Benefit of Neoral C2 monitoring in de novo cardiac transplant recipients receiving basiliximab induction

BACKGROUND: For cyclosporine (CsA), 2-hr postdose level (C2) is the best single time point predictor of the area under the curve and a critical measure for effective dosing. The therapeutic CsA microemulsion (Neoral) C2 range in de novo heart transplant patients remains to be determined. PURPOSE: The purpose of this study was to determine the efficacy of CsA C2 monitoring in de novo heart transplant patients receiving basiliximab induction. METHODS: This prospective, multicenter, randomized study enrolled 87 adult heart transplant recipients stratified according to 4 to 6 hrs posttransplant serum creatinine less than or equal to 170 micromol/L (cohort A) or more than 170 micromol/L (cohort B). Patients in cohort A were randomized into three C2 ranges (A1: "high" n=25, 1600-1800 ng/mL; A2: "intermediate" n=27, 1400-1600 ng/mL; and A3: "low" n=24, 1200-1400 ng/mL). Patients in cohort B were randomized into intermediate (n=5) and low C2 (n=6). Target ranges were progressively lowered after 1 month. Immunosuppression included basiliximab, Neoral, mycophenolate mofetil, and corticosteroids. Endpoints were acute rejection and renal function. RESULTS: The incidence of acute rejection at 12 months was 44% in group A1, 41% in group A2, 33% in group A3, and 27% in cohort B. Pretransplant and 12-month creatinine clearance (mL/min) were group A1, 72+/-25 and 64+/-24; group A2, 81+/-32 and 68+/-25; group A3, 91+/-28 and 86+/-26; and cohort B, 62+/-28 and 79+/-37. CONCLUSION: These results suggest that C2 monitoring is safe in de novo heart transplant patients. A low Neoral C2 range in combination with basiliximab induction resulted in preserved renal function without increased risk of acute rejection.     

Bioequivalence testing by statistical shape analysis

Bioequivalence testing has been traditionally centered in summary variables such as AUC, C _max and t _max which filter out the intrinsic information conveyed by discrete sequential concentration–time observations. Comparing entire concentration–time profiles between test and reference formulations for bioequivalence purposes provides stronger evidence about either their similarity or their discrepancy. The Kullback–Leibler information criterion (KLIC) may be computed for each concentration–time across all subjects between formulations of the same drug, with a standard crossover study design. It has been shown that if properly scaled it follow a chi-squared distribution and dependent p-values may be computed in order to construct a bioequivalence criterion. Extensive simulations and real data were used to compare it with the current standard procedures. This statistical shape analysis method may provide important clinical and regulatory advantages.     

Immunological and allergenic responses induced by latex fractions of Calotropis procera (Ait.) R.Br

Immunological and allergenic responses against the latex of Calotropis procera were investigated in mice by oral and subcutaneous routes. The latex was fractionated according to water solubility and molecular size of its components. The fractions were named as non-dialyzable latex (NDL) corresponding to the major latex proteins, dialyzable latex (DL) corresponding to low molecular size substances and rubber latex (RL) which was highly insoluble in water. Anti-sera against these fractions were assayed for total IgG and IgA titration by ELISA and IgE and IgG(1) were quantified by passive cutaneous anaphylaxis (PCA) in rats and mice, respectively. None of the fractions induced antibodies level increases when mice received latex fractions by oral route and thus, did not develop allergy. Nonetheless, anti-sera of mice sensitized with NDL and RL by subcutaneous route displayed considerable immunological response while DL did not. IgG level augmented consistently against NDL and RL while IgA response was detected only to NDL. NDL and RL induced very strong PCA reactions suggesting that both fractions would contain latex substances involved in allergy. Furthermore, protein analysis of NDL and RL suggests that RL still retain residual proteins abundantly found in NDL that could explain its similar allergenic effect. No IgG(1) reaction was detected in any of the anti-sera tested. According to the results, the proteins of latex of Calotropis procera can provoke allergy by subcutaneous route. The NDL has previously shown to display anti-inflammatory and analgesic activities by intraperitoneal injection. It should be relevant to determine whether NDL could induce such activities when assayed by oral route since it was ineffective to induce allergy by this way.     

Application of endograft to treat thoracic aortic pathologies: a single center experience

