Encapsulated islets in diabetes treatment

Encapsulation of insulin-producing cells in semipermeable membranes has the potential to provide an effective treatment for insulin-dependent diabetes with little or no immunosuppression of the host. Improvements in alginate, a marine polysaccharide commonly used for cell encapsulation, have revived interest in this material. However, serious obstacles, including a reliable cell source and a better understanding of immune acceptance issues, remain to be addressed before a clinically applicable therapeutic procedure based on encapsulated cells becomes available.     

Update on chemoradiotherapy for head and neck cancer

Locoregionally advanced head and neck cancer is associated with a poor prognosis despite treatment with surgery or radiation or both. In the past several years, chemotherapy has become an integral part of potentially curative therapy for head and neck cancer and has been increasingly used to achieve the goals of organ preservation and prolongation of survival. Since 1998, many randomized studies that compared concurrent chemoradiotherapy with radiotherapy alone have been published. These studies used different chemotherapy regimens, either single-agent or combination, and various radiation fractionation schemes and almost uniformly supported the superiority of chemoradiotherapy over radiotherapy alone in terms of locoregional control as well as overall survival. Given the toxicity of concurrent chemoradiotherapy, careful selection of patients is critical. Many issues remain to be addressed in future trials, including the optimal chemotherapy regimen, the use of altered fractionation radiotherapy, and the role of induction chemotherapy.     

Blood pressure elevation after phenylephrine infusion may adversely affect myocardial perfusion in patients with coronary artery disease

BACKGROUND: Although blood pressure is a major determinant of myocardial oxygen-demand, little information is currently available regarding the changes in blood pressure (BP) during myocardial ischemia. Since BP elevation may cause left ventricular (LV) wall stress and an increase in oxygen demand, infusion of an alpha-adrenergic agonist, such as phenylephrine (PH), may provoke changes in myocardial perfusion in coronary artery disease (CAD) patients. As the effects of BP changes alone on myocardial perfusion have never been assessed by thallium-201 (Tl) scintigraphy, we investigated the effects of BP elevation after PH infusion, in order to study the hypothesis that pressure loading alone without increases in heart rate, may provoke transient impairment of regional myocardial perfusion, in CAD patients. PATIENTS AND METHODS: Forty-one (41) patients with angiographically documented CAD, aged 54+/-8 years, were included in our study. Each patient was given, without any complications, a PH (0.1 mg/ml) dose infused at a rate of 0.8 ml/mm, determined by a standardisation procedure and producing a mean blood pressure elevation of approximately 30% above baseline levels and a heart rate response to levels of no less than 50 bpm. One minute after the desired blood pressure and heart rate responses were reached, 2 mCi of Tl were injected and the PH infusion continued until the termination of the test. Tl scintigraphy was performed both 2 min after Tl injection and 4 h later, while the results were correlated to coronary angiography findings. RESULTS: PH scintigraphy produced 152 total defects. The mean perfusion defect size (%) was 14+/-12 and was directly related to the number of diseased vessels, i.e., 2% for one-vessel disease, 15% for two-vessel disease and 25% for three-vessel disease (P<0.05). The lowest percentage Tl activity values were 56+/-14 and were inversely related to the number of diseased vessels (P<0.01). The mean Tl lung counts/pixel values were 25+/-8 while it increased as the number of diseased vessels increased (P<0.01). The mean lung/heart ratio values were 0.31+/-0.08 while it increased as the number of diseased vessels increased (P<0.01). CONCLUSION: BP elevation after PH loading, produces a significant impairment of myocardial perfusion, that correlates well with the extend of angiographic findings.     

CI-980 for the Treatment of Recurrent or Progressive Malignant Gliomas: National Central Nervous System Consortium Phase I-II Evaluation of CI-980

Objective: The purpose of this phase I/II trial was to determine the maximal tolerated dose of CI-980, and determine efficacy against malignant glioma.

Background: The CI-980 is a synthetic mitosis inhibitor that acts via the colchicine binding site on tubulin. Broad in vitro activity has been seen in a variety of human and murine tumor models. Phase I studies have demonstrated schedule dependent toxicity of CI-980. Dose-limiting toxicity was neurologic when CI-980 was given as a 24-hr infusion and hematologic when given over 72 hr at higher doses.

Methods: Twenty-four patients ages 29-65 entered this study. Six patients were treated on the phase I arm at three escalating dose levels ranging from 10.5 to 13.5 mg/m², given over 72 hr. Eighteen patients were then treated at the highest tolerated dose, 13.5 mg/m² per cycle. Treatment response was based on serial MRI imaging characteristics.

