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1.
Lincomycin, a chemically new antibiotic effective against Gram-positive organisms, was evaluated in vitro and tested clinically. In vitro testing indicated that lincomycin is especially effective against Staphylococcus aureus. Clinical testing showed that lincomycin was free of toxicity in a series of 18 cases of staphylococcal infection. Of particular interest was its pronounced effectiveness in nine cases of chronic osteomyelitis, one of which was of 15 years'' duration and unresponsive to all other forms of antibiotic and surgical treatment. The only side effect noted was loose stools in the occasional patient. 相似文献
2.
We studied the response of 31 migraine sufferers (20 women, 11 men) to intravenous tyramine (the tyraminedose)pressor response test). Patients were treated either with pacebo tablets or indoramin, and alpha-adrenergic blocking agent, in a double-blind crrossover trial. We found that patients with migraine required significantly less tyramine to increase their cystolic blod pressure by 30 mm Hg when compared with matched controls. Indoramin significantly increased the amount of tyramine needed to raise the systolic blood pressure among migraine suffers and reduced the incidence of posttyramine migraine for m 46% while patients were on placebo tablets to 8% when they were receiveing indoramin. There was no association between tyramine sensitivity and a history of premenstrual or dietary migraine, nor was there a significant difference in the indierenence in the incidence of post-tyramine migrain between men women. We conclude that the intravenous tyramine test may be valuable in assessing migraine suffers who will respond to an alpha-advenergic blocking agent such as indoramin. 相似文献
3.
Self-care interventions are promoted as effective strategies for improving the quality of life and health outcomes for individuals with long-term health conditions. Outcome measures used in evaluations using Randomised Controlled Trials (RCTs) are not designed to consider patients' prior management strategies and experience of illness. Yet the experience of illness literature suggests that adjusting to living with chronic illness, together with broader contextual influences, are likely to be relevant to understanding responses to self-management initiatives. Using group and individual interview data we attempt to illuminate the transposition of IBS from a condition unsatisfactorily managed by medicine to one successfully managed within the life worlds of individuals. If routine embedding of complex interventions depends on the accomplishment of integration and workability in patients' everyday lives then the design and evaluation of such interventions should view participation as part of a process of continuity as well as change. Responses to formal self-management can be extended beyond psychological and other quantitatively measured outcomes. A useful addendum to trial outcomes for self-management education is an understanding of change as being inextricably linked to people's previous attempts to, and experience of, managing long-term conditions. We suggest that the benefits of understanding the prior experience of managing illness and contact with health services include the acceptability and workability of complex interventions in patients' everyday lives. 相似文献
4.
Background
Adequate sedation is crucial to the management of children requiring assisted ventilation on Paediatric Intensive Care Units (PICU). The evidence-base of randomised controlled trials (RCTs) in this area is small and a trial was planned to compare midazolam and clonidine, two sedatives widely used within PICUs neither of which being licensed for that use. The application to obtain a Clinical Trials Authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) required a dossier summarising the safety profiles of each drug and the pharmacovigilance plan for the trial needed to be determined by this information. A systematic review was undertaken to identify reports relating to the safety of each drug.Methodology/Principal Findings
The Summary of Product Characteristics (SmPC) were obtained for each sedative. The MHRA were requested to provide reports relating to the use of each drug as a sedative in children under the age of 16. Medline was searched to identify RCTs, controlled clinical trials, observational studies, case reports and series. 288 abstracts were identified for midazolam and 16 for clonidine with full texts obtained for 80 and 6 articles respectively. Thirty-three studies provided data for midazolam and two for clonidine. The majority of data has come from observational studies and case reports. The MHRA provided details of 10 and 3 reports of suspected adverse drug reactions.Conclusions/Significance
No adverse reactions were identified in addition to those specified within the SmPC for the licensed use of the drugs. Based on this information and the wide spread use of both sedatives in routine practice the pharmacovigilance plan was restricted to adverse reactions. The Clinical Trials Authorisation was granted based on the data presented in the SmPC and the pharmacovigilance plan within the clinical trial protocol restricting collection and reporting to adverse reactions. 相似文献5.
We construct Bayesian methods for semiparametric modeling of a monotonic regression function when the predictors are measured with classical error. Berkson error, or a mixture of the two. Such methods require a distribution for the unobserved (latent) predictor, a distribution we also model semiparametrically. Such combinations of semiparametric methods for the dose response as well as the latent variable distribution have not been considered in the measurement error literature for any form of measurement error. In addition, our methods represent a new approach to those problems where the measurement error combines Berkson and classical components. While the methods are general, we develop them around a specific application, namely, the study of thyroid disease in relation to radiation fallout from the Nevada test site. We use this data to illustrate our methods, which suggest a point estimate (posterior mean) of relative risk at high doses nearly double that of previous analyses but that also suggest much greater uncertainty in the relative risk. 相似文献
6.
Stable telocentrics are present in a number of plant species but rarely form a major part of a complement and almost never constitute its whole. T. micrantha (2n=24) is an exceptional, possibly unique, plant in which all the chromosomes are of this type. They fall into three size categories (L, M, and S) each forming quadrivalents with frequencies positively correlated with chromosome length: it is concluded that the species is autotetraploid. Pairing and segregational errors result in high frequencies of gametic aneuploidy — a fact which is taken to reflect the vegetative vigour of the species and a low level of selection for sexual fertility. The cytological features determined in this study provide a basis for discussing the significance and mode of evolution of the complement. 相似文献
7.
