tbuckley/cabot-search huggingface dataset:
The effect of high dose inhaled corticosteroids on wheeze in infants after respiratory syncytial virus infection: randomised double blind placebo controlled trial
Authors: M. J J Ermers, M. M Rovers, J. B van Woensel, J. L L Kimpen, L. J Bont
Journal: BMJ (2009)

<b>Objective</b> To determine whether early initiated anti-inflammatory therapy with prolonged high dose inhaled glucocorticoids influences the occurrence and severity of recurrent wheeze after respiratory syncytial virus related lower respiratory tract infections. <b>Design</b> Randomised double blind placebo controlled trial. <b>Setting</b> Paediatric departments of 19 Dutch clinical centres. <b>Participants</b> 243 previously healthy infants (126 boys, 117 girls) aged less than 13 months and admitted to hospital with respiratory syncytial virus infection. <b>Interventions</b> 200 μg extra fine hydrofluoroalkane (HFA) beclometasone dipropionate twice daily or matched placebo administered by a pressurised metered dose inhaler and a spacer during the first three months after hospital admission. <b>Main outcome measure</b> The primary outcome was the number of days with wheeze in the year after the three month intervention period. <b>Results</b> Of the 243 eligible infants, 119 were randomised to receive beclometasone and 124 to receive placebo. No significant difference was found in the number of days with wheeze between the two groups (total days, 1761/33 568 in the beclometasone group <i>v</i> 2301/36 556 in the placebo group, P=0.31) and the proportion of infants with wheeze did not differ between the groups (61% in the beclometasone group <i>v</i> 62% in the placebo group, P=0.90). In the predefined subgroup of infants who did not need mechanical ventilation (n=221), beclometasone reduced the number of days with wheeze by 32% (relative reduction in total days, 1315/30 405 in the beclometasone group <i>v</i> 2120/33 149 in the placebo group, P=0.046). This reduction was most pronounced during the first six months of the follow-up year after intervention. The proportion of infants with wheeze did not differ between the groups (59% in the beclometasone group <i>v</i> 60% in the placebo group, P=0.89). <b>Conclusions</b> Early initiated high dose extra fine HFA beclometasone to infants during the first three months after hospital admission for respiratory syncytial virus infection has no major effect on recurrent wheeze. The general use of such treatment during lower respiratory tract infection with respiratory syncytial virus should not be advocated. <b>Trial registration</b> Current Controlled Trials ISRCTN12352714.
Operative Treatment in Idiopathic Hypertrophic Subaortic Stenosis
Authors: ANDREW G. MORROW, THOMAS J. FOGARTY, HAMNER HANNAH, EUGENE BRAUNWALD
Journal: Circulation (1968)

Operations designed to relieve obstruction to left ventricular outflow were carried out in 25 patients with idiopathic hypertrophic subaortic stenosis (IHSS). All of the patients were symptomatic and 23 were in functional classes III or IV. Preoperatively, a systolic pressure gradient within the left ventricle was demonstrated in every patient (average, 102 mm Hg), and the average left ventricular end-diastolic pressure was 19 mm Hg. Six patients had pulmonary hypertension. During cardiopulmonary bypass, the outflow tract of the left ventricle was exposed through an aortotomy. In five early patients only ventriculomyotomy was carried out, but in all subsequent operations myotomy was combined with a limited resection of the hypertrophied muscular tissue. One patient died, apparently of arrhythmia, on the eighth postoperative day, and another 8 months after operation following cerebral thrombosis. In two other patients complete heart block was produced, and they have implanted pacemakers. Twenty-one of the 23 surviving patients have been followed for periods of 1 to 8 years; 15 are asymptomatic (class I). Six patients have mild residual limitation of activity (class II), but none has had congestive heart failure or syncope postoperatively, and only one experiences significant angina. Left heart catheterization has been performed on one or more occasions after operation in all 21 patients. In 19, no systolic pressure gradient was evident within the left ventricle under resting conditions, and in the other two patients, gradients of 11 and 8 mm Hg were recorded. The left ventricular end-diastolic pressure was lower in 16 of the 17 patients in whom it was abnormally elevated preoperatively, and in nine of them it was normal. The pulmonary arterial pressure was normal postoperatively in all patients who had severe pulmonary hypertension.
Steroid profiles of professional soccer players: an international comparative study
Authors: E Strahm, P-E Sottas, C Schweizer, M Saugy, J Dvorak, C Saudan
Journal: British Journal of Sports Medicine (2009)

