tbuckley/cabot-search huggingface dataset:
Efficacy and safety of single-dose liposomal amphotericin B for visceral leishmaniasis in a rural public hospital in Bangladesh: a feasibility study
Authors: Dinesh Mondal, Jorge Alvar, Md Golam Hasnain, Md Shakhawat Hossain, Debashis Ghosh, M Mamun Huda, Shah Golam Nabi, Shyam Sundar, Greg Matlashewski, Byron Arana
Journal: The Lancet Global Health (2013)

To rapidly reduce the burden of visceral leishmaniasis for national elimination programmes, an acceptable, safe, and effective treatment is needed that can be delivered at primary health-care centres. We aimed to assess the tolerability, safety, and cure rate of single-dose liposomal amphotericin B (AmBisome, Gilead, USA) for visceral leishmaniasis treatment in such a setting in Bangladesh.We enrolled patients who had been diagnosed with visceral leishmaniasis at Muktagacha upazila (subdistrict) hospital, Bangladesh. Eligible participants were at least 5 years old and had a history of fever for more than 2 weeks, splenomegaly, rK39 rapid test positivity, and haemoglobin concentrations of at least 50 g/L. Participants were provided a one-off intravenous infusion of liposomal amphotericin B (10 mg/kg bodyweight). Clinical assessments were done during treatment, before hospital discharge, and on days 30 and 180 after treatment. Cure was defined as resolution of fever, decrease in spleen size, and an increase in haemoglobin by 10% compared with baseline or to at least 100 g/L. We estimated efficacy in terms of initial cure (at day 30) and final cure (at 6 months), and safety in all patients who were enrolled (intention-to-treat analysis). We also assessed efficacy in all patients who completed treatment and 6 month follow-up after treatment with or without visceral leishmaniasis relapse (per protocol analysis). We assessed acceptability in terms of proportion of patients who consented to treatment. This study was registered with the Australian New Zealand Clinical Trial Registry, number CTRN12612000367842.Between March 5, and Aug 14, 2012, 329 (55%) of 594 cases of suspected visceral leishmaniasis were confirmed. Of these cases, five patients did not consent to treatment and 24 were ineligible for treatment. In the intention-to-treat analysis, 261 (87%) of 300 patients achieved initial cure and 290 (97%) achieved final cure. In the per-protocol analysis, 260 (88%) of 296 patients achieved initial cure and 289 (98%) achieved final cure. One patient did not start treatment owing to an allergic reaction to liposomal amphotericin B. During treatment or within 2 h afterwards, 79 (26%) patients developed fever, 109 (36%) had fever with rigor, and 56 (19%) had hypotension. No patients needed referral to a tertiary hospital for management of adverse events.Treatment of visceral leishmaniasis in a primary health-care facility with single-dose liposomal amphotericin B could safely and effectively be adopted by the national visceral leishmaniasis elimination programme in Bangladesh.Neglected Tropical Diseases (WHO), Agencia Española de Cooperación Internacional.
24 hour and fractionated profiles of adrenocortical activity in asthmatic patients receiving inhaled and intranasal corticosteroids
Authors: A. M Wilson, B. J Lipworth
Journal: Thorax (1999)