Kavita Venkataraman Luor Shyuan Maudrene Tan Dianne Carrol Tan Bautista Konstadina Griva Yasmin Laura Marie Zuniga Mohamed Amir Yung Seng Lee Jeannette Lee E. Shyong Tai Eric Yin Hao Khoo Hwee Lin Wee 《PloS one》2015,10(9)
Background
Emotional distress is an important dimension in diabetes, and several instruments have been developed to measure this aspect. The Problem Areas in Diabetes (PAID) scale is one such instrument which has demonstrated validity and reliability in Western populations, but its psychometric properties in Asian populations have not been examined.Methods
This was a secondary analysis of data from patients with Type 2 diabetes mellitus recruited through convenience sampling from a diabetes specialist outpatient clinic in Singapore. The following psychometric properties were assessed: Construct validity through confirmatory factor analysis (CFA) and Rasch analysis, concurrent validity through correlation with related scales (Kessler Psychological Distress Scale, Diabetes Health Profile—psychological distress, Audit of Diabetes Dependent Quality of Life), reliability through assessment of internal consistency and floor and ceiling effects, and sensitivity by estimating effect sizes for known clinical and social functioning groups.Results
203 patients with mean age of 45±12 years were analysed. None of the previously published model structures achieved a good fit on CFA. On Rasch analysis, four items showed poor fit and were removed. The abridged 16-item PAID mapped to a single latent trait, with a high degree of internal consistency (Cronbach ɑ 0.95), but significant floor effect (24.6% scoring at floor). Both 20-item and 16-item PAID scores were moderately correlated with scores of related scales, and sensitive to differences in clinical and social functioning groups, with large effect sizes for glycemic control and diabetes related complications, nephropathy and neuropathy.Conclusion
The abridged 16-item PAID measures a single latent trait of emotional distress due to diabetes whereas the 20-item PAID appears to measures more than one latent trait. However, both the 16-item and 20-item PAID versions are valid, reliable and sensitive for use among Singaporean patients with diabetes. 相似文献8.
Ting Hway Wong Hai V. Nguyen Ming Terk Chiu Khuan Yew Chow Marcus Eng Hock Ong Gek Hsiang Lim Nivedita Vikas Nadkarni Dianne Carrol Tan Bautista Jolene Yu Xuan Cheng Lynette Mee Ann Loo Dennis Chuen Chai Seow 《PloS one》2015,10(9)
Background
Frailty is associated with adverse outcomes including disability, mortality and risk of falls. Trauma registries capture a broad range of injuries. However, frail patients who fall comprise a large proportion of the injuries occurring in ageing populations and are likely to have different outcomes compared to non-frail injured patients. The effect of frail fallers on mortality is under-explored but potentially significant. Currently, many trauma registries define low falls as less than three metres, a height that is likely to include non-frailty falls. We hypothesized that the low fall from less than 0.5 metres, including same-level falls, is a surrogate marker of frailty and predicts long-term mortality in older trauma patients.Methods
Using data from the Singapore National Trauma Registry, 2011–2013, matched till September 2014 to the death registry, we analysed adults aged over 45 admitted via the emergency department in public hospitals sustaining blunt injuries with an injury severity score (ISS) of 9 or more, excluding isolated hip fractures from same-level falls in the over 65. Patients injured by a low fall were compared to patients injured by high fall and other blunt mechanisms. Logistic regression was used to analyze 12-month mortality, controlling for mechanism of injury, ISS, revised trauma score (RTS), co-morbidities, gender, age and age-gender interaction. Different low fall height definitions, adjusting for injury regions, and analyzing the entire adult cohort were used in sensitivity analyses and did not change our findings.Results
Of the 8111 adults in our cohort, patients who suffered low falls were more likely to die of causes unrelated to their injuries (p<0.001), compared to other blunt trauma and higher fall heights. They were at higher risk of 12-month mortality (OR 1.75, 95% CI 1.18–2.58, p = 0.005), independent of ISS, RTS, age, gender, age-gender interaction and co-morbidities. Falls that were higher than 0.5m did not show this pattern. Males were at higher risk of mortality after low falls. The effect of age on mortality started at age 55 for males, and age 70 for females, and the difference was attributable to the additional mortality in male low-fallers.Conclusions
The low fall mechanism can optimize prediction of long-term mortality after moderate and severe injury, and may be a surrogate marker of frailty, complementing broader-based studies on aging. 相似文献9.
Jared Cumming Suresh Babu Ying Huang Carolyn Carrol Xia Chen Leonard Favreau William Greenlee Tao Guo Matthew Kennedy Reshma Kuvelkar Thuy Le Guoqing Li Nansie McHugh Peter Orth Lynne Ozgur Eric Parker Kurt Saionz Andrew Stamford Corey Strickland Dawit Tadesse Qi Zhang 《Bioorganic & medicinal chemistry letters》2010,20(9):2837-2842
With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2′ sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral Aβ40 in transgenic mice with a single subcutaneous dose. 相似文献
10.
Enitan D. Carrol Limangeni A. Mankhambo Graham Jeffers Deborah Parker Malcolm Guiver Paul Newland Daniel L. Banda The IPD Study Group Elizabeth M. Molyneux Robert S. Heyderman Malcolm E. Molyneux C. Anthony Hart 《PloS one》2009,4(8)