Results: The phase II study was stopped at the end of the first stage due to poor treatment response. There were no partial or complete responses, (0/24) 95% CI=0-14%. Four patients (4/24) had a best treatment response of stable disease/no change. Median time to progression for all patients was 6.4 weeks (95% CI: 6-9 weeks). Dose-limiting toxicity was grade 3-4 granulocytopenia. Three episodes of neurotoxicity manifested by a moderate cerebellar dysfunction were seen.

Conclusions: These results fail to demonstrate the significant activity of CI-980 against recurrent glioma.     

Revisiting induction chemotherapy for head and neck cancer. References and reviews

Squamous cell carcinomas of the head and neck are highly responsive to induction chemotherapy. However, randomized trials have failed to demonstrate a survival advantage with the addition of induction chemotherapy to locoregional therapy consisting of surgery and/or radiation therapy. Currently, concomitant radiation and chemotherapy has emerged as a standard and has optimized locoregional control in head and neck cancer. In this setting, the addition of induction chemotherapy may further improve outcome by enhancing both locoregional and distant control. As interest in induction regimens is renewed, we elected to conduct a systematic review of trials of induction chemotherapy for locoregionally advanced head and neck cancer. The most studied combination-cisplatin plus fluorouracil (5-FU)--achieves objective response rates of about 80%. In a meta-analysis, induction with platinum/5-FU resulted in a small survival advantage over locoregional therapy alone. The introduction of a taxane into induction chemotherapy regimens has produced promising results. Induction chemotherapy should be the subject of further clinical research in head and neck cancer. Randomized clinical trials in which the control arm is concurrent chemoradiotherapy and the experimental arm is induction chemotherapy followed by concurrent chemoradiotherapy are planned. Platinum/taxane combinations are the preferred regimens for further study in the induction setting and a suitable platform with which to investigate the addition of novel targeted agents.     

Bile Duct Injuries Associated with Laparoscopic and Open Cholecystectomy: An 11-Year Experience in One Institute

Purpose Bile duct injury (BDI) represents the most serious complication of laparoscopic cholecystectomy (LC). The aim of this retrospective single-institution study was to evaluate the real incidence of BDI during laparoscopic and open cholecystectomy (OC) in a tertiary academic center in Athens, Greece.Methods Between January 1991 and December 2001, 3 637 patients underwent cholecystectomy in our department; as LC in 2 079 patients (LC group) and as OC in 1 558 patients (OC group). All the LCs were performed or supervised by five staff surgeons and all the OCs were performed or supervised by another five staff surgeons.Results There were 13 BDIs associated with LC (0.62%) and 6 associated with OC (0.38%) (P = 0.317). There was one death associated with BDI after LC. Only two (15.4%) of the BDIs associated with LC occurred within the proposed learning curve limit of 50 LCs per individual surgeon.Conclusion Laparoscopic cholecystectomy is safe and is not associated with a higher incidence of BDI than OC. Moreover, we did not find that the learning curve for LC affected BDI occurrence.     

Effect of Nebivolol and Atenolol on Brachial Artery Flow-Mediated Vasodilation in Patients with Coronary Artery Disease

Summary Endothelial dysfunction is considered to be the first step in atherogenesis as well as a predictor of adverse cardiovascular events in patients with coronary artery disease (CAD), while endothelial function improvement is associated with improved clinical outcome. Nebivolol is a beta₁-adrenoreceptor antagonist with an independent beneficial action on endothelial function, increasing nitric oxide bioavailability. The aim of the present study was to examine the effects of nebivolol on endothelial function in the brachial artery in patients with CAD compared with another selective beta₁ adrenergic receptor antagonist, atenolol. Thirty-five patients with stable CAD were randomized to receive either 5 mg nebivolol (n = 17) or 50 mg atenolol (n = 18) daily for 4 weeks. Each patient underwent measurement of endothelial function by means of flow-mediated dilatation (FMD) of the brachial artery before and after 4 weeks of treatment. All vasoactive drugs and cardiovascular risk factors were comparable in the two groups. No significant differences were observed between the two groups at baseline in FMD. In the atenolol group FMD remained unchanged at the end of the 4-week treatment, but in patients treated with nebivolol FMD showed a significant increase by the end of the treatment period (3.9 ± 2.7% vs. 5.6 ± 2.9%, p = 0.047) leading to a significantly higher value compared to patients treated with atenolol (5.6 ± 2.9% vs. 3.4 ± 3.2%, p = 0.041). Beta₁ blockade by nebivolol but not atenolol improves endothelial dysfunction in patients with CAD, an effect that might further reduce the risk for cardiovascular events in patients with CAD.     

Unusual retrograde movement of a safety-pin ingested by an infant

Here we present the first reported case of an ingested open safety-pin in a 7-mo-old boy that migrated from the stomach to the oesophagus. CONCLUSION: This rare complication is probably due to a gastro-oesophageal reflux effect, and for this reason we propose that all infants with safety-pins and other sharp objects in the stomach should be positioned in a semi-upright position.