tbuckley/cabot-search huggingface dataset:
Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines
Authors: Scott M. Grundy, James I. Cleeman, C. Noel Bairey Merz, H. Bryan Brewer, Luther T. Clark, Donald B. Hunninghake, Richard C. Pasternak, Sidney C. Smith, Neil J. Stone
Journal: Circulation (2004)

The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) &lt;100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is &lt;100 mg/dL, but when risk is very high, an LDL-C goal of &lt;70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C &lt;100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is &lt;130 mg/dL, but an LDL-C goal &lt;100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.
IL-32 is a molecular marker of a host defense network in human tuberculosis
Authors: Dennis Montoya, Megan S. Inkeles, Phillip T. Liu, Susan Realegeno, Rosane M. B. Teles, Poorva Vaidya, Marcos A. Munoz, Mirjam Schenk, William R. Swindell, Rene Chun, Kathryn Zavala, Martin Hewison, John S. Adams, Steve Horvath, Matteo Pellegrini, Barry R. Bloom, Robert L. Modlin
Journal: Science Translational Medicine (2014)

IL-32 links the microbicidal peptide pathway with resistance to disease progression in clinical tuberculosis.
Incompletely and completely healed duodenal ulcers' outcome in maintenance treatment: a double blind controlled study.
Authors: P Paoluzi, G Ricotta, F Ripoli, F Proietti, E Zaccardelli, R Carratu, A Torsoli
Journal: Gut (1985)

A six month, double blind, controlled study was performed in 107 asymptomatic duodenal ulcer patients who, after short term cimetidine treatment, showed complete or incomplete endoscopic healing. Patients were stratified according to the type of healing and randomly allocated to cimetidine (200 mg at lunch, 400 mg at bedtime) or placebo. Endoscopic examinations were carried out after six months or when symptoms recurred. Eighty seven patients completed the maintenance trial. Of the 56 patients admitted to the study with complete healing, 30 were placed on cimetidine and 26 on placebo. Of the 31 patients admitted with incomplete healing, 15 were placed on cimetidine, and 16 on placebo. Results showed that, regardless of maintenance treatment, patients with incompletely healed ulcers had a higher ulcer crater recurrence rate, than patients with complete healing (71% vs 34%; p less than 0.005). A significantly higher ulcer crater recurrence was observed in incompletely healed ulcer patients, even when cimetidine or placebo treatment groups were considered separately. Irrespective of the type of healing, ulcer crater recurrence was more frequent in placebo treated patients than in those treated with cimetidine (67% vs 29%; p less than 0.001). We conclude that, in order to prevent a high ulcer recurrence rate, maintenance treatment should start only after the assessment of a complete endoscopic healing of duodenal ulcers.
Temozolomide in the treatment of children with newly diagnosed diffuse intrinsic pontine gliomas: a report from the Children's Oncology Group
Authors: K. J. Cohen, R. L. Heideman, T. Zhou, E. J. Holmes, R. S. Lavey, E. Bouffet, I. F. Pollack
Journal: Neuro-Oncology (2011)

An open-label phase II study (ACNS0126) testing the efficacy of chemoradiotherapy with temozolomide (TMZ) followed by adjuvant TMZ was conducted by the Children's Oncology Group. During the period from July 6, 2004 through September 6, 2005, 63 children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) were enrolled in the study. All patients received TMZ at a dosage of 90 mg/m2/day for 42 days to a dose of 59.4 Gy. Four weeks following irradiation, TMZ was given at a dosage of 200 mg/m2/day for 5 days every 28 days, for a total of 10 cycles. The primary objective of the statistical analysis was to determine whether the current treatment produced a 1-year event-free survival (EFS) rate higher than the historical baseline of 21.9% observed in CCG-9941. The mean 1-year EFS (± standard deviation) was 14% ± 4.5%, compared with 21.9% ± 5% for CCG-9941. The P value of the test of comparison of 1-year EFS, based on a 1-sided, 1-sample test of proportions, was .96. There was no evidence that temozolomide produced a 1-year EFS rate higher than 21.9%. The mean 1-year OS (± standard deviation) was 40% ± 6.5%, compared with 32% ± 6% for CCG-9941. The median time to death was 9.6 months. Chemoradiotherapy with TMZ followed by adjuvant TMZ is not more effective than previously reported regimens for the treatment of children with DIPG.
Prediction of the 10-Year Course of Borderline Personality Disorder
Authors: Mary C. Zanarini, Frances R. Frankenburg, John Hennen, D. Bradford Reich, Kenneth R. Silk
Journal: American Journal of Psychiatry (2006)

