Reversal of diabetes in BB rats by transplantation of encapsulated pancreatic islets

Prolonged survival of pancreatic islet allografts implanted in diabetic BB rats was achieved by encapsulation of individual islets in a protective biocompatible alginate-polylysine-alginate membrane without immunosuppression. Intraperitoneal transplantation of the encapsulated islets reversed the diabetic state of the recipients within 3 days and maintained normoglycemia for 190 days. Normal body weight and urine volume were maintained during this period, and no cataracts were detected in the transplant recipients. In contrast, control rats receiving transplants of unencapsulated islets experienced normoglycemia for less than 2 wk. These results demonstrated that microencapsulation can protect allografted islets from both graft rejection and autoimmune destruction without immunosuppression in an animal model that mimics human insulin-dependent diabetes.     

Insights into Mechanisms of Cisplatin Resistance and Potential for Its Clinical Reversal

Cisplatin in combination with other cytotoxic agents is the backbone for a potential cure of testicular germ cell neoplasms and is a critical factor in the substantial activity observed in the treatment of small cell lung cancer, bladder cancer, and ovarian germ cell tumors. Resistance to cisplatin at the onset of treatment or at relapse limits its curative potential, however. Laboratory studies using both cells selected for cisplatin resistance by exposure to sublethal concentrations and biopsy specimens from patients' tumors provide insights for the potential mechanisms of resistance. The mechanisms identified in vitro include a complex and wide array of related and unrelated pathways such as alterations in cellular drug transport, enhanced DNA repair dependent and independent of signal transduction pathways, and enhanced intracellular detoxification such as glutathione and metallothionein systems. Studies of these mechanisms have identified a number of agents with known potential for administration to humans and that reverse cisplatin resistance in vitro; for example, reversal of cellular accumulation defects by dipyridamole; inhibition of DNA repair by hydroxyurea, pentoxifylline, and novobiocin; inhibition of the glutathione system by ethacrynic acid and buthionine sulfoximine; and inhibition of signal transduction pathways by cyclosporine, tamoxifen, and calcium channel-blocking agents. Current phase I clinical trials are focusing on the most effective doses and schedules to administer these agents in combination with cisplatin. Initial uncontrolled trials in limited numbers of patients suggest that the addition of modulators of cisplatin has the potential to reverse resistance in patients previously failing therapy. Another promising avenue for circumventing cisplatin resistance is the development of noncross-resistant platinum analogs.     

Probable interaction of sodium divalproex with benzodiazepines.

1. After drug discontinuation and 1 week placebo washout, 12 patients with panic disorders received, for 6 weeks, either placebo or sodium divalproex. During 6 consecutive weeks, alternate medication was given. 2. Severity of panic and anxiety attacks was improved only in patients receiving sodium divalproex as a first medication. 3. Protracted benzodiazepine effects may occur in the dichotomous antipanic activity of sodium divalproex.     

Influence of cardiopulmonary bypass on water balance hormones in children.

OBJECTIVE--To determine the changes in the endocrine mechanisms of fluid balance after cardiopulmonary bypass in children. DESIGN--Prospective study; analysis of numbered plasma samples performed blind with respect to clinical data. SETTING--Regional paediatric cardiothoracic unit. PATIENTS--Nine patients, median age 4, range 2 to 9 years, five males. Patients under the age of 1 year were excluded because of the frequent blood sampling involved. MAIN OUTCOME MEASURES--Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin, plasma renin activity, aldosterone, noradrenaline and adrenaline, and urinary concentrations of cyclic guanosine monophosphate (cGMP) as measured by radioimmunoassay. RESULTS--After 30 minutes of cardiopulmonary bypass plasma atrial natriuretic peptide (ANP) decreased from (mean (SEM)) 151 (71) pg/ml to 52 (44) pg/ml (NS), and urinary production of its second messenger cyclic guanosine monophosphate (cGMP) decreased from 1286 (600) pmol/ml to 151 (414) pmol (p < 0.05). Other plasma concentrations of hormones studied did not change significantly although arginine vasopressin, adrenaline, and noradrenaline increased whereas aldosterone and plasma renin activity decreased. After cardiopulmonary bypass stopped there was an immediate and significant rise in plasma ANP, but within the next 24 hours plasma ANP declined significantly (p < 0.05), decreasing from 294 (49) pg/ml to 64 (29) pg/ml at 22 hours. In the postoperative period there was a significant correlation between plasma ANP and both mean fluid balance (r = 0.96, p < 0.001) and mean urine output (r = 0.97, p < 0.001). Plasma aldosterone peaked (p < 0.05) at 22 hours after operation, and argine vasopressin peaked (p < 0.05) at two hours and then declined (p < 0.05) to a trough at 24 hours. Plasma renin activity, adrenaline, noradrenaline, and urinary cGMP concentrations, and mean central venous pressure did not change significantly in the postoperative period. CONCLUSION--The changes documented show the differing pattern of release of water balance hormones invoked by cardiopulmonary bypass. The central role of ANP is shown by its strong correlation with urinary output and its similarly strong relation to fluid balance.     

