Evidence that drug flux across synthetic membranes is described by normally distributed permeability coefficients.

Over recent decades, the use of in vitro diffusion cell studies to assess skin permeability has evolved into a major research tool, providing key insights into the relationships between skin, drug and formulation. Sometimes, such studies involve synthetic membranes as this approach can yield useful inferences with respect to drug-skin partitioning and diffusion phenomena. Yet despite the popularity of such studies, it is still not at all known whether typical solute transport across synthetic barriers results in a normal distribution of permeability coefficients or alternatively some type of skewed distribution. The present study aims to shed light on this issue. To this end, five compounds (testosterone, oestradiol, corticosterone, aldosterone and adenosine) exhibiting a broad range of octanol-water partition coefficient values were selected as test penetrants. The protocol involved taking multiple replicate measurements of each drug's passive steady state flux through poly(dimethylsiloxane) membrane. Each penetrant's resultant permeability coefficient database was subjected to a Kolmogorov-Smirnov (KS) test for normality. It was found that the permeability coefficients of all five drugs were distributed in a Gaussian-normal fashion. The theoretical significance and practical impact of these findings are discussed.     

Executive functions and adaptive functioning in young adult attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is associated with impairments in occupational, social, and educational functioning in adults. This study examined relations of adaptive impairment to ADHD symptom domains (inattentive-disorganized and hyperactive-impulsive) and to deficits in executive functioning (EF) in 195 well-characterized adults (105 ADHD, 90 non-ADHD, between ages 18 and 37). Participants completed a battery of EF measures as well as assessments of adaptive functioning. Confirmatory factor analyses were used to validate latent factors for adaptive functioning and EF. In a measurement model, weaker EF was associated with poorer adaptive functioning (r = -.30). When multi-informant composite variables for current inattentive-disorganized and hyperactive-impulsive ADHD symptoms were included in the structural model, EF no longer predicted adaptive functioning. While both symptom composites were similarly related to EF (inattentive-disorganized r = .36; hyperactive-impulsive r = .29), inattentive-disorganized symptoms accounted for more variance in adaptive functioning (67.2% vs. 3.6%). Furthermore, for retrospectively reported childhood symptoms of ADHD, only the inattentive-disorganized symptom domain was related to EF or adaptive impairment. These results suggest that, in adults with ADHD, inattentive-disorganized symptoms may be the primary contributor to key aspects of poorer adaptive function and may be the behavioral path through which EF deficits lead to adaptive impairment.     

Non-HIV-Related Progressive Multifocal Leukoencephalopathy (PML): A Tertiary Cancer Center Experience

In the course of 1 year at a tertiary cancer center, 3 patients (2 men; 1 woman; age 51-75 years) were seen in neurological consultation (1.5% of all consultations). Clinical course in all patients was of a progressive neurologic disorder not consistent with either a primary or secondary malignancy. Magnetic resonance (MR) imaging was most informative with respect to diagnosis and subsequent management. Brain biopsy was performed in all patients to assist in both diagnosis and prognostication. All patients were determined to have progressive multifocal leukoencephalopathy (PML) by brain biopsy.     

Calcium intake in the elderly: validation of a dietary questionnaire

Epidemiological studies of calcium and osteoporosis have been hampered by the lack of a suitable tool for assessing calcium intake. This report describes a new frequency and amount questionnaire for measuring present and past calcium intake in the elderly. The validity of the questionnaire was tested against two commonly used standards of dietary assessment, five-day duplicate diets and seven-day weighed dietary inventories. The resulting correlation coefficients were, respectively, r = 0.76 and r = 0.69, while that for repeatability was r = 0.84. Furthermore, the questionnaire categorized subjects into thirds of the distribution of intake with almost no gross misclassification. It is suggested that the present findings may be extended to the majority of normal, healthy elderly subjects, implying wide application for the questionnaire in the assessment of calcium intake in the elderly.     

Intakes and major dietary sources of cholesterol and phytosterols in the British diet

Cholesterol intakes in Britain have been re-estimated by analysing Total Diet samples taken in 1991 and from 1993 National Food Survey records. The Total Diet samples contained only 284 mg/day compared with 319 mg/day in 1987 and 337 mg/day in 1981, while the National Food Survey showed intakes had fallen to 238 mg/day from 259 mg/day in 1990 and 405 mg/day in 1970-75. More details of the intakes by adults in 1986/87 are given, and compared with the results from the other methods. Daily intakes of eight phytosterols were also estimated, the main ones being β-sitosterol, campesterol, stigmasterol and 57-stigmastenol whose intakes were 104, 49, 10 and 4 mg/day, respectively, in 1991. These intakes had increased since 1981, reflecting the rising consumption of vegetable oils.     

An analysis for menstrual data with time-varying covariates

This paper concerns the analysis of menstrual data; in particular, methodology to identify variables that contribute to the variability of menstrual cycles both within and between women. The basis for the proposed methodology is a parameterization of the mean length of a menstrual cycle conditional upon the past cycles and covariates. This approach accommodates the length-bias and censoring commonly found in menstrual data. Data from a longitudinal study of menstrual patterns and other variables among Lese women of the Ituri Forest, Zaire, illustrate the methodology. A small simulation illustrates the bias caused by incorrectly deleting the censored cycles.