Unraveling the mysteries of serum theophylline levels: a patient care report in the light of pharmacokinetics

One of our patients had trouble maintaining therapeutic and safe levels of theophylline, even though we were careful in planning and monitoring her drug regimen. This case report shows how we were able to use principles of pharmacokinetics to distinguish among plausible explanations for her experience. We discovered that she was not taking the drug consistently as prescribed and that supervised administration resolved apparent contradictions between doses and serum levels. We believe that physicians can use the same information and methods that we used to get better and safer results from theophylline therapy.     

A new anthropometric scale for discrimination between sexes.

Sexual dimorphism with respect to body size and shape has been analysed by means of discriminant function. An anthropometric score has been derived from 111 adult normal males and 108 females, based on 11 anthropometric and three dermatoglyphic variables. The score represents the range of quantified physical phenotypes of 'maleness' and 'femaleness'. Complete separation between the distributions of this score in either sex has been achieved. Predominantly, application of the anthropometric score can be in assessing a relationship between the anthropometric status of 'maleness' or 'femaleness', and cytogenetic or submicroscopic anomalies of sex chromosomes, and in studies of normal inter- and intra-population variation in sexual dimorphism.     

From the Cover: Loss of phosphatidylinositol 4-kinase 2α activity causes late onset degeneration of spinal cord axons

Phosphoinositide (PI) lipids are intracellular membrane signaling intermediates and effectors produced by localized PI kinase and phosphatase activities. Although many signaling roles of PI kinases have been identified in cultured cell lines, transgenic animal studies have produced unexpected insight into the in vivo functions of specific PI 3- and 5-kinases, but no mammalian PI 4-kinase (PI4K) knockout has previously been reported. Prior studies using cultured cells implicated the PI4K2α isozyme in diverse functions, including receptor signaling, ion channel regulation, endosomal trafficking, and regulated secretion. We now show that despite these important functions, mice lacking PI4K2α kinase activity initially appear normal. However, adult Pi4k2a^GT/GT animals develop a progressive neurological disease characterized by tremor, limb weakness, urinary incontinence, and premature mortality. Histological analysis of aged Pi4k2a^GT/GT animals revealed lipofuscin-like deposition and gliosis in the cerebellum, and loss of Purkinje cells. Peripheral nerves are essentially normal, but massive axonal degeneration was found in the spinal cord in both ascending and descending tracts. These results reveal a previously undescribed role for aberrant PI signaling in neurological disease that resembles autosomal recessive hereditary spastic paraplegia.     

Genetic correlates of menarcheal age: a multivariate twin study

Multivariate genetic models were fitted to data from 44 pairs of MZ and 42 pairs of DZ twin girls on weight, height, and skeletal maturation at the age of menarche, in order to obtain information on genetic relationships of those measures with the age of menarche. The relationships of all three physical measures with this age were largely genetically controlled, but a genetic system controlling skeletal maturity was identified as the only genetic determinant of menarcheal age, independent of those systems of the two remaining physical measures. Heritabilities of all individual traits considered in the study were uniformly high. Possible links of genetic information with hormonal functions determining menarche are discussed.     

New evidence for,and challenges in,linking small CGG repeat expansion FMR1 alleles with Parkinson's disease

We recently reported a significant increase in the frequency of carriers of grey zone (GZ) alleles of FMR1 gene in Australian males with Parkinson's disease (PD) from Victoria and Tasmania. Here, we report data comparing an independent sample of 817 PD patients from Queensland to 1078 consecutive Australian male newborns from Victoria. We confirmed the earlier finding by observing a significant excess of GZ alleles in PD (4.8%) compared to controls (1.5%). Although both studies provided evidence in support of an association between GZ‐carrier status and increased risk for parkinsonism, the existing evidence in the literature from screening studies remains equivocal and we discuss the need for alternative approaches to resolve the issue.     

Ridgecounter: A program for obtaining semi-automated finger ridge counts

Finger ridge count is a valuable quantitative phenotype used in a wide range of biological and anthropological research. However, the scoring of the phenotype is both labour intensive and error prone. This paper describe a freely available software program, RIDGECOUNTER, that can be used to obtain ridge counts from digitized prints (either collected using a digital fingerprint scanner or scanned from an inked print). The program yields semi-automated ridge counts and logs the location of the user-selected core and delta points to aid in the training of new researchers and ensure the repeatability of count. In a validity study of 451 prints, the semi-automated ridge counts of digital prints showed good agreement (r?=?0.957) with traditional manual counts of inked-rolled prints (which were obtained 2 years apart and counted by different researchers). In a reliability study of 200 prints, semi-automated ridge counts derived from digital prints collected at two different time points also showed good agreement (r?=?0.962) (the prints were obtained 2 years apart and counted by the same researcher). Although designed for use with fingerprints, the program is suitable for use with palm, foot or toe prints using user-defined landmarks.