tbuckley/cabot-search huggingface dataset:
Assessment of Diastolic Function With Doppler Tissue Imaging to Predict Genotype in Preclinical Hypertrophic Cardiomyopathy
Authors: Carolyn Y. Ho, Nancy K. Sweitzer, Barbara McDonough, Barry J. Maron, Susan A. Casey, J.G. Seidman, Christine E. Seidman, Scott D. Solomon
Journal: Circulation (2002)

Background — Unexplained left ventricular hypertrophy (LVH) is considered diagnostic of hypertrophic cardiomyopathy (HCM) but fails to identify all genetically affected individuals. Altered diastolic function has been hypothesized to represent an earlier manifestation of HCM before the development of LVH; however, data regarding the clinical utility of imaging techniques that assess this parameter are limited. Methods and Results — Echocardiographic studies including Doppler tissue imaging (DTI) were performed in a genotyped HCM population with β-myosin heavy chain (β -MHC) mutations. Genotype (+) individuals with LVH (G+/LVH+; n=18) and genotype (+) individuals without LVH (G+/LVH−; n=18) were compared with normal control subjects (n=36). Left ventricular ejection fraction (EF) was significantly higher in both genotype (+) groups (75±5% and 71±6%, respectively, versus 64± 5% in control subjects; P &lt;0.0001). Mean early diastolic myocardial velocities (Ea) were significantly lower in both genotype (+) subgroups, irrespective of LVH ( P &lt;0.02). However, there was substantial overlap in Ea velocities between the G+/LVH− and control groups. An Ea velocity of ≤13.5 cm/s had 86% specificity and 75% sensitivity for identifying genotype-positive subjects. The combination of EF ≥68% and Ea velocity &lt;15 cm/s was 100% specific and 44% sensitive in predicting affected genotype. Conclusions — Abnormalities of diastolic function assessed by Doppler tissue imaging precede the development of LVH in individuals with HCM caused by β -MHC mutations. Although Ea velocity alone was not sufficiently sensitive as a sole diagnostic criterion, the combination of Ea velocity and EF was highly predictive of affected genotype in individuals without overt manifestations of HCM.
Turning round NHS deficits: Clinical governance, 1998-2006: RIP
Authors: Neville W Goodman
Journal: BMJ (2006)

EDITOR—With these words, we were introduced to the idea of clinical governance: “A commitment to deliver high quality care should be at the heart of everyday clinical practice. In the past many health professionals have watched as board agendas and management meetings have become dominated by financial issues and activity targets. The government's white paper on the NHS in …
Hyperlipidemia in Coronary Heart Disease III. EVALUATION OF LIPOPROTEIN PHENOTYPES OF 156 GENETICALLY DEFINED SURVIVORS OF MYOCARDIAL INFARCTION
Authors: William R. Hazzard, Joseph L. Goldstein, Helmut G. Schrott, Arno G. Motulsky, Edwin L. Bierman
Journal: Journal of Clinical Investigation (1973)

Although analysis of lipoprotein phenotypes is widely used to diagnose and classify the familial hyperlipidemias, an evaluation of this system as a method for genetic classification has hitherto not been published. The present study of 156 genetically defined survivors of myocardial infarction was therefore designed to examine the relationship between lipoprotein phenotypes and genetic lipid disorders. The lipoprotein phenotypes of each survivor was determined primarily by measurement of his plasma triglyceride and low density lipoprotein (LDL)-cholesterol concentrations; his genetic disorder was identified by analysis of whole plasma cholesterol and triglyceride levels in relatives. The mean levels of LDL-cholesterol discriminated statistically among the three monogenic lipid disorders; it was highest in survivors with familial hypercholesterolemia (261+/-61 mg/100 ml [mean +/-SD]); intermediate in those with familial combined hyperlipidemia (197+/-50); and lowest in those with familial hypertriglyceridemia (155+/-36) (P < 0.005 among the three groups). However, on an individual basis no lipoprotein pattern proved to be specific for any particular genetic lipid disorder; conversely, no genetic disorder was specified by a single lipoprotein pattern. This lack of correlation occurred for the following reasons: (a) individual LDL-cholesterol levels frequently overlapped between disorders; (b) in many instances a small quantitative change in the level of either LDL-cholesterol or whole plasma triglyceride caused qualitative differences in lipoprotein phenotypes, especially in individuals with familial combined hyperlipidemia, who showed variable expression (types IIa, IIb, IV, or V); (c) lipoprotein phenotypes failed to distinguish among monogenic, polygenic, and sporadic forms of hyperlipidemia; (d) clofibrate treatment of some survivors with genetic forms of hyperlipidemia caused their levels of triglyceride and LDL-cholesterol to fall below the 95th percentile, thus resulting in a normal phenotype; and (e) beta-migrating very low density lipoproteins (beta-VLDL), previously considered a specific marker for the type III hyperlipidemic disorder, was identified in several survivors with different lipoprotein characteristics and familial lipid distributions. These studies indicate that lipoprotein phenotypes are not qualitative markers in the genetic sense but instead are quantitative parameters which may vary among different individuals with the same genetic lipid disorder. It would therefore seem likely that a genetic classification of the individual hyperlipidemic patient with coronary heart disease made from a quantitative analysis of lipid levels in his relatives may provide a more meaningful approach than determination of lipoprotein phenotypes.
PSYCHOSOMATIC ASPECTS OF ROSACEA
Authors: F. A. WHITLOCK
Journal: British Journal of Dermatology (1961)