The application of methyl jasmonate (MeJA) or ethephon, an ethylene releasing agent, to Thompson Seedless grapes can reduce fruit detachment force (FDF) and promote the development of dry stem scars on berries, possibly improving the quality of machine harvested grapes. However, the amount of MeJA or ethephon needed to stimulate abscission may be prohibitively expensive and result in excessive residues. Thus, experiments were conducted to determine whether MeJA might interact with 1-aminocyclopropane-1-carboxylic acid (ACC), a natural biochemical precursor of ethylene, to promote abscission-related processes, and possibly reduce the amount of MeJA needed. In a preliminary trial, MeJA (672 and 1,344 mg/L) interacted with ACC (500 and 1,000 mg/L) to reduce FDF by 25% to 70% compared with non-treated grapes. However, MeJA and ACC did not interact to affect preharvest fruit drop, though treatment with 672 or 1,344 mg/L MeJA, caused 16% to 23% drop by 3 days after treatment (DAT). In a second trial, grapes treated with MeJA singly, or with ACC, produced ethylene which peaked at 1 DAT, remained elevated at 2 DAT, and declined rapidly thereafter, whereas grapes treated only with ACC maintained moderately elevated ethylene production throughout the 10-day study. Treatment with ACC or MeJA reduced FDF within 1 or 2 DAT, respectively. By 2 DAT, berries began to abscise from MeJA-treated clusters, regardless of whether they were also treated with ACC, but on 3, 4, and 10 DAT, ACC and MeJA interacted to greatly promote preharvest fruit drop. Moreover, the combination of ACC and MeJA also promoted dry stem-scar development. Thus, coapplication of MeJA and ACC is more effective at stimulating grape abscission-related processes than either compound applied singly.
THE GENETICIST'S APPROACH TO COMPLEX DISEASE
Authors: Soumitra Ghosh, M.D., Ph.D, Francis S. Collins, M.D., Ph.D
Journal: Annual Review of Medicine (1996)

▪ Abstract Many studies are in progress worldwide to elucidate the genetics of complex diseases. Nevertheless, few articles are available that provide the scientific rationale and give guidelines for such ambitious endeavours. We describe the methodology and background necessary to study the genetics of complex disease and discuss how to analyze the data. We also provide a table of some ongoing studies. In particular, we wish to emphasize the analysis of intermediate, heritable, quantitative traits as a means of dissecting the genetic basis of a complex trait.
Detection of Chronic Hepatitis C Virus Infection by Four Diagnostic Systems: First–Generation and Second–Generation Enzyme–Linked Immunosorbent Assay, Second–Generation Recombinant Immunoblot Assay and Nested Polymerase Chain Reaction Analysis
Authors: Yoshiyuki Nakatsuji, Akihiro Matsumoto, Eiji Tanaka, Hiroyuki Ogata, Kendo Kiyosawa
Journal: Hepatology (1992)

Serum samples from 100 patients with non-A, non-B hepatitis-related chronic liver disease and 100 patients with hepatitis B-related chronic liver disease were tested by first-generation and second-generation enzyme-linked immunosorbent assays, a second-generation recombinant immunoblot assay and the nested polymerase chain reaction. In non-A, non-B hepatitis-related chronic liver disease, second-generation enzyme-linked immunosorbent assay (anti-c22 and/or c200) and second-generation recombinant immunoblot assay showed 98% positivity, whereas first-generation enzyme-linked immunosorbent assay (anti-c100-3) showed 89% positivity. The two second-generation recombinant immunoblot assay-negative samples were positive by nested polymerase chain reaction, but one second-generation recombinant immunoblot assay-positive sample was polymerase chain reaction negative. However, when this second-generation recombinant immunoblot assay-positive sample was tested by polymerase chain reaction using another set of primers, it was polymerase chain reaction positive. Therefore, 100% of the non-A, non-B hepatitis-related chronic liver disease serum samples were hepatitis C virus RNA positive by polymerase chain reaction. Nine hepatitis B-related chronic liver disease samples were first-generation enzyme-linked immunosorbent assay positive. Of the eight second-generation enzyme-linked immunosorbent assay-positive hepatitis B-related chronic liver disease samples, six were first-generation enzyme-linked immunosorbent assay positive and five were second-generation recombinant immunoblot assay positive and polymerase chain reaction positive. One indeterminate second-generation recombinant immunoblot assay sample was polymerase chain reaction negative. Therefore, second-generation recombinant immunoblot assay appears to be as useful as polymerase chain reaction for detecting a chronic hepatitis C virus infection, although some discrepancies were noted.(ABSTRACT TRUNCATED AT 250 WORDS)
Saturated Fat Intake and Lung Cancer Risk Among Nonsmoking Women in Missouri
Authors: M. C. R. Alavanja, C. C. Brown, C. Swanson, R. C. Brownson
Journal: JNCI Journal of the National Cancer Institute (1993)

