Marked Q-T prolongation due to encainide therapy

Summary Encainide is a type Ic antiarrhythmie agent. During encainide therapy, mild Q-T interval prolongation can be seen, usually associated with prolongation of the Q-R-S interval. The present case report describes an unusual and marked prolongation of the Q-T interval with no Q-R-S interval prolongation in a patient who was treated with encainide for atrioventricular nodal reentrant tachycardia. The drug metabolite profile in this patient's serum indicated an unusual elevation of the 3-methoxy-O-demethyl encainide metabolite, versus O-demethyl encainide. This elevated metabolite level suggests that 3-methoxy-O-demethyl encainide has a significant effect on prolongation of repolarization. An abnormal metabolism of encainide may be the underlying mechanism by which some patients would manifest an unusual prolongation of Q-T interval during encainide therapy.     

Abnormality of type IX collagen in a patient with diastrophic dysplasia

There is growing evidence that a spectrum of chondrodysplasias are caused by mutations in the gene coding for type II collagen. The basic molecular defect in diastrophic dysplasia has not been defined, but it appears not to be in collagen type II. Cartilage contains other tissue-specific collagens, types IX, X, and XI, but no mutations have yet been found in their genes in clinical disease. Type IX collagen is hypothesized to play a role in the regulation of type II collagen fibril organization and structure in cartilage extracellular matrix. In this study, we have examined iliac crest growth cartilage from a patient with diastrophic dysplasia. Although collagen fibrils were markedly increased in diameter on transmission electron microscopy, type II collagen appeared to be normal biochemically. Type XI collagen was also normal. However, type IX collagen appeared abnormal on sodium dodecyl sulfate polyacrylamide gel electrophoresis with a pronounced excess of the COL1 domain of the molecule in pepsin extracts. The findings point to an abnormality in structure or metabolism of type IX collagen in diastrophic dysplasia. © 1994 Wiley-Liss, Inc.     

Airway responsiveness to beta-adrenergic agonist (salbutamol) in asthma.

Despite the controversy of airway responsiveness to beta2-agonist drugs in asthma, in a previous study we showed increased responsiveness of asthmatic airways to isoprenaline. Therefore, in the present study of airway sensitivity to other beta2-agonists, salbutamol and its relationship to histamine responsiveness was reexamined. The threshold bronchodilator concentrations of inhaled salbutamol required for a 20% increase in forced expiratory flow in 1 sec (FEV1), (PC20) was measured in 20 normal and 19 asthmatic adults. Airway responsiveness to histamine, as the concentration that caused a 20% decrease in FEV1, was also measured in 11 normal and 12 asthmatic subjects; and the correlation between PC20 salbutamol and PC20 histamine was evaluated. Sensitivity to salbutamol was greater in asthmatics (PC20 = 7.24 mg/L) than in non-asthmatics (PC20 = 124.25 mg/L, p < 0.001). Airway responsiveness to histamine in asthmatics (PC20 = 0.18 g/L) was also significantly greater than in normal subjects (PC20 = 19.46 g/L, p < 0.001). There was a significant correlation between PC20 salbutamol and histamine (Rs = 0.6052, p < 0.005). Maximum response to both salbutamol and histamine and slope of concentration-response curves of both agents were significantly greater in patients with asthma than in normal subjects (p < 0.001 and p < 0.005 for maximum response and slope, respectively). The increased sensitivity of asthmatics to inhaled salbutamol suggests that they also may be more sensitive to their endogenous adrenaline, which may thus dilate and stabilize their airways.     

Bilateral Duane syndrome and bilateral aniridia.

Duane retraction syndrome has been reported in association with structural abnormalities of the eye, including epibulbar dermoid, keratoconus, iris dysplasia, heterochromia iridis, persistent fetal vasculature, cataract, choroidal coloboma, microphthalmia, and optic nerve dysplasia. A novel association, that of bilateral Duane syndrome with bilateral aniridia, is the subject of this report.     

Low back pain education and short term quality of life: a randomized trial

Background  

Different interventions can reduce the burden of the chronic low back pain. One example is the use of a 'Back School Programme'. This is a brief therapy that uses a health education method to empower participants through a procedure of assessment, education and skill development. This study aimed to evaluate to what extent the programme could improve quality of life in those who suffer from the condition.     