Urinary steroid profiling is used in doping controls to detect testosterone abuse. A testosterone over epitestosterone (T/E) ratio exceeding 4.0 is considered as suspicious of testosterone administration, irrespectively of individual heterogeneous factors such as the athlete's ethnicity. A deletion polymorphism in the UGT2B17 gene was demonstrated to account for a significant part of the interindividual variability in the T/E between Caucasians and Asians. Here, the variability of urinary steroid profiles was examined in a widely heterogeneous cohort of professional soccer players.The steroid profile of 57 Africans, 32 Asians, 50 Caucasians and 32 Hispanics was determined by gas chromatography-mass spectrometry.Significant differences have been observed between all ethnic groups. After estimation of the prevalence of the UGT2B17 deletion/deletion genotype (African: 22%; Asian: 81%; Caucasian: 10%; Hispanic: 7%), ethnic-specific thresholds were developed for a specificity of 99% for the T/E (African: 5.6; Asian: 3.8; Caucasian: 5.7; Hispanic: 5.8). Finally, another polymorphism could be hypothesised in Asians based on specific concentration ratio of 5alpha-/5beta-androstane-3alpha,17beta-diol in urine.These results demonstrate that a unique and non-specific threshold to evidence testosterone misuse is not fit for purpose. An athlete's endocrinological passport consisting of a longitudinal follow-up together with the ethnicity and/or the genotype would strongly enhance the detection of testosterone abuse. Finally, additional genotyping studies should be undertaken to determine whether the remaining unexplained disparities have an environmental or a genetic origin.
Extensive intestinal ischaemic necrosis in Wegener's granulomatosis
Authors: F M Shaikh
Journal: Gut (2006)

and control subjects (x 2 = 8.12, p = 0.017).Positivity for the 2110G allele was significantly decreased in autoimmune pancreatitis patients (p = 0.012, odds ratio 0.13; table 1), indicating a significant association of the 2110A/A genotype with autoimmune pancreatitis.The frequency of 2110A/A alleles was significantly increased in patients with autoimmune pancreatitis compared with controls (p = 0.012, odds ratio = 7.45; table 1).There are two possible explanations for these findings: FCRL32110 may be functionally linked with susceptibility to autoimmune pancreatitis, or this allele may be a linkage marker for a neighbouring unidentified susceptibility gene on chromosome 1q 21.No other alleles were found to be significantly associated with autoimmune pancreatitis.Mean (SEM) serum IgG4 concentrations in patients with FCRL32110A/A, 2110A/G, and 2110G/G were 1279.4 (404.8)mg/dl, 794.8 (149.4)mg/dl, and 669.2 (78.5) mg/dl, respectively.Serum IgG4 concentrations in patients with autoimmune pancreatitis were found to be significantly positively correlated with the number of susceptible alleles (r 2 = 0.094, p = 0.014).However, no association between the HLA DRB1*0405-DQB1*0401 haplotype and FCRL32110 alleles was found in this study (data not shown).These results suggest that both the HLA DRB1*0405-DQB1*0401 haplotype and FCRL32110 alleles are related to susceptibility for autoimmune pancreatitis but play different roles in the mechanisms inducing autoimmune pancreatitis.
Anti-Müllerian hormone: ovarian reserve testing and its potential clinical implications
Authors: Simone L. Broer, Frank J.M. Broekmans, Joop S.E. Laven, Bart C.J.M. Fauser
Journal: Human Reproduction Update (2014)

