Effects of different calcium sources on iron absorption in postmenopausal women.

We measured the effect of calcium from food and supplement sources on whole-body retention of 59Fe in 19 normal postmenopausal women. Each woman received a placebo and 500 mg calcium from a mixed calcium citrate-malate salt (CCM), from orange juice plus CCM, and from milk after a test breakfast meal to which 59Fe had been added. The test meal contained 238 mg calcium. Whole-body countings of 59Fe were performed before and 30 min and 2 wk after each test meal. Retention of 59Fe was 8.3 +/- 1.1% (means +/- SEM) with placebo, 3.4 +/- 0.78% with milk, 6.0 +/- 0.97% with CCM, and 7.4 +/- 1.7% with CCM plus orange juice. When compared with placebo, milk and CCM significantly lowered iron retention (p less than 0.05) whereas CCM plus orange juice did not. The reduction with milk was greater than that with CCM (p less than 0.05) or CCM plus orange juice (p less than 0.05). The differences in the effects of these calcium sources on 59Fe retention may result from their varied contents of citric and ascorbic acids, known enhancers of iron absorption.

A nonparametric method for evaluating results from laboratory antinociceptive tests.

A method is presented in which Cox's proportional hazards model, a survival analysis technique, is used to assess the results of hot-plate antinociceptive testing. The method appropriately handles censored data values and variable pretest latency times without making arbitrary assumptions about the distribution of the data. It may be used to characterize and compare dose-response curves or to examine the effect of agent or other treatment variables on the response. The technique is easily implemented using the SAS statistical software package. Due to the similar way in which data is obtained, we believe the method to be applicable to several other laboratory models of pain, including the tail-flick, tail-immersion, and paw-pressure (Randall-Selitto) assays.

Age and diet effects on fecal bile acids in infants.

Fecal bile acid patterns and concentrations have been determined for 28 infants who were followed from average ages of 3-11 months. Half were solely breast-fed and half were solely formula-fed at the beginning of the study. Breast-fed infants were found to have significantly (p less than 0.05) lower concentrations of cholic acid than the formula-fed group, up to an average age of 5 months. Concentrations of deoxycholic and lithocholic acids were directionally lower in breast-fed infants at all ages. Concentrations of chenodeoxycholic acid were similar for both groups throughout the study. At the end of the study, breast-fed infants were excreting 17% of their total bile acids in the form of secondary acids, compared to 33% for formula-fed infants. This pattern persisted long after the infants began weaning. Formula-fed infants were found to have lithocholic acid in their stools at a significantly (p less than 0.05) earlier age than breast-fed infants. Appearance of deoxycholic acid was at similar ages for both groups. Both of these secondary acids were found to occur at much younger ages (approximately 2 months) than has been previously reported. These observed differences are attributed to the distinct intestinal microbial populations encouraged by the different diets.

The rapid hydrolysis and efficient absorption of triglycerides with octanoic acid in the 1 and 3 positions and long-chain fatty acid in the 2 position.

We describe rapid hydrolysis of triglycerides with medium-chain fatty acids in the 1 and 3 positions and a long-chain fatty acid in the 2 position. The triglycerides, 2-linoleoyl-1,3-dioctanoyl glycerol (8L8) and 2-oleoyl-1,3-dioctanoyl glycerol, hydrolyzed more rapidly than triglycerides comprising all long-chain fatty acids. The in vitro hydrolysis rate of 8L8 was similar to that of a medium-chain triglyceride of octanoic and decanoic acids in random positions. From intestinal recovery of 14C 45 min after injection into the isolated, irrigated loop of the small intestine of an anesthetized rat, the amount of 2-[1-14C]linoleoyl-1,3-dioctanoyl glycerol absorbed was greater than 2 1/2 times that of its long-chain analog, 2-[1-14C]linoleoyl-1,3-dioleoyl glycerol. These data support the ease of hydrolysis and absorption of 1,3-dioctanoyl triglycerides with long-chain fatty acids in the 2 position.

Sample size and duration for cohort studies of survival time with covariables.

The determination of sample size and duration for cohort studies with covariables is considered. An exponential model, using the form due to Feigl and Zelen (1965, Biometrics 21, 826-838) for the hazard with covariates and asymptotic normality of the maximum likelihood estimators of the parameters, is assumed. Emphasis is on applications involving two parameters, namely an underlying hazard and the coefficient of a single concomitant variable. The results of George and Desu (1974, Journal of Chronic Diseases 27, 15-24) are reproduced and extended to take account of censoring. An example with more than two dose groups is presented. For situations where the sample size is fixed and Type I error is specified, extension of the follow-up time is considered for the purpose of achieving the desired Type II error, given a null hypothesis and specific alternative hypothesis. Generalizations to situations with other forms for the hazard rate and multiple covariables are indicated.

A double-blind, placebo-controlled study of sucrose polyester in hypercholesterolemic outpatients.

Sucrose polyester (SPE) was studied in a double-blind, placebo-controlled trial in 91 outpatients with primary hypercholesterolemia. All patients maintained an isocaloric diet with cholesterol intake of 400 mg/day and a polyunsaturated to saturated fat ratio of 0.8 to 1.2 for the duration of the study. The study sequence consisted of a diet lead-in period, a first 8-wk treatment period, a 4-wk washout period, and a second 8-wk treatment period. Subjects were randomly assigned to six groups that differed by SPE dose (8, 16, and 32 g/day) and by the treatment period in which either SPE or an olive oil placebo was given in a bread spread formulation. Compared to placebo, the 8, 16, and 32 g/day doses of SPE decreased low-density lipoprotein cholesterol by 2%, 4% (p less than 0.05), and 5% (p less than 0.05) respectively, without changing high-density lipoprotein cholesterol. On SPE, 14/91 (15%) of the subjects experienced a decrease in low-density lipoprotein cholesterol greater than or equal to 10%, while only 2/91 (2%) showed this decrease with placebo.

Method for predicting fill weight variation when packing powders using vacuum/purge fillers.

The present report demonstrates that for at least four pharmaceutical powders, the variation in fill weight associated with a vacuum/purge filling port is correlated with the length-diameter ratio of that port. This relationship has been mathematically modeled, and a design curve based on production data is presented, which depicts this relationship over a wide range of length-diameter ratios. For powders with properties similar to those presented, the design curve may be used to determine the dimensions of the port which will yield acceptable process weight control. Fill weight variances also can be predicted given a fixed port diameter. For other powders, the model can be used to create design curves with a few data points.

Practical considerations for approximating relative risk by the standardized mortality ratio.

The standardized mortality ratio is a widely used and often criticized summary statistic for studies of occupational mortality. In this paper the authors discuss practical conditions under which relative risk can reasonably be approximated by the standardized mortality ratio. When the true relative risk is greater than 100%, the standardized mortality ratio overestimates relative risk no matter how small the mortality rates or how short the age bands utilized in the analysis. However, when the excessive mortality is consistent across the age bands, the standardized mortality ratio can usefully approximate relative risk for some applications, such as those involving site-specific cancers, providing the age bands employed are not too large.