Journal Article PSYCHOSOMATIC ASPECTS OF ROSACEA Get access F. A. WHITLOCK, M.D., M.R.C.P., D.P.M. F. A. WHITLOCK, M.D., M.R.C.P., D.P.M. Consultant Psychiatrist, Newcastle General Hospital, Newcastle‐upon‐Tyne Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 73, Issue 4, 1 April 1961, Pages 137–148, https://doi.org/10.1111/j.1365-2133.1961.tb14422.x Published: 01 April 1961
PKC-α regulates cardiac contractility and propensity toward heart failure
Authors: Julian C Braz, Kimberly Gregory, Anand Pathak, Wen Zhao, Bogachan Sahin, Raisa Klevitsky, Thomas F Kimball, John N Lorenz, Angus C Nairn, Stephen B Liggett, Ilona Bodi, Su Wang, Arnold Schwartz, Edward G Lakatta, Anna A DePaoli-Roach, Jeffrey Robbins, Timothy E Hewett, James A Bibb, Margaret V Westfall, Evangelia G Kranias, Jeffery D Molkentin
Journal: Nature Medicine (2004)
Probability of long-term disease-free survival for acute myeloid leukemia patients after first relapse: A single-centre experience
Authors: M. Vignetti, E. Orsini, M.C. Petti, M.L. Moleti, C. Andrizzi, R.M. Pinto, S. Amadori, G. Meloni
Journal: Annals of Oncology (1996)
RESTRICTION OF THE CAPACITY TO RESPOND TO TWO ANTIGENS BY SINGLE PRECURSORS OF ANTIBODY-PRODUCING CELLS IN CULTURE
Authors: David Osoba
Journal: The Journal of Experimental Medicine (1969)

Experiments were designed to determine whether or not precursors of antibody-producing cells are restricted in the number of antigens to which they can respond. An in vitro culture system was used, in which the successful production of hemolysin PFC was dependent on the presence of a large number of heavily irradiated spleen cells which did not themselves give rise to PFC, but which supported the production of PFC by a small number of normal spleen cells. All spleen cells were obtained from unimmunized CBA mice. The cells were mixed with either sheep or chicken erythrocytes, or both, cultured for 4 days and analyzed for hemolysin PFC. By reducing the number of unirradiated spleen cells to limiting dilution it was shown that normal spleen cell suspensions contain approximately three times as many precursors capable of responding to chicken erythrocytes as to sheep erythrocytes. In cultures containing both antigens, the number of precursors responding to one antigen was not affected by the presence of the other antigen. In addition, some cultures were positive for PFC-producing hemolysin against chicken erythrocytes, but not against sheep erythrocytes, and vice versa. This pattern of response was independent of the concentration of antigen in the cultures. Thus, the antigen-sensitive precursors for these non-cross-reacting antigens responded independently of each other, indicating that each precursor was restricted in its capacity to respond to more than one antigen prior to stimulation.
The recurrence patterns of stages I, II and III neuroblastoma: Experience with 77 relapsing patients
Authors: F. Berthold, B. Hero, H. Breu, H. Christiansen, R. Erttmann, A. Gnekow, F. Herrmann, T. Klingebiel, F. Lampert, St. Müller-Weihrich, P. Weinel
Journal: Annals of Oncology (1996)
Dutch model of maternity care May not suit Britain
Authors: E R Van Teijlingen
Journal: BMJ (1994)

limited by their specific range of skill and their professional role.Not all forms of protection count as medical care.While, for example, a doctor has a responsibility to protect Salman Rushdie from the consequences of an attempt on his life, he or she has no responsibility to protect him from that attack.Otlers, of course, do.
Nutritional and Socioeconomic Factors in Relation to Prostate Cancer Mortality: a Cross-National Study
Authors: J. R. Hebert, T. G. Hurley, B. C. Olendzki, J. Teas, Y. Ma, J. S. Hampl
Journal: JNCI Journal of the National Cancer Institute (1998)