PURPOSE: To evaluate our experience of thoracic endoluminal graft (ELG) repair of various thoracic aortic pathologies using a commercially available device approved by the Food and Drug Administration. Our patient population includes patients eligible for open surgical repair and those with prohibitive surgical risk. METHODS: From March 1998 to March 2006, endovascular stent repair of the thoracic aorta was performed on 406 patients with 324 patients (median age 72; 200 male) receiving the Gore Excluder endograft. Patient demographics, procedural characteristics, complications, including endoleak, spinal cord ischemia, and mortality, were retrospectively reviewed during follow-up. All patients were followed with chest computer tomography at 6 months and yearly. Statistical analysis was performed utilizing the SPSS Windows 11.0 program. Logistic regression (univariate) analysis used to identify risk factors for paraplegia; analysis of variance (ANOVA) for endoleak distribution; and chi(2) used to analyze variables. Survival analysis was done using SAS version 9.1 (SAS Institute, Cary, NC). RESULTS: Three hundred twenty-four patients were treated with Gore Excluder graft between March 1998 and March 2006. One hundred fifty-seven patients (48.5%) had atherosclerotic aneurysms, 82 (25.3%) had dissections type B (DTB), 34 (10.5%) had penetrating ulcers (PU), 26 (8.0%) with pseudoaneurysms (PSA), 11 (3.4%) had transections (MVAT), 9 (2.8%) aorto-bronchial fistulas (AoBF), 4 (1.2%) embolization, and 1 (0.3%) aorto-esophageal fistula (AoEF). Preoperative aneurysm sac size in TAA ranged from 5 to 12 centimeters, average size 6.3 cm. Sac shrinkage occurred in 65% (102 of 157) of patients. Average postoperative sac size of 5.4 cm in a mean follow-up of 20.4 months. One hundred cases (31.5%) were nonelective; 49 (15.1%) were ruptures. Overall complication was 22.7%, 14.2% (46) in elective cases and 8.5% (28) in nonelective cases. Paraplegia occurred in five (1.5%) patients and paresis in three (0.9%); two of the latter improved and one resolved completely prior to discharge. Incidence of paraplegia was statistically significant (P value < .05) with retroperitoneal approach, perioperative blood loss greater than 1000 cc, and aortic coverage greater than 40 cm. Early endoleaks included 18 (5.5%) type I, four (1.2%) type II, and two (0.6%) type III. Thirty-day mortality was 5.5% (18 related deaths, including three intraoperative deaths). A log rank test did not find statistical differences in actuarial survival with 30-day related mortality between TAA and other pathologies (P = .29) or between DTB and other pathologies (P = .97). Late mortality was 9.6% with 31 unrelated deaths. Follow-up ranged between 1 month and 70 months, average 17 months. CONCLUSIONS: Endoluminal grafting is a feasible alternative to open surgical repair for thoracic aortic pathologies. After more than 300 cases, 30-day morbidity and mortality compares favorably with open repair. Paraplegia remains low as a complication and increases in incidence with retroperitoneal approach, increased perioperative blood loss, and increased aortic coverage.     

C-type natriuretic peptide stimulates pancreatic exocrine secretion in the rat: role of vagal afferent and efferent pathways

We previously reported that C-type natriuretic peptide (CNP) increases amylase release in isolated pancreatic acini through natriuretic peptide receptor C activation and enhances pancreatic exocrine secretion via vagal pathways when applied to the brain. In the present study we sought to establish whether CNP was involved in the peripheral regulation of pancreatic secretion. Anesthetized rats were prepared with pancreatic duct cannulation, pyloric ligation and bile diversion into the duodenum. CNP dose-dependently enhanced pancreatic flow, chloride and protein excretion but did not modify bicarbonate output. A selective natriuretic peptide receptor C agonist enhanced pancreatic flow and mimicked CNP-evoked protein output but failed to modify chloride secretion. Truncal vagotomy, perivagal application of capsaicin and hexamethonium reduced CNP-evoked pancreatic flow and abolished chloride excretion but did not affect protein output. Furthermore, pre-treatment with atropine reduced both CNP-stimulated pancreatic flow and chloride excretion but failed to modify protein excretion. Partial muscarinic blockade of CNP-evoked chloride output suggested that mediators other than acetylcholine were involved. However, CNP response was unaltered by cholecystokinin and vasoactive intestinal peptide receptor blockade or by nitric oxide synthase inhibition. In conclusion, CNP-stimulated pancreatic flow through the activation of the natriuretic peptide receptor C and the vago-vagal reflex but it increased protein output only by natriuretic peptide receptor C activation and chloride excretion by vago-vagal reflexes. Present results suggest that CNP may play a role as a local regulator of the exocrine pancreas.     

Could a rural lifestyle decrease the prevalence of erectile dysfunction?

OBJECTIVE: To determine the prevalence of erectile dysfunction (ED) in a specific population and explore potential correlates with lifestyle. SUBJECTS AND METHODS: This prospective observational study, covering a population of a very small rural town, included 2000 men aged > or = 20 years from a total population of 121 831 (51% female and 49% male). The International Index of Erectile Function was completed by each of the 2000 men at their homes over a 1-year period. Another questionnaire assessing socio-economic status and health-related determinants of ED were also completed. RESULTS: All 2000 men completed the questionnaires; overall, only 34 reported ED (1.7%). The frequency of mild, mild to moderate, moderate and severe ED was 12%, 29%, 20% and 38%, respectively. Significantly more men aged > 51 years had ED than those aged <41 years (0.05% and 0.45%, respectively; P < 0.001). There was no difference in ED with salary levels. CONCLUSION: The prevalence of ED in this particular rural population of Brazil was very low, at only 1.7%. Although ED increases with age, this association was not apparent for all age groups. It seems that several others factors, e.g. lifestyle, culture and diet, could be important for the onset of ED.     

Randomized trial of skin closure after laparotomy for gynaecological surgery

BACKGROUND: New suture materials may provide patients with a better cosmetic outcome at similar pain and wound complication rate. METHODS: To assess pain and cosmetic outcome among patients randomized to receive wound closure after laparotomy for gynaecological surgery using staples, polyglecaprone 25 or polyglecaprone 6211 subcuticular sutures. RESULTS: Overall, 90 patients (87.4% consent rate) were randomized. There was no difference in wound complications and pain between the three groups. Patients randomized to polyglecaprone 6211 subcuticular sutures rated the cosmetic result at 1 and 6 weeks after surgery somewhat lower than patients randomized to the two alternative groups; however, at 3 months after surgery, all three groups rated the cosmetic result as similar. CONCLUSIONS: This study suggests that the three wound closure methods have similar short-term pain and cosmetic outcomes, as well as a similar rate of wound complications, leaving the decision of the most appropriate closure method to individual surgeons.