Statistical considerations in the interpretation of negative carcinogenicity data

The regulation of toxic substances present in the environment requires that carcinogens be distinguished from noncarcinogens on the strength of the available toxicological and epidemiological evidence for carcinogenicity. In this article, we consider the difficulties associated with establishing strong evidence against carcinogenicity. In particular, the ability of both animal and human studies to detect small increases in tumor occurrence rates is evaluated in statistical terms. Consideration is also given to resolving apparent conflicts between the toxicological and the epidemiological sources of data.     

Reversible changes in cerebral activity associated with acidosis in preterm neonates

Murdoch Eaton DG, Wertheim D, Oozeer R, Dubowitz LMS, Dubowitz V. Reversible changes in cerebral activity associated with acidosis in preterm neonates. Acta Paediatr 1994;83:486–92. Stockholm. ISSN 0803–5253
Computerized online EEG monitoring in ventilated preterm infants less than 32 weeks' gestation enabled evaluation of the effect of acidosis on cerebral function. All episodes of acidosis were found to be associated with changes in the levels of cerebral activity. In 21 of the 32 episodes, EEG activity returned to pre-acidosis levels after therapeutic intervention. The duration of EEG abnormality was related to the severity of acidosis. However, the time to recovery of the EEG after therapeutic procedures was not related to duration of the EEG change.     

Effects of coenzyme athletic performance system as an ergogenic aid on endurance performance to exhaustion.

This study examined the effects of the Coenzyme Athletic Performance System (CAPS) on endurance performance to exhaustion. CAPS contains 100 mg coenzyme Q10, 500 mg cytochrome C, 100 mg inosine, and 200 IU vitamin E. Eleven highly trained male triathletes were given three daily doses of either CAPS or placebo (dicalcium phosphate) for two 4-week periods using a double-blind crossover design. A 4-week washout period separated the two treatment periods. An exhaustive performance test, consisting of 90 minutes of running on a treadmill (70% VO2max) followed by cycling (70% VO2max) until exhaustion, was conducted after each treatment period. The mean (+/- SEM) time to exhaustion for the subjects using CAPS (223 +/- 17 min) was not significantly different (p = 0.57) from the placebo trial (215 +/- 9 min). Blood glucose, lactate, and free fatty acid concentrations at exhaustion did not differ between treatments (p < 0.05). CAPS had no apparent benefit on exercise to exhaustion.     

Fosinopril. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in essential hypertension.

Fosinopril is a phosphinic acid prodrug which, after oral administration, undergoes rapid hydrolysis to its active diacid, the angiotensin converting enzyme (ACE) inhibitor fosinoprilat. Unlike other ACE inhibitors, fosinoprilat has a compensatory dual route of elimination and is cleared by the liver and kidneys. Thus, in patients with diminished renal function increased hepatic clearance of fosinoprilat is noted and, similarly, in patients with diminished hepatic function increased renal clearance seems to occur. Because of this compensatory elimination, fosinopril therapy for all patients can begin with the same recommended dosage. Fosinopril 10 to 40mg administered once daily is an effective antihypertensive regimen that has shown efficacy similar to that of enalapril 5 to 10 mg/day, propranolol 80 to 160 mg/day, hydrochlorothiazide 25 to 50 mg/day and sustained release nifedipine 40 mg/day in preliminary clinical trials. Generally, fosinopril is well tolerated and adverse events associated with the drug are usually mild and similar to those associated with other ACE inhibitors. Thus, fosinopril appears to be a useful alternative to certain 'established' agents used for treating patients with essential hypertension.     

Triplets and embryo transfer policy

The social and financial consequences of multiple pregnancies following embryo transfer have led us to question our policies and re-evaluate 'good practice' recommendations. A postal survey was carried out to assess current practice regarding embryo transfer policy and to understand the factors on which these decisions are based. The results demonstrated a wide variation in practice throughout the country despite the finding that most centres use the same criteria on which to base their decision to transfer either two or three embryos. Doctors seem to be the most influential individuals in the decision-making process, although when three embryos are transferred, the opinion of the patient is paramount. Patients are usually given information about the risks of multiple pregnancy but despite this, 69% felt that a multiple pregnancy would be the ideal outcome of in-vitro fertilization (IVF). It is strongly advised that patients are given more details of the consequences of multiple pregnancy and that centres which have a high multiple pregnancy rate adopt a policy of transferring only two embryos.      

Tissue distribution metabolism and excretion of 2,2′,4,4′, 5-pentachlorodiphenyl ether in the rat

The tissue distribution, metabolism and excretion of ¹⁴C-2,2,4,4,5-pentachlorodiphenyl ether (PCDE) were studied in the rat. Radioactivity was distributed in all tissues examined, with the highest concentrations being found in the fat followed by the skin, liver, kidney and muscle. Most of the radioactivity found in the tissues was due to unchanged PCDE. Decay of PCDE in the blood was fitted to a four-compartment pharmacokinetic model, and the last compartment had a half-life of 5.8 days. A total of 55% and 1.3% of an orally administered dose was excreted in feces and urine, respectively, in 7 days. More than 64% of the fecal radioactivity was due to unchanged PCDE, while hydroxylated PCDE accounted for 23%.