Large international variations in rates of prostate cancer incidence and mortality suggest that environmental factors have a strong influence on the development of this disease. The purpose of this study was to identify predictive variables for prostate cancer mortality in data from 59 countries.Data on prostate cancer mortality, food consumption, tobacco use, socioeconomic factors, reproductive factors, and health indicators were obtained from United Nations sources. Linear regression models were fit to these data. The influence of each variable fit in the regression models was assessed by multiplying the regression coefficient b by the 75th (X75) and 25th (X25) percentile values of the variable. The difference, bX75 - bX25, is the estimated effect of the variable across its interquartile range on mortality rates measured as deaths per 100000 males aged 45-74 years. Reported P values are two-sided.Prostate cancer mortality was inversely associated with estimated consumption of cereals (bX75 - bX25 = -7.31 deaths; P = .001), nuts and oilseeds (bX75 - bX25 = -1.72 deaths; P = .003), and fish (bX75 - bX25 = -1.47 deaths; P = .001). In the 42 countries for which we had appropriate data, soy products were found to be significantly protective (P = .0001), with an effect size per kilocalorie at least four times as large as that of any other dietary factor. Besides variables related to diet, we observed an association between prostate cancer mortality rates and a composite of other health-related, sanitation, and economic variables (P = .003).The specific food-related results from this study are consistent with previous information and support the current dietary guidelines and hypothesis that grains, cereals, and nuts are protective against prostate cancer. The findings also provide a rationale for future study of soy products in prostate cancer prevention trials.
AMP-Activated Protein Kinase Phosphorylates Cardiac Troponin I and Alters Contractility of Murine Ventricular Myocytes
Authors: Sandra Marisa Oliveira, Yin-Hua Zhang, Raquel Sancho Solis, Henrik Isackson, Mohamed Bellahcene, Arash Yavari, Katalin Pinter, Joanna K. Davies, Ying Ge, Houman Ashrafian, Jeffery W. Walker, David Carling, Hugh Watkins, Barbara Casadei, Charles Redwood
Journal: Circulation Research (2012)

AMP-activated protein kinase (AMPK) is an important regulator of energy balance and signaling in the heart. Mutations affecting the regulatory γ2 subunit have been shown to cause an essentially cardiac-restricted phenotype of hypertrophy and conduction disease, suggesting a specific role for this subunit in the heart.
Genetic Variation in Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 (LOX1) Gene and the Risk of Coronary Artery Disease
Authors: Qi Chen, Steven E. Reis, Candace Kammerer, Wendy Y. Craig, Sue E. LaPierre, Erin Luedecking Zimmer, Dennis M. McNamara, Daniel F. Pauly, Barry Sharaf, Richard Holubkov, C. Noel Bairey Merz, George Sopko, Franklin Bontempo, M. Ilyas Kamboh
Journal: Circulation (2003)