The purpose of this study was to determine the most clinically relevant baseline predictors of time to remission for patients with borderline personality disorder.A total of 290 inpatients meeting criteria for both the Revised Diagnostic Interview for Borderlines and DSM-III-R for borderline personality disorder were assessed during their index admission with a series of semistructured interviews and self-report measures. Diagnostic status was reassessed at five contiguous 2-year time periods. Discrete survival analytic methods, which controlled for baseline severity of borderline psychopathology and time, were used to estimate hazard ratios.Eighty-eight percent of the patients with borderline personality disorder studied achieved remission. In terms of time to remission, 39.3% of the 242 patients who experienced a remission of their disorder first remitted by their 2-year follow-up, an additional 22.3% first remitted by their 4-year follow-up, an additional 21.9% by their 6-year follow-up, an additional 12.8% by their 8-year follow-up, and another 3.7% by their 10-year follow-up. Sixteen variables were found to be significant bivariate predictors of earlier time to remission. Seven of these remained significant in multivariate analyses: younger age, absence of childhood sexual abuse, no family history of substance use disorder, good vocational record, absence of an anxious cluster personality disorder, low neuroticism, and high agreeableness.The results of this study suggest that prediction of time to remission from borderline personality disorder is multifactorial in nature, involving factors that are routinely assessed in clinical practice and factors, particularly aspects of temperament, that are not.
α-Lipoic Acid Attenuates Hyperglycemia and Prevents Glomerular Mesangial Matrix Expansion in Diabetes
Authors: Mona F. Melhem, Patricia A. Craven, Julia Liachenko, Frederick R. DeRubertis
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Previous studies demonstrated that 2 mo of dietary supplementation with α-lipoic acid (LA) prevented early glomerular injury in non-insulin-treated streptozotocin diabetic rats (D). The present study examined the effects of chronic LA supplementation (30 mg/kg body wt per d) on nephropathy in D after 7 mo of diabetes. Compared with control rats, D developed increased urinary excretion of albumin and transforming growth factor β, renal insufficiency, glomerular mesangial matrix expansion, and glomerulosclerosis in association with depletion of glutathione and accumulation of malondialdehyde in renal cortex. LA prevented or ameliorated all of these changes in D. Because chronic LA supplementation also attenuated hyperglycemia in D after 3 mo, its effects on renal injury were compared with treatment of rats with sufficient insulin to maintain a level of glycemic control for the entire 7-mo period (D-INS) equivalent to that observed with LA during the final 4 mo. Despite superior longitudinal glycemic control in D-INS, urinary excretion of albumin and transforming growth factor β, glomerular mesangial matrix expansion, the extent of glomerulosclerosis, and renal cortical malondialdehyde content were all significantly greater, whereas cortical glutathione content was lower than corresponding values in D given LA. Thus, the renoprotective effects of LA in D were not attributable to improved glycemic control alone but also likely reflected its antioxidant activity. The combined antioxidant and hypoglycemic actions of LA both may contribute to its utility in preventing renal injury and other complications of diabetes.
Field of Needs
Authors: Eric Boerwinkle, Peter A. Doris, Myriam Fornage
Journal: Circulation (1999)

