Report of the first annual Hawaii Asthma Research Consortium

The first Hawaii Asthma Research Consortium was held on 7 May 2001 at Tripler Army Medical Center. Researchers investigating asthma-related problems and program directors of asthma projects were solicited statewide to present their projects. Ten lecturers focused on research and asthma projects in Hawaii in 20-minute presentations. An informal ten-minute discussion followed each presentation to encourage audience questions about the project and to discuss possible collaboration efforts between institutions. The institutions that were represented include: American Lung Association-Hawaii, Kaiser Permanente Center for Health Research Hawaii, Kapiolani Medical Center, Tripler Army Medical Center, University of Hawaii at Manoa, and Waianae Coast Comprehensive Health Center.     

Renal allograft laceration treated by superselective embolization.

PURPOSE: To report an illustrative case demonstrating the efficacy of endovascular treatment for traumatic blunt renal allograft injury. CASE REPORT: A 19-year-old man sustained an injury to his renal allograft after a traffic accident secondary to lap belt compression. Angiography revealed contrast extravasation from 2 disrupted upper pole renal artery branches, which were successfully embolized with microcoils. The creatinine level was transiently elevated to 4.1 mg/dL, but it improved to 2.9 mg/dL at discharge 13 days after admission. After 1 year, the serum creatinine level was 1.9 mg/dL. CONCLUSION: As in the native kidney, superselective embolization can also be used safely in the management of blunt injury to a renal allograft, avoiding surgery and preserving graft function.     

Preferences of Women Evaluating Risks of Tamoxifen (POWER) study of preferences for tamoxifen for breast cancer risk reduction

BACKGROUND: The objective of this study was to understand the attitudes and preferences of risk-eligible women regarding use of tamoxifen for breast cancer risk reduction. METHODS: A cross-sectional, mixed-methods interview study was conducted at a university medical center and at community sites. Participants were women who had an estimated 5-year breast cancer risk > or = 1.7% and no prior breast cancer. Interviews were conducted in English or Spanish. The interview included a 15-minute, standardized educational session on the potential benefits and harms of tamoxifen followed by close-ended and open-ended questions about participants' inclinations to take tamoxifen and factors important to their decision. A demographic questionnaire, a test on knowledge of potential benefits and harms of tamoxifen, and an interview evaluation were included. RESULTS: Two hundred fifty-five women completed interviews. Their estimated mean 5-year breast cancer risk was 2.8%; and their mean self-perceived 5-year risk was 32.7%. After the educational intervention, 45 women (17.6%) were inclined to take tamoxifen. Very high risk women (> 3.5%) were no more inclined to take it than women with lower risk (1.7-3.5%). In a multivariable analysis, lower income, confidence in the effectiveness of tamoxifen, and concern about fractures were associated with being inclined to take it; concern about pulmonary embolism, dyspareunia, cataracts, and low self-perceived breast cancer risk were associated negatively with taking tamoxifen. Participants expressed concerns about adverse effects. CONCLUSIONS: Less than 20% of women were interested in tamoxifen after education about potential benefits and harms, despite a very high self-perceived breast cancer risk. Candidate chemoprevention agents must have few potential adverse effects to achieve widespread acceptance.     

Efficacy and limits of the bariatric surgery

Morbid obesity is associated with and increased risk of serious comorbidities, including type 2 diabetes, sleep apnoea, cardiovascular diseases, and orthopedic disabilities. Not operative treatments for superobese patients have not been shown to produce reliable long-term benefits, therefore surgical therapy has became the treatment of choice. The number of surgical procedures increased in the last year confirm these data. However, before recommended a specific surgical procedures to a superobese patients it is necessary to consider some variables, such as: patient, health structure, and multidisciplinary equipe. Since there are not recommended or condemned surgical procedures, in this paper the Authors tried to evaluate the effectiveness and limits of the most performed surgical procedures for the treatment of pathologic obesity: gastric by-pass, biliopancreatic diversion (duodenal switch), vertical gastroplasty, banding gastric. The Authors used some pointer of outcome to measure effectiveness and limits: five year post-operative percentage excess weight loss >/< 50, peri-operative >/< 1%, early and late complications >/< 15%, reoperation >/< 3%, improvement of quality of life. Thanks to new surgical technique, restrictive options are losing ground, while malabsorbitive bariatric procedures are collecting successful.     

Melatonin corrects reticuloendothelial blockade and iron status in haemodialysed patients