We examined the association of 3 polymorphisms in the lectin-like oxidized LDL receptor-1 (LOX1 or OLR1) gene with coronary artery disease in the Women's Ischemia Syndrome Evaluation (WISE) study population. The WISE sample comprised 589 white and 122 black women who underwent angiography for suspected ischemia. The sample was divided into 3 groups: <20% stenosis (38.7%), 20% to 49% stenosis (24.9%), and >or=50% stenosis (35.3%). The three LOX1 polymorphisms (intron 4/G-->A, intron 5/T-->G, and 3' UTR/T-->C) were in linkage disequilibrium and thus behaved as a single polymorphism. The frequency of the 3'UTR/T allele was significantly higher in whites than blacks (49% versus 19%; P<0.0001). Among white women, the frequency of the 3'UTR/T allele carriers (TC+TT genotypes) increased gradually from 67.9% to 75.0% and 79.2% in the <20%, 20% to 49%, and >or=50% stenosis groups, respectively (chi2 trend=6.23; P=0.013). Logistic regression analyses indicated that APOE (odds ratio, 1.90; P=0.007) and LOX1 (odds ratio, 1.67; P=0.025) genotypes were independently associated with the risk of disease and that there was no interaction between the two genes. The 3'UTR/T allele carriers also had significantly higher IgG anti-oxLDL levels than individuals carrying the CC genotype (0.94+/-0.20 versus 0.86+/-0.16; P=0.032). Furthermore, our electrophoretic mobility shift assay data show that the 3'UTR polymorphic sequence affects the binding of a putative transcription factor in an allele-specific manner. Our data suggest that common genetic variation in the LOX1 gene may be associated with the risk of coronary artery disease in white women.
Epidemiological study of hepatitis B virus genotypes, core promoter and precore mutations of chronic hepatitis B infection in Hong Kong
Authors: Man-Fung Yuen, Erwin Sablon, Yasuhito Tanaka, Takanobu Kato, Masashi Mizokami, Joke Doutreloigne, He-Jun Yuan, Danny Ka-Ho Wong, Siu-Man Sum, Ching-Lung Lai
Journal: Journal of Hepatology (2004)
Childhood Trauma and Psychosis: A Case-Control and Case-Sibling Comparison Across Different Levels of Genetic Liability, Psychopathology, and Type of Trauma
Authors: Manuela Heins, Claudia Simons, Tineke Lataster, Stefanie Pfeifer, Dagmar Versmissen, Marielle Lardinois, Machteld Marcelis, Philippe Delespaul, Lydia Krabbendam, Jim van Os, Inez Myin-Germeys
Journal: American Journal of Psychiatry (2011)

The associations of two types of childhood trauma (abuse and neglect) with psychosis symptom domains were investigated in subjects with psychotic illness, high psychosis vulnerability, and average psychosis vulnerability.Childhood trauma was assessed with the Childhood Trauma Questionnaire. Symptoms were assessed with the Positive and Negative Syndrome Scale in the patients (N=272) and with the Structured Interview for Schizotypy-Revised in the patients' siblings (N=258), and healthy comparison subjects (N=227).Childhood trauma was associated with psychotic disorder in a dose-response fashion in the comparison of patients and healthy subjects (adjusted odds ratio=4.53, 95% CI=2.79-7.35). The comparison of siblings and healthy subjects suggested that siblings shared a degree of trauma with the patients (adjusted odds ratio=1.61, 95% CI=0.95-2.61), but the patient-sibling comparison indicated much greater exposure in patients than in siblings (adjusted odds ratio=2.60, 95% CI=1.78-3.78). Childhood abuse but not neglect was associated with positive but not negative symptoms in a dose-response fashion in all three groups. There was no evidence for moderation by sex.Discordance in psychotic illness across related individuals can be traced to differential exposure to trauma. The association between trauma and psychosis is apparent across different levels of illness and vulnerability to psychotic disorder, suggesting true association rather than reporting bias, reverse causality, or passive gene-environment correlation. Positive psychotic symptoms in vulnerable individuals may arise as a consequence of the level and frequency of exposure to abuse rather than neglect, suggesting symptom-specific and exposure-specific underlying mechanisms.
Economic Analysis of Vinorelbine Plus Cisplatin Versus Paclitaxel Plus Carboplatin for Advanced Non-Small-Cell Lung Cancer
Authors: Scott D Ramsey, Carol M Moinpour, Laura C Lovato, John J Crowley, Patra Grevstad, Cary A Presant, Saul E Rivkin, Karen Kelly, David R Gandara
Journal: JNCI Journal of the National Cancer Institute (2002)