troke is the single leading cause of severe disability and the third leading cause of death in the United States. 1 A large number of studies have evaluated the prevalence of stroke in various populations, and these studies have identified sex, age, race, uncontrolled hypertension, diabetes, cigarette smoking, and family history as significant risk factors.Of the Ϸ250 000 deaths each year due to the complications of untreated hypertension, one third are due to stroke, and blood pressure control is known to reduce the risk of stroke and stroke mortality. 2However, these risk factors play different roles in the 2 major stroke types, hemorrhagic and infarctive, 3 infarctive being the more common type in the United States.
Accelerated Evolution of the Surface Amino Acids in the WD-Repeat Domain Encoded by the hagoromo Gene in an Explosively Speciated Lineage of East African Cichlid Fishes
Authors: Yohey Terai, Naoko Morikawa, Koichi Kawakami, Norihiro Okada
Journal: Molecular Biology and Evolution (2002)

Lakes Victoria, Malawi, and Tanganyika in the East African Rift Valley harbor approximately 200, 400, and 170 endemic species of cichlid fishes, respectively (Fryer and Iles 1972; Greenwood 1984). These fishes provide a spectacular example of the explosive adaptive radiation of living vertebrates (Fryer and Iles 1972; Greenwood 1984). They exploit almost all resources that are available to freshwater fishes in general (Fryer and Iles 1972; Greenwood 1984) and are extremely diverse, both ecologically and morphologically, despite having evolved during a very short evolutionary period (Meyer et al. 1990; Johnson et al. 1996). In cichlids, species are sexually isolated as a consequence of mate choice (Crapon De Caprona 1996; Seehausen, Van Alphen, and Witte 1997), which is based on coloration. Assortative mating among individuals with various colorations can rapidly lead to sexual isolation of color morphs (Seehausen, Van Alphen, and Witte 1997). Therefore, it is reasonable to postulate that genes that control formation of pigment patterns that are responsible for cichlid speciation must have changed at an accelerated rate in parallel with the diversification of the pigment patterns of species. In an attempt to identify such genes, we have focused our attention on genes responsible for the formation of pigment patterns in cichlids. Mechanisms underlying patterns of pigmentation remain, however, totally unknown. In zebrafish, various mutations affecting pigmentation have been described (Johnson et al. 1995; Haffer et al. 1996), and some relevant genes have been cloned and characterized (e.g., sparse, nacre, and hagoromo [hag]; Lister et al. 1999; Parichy et al. 1999; Kawakami et al. 2000). The genes that have been identified in zebrafish should help us to analyze pigmentation in other species of fishes, including cichlids. As a first step toward an understanding of the molecular basis for the divergence of pigment patterns and speciation in cichlids, we cloned and characterized a cichlid homolog of the zebrafish hag gene. We cloned a partial cDNA of cichlid hag by RTPCR, using degenerate primers hagdF1 (59-AGTGCAGGAGGAGAYGGKAARAT-39) and hagdR1 (59-GTCTCTGGAGCCACTSACDAT-39) and, subsequently, we isolated full-length cDNAs from the RNA of Labidoch-
An eight year prospective study of outcome prediction by antiperinuclear factor and antikeratin antibodies at onset of rheumatoid arthritis
Authors: S Genevay
Journal: Annals of the Rheumatic Diseases (2002)

