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 Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy.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.     

Disposition of Tablet and Capsule Formulations of Digoxin in the Elderly

Study Objective . To compare digoxin tablets and liquid-filled capsules with respect to excretion of the drug and its metabolites in urine and feces at steady state. Design . A randomized, crossover trial, each period lasting 3 weeks, with no washout period. Setting . A university hospital. Patients . Six patients, five of whom were elderly, with histories of gastrointestinal disorders, such as hypochlorhydria, intestinal bacterial overgrowth, and inflammatory bowel disease. Interventions . The patients received digoxin once/day in either tablet or capsule form for 3 weeks, and then were switched to the other formulation. Total urinary and fecal excretion from the last 3 days of each regimen were analyzed for the drug and metabolites. Measurements and Main Results . No statistically significant differences were found between tablets and capsules in recovery of digoxin or its metabolites in urine or feces (p=0.05). One subject had a 4-fold increase in urinary drug excretion and 50% decrease in fecal excretion after taking the capsules compared with tablets. Intersubject variability in extent and type of metabolite excretion was greater than intrasubject variability. Conclusions . Fecal analyses may be an accurate way to classify patients as formers of digoxin reduction products.     

The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.     

CONGENITAL DISLOCATION OF THE KNEE AS A CONSEQUENCE OF PERSISTENT AMNIOTIC FLUID LEAKAGE

SUMMARY A case congenital dislocation of both knees and dislocation of the left hip in an infant whose mother had a chronic amniotic fluid leakage after mid-trimester amniocentesis.     

Hand-assisted laparoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma.

OBJECTIVE: We report our experience with hand-assisted laparoscopic nephroureterectomy (HALN) for upper urinary tract transitional cell carcinoma and compare our results with a contemporary series of open nephroureterectomy (ON) performed at our institution. METHODS: Between August 1996 and May 2003, 90 patients underwent nephroureterectomy for upper-tract transitional cell carcinoma (TCC). Thirty-eight patients underwent HALN, while 52 had an ON. End-points of comparison included operative time, estimated blood loss (EBL), intraoperative and postoperative complications, length of hospital stay, pathologic grade and stage of tumor, and tumor recurrence. RESULTS: The mean patient age was 72.3 and 70.6 years in the ON and HALN groups, respectively. Mean operative duration was 243 minutes (ON) and 244 minutes (HALN), with an EBL of 478mL in the open group versus 191 mL in the hand-assisted group (P<0.001). No intraoperative complications occurred, but postoperative complications occurred in 4% and 11% of the ON and HALN groups, respectively (P=0.21). The mean hospital duration was 7.1 days (ON) versus 4.6 days (HALN) (P<0.01). No difference existed in the pathologic grade or stage distribution of urothelial tumors between the 2 groups. The mean follow-up was 51.0 months in the ON group and 31.7 months in the HALN group. Recurrence of urothelial carcinoma occurred in 50% of patients who underwent ON and 40% treated by HALN (P=0.38) at a median interval of 9.1 and 7.7 months, respectively, after surgery. CONCLUSION: Hand-assisted laparoscopic nephroureterectomy is an effective modality for the treatment of upper urinary tract urothelial carcinoma. Patients benefited from less intraoperative blood loss and a shorter hospitalization with an equivalent intermediate-term oncologic outcome compared with that of the open approach.