Generation of islet-like hormone-producing cells in vitro from adult human pancreas

Transplantation of pancreatic islets can provide long-lasting insulin independence for diabetic patients, but the current islet supply is limited. Here we describe a new in vitro system that utilizes adult human pancreatic islet-enriched fractions to generate hormone-producing cells over 3-4 weeks of culture. By labeling proliferating cells with a retrovirus-expressing green fluorescent protein, we show that in this system hormone-producing cells are generated de novo. These hormone-producing cells aggregate to form islet-like cell clusters. The cell clusters, when tested in vitro, release insulin in response to glucose and other secretagogues. After transplantation into immunodeficient, nondiabetic mice, the islet-like cell clusters survive and release human insulin. We propose that this system will be useful as an experimental tool for investigating mechanisms for generating new islet cells from the postnatal pancreas, and for designing strategies to generate physiologically competent pancreatic islet cells ex vivo.     

Red blood cell exchange transfusion as an adjunct treatment for severe pediatric falciparum malaria, using automated or manual procedures

Pediatric falciparum malaria is associated with high morbidity and mortality rates. Cerebral malaria and renal failure are common among children with a high percentage of malaria-infected red blood cells. We report 3 cases of imported pediatric falciparum malaria with central nervous system involvement and/or renal failure that were treated initially with intravenous antimalarial therapy, with no clinical improvement. Red blood cell exchange transfusion (RBCET) was started; this resulted in decreases in the percentages of parasitized red blood cells of 80% to 90%. The RBCET was performed with either an automated 1-blood volume or manual 1.5-blood volume exchange. Most cases of falciparum malaria can be treated with intravenously administered antimalarial agents alone. However, for children who have high percentages of parasitized red blood cells with central nervous system involvement and/or renal failure, the use of RBCET as an adjunct treatment should be considered.     

The relationship of "shisha" (water pipe) smoking to postextraction dry socket.

PURPOSE: This study was undertaken to determine whether "shisha" (water pipe) smokers (SS) were at a different risk of developing dry socket (DS) than were cigarette smokers (CS) or nonsmokers (NS) and to assess the effect of preoperative and postoperative smoking habits on the incidence of DS. MATERIALS AND METHODS: One hundred NS, 100 CS, and 100 SS were enrolled. Surgery for removal of mandibular third molars was performed under local anesthesia with no incision or bone removal. At 1, 4, and 7 days after surgery, postoperative evaluation and postoperative smoking were recorded by the same examiner. The chi(2) test was used for statistical analysis of results. Statistical significance was defined as a value of P <.05. RESULTS: Smokers had 2 to 3 times the risk of NS for developing DS. Although SS had a greater incidence of DS than did CS, the difference was not significant (P =.083). The incidence of DS was not age dependent. Smokers who smoked the day of surgery had a significantly higher incidence of DS than did smokers who smoked the second day after surgery. Compared with NS, CS who smoked the day of surgery and SS who smoked the day of surgery or the first day after surgery had a significantly increased incidence of DS (CS/NS, day 0, P =.001; SS/NS, day 0, P =.001; day 1, P =.005). CONCLUSION: SS had 3 times the risk of NS for developing DS, but there was no statistically significant difference between SS and CS. Increased frequency of smoking and smoking during the day of surgery significantly increased the incidence of DS.     

Cardiac heart disease in the era of sucrose polyester, Helicobacter pylori and Chlamydia pneumoniae

Recent evidence associates inflammatory mediators with coronary heart disease. Elevation of acute-phase reaction (APR) proteins such as serum amyloid A, fibrinogen, CRP and haptoglobin in response to Helicobacter pylori (H. pylori) infection was shown to initiate gastritis and ischemic heart disease. Positive Chlamydia pneumoniae (C. pneumoniae) serology is associated with increased levels of inflammatory cytokines and tumor necrosis factor-alpha (TNF-alpha), which stimulates endothelial cell activation, procoagulant activity and angiogenesis in patients with coronary heart disease. As a final example, interleukin-6 (IL-6) has been proposed to mediate cardiovascular disorders. Public awareness of risks of excessive body weight and high levels of serum cholesterol propelled the development of synthetic dietary components such as sucrose polyester (SPE) to substitute for natural lipids. SPE is a synthetic lipid whose physical properties are similar to a natural triacylglycerol with a similar assortment of fatty acids and is resistant to lipolysis by gastric and pancreatic enzymes. Intake of SPE in lieu of natural lipids is expected to decrease absorption of essential fatty acids (EFA) and fat-soluble vitamins among other essentials. Deficiency of EFA leads to the formation of faulty cellular membranes, which is manifested as skin lesions, growth failure, erythrocyte fragility, impairment of fertility and uncoupling of oxidation and phosphorylation. Possibilities of absorption of these synthetic lipids into the circulation may represent an unexpected health hazard. We have shown that subcutaneous (sc) administration to rabbits of a range of lipolysis-resistant lipid-like sorbitol, mannitol and arabitol esters of palmitic (P) and lauric (L) acids was found to evoke a mild APR, which in humans could contribute to CHD incidence. We suggest a reversal in the commonly accepted role of SPE as a sequestor of dietary lipid: SPE may be the lipophilic solute contained within the dietary lipid solvent micelle. An alternative conclusion regarding the biological effects of excessive dose of SPE in human and pig for a short time span should be considered.     

Special populations recruitment for the Women's Health Initiative: successes and limitations

The Women's Health Initiative (WHI) is a study designed to examine the major causes of death and disability in women. This multi-arm, randomized, controlled trial of over 160,000 post-menopausal women of varying ethnic and socioeconomic backgrounds and a goal of 20% of the study participants from minority populations is perhaps one of the most challenging recruitment efforts ever undertaken. Of the two main study arms, the Clinical Trial (CT) and the Observational Study (OS), the CT arm recruitment goal was to randomize 64,500 postmenopausal women 50-79 years of age. Women enrolled in the study will be followed for a period of 8-12 years. Ten clinical centers, out of a total of 40 throughout the United States, were selected as minority recruitment centers on the basis of their history of interaction with and access to large numbers of women from certain population subgroups. WHI enrollment began in September 1993 and ended in December 1998, resulting in the randomization and enrollment of a total of 161,856 (17.5% minority) women participants (68,135 (18.5% minority) in the CT and 93,721 (16.7%) in the OS). Within the CT arm, WHI achieved 101.7% of the goal of 48,000 participants in the Dietary Modification (DM) component, and 99.4% of the goal of 27,500 in the hormone-replacement component (HRT), with 11.8% overlap between DM and HRT. Of those who expressed initial interest in WHI, African Americans had the highest randomization yields in the DM component and Hispanics had the highest in the HRT component (15.2% and 10.2%, respectively). Overall, mass mailing was the greatest source of randomized participants. In addition, minority clinics found community outreach, personal referrals, and culturally appropriate recruitment materials particularly effective recruitment tools. For minority recruitment, our findings suggest that the key to high yield is reaching the target population through appropriate recruitment strategies and study information that get their attention. Also, once minority subjects are reached, they tend to participate.