Antikeratin antibodies (AKA) and antiperinuclear factor (APF) are specific antibodies found very early in rheumatoid arthritis (RA). The objective of this eight year follow up study was to assess the value of early AKA and APF assays in predicting functional disability and cartilage damage.In 2000, 64 patients tested for AKA and APF (antifilaggrin antibodies) between 1990 and 1993 during evaluation of early symmetric oligoarthritis or polyarthritis (suspected RA) were invited to participate in this non-concurrent cohort study. The Health Assessment Questionnaire (HAQ) score, disease activity score (DAS), and Larsen radiographic score were the primary evaluation criteria.Twenty nine patients were re-evaluated. Clinical and laboratory data obtained in 1993 were similar in this group and in the 35 other patients. Twenty five patients had received a diagnosis of RA. Nine (31%) were rheumatoid factor (RF) positive, nine (31%) were AKA positive, and six (21%) were APF positive during the first year of the disease. APF was correlated with the Larsen score (p=0.011) and DAS (p=0.035) evaluated after a mean disease duration of 8.55 years. All APF positive patients had erosive disease. AKA was correlated with the DAS (p=0.035).The presence of AKA or APF early in the course of RA was associated with the DAS or Larsen score eight years later. The number of patients was small, but the findings confirmed those of studies with shorter follow ups. Antifilaggrin antibodies should be included in the initial investigation of patients with RA and, when positive, should alert to a high risk of poor outcomes.
Use of outcomes in monitoring healthcare – how many outcome measures are needed in monitoring diabetes in primary care?
Authors: Javid Suleman, Mohammed Saqib Anwar, Claire Weston, Richard Baker
Journal: Journal of the Royal Society of Medicine (2011)

Objectives To investigate the relationship between patient experience assessed through surveys of random samples of practice populations and intermediate outcome targets in those patients with diabetes, collected in the Quality and Outcomes Framework pay-for-performance scheme. Design Cross-sectional study. Setting The East Midlands region of England. Participants Six hundred and twenty-nine general practices. Main outcome measures Logistic regression models were used to assess whether practice-level reports of patient experience of access and consultations were associated with achievement of treatment targets (HbA1c of 7.5% and 10% or lower, BP 145/85 mmHg or lower, and cholesterol 5 mmol/L or lower) in people with diabetes. Survey respondent characteristics (ethnicity, age, sex) and practice size, deprivation, and prevalence of diabetes and obesity were also assessed within the models. Results Patient experience of practice populations explained little of the variation in diabetes treatment targets. In the practice survey, the proportion of respondents who had seen a nurse in the last 6 months was associated with increased likelihood of achieving HbA1c of 7.5%, and being involved in decision-making or having tests and treatment explained were associated with achievement of HbA1c of 10% or less, cholesterol of 5 mmol/L or less, and BP of 145/85 or less. Conclusions Although patient experience at practice level should be included in monitoring outcomes, it should not replace monitoring clinical outcomes in diabetes. A mix of clinical and patient experience measures will have to be used to monitor outcomes in general practice.
Paradoxical effects of pyrazinoate and nicotinate on urate transport in dog renal microvillus membranes.
Authors: S E Guggino, P S Aronson
Journal: Journal of Clinical Investigation (1985)

The effects of pyrazinoate and nicotinate on urate transport in microvillus membrane vesicles isolated from canine renal cortex were evaluated. An outwardly directed gradient of pyrazinoate stimulated uphill urate accumulation, suggesting urate-pyrazinoate exchange. An inside-alkaline pH gradient stimulated uphill pyrazinoate accumulation, which suggested pyrazinoate-OH- exchange. Pyrazinoate-OH- exchange and urate-OH- exchange were similarly sensitive to inhibitors, implying that both processes occur via the same transport system. In addition, an inward Na+ gradient stimulated uphill pyrazinoate accumulation, suggesting Na+-pyrazinoate cotransport. Inhibitor studies demonstrated that Na+-pyrazinoate cotransport takes place via the same pathway that mediates Na+-lactate cotransport in these membrane vesicles. Previously we found that urate does not share this Na+-dependent cotransport pathway. Nicotinate inhibited transport of pyrazinoate by the anion exchange pathway and the Na+ cotransport pathway, suggesting that it is a substrate for both transport systems. Finally, in the presence of an inward Na+ gradient, low doses of pyrazinoate or nicotinate stimulated urate uptake, and higher doses of pyrazinoate or nicotinate inhibited urate accumulation, thereby mimicking in vitro the paradoxical effects of drugs on renal urate excretion that have been observed in vivo. These findings indicate that the paradoxical effect of uricosuric drugs at low doses to cause urate retention may result at least in part from stimulation of urate reabsorption across the luminal membrane of the proximal tubular cell.
Effect of age and occupational exposure to airway irritants on lung function in non-smoking individuals with alpha 1-antitrypsin deficiency (PiZZ)
Authors: E. Piitulainen, G. Tornling, S. Eriksson
Journal: Thorax (1997)