Long-term Outcomes of Patients Undergoing War-related Amputations of the Foot and Ankle

Long-term clinical and functional outcomes for patients undergoing foot and ankle amputations are not well documented. We attempted to document long-term outcomes for patients who required lower extremity amputations as a result of wounds suffered during wartime. For this study, 27 Iranian soldiers who had wounds requiring amputation of the foot and ankle were selected for follow-up. The participants' wartime medical records were reviewed, a clinical examination was performed, and each participant completed a questionnaire. Postamputation follow-up averaged 17.5 years. The most prevalent (66.6%) cause of injury was a land mine. The prevalences of different clinical symptoms reported by the amputees at the time of the last follow-up were as follows: 11 (40.7%) with phantom sensation, 6 (22.2%) with phantom pain, 12 (44.4%) with stump pain, 12 (44.4%) with back pain, 9 (33.3%) with contralateral knee pain, and 4 (14.8%) with ipsilateral knee pain; 20 (74%) reported treatment for psychological conditions. In regard to social conditions, 13 (48.1) were currently employed, or had been employed, for a number of years after the amputation; 26 (96%) had children, and all of the patients were married. The results of this observational study indicate that individuals have significant long-term pain and discomfort after war-related lower extremity amputation. Although all 27 (100%) of the amputees were able to maintain satisfactory family functioning, only 13 (48.1%) of the study participants were able to remain productively employed after undergoing amputation, and 20 (74%) reported long-term psychological problems in addition to their physical pain.     

The program for phenotyping of genetically modified animals at AstraZeneca

Genetically modified mice offer a wide range of possibilities in preclinical drug discovery, e.g. for use in target identification, target validation and disease model generation. However, genomic modification and alteration in gene expression may cause unpredicted phenotypic alterations in the organism other than the intended ones. The aim of this study was to determine the importance of establishing the phenotype of transgenic and knockout mice models for use in pharmaceutical research.

A total number of 51 mouse models (transgenic and knockout) produced at AstraZeneca during a 4 year period were subjected to a thorough phenotyping package covering clinical as well as morphological aspects. Phenotype abnormalities were recorded in 36 (70.6%) of the mouse models. The majority of findings were considered to be minor in magnitude. Histopathological changes related to the genotype of the animals were observed in 33% of the mouse models, underlining the importance of pathology in the phenotyping program.     

Impact of major co-morbidities on mortality and complications after gastric bypass

BACKGROUND: We hypothesized that major co-morbidities affect survival and complications after gastric bypass. METHODS: A total of 1465 patients undergoing laparoscopic and open gastric bypass between 1995 and 2002 were studied. Patients with a body mass index >or= 35 kg/m(2) and major co-morbidities (group 1, n = 1045) were compared with patients with a body mass index >or= 40 kg/m(2) with minor/no co-morbidities (group 2, n = 420). RESULTS: Group 1 patients were older (43 versus 36 years, P < 0.001) and had a greater BMI (53 versus 50 kg/m(2), P < 0.001). Early postoperative complications were greater in group 1 than in group 2 and included leaks (4.1% versus 1.2%, P < 0.0032) and wound infections (3.9% versus 1.4%, P < 0.0133). Procedure-related mortality in the series was 1.7%. Mortality was 10-fold greater in group 1 (2.3% versus 0.2%, P < 0.0032). The incidence of small bowel obstruction, incisional hernia, and pulmonary embolism was similar in the two groups. Excess weight loss was significantly greater in group 2 (68% versus 62%, P < 0.001) at 1 year. Resolution of group 1 co-morbidities was great, including hypertension in 62%, diabetes in 75%, venous stasis disease in 96%, and pseudotumor cerebri in 98%. CONCLUSION: Outcomes analysis of obesity surgery requires risk stratification. The very low mortality rates in published studies are likely explained by surgical treatment of low-risk patients with minor co-morbidities, such as those seen in group 2. However, despite the increased perioperative risk, the group 1 patients (with major co-morbidities) demonstrated dramatic resolution of their co-morbid conditions, justifying the decision to go forward with surgery. The data support a radical change in treatment philosophy in which morbidly obese individuals should be offered bariatric surgery before major co-morbid conditions develop as a strategy to decrease the operative risk.