Although the vast majority of lung cancer cases in women are caused by smoking, 9%-20% of cases occur in nonsmokers. Previous epidemiologic research on the relationship between lung cancer and diet has shown that fruit and vegetable consumption may confer a protective effect against lung cancer, while a diet rich in cholesterol and fat may increase risk.The purpose of this case-control study was to examine the effects of a broad range of dietary factors on the risk of lung cancer in a population of nonsmoking white women 30-84 years of age.A telephone-administered questionnaire was used to determine and/or verify eligibility with regard to age, gender, race, and smoking status. In a second interview at the participant's home, a widely used food frequency questionnaire was filled out, and logistic regression was subsequently used to analyze the responses. We obtained dietary information on 429 case subjects who had a diagnosis of lung cancer reported to the Missouri Cancer Registry between June 1, 1986, and June 1, 1991, and 1021 control subjects. If a case subject had died or was too ill to be interviewed, next-of-kin familiar with the woman's diet were interviewed instead. Of the 429 women with lung cancer, 211 (49%) had lung adenocarcinoma.A strongly increasing trend in lung cancer risk was observed with increased saturated fat consumption among these non-smoking women; the relative risk was more than sixfold greater for the highest quintile of consumption than for the lowest quintile. The effect of saturated fat was more pronounced for adenocarcinoma than for other cell types. Weekly servings of beans and peas were significantly related to decreased lung cancer risk, while citrus fruit and juice showed a twofold increase in risk; this trend was also significant.By focusing on non-smoking women with lung cancer, including a large number with adenocarcinoma, we observed a clear association with saturated fat consumption that may have been masked in earlier studies of lung cancer involving a high percentage of smokers.
Viral infections and asthma: an inflammatory interface?
Authors: Brian G.G. Oliver, Paul Robinson, Mathew Peters, Judy Black
Journal: European Respiratory Journal (2014)

Asthma is a chronic inflammatory disease of the airways in which the majority of patients respond to treatment with corticosteroids and β 2 -adrenoceptor agonists. Acute exacerbations of asthma substantially contribute to disease morbidity, mortality and healthcare costs, and are not restricted to patients who are not compliant with their treatment regimens. Given that respiratory viral infections are the principal cause of asthma exacerbations, this review article will explore the relationship between viral infections and asthma, and will put forward hypotheses as to why virus-induced exacerbations occur. Potential mechanisms that may explain why current therapeutics do not fully inhibit virus-induced exacerbations, for example, β 2 -adrenergic desensitisation and corticosteroid insensitivity, are explored, as well as which aspects of virus-induced inflammation are likely to be attenuated by current therapy.
Recombinant human granulocyte-macrophage colony-stimulating factor stimulates in vitro mature human neutrophil and eosinophil function, surface receptor expression, and survival.
Authors: A F Lopez, D J Williamson, J R Gamble, C G Begley, J M Harlan, S J Klebanoff, A Waltersdorph, G Wong, S C Clark, M A Vadas
Journal: Journal of Clinical Investigation (1986)

A purified recombinant human granulocyte-macrophage colony stimulating factor (rH GM-CSF) was a powerful stimulator of mature human eosinophils and neutrophils. The purified rH GM-CSF enhanced the cytotoxic activity of neutrophils and eosinophils against antibody-coated targets, stimulated phagocytosis of serum-opsonized yeast by both cell types in a dose-dependent manner, and stimulated neutrophil-mediated iodination in the presence of zymosan. In addition, rH GM-CSF enhanced N-formylmethionylleucylphenylalanine(FMLP)-stimulated degranulation of Cytochalasin B pretreated neutrophils and FMLP-stimulated superoxide production. In contrast, rH GM-CSF did not promote adherence of granulocytes to endothelial cells or plastic surfaces. rH GM-CSF selectively enhanced the surface expression of granulocyte functional antigens 1 and 2, and the Mo1 antigen. rH GM-CSF induced morphological changes and enhanced the survival of both neutrophils and eosinophils by 6 and 9 h, respectively. These experiments show that granulocyte-macrophage colony stimulating factor can selectively stimulate mature granulocyte function.
Suprapontlne Contributions to the Carotld Sinus Reflex in the Cat
Authors: Barbara B. Kent, J. Wanzer Drane, John W. Manning
Journal: Circulation Research (1971)