Severe alpha 1-antitrypsin (AAT) deficiency (PiZZ) is associated with an increased risk of lung emphysema, especially in smokers. The aim of this study was to identify risk factors other than smoking for declining lung function.Lung function was studied in 225 self-reported never-smoking PiZZ individuals included in the Swedish AAT deficiency register.Lung function was poorer in men than in women (mean (SD) forced expiratory volume in one second (FEV1) 80 (30) versus 88 (17)% predicted) despite the fact that the men were younger (mean (SD) age 45 (18) versus 51 (17) years), and poorer in those aged 50 or older than in those aged under 50 (mean (SD) FEV1 70 (30) versus 98 (16)% predicted). Self-reported occupational exposure to gas, fumes, or dust occurred more frequently in men than in women. In those aged 50 or older lung function was lower in individuals exposed to airway irritants than those who were not exposed (mean (SD) FEV1 63 (29) versus 76 (31)% predicted). Male sex, increasing age, and previous symptoms of wheezing were independent risk factors for lung function impairment, and male sex, wheeziness, and occupational exposure to airway irritants were independent risk factors in the subjects aged 50 years or more.In non-smoking PiZZ individuals lung function declines with increasing age, especially after 50. Men are at greater risk of lung function deterioration than women. Asthmatic symptoms and occupational exposure to airway irritants appear to constitute additional risk factors.
HLA-B27 and ankylosing spondylitis geographic distribution versus malaria endemic: casual or causal liaison?
Authors: A Mathieu, A Cauli, M T Fiorillo, R Sorrentino
Journal: Annals of the Rheumatic Diseases (2007)

The distinctive feature of the strikingly non-homogeneous geographical distribution of HLA-B271 (fig 1A) is that its frequency is lowest (0%) in the equatorial region and highest (40%) in the arctic and furthest north populations.2 This is compatible with the hypothesis that HLA alleles in general, and –B27 in particular, have been selected by environmental factors.3 Accordingly, it has been shown that HLA-B27 is associated with protection from several viral diseases (AIDS, hepatitis C, and influenza). Although a high frequency of HLA-B27 in some areas may be explained by a founder effect, there are features to suggest that negative selection by …
Injuries in female football players in top-level international tournaments
Authors: Astrid Junge, Jiri Dvorak
Journal: British Journal of Sports Medicine (2007)

Despite the growing popularity of women's football and the increasing number of female players, there has been little research on injuries sustained by female football players.Analysis of the incidence, characteristics and circumstances of injury in elite female football players in top-level international tournaments.Prospective survey.Injuries incurred in seven international football tournaments were analysed using an established injury report system. Doctors of all participating teams reported all injuries after each match on a standardised injury reporting form. The mean response rate was 95%.387 injuries were reported from 174 matches, equivalent to an incidence of 67.4 injuries/1000 player hours (95% CI 60.7 to 74.1) or 2.2 injuries/match (95% CI 2.0 to 2.4). Most injuries (84%; 317/378) were caused by contact with another player. The injuries most commonly involved the lower extremity (n = 248; 65%), followed by injuries of the head and neck (n = 67, 18%), trunk (n = 33, 9%) and upper extremity (n = 32, 8%). Contusions (n = 166; 45%) were the most frequent type of injury, followed by sprains or ligament rupture (n = 96; 26%) and strains or muscle fibre ruptures (n = 31; 8%). The most common diagnosis was an ankle sprain. There were 7 ligament ruptures and 15 sprains of the knee. On average 1 injury/match (95% CI 0.8 to 1.2) was expected to result in absence from a match or training.The injury rate in women's top-level tournaments was within the range reported previously for match injuries in elite male and female players. However, the diagnoses and mechanisms of injury among the female players differed substantially from those previously reported in male football players.