Cast syndrome

The term cast syndrome is used to denote duodenal obstruction occurring after application of a corrective plaster cast to patients with scoliosis. We report a classical case in a 14-year-old female who required surgical intervention after conservative treatment failed. Six months later the patient had no further gastrointestinal symptoms. Clinical, radiological, and pathological details as well as the surgical treatment are described and discussed. Offprint requests to: M. E. Martín Hortigüela     

An evaluation of the cardiovascular safety profile of duloxetine: findings from 42 placebo-controlled studies.

BACKGROUND AND OBJECTIVE: In recent years, new classes of medication, such as the serotonin-noradrenaline reuptake inhibitors (SNRIs), have been developed for use in the treatment of major depressive disorder (MDD). For many years, treatment options were largely limited to the use of monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). However, there have been published reports of orthostatic hypotension, arrhythmias and corrected QT (QTc) interval changes in patients treated with TCAs. As new medications become available, it is important to understand how their cardiovascular safety profile compares with that of more established agents to aid clinicians and patients in choosing the best treatment options. This study was designed to evaluate the cardiovascular safety profile of the SNRI duloxetine through evaluation of cardiovascular-related parameters and adverse events (AEs). METHODS: The cardiovascular safety of duloxetine was assessed using all placebo-controlled duloxetine clinical trial data as of December 2005. This consisted of data from 42 placebo-controlled clinical trials of 8504 patients who were treated with duloxetine. Additional information from a high-dose clinical pharmacology study and postmarketing safety surveillance are also presented. Of the placebo-controlled trials included in this analysis, clinical indications under investigation included MDD (15 studies), diabetic peripheral neuropathic pain (3 studies), fibromyalgia (2 studies), generalised anxiety disorder (3 studies) and lower urinary tract disorders (19 studies, all related to incontinence). Cardiovascular safety was evaluated based on vital signs, ECGs and the incidence of treatment-emergent AEs potentially related to cardiovascular safety. These safety parameters were analysed across all indications. To identify both serious and non-serious cardiovascular-related AEs, as well as AEs reported as the reason for discontinuation, a comprehensive list of terms derived from the Medical Dictionary for Regulatory Activities (version 8.0) was generated and used to search the duloxetine databases for cardiovascular-related events. RESULTS: Calculation of change from baseline to maximum in ECG parameters showed significant differences between treatment groups for all parameters, with decreases from baseline in RR, QRS and QT intervals for patients receiving duloxetine and increases from baseline for patients treated with placebo. These shifts were related to small heart rate changes, but the mean differences were not considered clinically relevant. Categorical analyses of shifts from normal to abnormal (or abnormal to normal) for heart rate and QT corrected for heart rate using Fridericia's formula (QTcF) values showed that most patients did not shift from their baseline category. Patients with MDD who were treated for up to 1 year with duloxetine had blood pressure changes early in treatment that then stabilised. Even in patients with elevated blood pressure at baseline in these clinical trials, no increased risk of sustained blood pressure elevation with duloxetine treatment was found. CONCLUSION: Overall, the findings presented here support our conclusions that use of duloxetine does not appear to be associated with significant cardiovascular risks in patients with conditions for which the drug has been approved or studied.     

Direct measurement of the lambda of the lumped constant of the deoxyglucose method in rat brain: determination of lambda and lumped constant from tissue glucose concentration or equilibrium brain/plasma distribution ratio for methylglucose

Steady-state distribution spaces of 2-[14C]deoxyglucose ([14C]DG), glucose, and 3-O-[14C]methylglucose at various concentrations of glucose in brain and plasma ranging from hypoglycemic to hyperglycemic levels have been determined by direct chemical analyses in the brains of conscious rats. The hexose concentrations were measured chemically in freeze-blown brain extracted with ethanol to avoid the degradation of acid-labile products of [14C]DG back to free [14C]DG that has been found to occur with the more commonly used perchloric acid extraction of brain. Corrections were also made for nonphosphorylatable, labeled products of [14C]DG found in the nonacidic fractions of the brain extracts, which were previously included with the assayed [14C]DG, and for the contribution of the hexose contents in the blood in the brain, which was found to be particularly critical for the determination of the glucose distribution space, especially in hypoglycemic states. From the measured contents of the hexoses in brain and plasma, the relationships of the tissue concentrations and distribution spaces of each of the hexoses and of the lambda (i.e., ratio of tissue distribution space of DG to that of glucose) of the DG method to the tissue glucose concentration were derived. The lambda was then quantitatively related to the measured equilibrium ratio for [14C]methylglucose over the full range of brain and plasma glucose levels. By combining these new data with the values for the lumped constant, the factor that converts the rate of DG phosphorylation to glucose phosphorylation, previously determined in rats over the same range of plasma glucose levels, the phosphorylation coefficient was calculated and the lumped constant graphed as a function of the measured distribution space in brain for [14C]methylglucose.     

The effect of laser refractive surgery on the on-field performance of professional baseball players.

BACKGROUND: The aim of this study was to determine the effect of laser refractive surgery on the offensive performance of professional baseball players. METHODS: Extensive search of the public media was conducted to determine which major league baseball players had undergone laser refractive surgery and when the procedure was performed. Baseball performance data were then used to determine presurgery and postsurgery baseball performance averages. A total of 17 position players were identified; however, 5 of these players were not considered in the analysis owing to insufficient playing experience either before or after the laser procedure. RESULTS: No statistically significant or practically significant difference was found between the presurgery and postsurgery means on either on-base percentage (P = 0.31), batting average (P = 0.39), slugging percentage (P = 0.66) or on-base plus slugging (OPS; P = 0.997) of major league baseball players. CONCLUSIONS: These preliminary findings suggest that professional baseball players should not expect a laser refractive surgical procedure to significantly improve their offensive baseball performance, despite the elimination of glasses or contact lens wear.     

Auer rod positive dysmyelopoietic syndrome

Twenty-five patients with refractory anemia with excess blasts (RAEB) were studied. Five of these patients showed Auer rods in their myeloblasts, but met other criteria for RAEB. Median survival of the Auer rod-positive group was 14 months (range 2–27) from diagnosis with survival of 7 months after Auer rods were first observed. Median survival for the Auer rod-negative group was 12 months. Two patients developed overt acute leukemia, both from the Auer rod-negative group. The clinical course of Auer rod-positive RAEB, like that of Auer rod-negative RAEB, was one of progressive bone marrow failure complicated by infection, serious bleeding and the development of absolute transfusion requirement. These findings suggest that Auer rod-positive RAEB is a morphologic variant dysmyelopoietic syndrome that may pursue a similar clinical course to Auer rod-negative disease. Formulation of a separate treatment approach for those RAEB patients who possess Auer rods would appear ill advised.     

Combining two-point genetic linkage analyses using mapping functions

A likelihood ratio statistic is proposed for combining two-point genetic linkage analyses when the two-point analyses are between a trait and a well-defined map of markers. It is assumed that the two-point analyses are independent, as in the case of choosing only the most informative marker per family. The asymptotic distribution of the likelihood ratio statistic is derived under the null hypothesis of no linkage of the trait with a map of 2 markers, with intermarker genetic distance δ. This distribution is shown to be a chi-square mixture distribution with mixing probability depending on δ and the assumed mapping function. We use this asymptotic result to approximate the distribution of the likelihood ratio statistic for the more general case of more than 2 markers. Simulation results indicate that this may be reasonable. Power is evaluated by simulations and results indicate that this approach, which constrains the intermarker distances to their known values, tends to be more powerful than other methods proposed in the literature. © 1994 Wiley-Liss, Inc.