In women, anti-Müllerian hormone (AMH) is exclusively produced by granulosa cells of ovarian follicles during the early stages of follicle development. After an initial increase until early adulthood, AMH concentrations slowly decrease with increasing age until becoming undetectable ∼5 years before menopause when the stock of primordial follicles is exhausted. However, major individual variability exists in the pace of follicle pool depletion and the initial size of the follicle pool, reflected by a wide range of age at menopause. Individual AMH serum concentration does accurately reflect the size of the pool of antral follicles, representing the quantity of the remaining primordial follicles. Accordingly, AMH levels may vary significantly in women of the same chronological age, allowing AMH to predict the remaining length of a woman's reproductive lifespan. Following 10 years of intense clinical research in this area (with over 300 papers published in core clinical journals every year), the level of evidence justifying use of AMH in ovarian reserve testing is rapidly increasing. We have conducted a summarizing review regarding all evidence published. Many studies have convincingly demonstrated that AMH is the best currently available measure of ovarian reserve under a variety of clinical situations, such as infertility treatment (especially IVF), the forecasting of reproductive lifespan, ovarian dysfunction (especially polycystic ovary syndrome) and gonadotoxic cancer treatment or ovarian surgery. Moreover, AMH may help to individualize dosing for ovarian stimulation thereby improving the efficiency and safety of IVF. However, there are concerns about the performance of the AMH assay under different conditions regarding storage of samples and handling techniques. Therefore an international guideline for laboratories and a reference preparation are needed to make test results between laboratories truly comparable. AMH is the best current available measure of ovarian reserve for different clinical conditions. However, prospective well powered studies comparing different infertility treatment strategies based on initial AMH levels using appropriate end-points, such as live birth and cost-effectiveness, are urgently awaited. Such studies could represent a true step forward in rendering counseling and infertility care more patient tailored.
Causal Relationship between Obesity and Vitamin D Status: Bi-Directional Mendelian Randomization Analysis of Multiple Cohorts
Authors: Karani S. Vimaleswaran, Diane J. Berry, Chen Lu, Emmi Tikkanen, Stefan Pilz, Linda T. Hiraki, Jason D. Cooper, Zari Dastani, Rui Li, Denise K. Houston, Andrew R. Wood, Karl Michaëlsson, Liesbeth Vandenput, Lina Zgaga, Laura M. Yerges-Armstrong, Mark I. McCarthy, Josée Dupuis, Marika Kaakinen, Marcus E. Kleber, Karen Jameson, Nigel Arden, Olli Raitakari, Jorma Viikari, Kurt K. Lohman, Luigi Ferrucci, Håkan Melhus, Erik Ingelsson, Liisa Byberg, Lars Lind, Mattias Lorentzon, Veikko Salomaa, Harry Campbell, Malcolm Dunlop, Braxton D. Mitchell, Karl-Heinz Herzig, Anneli Pouta, Anna-Liisa Hartikainen, Elizabeth A. Streeten, Evropi Theodoratou, Antti Jula, Nicholas J. Wareham, Claes Ohlsson, Timothy M. Frayling, Stephen B. Kritchevsky, Timothy D. Spector, J. Brent Richards, Terho Lehtimäki, Willem H. Ouwehand, Peter Kraft, Cyrus Cooper, Winfried März, Chris Power, Ruth J. F. Loos, Thomas J. Wang, Marjo-Riitta Järvelin, John C. Whittaker, Aroon D. Hingorani, Elina Hyppönen
Journal: PLoS Medicine (2013)

A mendelian randomization study based on data from multiple cohorts conducted by Karani Santhanakrishnan Vimaleswaran and colleagues re-examines the causal nature of the relationship between vitamin D levels and obesity.
Impaired V(D)J Recombination and Lymphocyte Development in Core RAG1-expressing Mice
Authors: Darryll D. Dudley, JoAnn Sekiguchi, Chengming Zhu, Moshe J. Sadofsky, Scott Whitlow, Jeffrey DeVido, Robert J. Monroe, Craig H. Bassing, Frederick W. Alt
Journal: The Journal of Experimental Medicine (2003)

RAG1 and RAG2 are the lymphocyte-specific components of the V(D)J recombinase. In vitro analyses of RAG function have relied on soluble, highly truncated “core” RAG proteins. To identify potential functions for noncore regions and assess functionality of core RAG1 in vivo, we generated core RAG1 knockin (RAG1c/c) mice. Significant B and T cell numbers are generated in RAG1c/c mice, showing that core RAG1, despite missing ∼40% of the RAG1 sequence, retains significant in vivo function. However, lymphocyte development and the overall level of V(D)J recombination are impaired at the progenitor stage in RAG1c/c mice. Correspondingly, there are reduced numbers of peripheral RAG1c/c B and T lymphocytes. Whereas normal B lymphocytes undergo rearrangement of both JH loci, substantial levels of germline JH loci persist in mature B cells of RAG1c/c mice, demonstrating that DJH rearrangement on both IgH alleles is not required for developmental progression to the stage of VH to DJH recombination. Whereas VH to DJH rearrangements occur, albeit at reduced levels, on the nonselected alleles of RAG1c/c B cells that have undergone D to JH rearrangements, we do not detect VH to DH rearrangements in RAG1c/c B cells that retain germline JH alleles. We discuss the potential implications of these findings for noncore RAG1 functions and for the ordered assembly of VH, DH, and JH segments.
Biosynthesis of bile acids in cerebrotendinous xanthomatosis. Relationship of bile acid pool sizes and synthesis rates to hydroxylations at C-12, C-25, and C-26.
Authors: G Salen, S Shefer, G S Tint, G Nicolau, B Dayal, A K Batta
Journal: Journal of Clinical Investigation (1985)

