Variance imputation for overviews of clinical trials with continuous response.

Overviews of clinical trials are an efficient and important means of summarizing information about a particular scientific area. When the outcome is a continuous variable, both treatment effect and variance estimates are required to construct a confidence interval for the overall treatment effect. Often, only partial information about the variance is provided in the publication of the clinical trial. This paper provides heuristic suggestions for variance imputation based on partial variance information. Both pretest-posttest (parallel groups) and crossover designs are considered. A key idea is to use separate sources of incomplete information to help choose a better variance estimate. The imputation suggestions are illustrated with a data set.     

Correlates of self-reported everyday memory problems

Using the 1984 Supplement on Aging to the National Health Interview Survey, this study examined the prevalence and correlates of self-reported everyday memory problems in a sample of persons aged 55 and older (N = 14,783). Fifteen percent of the respondents reported having had trouble remembering things frequently during the past year, but 26 percent indicated having had no trouble. Of those reporting any problems, only 18 percent said the problem was happening with increasing frequency. Sex, age, educational attainment, subjective health status, perceived changes in health status, number of functional limitations, and vision and hearing impairments were examined in bivariate and multivariate analyses to identify significant predictors of self-reported memory problems.     

Corticotropin releasing factor: basic studies and clinical applications

Corticotropin releasing factor (CRF) is a newly sequenced peptide first isolated from sheep hypothalami and thought to be an important modulator of both the pituitary-adrenal axis and the sympathetic nervous system. We administered intravenous, intramuscular, and intracerebroventricular CRH to non-human primates and measured plasma ACTH, beta endorphin, cortisol, GH and PRL responses to CRF. In addition, we determined the pharmacokinetic properties of I125 in these primates. We administered CRF as an intravenous bolus or as a continuous infusion to normal volunteers and as an intravenous bolus to patients with disorders of the hypothalamic-pituitary-adrenal axis, such as Cushing's syndrome and adrenal insufficiency, and patients with endogenous depression and mild hypercortisolism, and assessed their plasma ACTH, cortisol, GH and PRL responses. In addition, we determined the pharmacokinetic properties of CRF in man by measuring CRF immunoreactivity in plasma. CRF given intravenously to primates or man is a slowly metabolized, long-acting, secretagogue of ACTH, beta-endorphin and cortisol. When given intracerebroventricularly to primates it stimulates the hypothalamic-pituitary-adrenal axis without escaping into the plasma and it is actively cleared in the CNS. It does not cross the blood brain barrier appreciably when given intravenously. CRF given to primates and men as an intravenous continuous infusion has only mild ACTH stimulating effects and this may be due to an intact cortisol negative feedback system. Finally, CRF causes characteristic plasma hormone responses in patients with Cushing's disease, adrenal insufficiency and depression.     

Characterization of murine erythropoietin

Although erythropoietins from human and sheep sources have been purified, a mouse erythropoietin remains essentially uncharacterized despite the fact that the mouse is most commonly used to assay for erythropoietin. Because other murine growth factors may have erythropoietic activity it will be essential to compare these with erythropoietin from murine sources rather than from other species. Here we compare the physicochemical properties and some of the bioactivities of erythropoietins from anemic mouse serum and human urine in parallel fractionations. Both molecules showed similar molecular weights (40-45,000) by gel filtration and similar retention characteristics on reverse-phase high-performance columns. However, they differed in their relative solubility in ammonium sulfate, hydrophobicity on phenyl-Sepharose, and in their ability to bind to a phenyl-boronate agarose column. Despite these differences the two molecules stimulated the same number of CFU-E in the mouse fetal liver assay and did so with similar dose-response relationships. The data indicate that putative murine erythropoietic stimuli must be compared with murine erythropoietin and not human urine erythropoietin before concluding, on the basis of fractionation results, that a factor is different from erythropoietin.     

Survival in Chronic Lymphocytic Leukemia

Survival of 839 chronic lymphocytic leukemia patients has been reviewed in relationto a number of patient and disease characteristics. Over-all, the relative 5-yr survival rate was 44%. Studying survival byage and sex led to the following observations: Dividing age into intervals < 50,50-59, 60-69, 70-79, and 80 yr and over,relative survival declined with increasingage; relative 5-yr survival for females washigher than that for males-50% versus 41%.This pattern of superior survival of femalesover males was noted in all but one of theage intervals. Survival was negatively associated with the presence of recordedclinical signs and symptoms, hematologicalabnormalities, and pathological bone marrow findings. Differences in survival werealso found by treatment category and interval from diagnosis to initiation of treatment. Adjustment for differences in distribution of each of these variables did notmaterially diminish the survival differencesnoted by age and sex. An unexpected pattern of survival in relation to white bloodcount level was noted. Survival increasedwith increasing white blood count at diagnosis, peaking in the interval at 25,000-49,000, and decreasing after that. Whensurvival by white blood count was adjustedfor some variables which were found to beassociated with survival, the gradient wasstill noted, though somewhat reduced.

Submitted on June 12, 1972 Revised on February 12, 1973 Accepted on February 16, 1973     

Effects of the environment on the behavioural response of mice to non-ataxic doses of ethyl alcohol.

An ethological analysis was used to examine the effects of ethyl alcohol on social behaviour in mice which were placed in different social contexts. In encounters between unfamiliar males, alcohol-treated mice from a diverse environment showed more exploration on the bars of an unfamiliar cage and less social investigation than controls. In an encounter situation between males and females, male mice given alcohol showed a significant increase in frequency and duration of all forms of social and sexual investigation other than mounts and attempted mounts compared with untreated males. In a territorial situation, alcohol administration before territory establishment resulted, on each of four occasions, in the dominant mouse of the alcohol-treated group becoming despot over the whole enclosure, whereas after territory establishment this effect was not seen. The overall effect of alcohol was, therefore, to increase the type of behaviour that was already stimulated by the test situation. The significance of these findings in relation to the differential effects of alcohol on different areas of the nervous system is discussed.     

Epilepsy and behaviour of the Mongolian gerbil: an ethological study

Ethological procedures were used to compare behaviour characterizing seizure-sensitive and seizure-resistant gerbils and to examine motor components of their major convulsions. Seizure-sensitive gerbils showed less social investigation when encountering an unfamiliar resident than their seizure-resistant counterparts. Sequence analysis showed the motor components of major seizures to segregate into three largely independent groups comprising elements associated with clonic-tonic spasms, with subsequent extensor immobility and with returning abnormal activity which preceded the resumption of normal behaviour. In grade 4 and 5 convulsions, the motor components of clonic-tonic spasms included the elements "rigid upright posture," "foreleg treading," "fall over," "mouth spasms." Straub tail and opisthotonus which were not seen in grade 3 seizures. The durations of clonic spasms and extensor immobility were longer in seizures of grades 4 and 5 than in those of grade 3. The abnormal motor activity following extensor immobility was complex and unrelated to seizure severity. It is suggested that observational studies in epilepsy may contribute to our understanding of the underlying pathophysiological processes.