AIM: Treatment of anaemia in haemodialysed patients in the setting of inflammation usually displays high levels of serum ferritin (>800 ng/mL) and low transferrin saturation (TSAT) (<20%) despite i.v. iron supplementation, thus proving iron trapping in the reticuloendothelial system. Melatonin has been reported to reduce cytokine production and, in dialysis patients, to prevent oxidative stress resulting from iron and erythropoietin treatment. METHOD: In this study, we evaluated a group of 10 patients undergoing haemodialysis who displayed elevated serum ferritin (981 +/- 44.6 ng/mL) and TSAT <20% (15.6 +/- 3.8%) after having received 1.2 g of i.v. iron dextran over a period of 8 weeks. These patients received oral melatonin, 6 mg/day at night for 30 days. RESULTS: After this treatment, all of them markedly increased TSAT values, reaching 35.5 +/- 6.7% (P < 0.0001 vs basal values). In addition, ferritin values decreased to 754.4 +/- 263.7 ng/mL (P < 0.05), and serum iron dramatically increased in all of the patients under study (42.4 +/- 9.4 vs 109.7 +/- 24.3 microg/dL; P < 0.0001). Values for haematocrit (28.6 +/- 2.7 vs 31.9 +/- 3.57%; P < 0.05) and haemoglobin (9.19 +/- 0.97 vs 10.04 +/- 1.29 g/dL; P < 0.05) were also improved. Measurements were then repeated 2 weeks after melatonin withdrawal, showing an impressive decrease in TSAT (16.4 +/- 5.3%; P < 0.00001) and serum iron (48 +/- 14.7 microg/dL; P < 0.0001) values and an almost significant increase in ferritin values (954.4 +/- 86 ng/mL; P < 0.054). CONCLUSION: The present study demonstrates that melatonin may strongly correct the reticuloendothelial blockade seen in dialysis patients under an inflammatory status, thus allowing a better management of iron derangements and renal anaemia.     

Tropisetron: optimal dosage for children in prevention of chemotherapy-induced vomiting

The antiemetic efficacy and tolerability of Tropisetron (Navoban, Novartis Pharma Switzerland AG, Bern), a selective 5-hydroxytriptamine receptor antagonist, has been assessed in the prevention of acute vomiting in children receiving chemotherapy for solid tumors. Tropisetron iv was given 30 min before administration of chemotherapy at a dose of 5 mg in children <20 kg body weight and at a dose of 10 mg in those >20 kg. A total of 50 children were studied in 189 courses of chemotherapy. Control of emesis was defined as total in absence of acute vomiting, as major if 1 or 2 events of acute vomiting occurred, and as not controlled if >2 events of acute vomiting occurred. Response was studied, taking into account Tropisetron dosage, degree of emetogenicity of the chemotherapeutic agents in pretreated and non-pretreated patients, and according to age groups. Tropisetron, administered in a single daily dose of 8-12 mg/m(2), was found to be very effective in completely controlling acute emesis in 92% of the courses of moderately and highly emetogenic chemotherapy administered to pediatric patients with solid tumors. Moreover, Tropisetron, at this dosage, did not lead to any adverse effects.     

Glial transcytosis of a photoreceptor-secreted signaling protein, retinoschisin

In vitro studies have clearly shown that signaling/guidance proteins can diffuse to their targets. However, it is unclear whether they can travel by diffusion in vivo, or if they are distributed in the tissue by an active mechanism. Retinoschisin, a signaling molecule related to neuropilins, is synthesized and secreted by photoreceptor cells in the outer retina; then it interacts with inner retinal cells contributing to synaptic organization and optic nerve fiber integrity. We developed an assay to examine how retinoschisin, which is secreted a distance away, reaches its inner retinal targets. We found that retinoschisin is preferentially taken up and carried into the inner retina from the retinal outer border (the photoreceptor side) by Müller cells (the main glial cells of the vertebrate retina). This transcytosis is disrupted by DL-alpha-aminoadipic acid, a Müller cell/glia-specific toxin. Our results suggest that glial uptake/transcytosis can provide an effective and precise alternative for distributing signaling molecules in the nervous system.     

Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase

It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute Gi/o- coupled receptor activation inhibits the activity of several AC isozymes, including Ca2+/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report that both acute Mu-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin sensitive. In addition, we show that proteins that interfere with the activity of Gbetagamma subunits (Gbetagamma scavengers) strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation of AC-VIII. Based on these results, we suggest that Gbetagamma is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.     

eNOS genotype is without effect on circulating nitrite/nitrate level in healthy male population

INTRODUCTION: Nitric oxide (NO) plays an important role in the regulation of the cardiovascular system. It is produced by endothelial nitric oxide synthase (eNOS), which exhibits genetic polymorphisms. Although the clinically relevant polymorphism T(+IhI-786)C reduces eNOS-promoter activity, it is not clear whether circulating nitrite/nitrate (NOx) are affected by this polymorphism. MATERIALS AND METHODS: We addressed this issue by studying a homogeneous group of 200 healthy subjects (males, Caucasians, nonsmokers, 18+IBM-56 years of age, and not taking any medication). Genotypes were determined by restriction fragment length polymorphism and circulating NOx were determined by chemiluminescence. RESULTS: We found nonsignificant effects of the T(+IhI-786)C polymorphism on circulating NOx (mean+ALE-S.D.=52.2+ALE-21.4, 49.0+ALE-17.8, and 45.9+ALE-16.8 +A7w-mol/L for genotypes +IBw-TT,+IB0 +IBw-TC,+IB0 and +IBw-CC,+IB0 respectively) and on total plasma cholesterol concentrations (both P>.05). No correlation was found between circulating NOx and total plasma cholesterol concentrations (P>.05). CONCLUSIONS: Our study provides strong evidence that the T(+IhI-786)C polymorphism does not affect plasma NOx concentrations, which are believed to reflect endogenous production of NO. Therefore, our results suggest that this polymorphism does not affect endogenous NO production.