Zinc Gluconate Induces Potentially Cancer Chemopreventive Activity in Barrett's Esophagus: A Phase 1 Pilot Study.

BACKGROUND: Chemopreventive effects of zinc for esophageal cancer have been well documented in animal models. This prospective study explores if a similar, potentially chemopreventive action can be seen in Barrett's esophagus (BE) in humans. AIMS: To determine if molecular evidence can be obtained potentially indicating zinc's chemopreventive action in Barrett's metaplasia. METHODS: Patients with a prior BE diagnosis were placed on oral zinc gluconate (14 days of 26.4 mg zinc BID) or a sodium gluconate placebo, prior to their surveillance endoscopy procedure. Biopsies of Barrett's mucosa were then obtained for miRNA and mRNA microarrays, or protein analyses. RESULTS: Zinc-induced mRNA changes were observed for a large number of transcripts. These included downregulation of transcripts encoding proinflammatory proteins (IL32, IL1ß, IL15, IL7R, IL2R, IL15R, IL3R), upregulation of anti-inflammatory mediators (IL1RA), downregulation of transcripts mediating epithelial-to-mesenchymal transition (EMT) (LIF, MYB, LYN, MTA1, SRC, SNAIL1, and TWIST1), and upregulation of transcripts that oppose EMT (BMP7, MTSS1, TRIB3, GRHL1). miRNA arrays showed significant upregulation of seven miRs with tumor suppressor activity (-125b-5P, -132-3P, -548z, -551a, -504, -518, and -34a-5P). Of proteins analyzed by Western blot, increased expression of the pro-apoptotic protein, BAX, and the tight junctional protein, CLAUDIN-7, along with decreased expression of BCL-2 and VEGF-R2 were noteworthy. CONCLUSIONS: When these mRNA, miRNA, and protein molecular data are considered collectively, a cancer chemopreventive action by zinc in Barrett's metaplasia may be possible for this precancerous esophageal tissue. These results and the extensive prior animal model studies argue for a future prospective clinical trial for this safe, easily-administered, and inexpensive micronutrient, that could determine if a chemopreventive action truly exists.

Sweat testing by capillary collection and osmometry: suitability of the Wescor Macroduct System for screening suspected cystic fibrosis patients.

A new method of collecting and analysing sweat (Wescor Macroduct) has advantages of simplicity of collection and direct reading of results by osmometry. Forty-seven children with cystic fibrosis and 47 normal children had sweat tests performed simultaneously by the Gibson and Cooke method and by the Wescor Macroduct method. The new method had a higher rate of inadequate collection (19% vs 6%) which was more marked in children under 5 years of age. This was due partly to the difficulty of fitting a 2.5 cm pilocarpine gel disc to small arms. When an adequate collection was obtained, results were reliable with no false negatives occurring during this study. The Wescor Macroduct sweat test is a reliable method for use in peripheral centres to screen patients suspected of having cystic fibrosis. All children with an inadequate collection or a positive result should be referred to a reference centre for confirmation of the diagnosis. However, the majority will be saved the expense and disruption of travel.

Low immunization uptake rates in an inner-city health district: fact or fiction?

Immunization uptake rates are assuming considerable importance as performance indicators for district health authorities (DHAs) and general practitioners (GPs). Data from the Cover of Vaccination Evaluated Rapidly (COVER) programme suggest that immunization uptake rates in innercity districts are well below the 90 per cent target. Using Parkside DHA, a district with consistently poor uptake, as an example, this paper has examined the accuracy of the Child Health Computer (CHC) records on which the COVER figures are based. In October 1989 a cohort of 1485 children born between April and June 1988 were identified. The 462 children identified by the CHC as immunization defaulters (using diphtheria and tetanus immunizations) were followed up by contacting child health clinics, GP surgeries and parents. This exercise revealed that 195 children were in fact immunized and 176 children were erroneously listed, largely because they were no longer resident at the address given. Only a small proportion of this information had reached the CHC by the end of the follow-up period. In addition to high population mobility, information inaccuracies appeared to be caused partly by a failure in data transfer between GPs and the DHA and by failures in data transfer between districts. Overall, the results of the study suggest that there is a considerable discrepancy between actual and recorded immunization uptake levels in Parkside and probably other inner-city areas. This will have a considerable impact on GPs and other health professionals who are striving to achieve 90 per cent targets.

Cortical asymmetry--a preliminary study: neurons-glia, female-male.

Previous studies on human cortical area 39 suggested that neuron:glial ratios differed between the sexes. These findings were the inspiration for the present investigation which dealt with neuronal and glial counts in area 39 in the male and female rat cerebral cortex. Transverse, celloidin or frozen sections, were cut from male and female brains (respectively) from 90-day-old Long-Evans rats. Neurons and glia were counted on enlarged photographs of stained sections, including area 39, with 35-mm Kodak Panatomic-X film using a Zeiss photomicroscope (X400). Five-by-three-inch prints were taped together in sequence to yield a 640X enlarged "montage" of area 39. Five cell types were differentiated with reference to a standard: neurons, astrocytes, oligodendrocytes, "dark astrocytes," and unidentified glia. The data were analyzed with a two-way analysis of variance (ANOVA: five cell types by two hemispheres). Student's t test and a paired t test were used when appropriate. The neuron:glial ratios in the male rats were consistently higher than those in the females in both hemispheres. The male right side had 12% (P less than 0.05) more neurons than the left; the female had 13% (P less than 0.05) more neurons on the left than the right. Similar, but not identical, asymmetrical patterns were seen with the glial cells.