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BACKGROUND & AIMS: Shwachman syndrome is an inherited condition with multisystemic abnormalities, including exocrine pancreatic dysfunction. The aim of this study was to evaluate the occurrence and progression of features in a large cohort of patients. METHODS: Clinical records of 25 patients with Shwachman syndrome were reviewed. RESULTS: Mean birth weight (2.92 +/- 0.51 kg) was at the 25th percentile. However, by 6 months of age, mean heights and weights were less than the 5th percentile. After 6 months of age, growth velocity was normal. Severe fat maldigestion due to pancreatic insufficiency was present in early life (fecal fat, 26% +/- 17% of fat intake; age, < 2 years). Serial assessment of exocrine pancreatic function showed persistent deficits of enzyme secretion, but 45% of patients showed moderate age-related improvements leading to pancreatic sufficiency. Neutropenia was the most common hematologic abnormality (88%), but leukopenia, thrombocytopenia, and anemia were also frequently encountered. Patients with hypoplasia of all three bone marrow cellular lines (n = 11) had the worst prognosis; 5 patients died, 2 of sepsis and 3 of acute myelogenous leukemia. Other findings included hepatomegaly and/or abnormal liver function test results and skeletal abnormalities. CONCLUSIONS: A wide and varied spectrum of phenotypic abnormalities among patients with Shwachman syndrome is described. Pancreatic acinar dysfunction is an invariable abnormality. Patients with severe bone marrow involvement may have a guarded prognosis. (Gastroenterology 1996 Dec;111(6):1593-602) 相似文献
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Forest Fire Smoke Exposures and Out-of-Hospital Cardiac Arrests in Melbourne,Australia: A Case-Crossover Study 总被引:1,自引:0,他引:1
Martine Dennekamp Lahn D. Straney Bircan Erbas Michael J. Abramson Melita Keywood Karen Smith Malcolm R. Sim Deborah C. Glass Anthony Del Monaco Anjali Haikerwal Andrew M. Tonkin 《Environmental health perspectives》2015,123(10):959-964
Background
Millions of people can potentially be exposed to smoke from forest fires, making this an important public health problem in many countries.Objective
In this study we aimed to measure the association between out-of-hospital cardiac arrest (OHCA) and forest fire smoke exposures in a large city during a severe forest fire season, and estimate the number of excess OHCAs due to the fire smoke.Methods
We investigated the association between particulate matter (PM) and other air pollutants and OHCA using a case-crossover study of adults (≥ 35 years of age) in Melbourne, Australia. Conditional logistic regression models were used to derive estimates of the percent change in the rate of OHCA associated with an interquartile range (IQR) increase in exposure. From July 2006 through June 2007, OHCA data were collected from the Victorian Ambulance Cardiac Arrest Registry. Hourly air pollution concentrations and meteorological data were obtained from a central monitoring site.Results
There were 2,046 OHCAs with presumed cardiac etiology during our study period. Among men during the fire season, greater increases in OHCA were observed with IQR increases in the 48-hr lagged PM with diameter ≤ 2.5 μm (PM2.5) (8.05%; 95% CI: 2.30, 14.13%; IQR = 6.1 μg/m3) or ≤ 10 μm (PM10) (11.1%; 95% CI: 1.55, 21.48%; IQR = 13.7 μg/m3) and carbon monoxide (35.7%; 95% CI: 8.98, 68.92%; IQR = 0.3 ppm). There was no significant association between the rate of OHCA and air pollutants among women. One hundred seventy-four “fire-hours” (i.e., hours in which Melbourne’s air quality was affected by forest fire smoke) were identified during 12 days of the 2006/2007 fire season, and 23.9 (95% CI: 3.1, 40.2) excess OHCAs were estimated to occur due to elevations in PM2.5 during these fire-hours.Conclusions
This study found an association between exposure to forest fire smoke and an increase in the rate of OHCA. These findings have implications for public health messages to raise community awareness and for planning of emergency services during forest fire seasons.Citation
Dennekamp M, Straney LD, Erbas B, Abramson MJ, Keywood M, Smith K, Sim MR, Glass DC, Del Monaco A, Haikerwal A, Tonkin AM. 2015. Forest fire smoke exposures and out-of-hospital cardiac arrests in Melbourne, Australia: a case-crossover study. Environ Health Perspect 123:959–964; http://dx.doi.org/10.1289/ehp.1408436 相似文献34.