To examine the defect in side-chain oxidation during the formation of bile acids in cerebrotendinous xanthomatosis, we measured in vitro hepatic microsomal hydroxylations at C-12 and C-25 and mitochondrial hydroxylation at C-26 and related them to the pool size and synthesis rates of cholic acid and chenodeoxycholic acid as determined by the isotope dilution technique. Hepatic microsomes and mitochondria were prepared from seven subjects with cerebrotendinous xanthomatosis and five controls. Primary bile acid synthesis was markedly reduced in cerebrotendinous xanthomatosis as follows: cholic acid, 133 +/- 30 vs. 260 +/- 60 mg/d in controls; and chenodeoxycholic acid, 22 +/- 10 vs. 150 +/- 30 mg/d in controls. As postulated for chenodeoxycholic acid synthesis, mitochondrial 26-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha-diol was present in all specimens and was 30-fold more active than the corresponding microsomal 25-hydroxylation. However, mean mitochondrial 26-hydroxylation of 5 beta-cholestane-3 alpha,7 alpha-diol was less active in cerebrotendinous xanthomatosis than in controls: 59 +/- 17 compared with 126 +/- 21 pmol/mg protein per min. As for cholic acid synthesis, microsomal 25-hydroxylation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol was substantially higher in cerebrotendinous xanthomatosis and control preparations (620 +/- 103 and 515 +/- 64 pmol/mg protein per min, respectively) than the corresponding control mitochondrial 26-hydroxylation of the same substrate (165 +/- 25 pmol/mg protein per min). Moreover in cerebrotendinous xanthomatosis, mitochondrial 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol-26-hydroxylase activity was one-seventh as great as in controls. Hepatic microsomal 12 alpha-hydroxylation, which may be rate-controlling for the cholic acid pathway, was three times more active in cerebrotendinous xanthomatosis than in controls: 1,600 vs. 500 pmol/mg protein per min. These results demonstrate severely depressed primary bile acid synthesis in cerebrotendinous xanthomatosis with a reduction in chenodeoxycholic acid formation and pool size disproportionately greater than that for cholic acid. The deficiency of chenodeoxycholic acid can be accounted for by hyperactive microsomal 12 alpha-hydroxylation that diverts precursors into the cholic acid pathway combined with decreased side-chain oxidation (mitochondrial 26-hydroxylation). However, side-chain oxidation in cholic acid biosynthesis may be initiated via microsomal 25-hydroxylation of 5beta-cholestane-3alpha,7alpha,12alpha-triol was substantially lower in control and cerebrotendinous xanthomatosis liver. Thus, separate mechanisms may exist for the cleavage of the cholesterol side chain in cholic acid and chenodeoxycholic acid biosynthesis.
Health Insurance for Drug Addiction: A Survey
Authors: CHARLOTTE MULLER
Journal: American Journal of Psychiatry (1972)

Coverage for drug addiction is fairly common in both commercial and other health insurance policies, but benefits are often limited. Restrictions pertaining to treatment in specialized facilities or after incarceration, and to care by less traditional types of health personnel, are often found. Improved coverage will require ambulatory benefits and other adaptations of present insurance practices to newer settings and modalities of care.
Pemetrexed Plus Bevacizumab for Second-Line Therapy of Non–Small-Cell Lung Cancer: The Importance of Patient Selection
Authors: Antonio M. Araujo
Journal: Journal of Clinical Oncology (2010)