Carotid sinus reflex response was measured before and after decerebration in 27 cats with and without the vagus nerves intact. Body temperature, central venous pressure, arterial oxygen saturation, P CO 2 and pH were kept within normal limits. The anesthetized animals were uniformiy subjected to a wide range of controlied sirius pressure changes in each condition. A mathematical analog with four parameters was empioyed to relate carotid sinus pressure to systemic arterial pressure. The expression takes the form of a logistic curve, describes the reflex response with an accuracy of 98%, and provides a design in which errors are normally distributed for statistical testing of differences in parameters occurring with experimental intervention. The major effect on the sinus reflex of brainstem transection at the collicular level was a decrease in the effective range over which arterial pressure could be varied by changes in sinus pressure. Although a given change in sinus pressure in the median range of 70 to 100 mm Hg produced a proportional change in arterial pressure, transection markedly decreased reflex responses to lower sinus pressures. It was concluded that a transection at the coflicular level may not significantly change mean systemic pressure, but it does decrease the animal's ability to adjust to variations in arterial pressure. The data lend credence to the hypothesis that supramedullary areas can and do function in directing autonomic activity during the carotid sinus reflex.
Plasma 25-hydroxyvitamin D and colorectal cancer risk according to tumour immunity status
Authors: Mingyang Song, Reiko Nishihara, Molin Wang, Andrew T Chan, Zhi Rong Qian, Kentaro Inamura, Xuehong Zhang, Kimmie Ng, Sun A Kim, Kosuke Mima, Yasutaka Sukawa, Katsuhiko Nosho, Charles S Fuchs, Edward L Giovannucci, Kana Wu, Shuji Ogino
Journal: Gut (2015)

Objective Evidence suggests protective effects of vitamin D and antitumour immunity on colorectal cancer risk. Immune cells in tumour microenvironment can convert 25-hydroxyvitamin D [25(OH)D] to bioactive 1α,25-dihydroxyvitamin D3, which influences neoplastic and immune cells as an autocrine and paracrine factor. Thus, we hypothesised that the inverse association between vitamin D and colorectal cancer risk might be stronger for cancers with high-level immune response than those with low-level immune response. Design We designed a nested case–control study (318 rectal and colon carcinoma cases and 624 matched controls) within the Nurses' Health Study and Health Professionals Follow-up Study using molecular pathological epidemiology database. Multivariable conditional logistic regression was used to assess the association of plasma 25(OH)D with tumour subtypes according to the degree of lymphocytic reaction, tumour-infiltrating T cells (CD3+, CD8+, CD45RO+ (PTPRC) and FOXP3+ cells), microsatellite instability or CpG island methylator phenotype. Results The association of plasma 25(OH)D with colorectal carcinoma differed by the degree of intratumoural periglandular reaction (p for heterogeneity=0.001); high 25(OH)D was associated with lower risk of tumour with high-level reaction (comparing the highest versus lowest tertile: OR 0.10; 95% CI 0.03 to 0.35; p for trend<0.001), but not risk of tumour with lower-level reaction (p for trend>0.50). A statistically non-significant difference was observed for the associations of 25(OH)D with tumour subtypes according to CD3+ T cell density (p for heterogeneity=0.03; adjusted statistical significance level of α=0.006). Conclusions High plasma 25(OH)D level is associated with lower risk of colorectal cancer with intense immune reaction, supporting a role of vitamin D in cancer immunoprevention through tumour–host interaction.
MSEA: detection and quantification of mutation hotspots through mutation set enrichment analysis
Authors: Peilin Jia, Quan Wang, Qingxia Chen, Katherine E Hutchinson, William Pao, Zhongming Zhao
Journal: Genome biology (2014)