Sinoatrial conduction is commonly assessed from features of the initial cycle after a single atrial extrastimulus or eight beats atrial pacing. In contrast, sinus node automaticity is assessed by the duration of the first interval after prolonged atrial pacing. The return cycle and initial sequences after these different methods were compared in 10 subjects with normal sinus node function and 30 patients with sick sinus syndrome. Typically, sequences after all three methods showed a maximally prolonged first interval with a progressive decrease over five or more cycles. A model of recovery from overdrive suppression was used to compute the elements of conduction time and automaticity in the first interval. The sequences which followed a single extrastimulus and pacing were similar, the only index which increased significantly with prolonged pacing was associated with the degree of suppression of automaticity. The computed component of sinoatrial conduction in the return cycle was similar for all three methods. Thus all three conventional methods which consider only the initial post-stimulation interval measure both sinoatrial conduction and sinus node automaticity. The separate components of automaticity and conduction may be assessed by analysis of the total sequence. 相似文献
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NA Hanchard DR Murdock PL Magoulas M Bainbridge D Muzny YQ Wu M Wang AL McGuire JR Lupski RA Gibbs CW Brown 《Clinical genetics》2013,83(5):457-461
The advent of whole‐exome next‐generation sequencing (WES) has been pivotal for the molecular characterization of Mendelian disease; however, the clinical applicability of WES has remained relatively unexplored. We describe our exploration of WES as a diagnostic tool in a 3½‐year old female patient with a 2‐year history of episodic muscle weakness and paroxysmal dystonia who presented following a previous extensive but unrevealing diagnostic work‐up. WES was performed on the proband and her two parents. Parental exome data was used to filter potential de novo genomic events in the proband and suspected variants were confirmed using di‐deoxy sequencing. WES revealed a de novo non‐synonymous mutation in exon 21 of the calcium channel gene CACNA1S that has been previously reported in a single patient as a rare cause of atypical hypokalemic periodic paralysis. This was unexpected, as the proband's original differential diagnosis had included hypokalemic periodic paralysis, but clinical and laboratory features were equivocal, and standard clinical molecular testing for hypokalemic periodic paralysis and related disorders was negative. This report highlights the potential diagnostic utility of WES in clinical practice, with implications for the approach to similar diagnostic dilemmas in the future. 相似文献
38.
Aubé Mélanie Chua Michael DeLong Jessica McCammon Kurt Tonkin Jeremy Gilbert David Virasoro Ramón 《International urology and nephrology》2020,52(4):687-692
International Urology and Nephrology - To determine predictors for surgical complications and assess patient satisfaction after surgical treatment of Adult-Acquired Buried Penis (AABP). A... 相似文献
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Harold M. Hudson Serigne N. Lô R. John Simes Andrew M. Tonkin Stephane Heritier 《Statistics in medicine》2014,33(10):1621-1645
Transform methods have proved effective for networks describing a progression of events. In semi‐Markov networks, we calculated the transform of time to a terminating event from corresponding transforms of intermediate steps. Saddlepoint inversion then provided survival and hazard functions, which integrated, and fully utilised, the network data. However, the presence of censored data introduces significant difficulties for these methods. Many participants in controlled trials commonly remain event‐free at study completion, a consequence of the limited period of follow‐up specified in the trial design. Transforms are not estimable using nonparametric methods in states with survival truncated by end‐of‐study censoring. We propose the use of parametric models specifying residual survival to next event. As a simple approach to extrapolation with competing alternative states, we imposed a proportional incidence (constant relative hazard) assumption beyond the range of study data. No proportional hazards assumptions are necessary for inferences concerning time to endpoint; indeed, estimation of survival and hazard functions can proceed in a single study arm. We demonstrate feasibility and efficiency of transform inversion in a large randomised controlled trial of cholesterol‐lowering therapy, the Long‐Term Intervention with Pravastatin in Ischaemic Disease study. Transform inversion integrates information available in components of multistate models: estimates of transition probabilities and empirical survival distributions. As a by‐product, it provides some ability to forecast survival and hazard functions forward, beyond the time horizon of available follow‐up. Functionals of survival and hazard functions provide inference, which proves sharper than that of log‐rank and related methods for survival comparisons ignoring intermediate events. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献