate the evidence into their lives. These failures reflect the difficulty faced by clinicians attempting to address multiple issues while providing sufficient information and engaging in collaborative decision making during a brief clinical visit.
A Doppler echocardiographic method for calculating volume flow across the tricuspid valve: correlative laboratory and clinical studies.
Authors: E J Meijboom, S Horowitz, L M Valdes-Cruz, D J Sahn, D F Larson, C Oliveira Lima
Journal: Circulation (1985)

In this study we tested a two-dimensional Doppler echocardiographic method for measuring volume flow across the tricuspid valve. Five anesthetized, open-chest dogs had a calibrated electromagnetic flow probe placed on the ascending aorta. Volume flow across the tricuspid valve was controlled by creating a variable femoral-to-pulmonary arterial shunt. Since no standard plane provided a direct view of the tricuspid valve orifice, tricuspid flow area was estimated by calculating a fixed circular flow orifice from the maximal late diastolic diameter of the tricuspid anulus in a four-chamber view. Doppler-determined velocities across the tricuspid valve and tricuspid anulus images in the four-chamber view were obtained in inspiration and expiration. For 24 cardiac outputs (0.6 to 4.0 liters/min), inspiratory tricuspid flow determined by the Doppler method correlated minimally better (r = .90, SEE = 0.30 liter/min) than did expiratory measurements (r = .89, SEE = 0.35 liter/min) with the time-averaged systemic flow determined electromagnetically. Doppler-determined tricuspid volume flows in four-chamber and short-axis two-dimensional echocardiographic views from 10 children were then compared with values determined simultaneously by thermodilution during cardiac catheterization. In the children, Doppler-determined flows in short-axis and four-chamber views, both in inspiration and expiration, were similar; when results for the two views were averaged in inspiration and expiration, the tricuspid flows predicted by the Doppler method were highly correlated (r = .98, SEE = 0.48 liter/min) with the results of thermodilution. The two-dimensional Doppler echocardiographic method provides a means of estimating volume flow across the tricuspid valve noninvasively.
Chemotaxis of Polymorphonuclear Leukocytes from Patients with Diabetes Mellitus
Authors: Alastair G. Mowat, John Baum
Journal: New England Journal of Medicine (1971)

With a new in vitro method of measuring the chemotaxis of polymorphonuclear leukocytes from peripheral blood, a chemotactic index was calculated. The mean chemotactic index in 31 patients with diabetes mellitus was significantly less (p less than 0.0005) than that in 31 matched controls. The defect in chemotaxis could not be correlated with plasma insulin, plasma glucose, serum carbon dioxide and blood urea nitrogen values, or with any therapeutic agents. Incubation of the leukocytes from 11 normals with glucose in concentrations of 300 to 900 mg per 100 ml did not alter indexes. The defect in chemotaxis of the diabetic leukocyte was corrected by incubation of the cells with insulin in concentrations of 100 μU to 10 mU per milliliter. Insulin with phenol was less effective than insulin without preservative. Insulin was ineffective in the absence of glucose. It is suggested that this defect in the chemotaxis of diabetic leukocytes could contribute to increased infections in these patients.
Recovery from Presumed Subacute Inclusion-body Encephalitis
Authors: J. M. S. Pearce, D. D. Barwick
Journal: BMJ (1964)

A 17-year-old boy was sent home from school on 14 June 1963 complaining of tiredness, loss of appetite, and a sore throat.He developed a generalized headache and drowsiness, and in the next few days exhibited severe behaviour disturbances, notably swearing, saying and doing inappropriate things, and being restless and totally disorientated.These symptoms led to his admission to a psychiatric unit, where physical examination disclosed no neurological signs, but an E.E.G. showed a doubtful focus in the right posterior temporal region.On 22 June, after an injection of methedrine, he had a major epileptic seizure followed by status epilepticus, which was controlled with paraldehyde and barbiturates.
LOWER EXTREMITY INJURIES AMONG NIGERIAN MALE YOUTH FOOTBALL PLAYERS
Authors: OBA Owoeye, SRA Akinbo, OA Olawale, BA Tella
Journal: British Journal of Sports Medicine (2014)