It is increasingly important to have timely information about the economic impact of new cancer therapies in today's cost-conscious environment. Nearly 170 000 people are diagnosed with lung cancer annually in the United States. We performed an economic analysis alongside Southwest Oncology Group Trial S9509 to estimate the cost-effectiveness of cisplatin plus vinorelbine versus carboplatin plus paclitaxel for patients with advanced non-small-cell lung cancer. There were no statistically significant differences in survival or cancer-related quality of life between the treatment arms.Use of both protocol and nonprotocol lung cancer-related health care was tracked for 24 months from the initiation of therapy. To determine expenditures, nationally standardized costs were applied to each type of health care service used, and these were summed over time. Lifetime expenditures and 95% confidence intervals (CIs) for each arm of the trial were calculated with the use of a multivariate regression technique that accounts for censoring. Student's t tests were used to compare the difference in costs between the arms. All statistical tests were two-sided.Cancer-related health care costs over the period of observation averaged 40,292 dollars (95% CI = 36,226 dollars to 44,359 dollars) for patients in the cisplatin plus vinorelbine arm versus 48,940 dollars (95% CI = 44,674 dollars to 53,208 dollars) for patients in the carboplatin plus paclitaxel arm (P =.004), with a mean difference of 8648 dollars (95% CI = 2634 dollars to 14,662 dollars). Protocol chemotherapy drugs and medical procedures costs were statistically significantly higher in the paclitaxel arm (P =.0003 and P<.0001, respectively), whereas protocol chemotherapy delivery costs were statistically significantly higher in the vinorelbine arm (P<.0001). There was no difference between the arms in costs for blood products, supportive care medications, nonprotocol-related inpatient or outpatient care, and nonprotocol chemotherapy.Treatment with carboplatin plus paclitaxel is substantially and statistically significantly more expensive than treatment with cisplatin plus vinorelbine. The majority of the cost difference is due to the additional cost of the protocol chemotherapy (approximately 12,000 dollars). Notable differences in costs of downstream health care were not apparent.
Fluvoxamine Treatment of Social Phobia (Social Anxiety Disorder): A Double-Blind, Placebo-Controlled Study
Authors: M B Stein, A J Fyer, J R Davidson, M H Pollack, B Wiita
Journal: American Journal of Psychiatry (1999)

The purpose of this study was to determine the efficacy of fluvoxamine for the treatment of social phobia (social anxiety disorder).In a 12-week multicenter, double-blind, randomized, placebo-controlled trial, 92 patients with social phobia were treated with the selective serotonin reuptake inhibitor fluvoxamine; 91.3% of the patients had the generalized subtype of the disorder. The primary criterion for response was a rating of "much improved" or "very much improved" on the Clinical Global Impression of Improvement scale. Secondary response criteria were changes on three specialized rating scales for social phobia symptoms: the Brief Social Phobia Scale, the Social Phobia Inventory, and the Liebowitz Social Anxiety Scale. Psychosocial impairment was assessed in three domains (disruption of work, social life, and home/family life) by using the Sheehan Disability Scale.The mean daily dose of fluvoxamine was 202 mg (SD = 86). At study end or with the last observation carried forward, within the evaluable subjects (N = 86) there was a significantly higher proportion of responders in the fluvoxamine group (42.9%, N = 18) than in the placebo group (22.7%, N = 10). Similarly, fluvoxamine was superior to placebo on all social phobia rating scales at week 8 and beyond. Fluvoxamine also resulted in significantly greater decreases in measures of psychosocial disability than did placebo. Overall, fluvoxamine was well tolerated and safe.These findings indicate that fluvoxamine is efficacious in the pharmacologic management of serious forms of social phobia.
Application of Benzo( <i>a</i> )pyrene and Coal Tar Tumor Dose–Response Data to a Modified Benchmark Dose Method of Guideline Development
Authors: D. James Fitzgerald, Neville I. Robinson, Beverly A. Pester
Journal: Environmental Health Perspectives (2004)

Assessment of cancer risk from exposure to polycyclic aromatic hydrocarbons (PAHs) has been traditionally conducted by applying the conservative linearized multistage (LMS) model to animal tumor data for benzo(a)pyrene (BaP), considered the most potent carcinogen in PAH mixtures. Because it has been argued that LMS use of 95% lower confidence limits on dose is unnecessarily conservative, that assumptions of low-dose linearity to zero in the dose response imply clear mechanistic understanding, and that "acceptable" cancer risk rests on a policy decision, an alternative cancer risk assessment approach has been developed. Based in part on the emerging benchmark dose (BMD) method, the modified BMD method we used involves applying a suite of conventional mathematical models to tumor dose-response data. This permits derivation of the average dose corresponding to 5% extra tumor incidence (BMD0.05) to which a number of modifying factors are applied to achieve a guideline dose, that is, a daily dose considered safe for human lifetime exposure. Application of the modified BMD method to recent forestomach tumor data from BaP ingestion studies in mice suggests a guideline dose of 0.08 microg/kg/day. Based on this and an understanding of dietary BaP, and considering that BaP is a common contaminant in soil and therefore poses human health risk via soil ingestion, we propose a BaP soil guideline value of 5 ppm (milligrams per kilogram). Mouse tumor data from ingestion of coal tar mixtures containing PAHs and BaP show that lung and not forestomach tumors are most prevalent and that BaP content cannot explain the lung tumors. This calls into question the common use of toxicity equivalence factors based on BaP for assessing risk from complex PAH mixtures. Emerging data point to another PAH compound--H-benzo(c)fluorene--as the possible lung tumorigen.