Abstract Many cancer genes form mutation hotspots that disrupt their functional domains or active sites, leading to gain- or loss-of-function. We propose a mutation set enrichment analysis (MSEA) implemented by two novel methods, MSEA-clust and MSEA-domain, to predict cancer genes based on mutation hotspot patterns. MSEA methods are evaluated by both simulated and real cancer data. We find approximately 51% of the eligible known cancer genes form detectable mutation hotspots. Application of MSEA in eight cancers reveals a total of 82 genes with mutation hotspots, including well-studied cancer genes, known cancer genes re-found in new cancer types, and novel cancer genes.
Who is prone to high levels of distress after prophylactic mastectomy and/or salpingo-ovariectomy?
Authors: P.J.C. Bresser, A.R. Van Gool, C. Seynaeve, H.J. Duivenvoorden, M.F. Niermeijer, A.N. van Geel, M. Menke, J.G.M. Klijn, A. Tibben
Journal: Annals of Oncology (2007)
Improving the quality of health care: Methods for incorporating patients' views in health care
Authors: M. Wensing
Journal: BMJ (2003)

This is the third of three articles on research into improving the quality of health care 

Efforts to improve health care will be wasted unless they reflect what patients want from the service. But to be sure that surveys of patients' views are valid and have an effect on care, the methods used must be evaluated rigorously 

Society now acknowledges the importance of the views of users in developing services, and the healthcare sector has used a range of methods to identify the views of patients and the public. Examples are questionnaires to assess patients' needs before a consultation with the clinician, shared decision making, focus groups with patients to include their views in clinical guidelines, and surveys among patients to provide feedback to care providers or the public. Such methods need to be examined in terms of validity, effectiveness, and implementation.1 We describe some of the important issues related to measuring patients' views and evaluating their use in improving health care.

#### Summary points

Patients can contribute to debates on health care by giving their preferences for care, evaluations of what occurred, or factual reports of care

Measures of patients' views should be assessed for validity, preferably by rigorous qualitative studies

Methods to include patients' views must be shown to affect the processes and outcomes of health care; possible negative consequences should also be considered

The methods used to determine patients' views can be divided into three types: measures of preferences, evaluations by users, and reports of health care (box). The types of measure used will depend on what aspect of health care is being assessed, but all have limitations.

One problem with assessing preferences is that patients' decisions about what is important in health care often reflect their individual experience rather than a general view. Interaction between patients in focus …
A survey of nocturnal hypoxaemia and health related quality of life in patients with cryptogenic fibrosing alveolitis
Authors: M Clark
Journal: Thorax (2001)

Background-A survey of overnight oximetry was conducted to estimate the prevalence of nocturnal hypoxaemia in patients with cryptogenic fibrosing alveolitis and to establish whether nocturnal hypoxaemia is related to quality of life.Methods-All patients with cryptogenic fibrosing alveolitis attending Nottingham City Hospital were invited to enter the study.Spirometric measurements and capillary blood gas tensions were obtained and overnight oxygen saturation was recorded at home.Quality of life was assessed using the Short Form-36, Chronic Respiratory Questionnaire, Hospital Anxiety Depression Scale, and Epworth Sleepiness Score questionnaires.Results-Sixty seven eligible patients were identified and 50 agreed to enter the study, although two were subsequently excluded because they already used oxygen overnight.In the remaining 48 the mean (SD) overnight oxygen saturation (SaO 2 ) was 92.5 (4.3)% and the median number of dips greater than 4% per hour was 2.3 (interquartile range 1.5-5.3).Daytime oxygen level predicted mean overnight SaO 2 (1.94%/kPa, 95% CI 1.22 to 2.66, p<0.001) but percentage predicted forced vital capacity (FVC) did not (0.018%/% predicted FVC, 95% CI -0.04 to 0.08, p=0.5).Nocturnal hypoxaemia was associated with decreased energy levels and impaired daytime social and physical functioning, and these eVects were independent of FVC.Conclusions-Nocturnal hypoxaemia is common in patients with cryptogenic fibrosing alveolitis and may have an impact on health related quality of life.
Participant Observation and Attempted Mental Health Consultation in a Public Defender Agency
Authors: MARC F. ABRAMSON
Journal: American Journal of Psychiatry (1971)

The author describes some problems of the psychiatrist working in a public defender agency. He deals particularly with plea bargaining; differences between therapeutic and legal approaches to offenders; the various "models" of criminal justice; and the public defender's comfort in his role. The author concludes that the mental health consultant may be more effective working with police, judge, or probation officers than with lawyers.