Tacrolimus Combined with Two Different Dosages of Sirolimus in Kidney Transplantation: Results of a Multicenter Study

Tacrolimus combined with mycophenolate mofetil (MMF) is an effective regimen in kidney transplantation. This study compared the efficacy of combining tacrolimus and two different dosages of sirolimus with an established tacrolimus-MMF regimen. Each day in addition to tacrolimus, 325 patients received 2 mg sirolimus (TAC-SRL2 mg), 325 patients received 0.5 mg sirolimus (TAC-SRL0.5 mg) and 327 patients 1 g MMF (TAC-MMF). The initial tacrolimus dose was 0.2 mg/kg/day. Sirolimus patients received loading doses of 6 or 1.5 mg, and daily doses of 2 or 0.5 mg thereafter. Steroid administration was identical for all groups. The incidence of biopsy-proven acute rejection was lower in the TAC-SRL2 mg group (15.7%) compared with the TAC-SRL0.5 mg (25.2%, p = 0.003) and the TAC-MMF groups (22.3%, p = 0.036). Six-month graft survival was 91.0% (TAC-SRL2 mg), 92.6% (TAC-SRL0.5 mg) and 92.4% (TAC-MMF); the respective values for patient survival were 98.1%, 97.8% and 97.9%. Thirty-four patients (10.5%), 19 patients (5.8%) and 16 patients (4.9%) in the TAC-SRL2 mg, TAC-SRL0.5 mg and TAC-MMF groups, respectively, discontinued the study because of adverse events. Hyperlipemia was reported more often in the TAC-SRL2 mg group (24.0%) compared with 19.4% (TAC-SRL0.5 mg) and 11.0% (TAC-MMF; p < 0.05). Combining 2 mg sirolimus/day with tacrolimus results in lower rates of acute rejection, but a higher incidence of adverse events.     

Effect of maternal and infant covariates on sibship correlation in birth weight

Birth weight on 12,644 singleton infants from 6,196 sibships born in Maryland between 1980 and 1984 were used to estimate the effects of nine maternal and infant covariates on the sibship correlation in birth weight. Assuming a homogeneous correlation across all families, the estimated intraclass correlation was 0.4664 (+/- 0.0099). This high sibship correlation makes it possible to predict, with reasonable accuracy, the birth weight of a child given information on previous sibs, as well as covariates on the mother and/or infant pertinent to a given pregnancy. The reduction in variance associated with incorporating information on the nine covariates used here was approximately equal to that obtained by conditioning on a single previous sib. Testing for heterogeneity in correlation among different groups of families showed that a crude measure of parity (first live birth vs. other), time between births, mother's marital status, and maternal age at the birth of the last child significantly influenced the sibship correlation in birth weight.     

Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

Value of a random single Doppler study of the umbilical artery for predicting perinatal outcome

A prospective blinded study was performed on 191 high-risk patients with pregnancies ranging from 25 to 42 weeks gestation to investigate the value of a single Doppler analysis of the umbilical artery blood flow waveform (systolic-to-diastolic ratio, S/D) for predicting poor perinatal outcome. This was defined as the presence of heavy meconium, delivery of a growth-retarded infant, an umbilical cord arterial pH less than 7.2, or a 5-minute Apgar score less than 7. The interval between Doppler examination and delivery ranged from 12 hours to 15 weeks. No clinical data were available to the examiner performing the Doppler study. Moreover, the Doppler measurements were unknown to the attending physicians. The sensitivity, specificity, and positive and negative predictive values of the Doppler study in predicting outcome were 30.4%, 92.9%, 36.8%, and 92.6%, respectively, with an adverse outcome prevalence of 12%. These results indicate that a single random S/D ratio from the umbilical artery is not an adequate screening test for the risk of perinatal complications.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Intraperitoneal secretion of interleukin-6 during continuous ambulatory peritoneal dialysis

Interleukin-6 (IL-6) was determined in serum and peritoneal dialysis effluent (PDE) of patients on chronic ambulatory peritoneal dialysis (CAPD) by a biological assay measuring the proliferation of the IL-6-dependent 7TD1 cell line. Six patients free of peritonitis displayed low but significant levels of IL-6 (mean +/- 42 pg/ml) in PDE, while IL-6 was undetectable in serum. In 6 patients with staphylococcal peritonitis, a tremendous increase in PDE levels of IL-6 was noted (range: 5,832-37,491 pg/ml), while serum IL-6 remained either undetectable or on a low level except in one case. After 5 days of antibiotic treatment, IL-6 levels in PDE returned to basal values. We conclude that CAPD results in an intraperitoneal secretion of IL-6 which is markedly but transiently increased during peritonitis episodes.