Background Football (soccer) is the leading sport for participation among Nigerian youths. Studies on youth football injuries and their risk factors in Nigeria are lacking. Objective To assess the risk and pattern of lower extremity (LE) injuries in Nigerian male youth football players. Design A retrospective cohort study. Setting Sub-elite youth football. Participants The study involved 706 players (aged 17.67±1.11 years [14–19 years]) from 36 teams in the Premier League and League I of a Nigerian youth football league. Interventions: A structured questionnaire based on the FIFA Medical and Research Centre consensus for studies relating to football injuries was administered to players at a pre-season screening programme. Main Outcome Measurements: Information collected from the players included occurrence of time-loss LE injuries in the past 1 year, injury type, location, severity and exposure type. Furthermore, descriptive data on potential risk factors such as age, level and position of play, leg dominance and total number of matches played were documented. Results A total of 227 players sustained 307 time-loss LE injuries (range, 1–6 injuries) with an overall 1-year prevalence rate of 32.5%; equivalent to 1.4 injuries per player per year. There was no significant difference in injury prevalence between the Premier League and Division I players (P=.659). Injuries sustained were mostly located on the ankle (45.6%) and the knee joints (27.8%). Moderate injuries (48.5%) were mostly reported and more injuries were sustained during matches than training (P&lt;.001). Exposure to high frequency of matches (&gt;50 matches per year) (OR=2.49, P=.002) was significantly associated with injury occurrence. Conclusions There is a high risk of moderate and severe LE injuries among Nigerian male youth footballers, however, pattern of injuries are mostly consistent with literatures on football injuries. This study suggests the need for injury prevention and rehabilitation interventions for players.
Self-Inactivating Lentiviral Vectors Resist Proviral Methylation but Do Not Confer Position-Independent Expression in Hematopoietic Stem Cells
Authors: Azim Mohamedali, Francois Moreau-Gaudry, Emmanuel Richard, Ping Xia, Jan Nolta, Punam Malik
Journal: Molecular Therapy (2004)

Oncoretroviral expression is transcriptionally silenced in embryonic and hematopoietic stem cells (HSCs). This is associated with methylation of viral and internal promoters. We determined whether self-inactivating (SIN) lentiviral vectors (LV) would circumvent proviral silencing in HSCs. We studied long-term expression, methylation, and position effects (PE) from two GFP-encoding SIN-LV containing erythroid enhancers and the human ankyrin-1 promoter (h-Ank-P) using the murine secondary bone marrow (BM) transplant assay. Proviral expression was detected in RBC 6-11 months following transplant only in 28 of 49 secondary mice, with 0.9 +/- 0.2 copy/cell and oligoclonally integrated provirus in BM, spleen, and thymus. Twenty-one of 49 secondary mice lacked integrated provirus. Secondary mice containing provirus also had GFP-expressing RBCs, although proviral copy number did not always correlate with expression, suggesting either proviral methylation or chromatin PE. The endogenous h-Ank-P was partially methylated in nonerythroid cell lines and unmethylated in erythroid cell lines. However, h-Ank-P in the provirus was unmethylated in erythroid and nonerythroid cells within secondary murine BM. Despite lack of methylation, GFP expression was variable in secondary BFU-e and in single-copy mouse erythroleukemia cell clones. Taken together, these data show that erythroid-specific SIN-LV express long term and resist methylation-associated proviral silencing, but may require additional elements to confer position-independent expression.
Expression and ultrastructural localization of HMB-45 antigen
Authors: A. KIKUCHI, H. SHIMIZU, T. NISHIKAWA
Journal: British Journal of Dermatology (1996)

HMB-45 is a monoclonal antibody specific for melanoma cells and premature developing melanocytes. We examined the expression and specific subcellular binding sites of HMB-45 in various types of melanocytes including epidermal melanocytes from fetuses and infants with or without tyrosinase-negative oculocutaneous albinism (type IA), melanin-producing and non-producing melanoma cell lines (G361 and MeWo), and in vivo melanoma cells (melanotic and amelanotic malignant melanoma). Subcellular HMB-45 binding was examined by using post-embedding immunogold electron microscopy with rapid freezing and freeze substitution fixation methods without the use of chemical fixatives to preserve the intracytoplasmic delicate antigen property of HMB-45. HMB-45 antigen was detected not only in in vivo melanoma cells and normal fetal melanocytes, but also in melanocytes in the other conditions. Post-embedding immunogold electron microscopy revealed that HMB-45 antigen was exclusively localized to stages I and II melanosomes in the cytoplasm of neoplastic melanocytes, but was detected mainly on stages II and III melanosomes in the melanocytes from fetuses and infants. In tyrosinase-negative oculocutaneous albinism, only stages I and II melanosomes were detected in the cytoplasm, but both stages of melanosomes were HMB-45 positive. We conclude that HMB-45 appears mainly on the immature melanosomes during melanogenesis in both neoplastic and non-neoplastic melanocytes regardless of their tyrosinase activity, but the intracytoplasmic localization of HMB-45 antigen is different by each condition of melanocytes.