Performance standards for toric soft contact lenses.

PURPOSE: To simplify the clinical assessment of toric soft contact lens (TSCL) on-eye behavior by establishing a set of standard clinical evaluation techniques. The likely performance range expected among the TSCL wearing population was determined for a series of lens designs and acceptable performance standards indicated for each variable. METHODS: Four prism-ballast, two peri-ballast and one dynamic stabilization TSCL designs were each worn by groups of 20 subjects in a nondispensing study. After 20 min of lens wear, lenses were assessed, in right eyes only, for subjective comfort (100-point scale), lens mislocation (degrees deviation from vertical) and rotational recovery after deliberate 30 degrees mislocation (degrees/10 blinks). The percentage of lenses orienting within +/-10 degrees of target orientation (zero rotation) and the variability of orientation (standard deviation of mislocation) were also calculated for each lens group. RESULTS: Based on partitioning of the data distributions for each variable, performance was designated as excellent, acceptable or poor. Corresponding performance cut-offs were determined at > or =90, 89 to 80, and <80 for subjective comfort, < or =+/-6 degrees , +/-7 degrees to 10 degrees , and >+/-10 degrees for mislocation, >10 degrees /10 blinks, 10 degrees to 6 degrees /10 blinks, and <6 degrees /10 blinks for rotational recovery. For groups of wearers the appropriate cut-offs were > or =90%, 89 to 70%, and <70% of lenses orienting within +/-10 degrees of target orientation and <+/-6 degrees , +/-6 degrees to 10 degrees , and >+/-10 degrees for variability of orientation. CONCLUSION: Techniques suitable for the evaluation of TSCL clinical performance have been described and guidelines for the assessment of such lenses established. In the process, we have identified potential performance differences that may relate to variations in TSCL design.     

创伤后迟发性脑肿胀的临床特点与治疗

目的 探讨创伤后迟发性脑肿胀的临床特点、发病机制与治疗。方法 回顾性分析1998年1月～2005年6月年收治的17例迟发性脑肿胀患者的临床特点和救治情况。结果 所有颅脑损伤患者采用保守治疗后均有好转，但于伤后5-10d出现恶化，CT复查有脑肿胀，经加强综合脱水等治疗后16例治愈，1例死亡。结论 迟发性脑肿胀好发于对冲性额、颞叶挫裂伤伴明显蛛网膜下腔出血、硬膜下薄层血肿及早期CT有脑肿胀者。其发病机制可能与创伤后的迟发性脑血管痉挛、微循环障碍、静脉回流障碍及甘露醇作用下降等因素有关。此类患者病情隐蔽性强，应加强观察、积极行CT复查，如能早期明确诊断，保守治疗多数效果良好。     

Retrorenal colon: implications for percutaneous diskectomy

It has been recommended that computed tomography (CT) with the patient prone be performed in every patient undergoing percutaneous diskectomy; this would enable detection of a retrorenal location of the colon, which could interfere with the percutaneous procedure. In this evaluation of 346 prone CT studies, only one patient (0.29%) was found to have retrorenal or retropsoas bowel that would have been perforated at diskectomy. Because of this extremely low prevalence, the performance of prone CT in every patient undergoing percutaneous lumbar diskectomy is not believed to be necessary.