Effect of maternal and infant covariates on sibship correlation in birth weight

Birth weight on 12,644 singleton infants from 6,196 sibships born in Maryland between 1980 and 1984 were used to estimate the effects of nine maternal and infant covariates on the sibship correlation in birth weight. Assuming a homogeneous correlation across all families, the estimated intraclass correlation was 0.4664 (+/- 0.0099). This high sibship correlation makes it possible to predict, with reasonable accuracy, the birth weight of a child given information on previous sibs, as well as covariates on the mother and/or infant pertinent to a given pregnancy. The reduction in variance associated with incorporating information on the nine covariates used here was approximately equal to that obtained by conditioning on a single previous sib. Testing for heterogeneity in correlation among different groups of families showed that a crude measure of parity (first live birth vs. other), time between births, mother's marital status, and maternal age at the birth of the last child significantly influenced the sibship correlation in birth weight.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Loss of c-kit expression in cultured melanoma cells.

The proto-oncogene c-kit encodes a receptor tyrosine kinase which has been shown to play a key role in melanocyte development. In this report we asked whether the c-kit gene product is also involved in promoting the growth of transformed melanocytes. We found that, while c-Kit protein was readily observed in normal human neonatal and adult melanocytes, the majority of cell lines established from human melanoma samples did not express detectable levels of c-kit mRNA or protein. A similar pattern of differential expression was also observed in normal and transformed murine melanocytes. Our findings raise the possibility that a marked reduction in c-kit gene expression either promotes or is a consequence of transformation in melanocytes.     

The nigral projection to predorsal bundle cells in the superior colliculus of the rat.

Predorsal bundle cells give rise to the major efferent pathway from the superior colliculus to the premotor centers of the brainstem and spinal cord responsible for initiating orienting movements. The activity of predorsal bundle cells is profoundly influenced by an inhibitory pathway from substantia nigra pars reticulata that uses gamma aminobutyric acid (GABA) as a neurotransmitter. The present study examines the morphological basis for this influence of substantia nigra on predorsal bundle cells in the rat. In the first experiments, the laminar distributions of the nigrotectal tract terminals and the predorsal bundle cells were compared. The predorsal bundle cells were labeled by the retrograde axonal transport of horseradish peroxidase from either the decussation of the predorsal bundle or the cervical spinal cord, while the terminations of the pathway from substantia nigra pars reticulata were labeled by anterograde axonal transport from the substantia nigra. Either horseradish peroxidase, wheat germ agglutinin conjugated to horseradish peroxidase, or Phaseolus vulgaris leucoagglutinin were used as anterograde tracers. The results showed that the distributions of both the predorsal bundle cells and the nigrotectal terminals are restricted almost entirely to the intermediate grey layer and that they overlap extensively. Predorsal bundle cells varied in size. Within the areas of maximum overlap, the majority, regardless of size, was closely apposed by nigrotectal terminals. In a second series of experiments, the synaptic contacts between nigrotectal terminals and the tectospinal component of the predorsal bundle were examined in tissue in which both the terminals and the tectospinal cells were labeled for electron microscopy. In the final experiments, the distribution and fine structure of the nigrotectal terminals were compared to those of terminals that had been labeled immunocytochemically with an antibody to glutamic acid decarboxylase, the synthesizing enzyme for GABA. The results showed that nigrotectal terminals contain large numbers of mitochondria and pleomorphic vesicles, and form synaptic contacts with the somas and proximal dendrites of tectospinal cells. These synapses have modest postsynaptic densities. In both their distribution and fine structure, these terminations resemble the glutamic acid decarboxylase immunoreactive terminals that contact tectospinal cells. Taken together, these results support the view that the nigrotectal tract is an important source of GABAergic input to most, if not all, predorsal bundle cells.     

A diagnostic algorithm for male genital oedema

Male genital oedema can be defined as swelling or the appearance of swelling of the scrotum and/or the penile shaft and prepuce. Despite the various causes of genital oedema reported in the published work, a concise approach to the evaluation and management has not been sufficiently addressed.     

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.     

A GABAergic projection from the pretectum to the dorsal lateral geniculate nucleus in the cat.

To study the projection from the pretectum to the lateral geniculate nucleus, we placed wheat-germ agglutinin conjugated to horseradish peroxidase into the lateral geniculate nuclei of six cats, allowed this marker to be retrogradely transported by afferent axons to their parent somata in the pretectum, and revealed the label in these cells with stabilized tetramethylbenzidine histochemistry. In three cases we made large pressure injections that completely infiltrated the lateral geniculate nucleus and extended into neighboring thalamic nuclei; in the other three we made smaller iontophoretic injections largely confined to the A- and C-laminae of the lateral geniculate nucleus. In both types of injection we found labeled pretectal cells mainly in the nucleus of the optic tract but also found some cells labeled in the olivary pretectal nucleus and the posterior pretectal nucleus. After one of the larger injections we analysed both sides of the pretectum and found that 11% of the labeled cells were located contralaterally and were distributed in the same three nuclei. We analysed only the ipsilateral side in the remaining five cats. In those five experiments we also immunohistochemically stained the pretectal sections with an antibody directed against the neurotransmitter, GABA. Of the retrogradely labeled pretectal cells, 40% were also labeled for GABA, and those were similar in soma size (350 microns 2 in cross-sectional area) to those labeled only with the retrograde marker (331 microns 2). GABA-positive cells not labeled by retrograde transport were smaller (246 microns 2) than either of these other cells populations. These results indicate that at least 40% of the cells involved in the projection from the pretectum to the lateral geniculate nucleus are GABAergic. We suggest that this extrathalamic projection may serve to inhibit thalamic GABAergic cells. This, in turn, would disinhibit geniculate relay cells, thereby facilitating the geniculate relay of retinal information to cortex.     

Relative carriage rates of nuclear dehydrogenating clostridia in two populations of different colorectal cancer risk

Carriage of nuclear dehydrogenating clostridia has been associated with colon cancer and implicated in its aetiology. This study has compared the carriage of these organisms in a British population at high risk for the development of colon cancer with a low risk Nigerian population. Clostridia were found in all of the stools from both populations. Nuclear dehydrogenating clostridia were only found in the stools of the British subjects (32%). These results support the suggestion that the carriage rate of nuclear dehydrogenating clostridia in a population is related to the risk of colon cancer.