Pemetrexed is an antifolate drug that inhibits multiple enzymes involved in purine and pyrimidine synthesis, but thymidylate syntase is its primary target.Dihydrofolate reductase and glycinamide ribonucleotide formyl transferase are its secondary targets.The differential expression of thymidylate syntase between adenocarcinoma and squamous cell carcinoma could explain the differential efficacy according to histology in non-small-cell lung cancer (NSCLC). 1 The results of two published phase III trials with pemetrexed versus docetaxel 2 and cisplatin plus pemetrexed versus cisplatin plus gemcitabine 3 were consistent with those of the phase III study comparing pemetrexed with placebo. 4evacizumab is a humanized monoclonal antivascular endothelial growth factor antibody with demonstrated significant clinical benefit in first-line treatment of nonsquamous NSCLC.] On the basis of these studies, tumor histology should be carefully assessed when selecting treatment options for patients with advanced NSCLC.Both pemetrexed and bevacizumab have demonstrated significant clinical activity for nonsquamous NSCLC.In the recent published North Central Cancer Treatment Group and Southwest Oncology Group study N0426, Adjei et al 7 evaluated the combination of pemetrexed and bevacizumab as second-line therapy for NSCLC.Then they evaluated the impact of three single nucleotide polymorphisms (SNPs) in genes that code proteins linked to pemetrexed activity: SLC19A1 codes a protein responsible for the transport, FPGS codes a protein linked to activation, and GGH codes a protein important for inactivation.The authors reported a promising progression-free survival of 4 months but no correlation of these polymorphisms with efficacy and toxicity.They concluded that the small sample size and the bevacizumab were confounding variables.The article was unclear about the histologic types of the patients' samples, and this is a main issue when evaluating the clinical importance of any treatment combination in NSCLC.We should evaluate this combination for second-line treatment of nonsquamous NSCLC in a phase III trial versus the standard arm of pemetrexed alone and probably analyze the importance of these SNPs for this specific population.
Role of RANKL and RANK in bone loss and arthritis
Authors: D H. Jones, Y-Y Kong, J M Penninger
Journal: Annals of the Rheumatic Diseases (2002)

The tumour necrosis factor family molecule RANKL (RANKL, TRANCE, ODF) and its receptor RANK are key regulators of bone remodelling and regulate T cell/dendritic cell communications, and lymph node formation. Moreover, RANKL and RANK are expressed in mammary gland epithelial cells and control the development of a lactating mammary gland during pregnancy and the propagation of mammalian species. Importantly, RANKL and RANK are essential for the development and activation of osteoclasts and bone loss in response to virtually all triggers tested. Therapeutically, inhibition of RANKL function via the decoy receptor osteoprotegerin completely prevents bone loss at inflammed joints and has partially beneficial effects on cartilage destruction in all arthritis models studied. Modulation of these systems provides a unique opportunity to design novel treatments to inhibit bone loss and crippling in arthritis.
Psychological Responses to Continuous Terror: A Study of Two Communities in Israel
Authors: Arieh Shalev
Journal: American Journal of Psychiatry (2006)

Objective: The authors evaluated psychological responses to continuous terror. Method: Data were collected after 10 months of escalating hostilities against civilians in Israel. The study's participants were randomly selected adults living in two suburbs of Jerusalem, one frequently and directly exposed to acts of terrorism (N=167) and the other indirectly exposed (N=89). Participants provided information about exposure to terror-related incidents, disruption of daily living, symptoms of posttraumatic stress disorder (PTSD), and general distress (assessed with the Brief Symptom Inventory). Results: Residents of the directly exposed community reported more frequent exposure to terror and deeper disruption of daily living. Notwithstanding, the directly and indirectly exposed groups reported comparable rates of PTSD and similar levels of symptoms: 26.95% of the directly exposed group and 21.35% of the indirectly exposed group met DSM-IV PTSD symptom criteria (criteria B through D), and about one-third of those with PTSD symptoms (35.7% in the directly exposed group and 31.5% in the indirectly exposed group) reported significant distress and dysfunction. Subjects who did not meet PTSD symptom criteria had very low levels of PTSD symptoms, and their Brief Symptom Inventory scores were within population norms. Exposure and disruption of daily living contributed to PTSD symptoms in the directly exposed group. Disruption of daily routines contributed to Brief Symptom Inventory scores in both groups. Conclusions: Continuous terror created similar distress in proximal and remote communities. Exposure to discrete events was not a necessary mediator of terror threat. A subgroup of those exposed developed serious symptoms, whereas others were surprisingly resilient. Disruption of daily routines was a major secondary stressor.