PILOT PROJECTS TO STIMULATE ADVERSE DRUG REACTION REPORTING

Schemes for stimulating adverse drug reporting are described with particular emphasis on a recently introduced Mississippi Adverse Drug Reaction Reporting Programme.     

Short-Ti inversion-recovery pulse sequence: analysis and initial experience in cancer imaging

Inversion recovery (IR), commonly considered a pulse sequence capable of producing T1-weighted images with excellent display of normal anatomy, is versatile: The null point and peak time provide a useful, succinct summary of the properties of IR and its capacity for producing both T1- and T2-weighted images. Shortening of the inversion time (TI) and creation of a short-TI inversion-recovery (STIR) pulse sequence increases sensitivity to malignancy and other abnormalities by making the effects of prolonged T1 and T2 on signal intensity additive and by nulling the signal from fat. The authors examined over 300 patients with various malignancies and compared STIR images with T1- and T2-weighted images obtained at 0.5 T. In 43 cases, signal-difference-to-noise ratios (SD/Ns) were calculated between tumor, fat, and muscle. In general, STIR images demonstrated tumor as a conspicuously high-intensity area in a background of muted, discernible anatomic detail. The good contrast achieved with STIR sequences between tumor and fat (SD/N = 18.1) and tumor and muscle (SD/N = 12.9) consolidated into a single image the information contained separately on T1- and T2-weighted images, which facilitates efficient detection and localization of malignancy.     

Respiratory atopic disease, Ascaris-immunoglobulin E and tuberculin testing in urban South African children

BACKGROUND: Epidemiological relation of intestinal helminth infection and atopic disease, both associated with a T-helper (Th) 2 immune response, is controversial, as it has been reported that helminth infection may either suppress or pre-dispose to atopic disease. This relation has not been tested in an area with a high burden of Mycobacterium tuberculosis (MTB) infection, a known Th1-stimulating infection. OBJECTIVE: To study the association of intestinal helminth infection and atopic disease in a community where helminth infection is endemic and MTB infection is high. METHODS: Three-hundred and fifty-nine randomly selected children aged 6-14 years from a poor urban suburb were tested with allergy questionnaire, skin prick test (SPT) to common aeroallergens, Ascaris-specific IgE (Ascaris-sIgE), fecal examination for pathogenic intestinal helminths and tuberculin skin testing (TST). Histamine bronchoprovocation was tested in the group of children aged 10 years and older. RESULTS: were corrected for demographic variables, socioeconomic status, parental allergy, environmental tobacco smoke (ETS) exposure in the household, recent anthelminthic treatment and for clustering in the sampling unit. Results Ascaris-sIgE was elevated in 48% of children, Ascaris eggs were found in 15% and TST was positive in 53%. Children with elevated Ascaris-sIgE had significantly increased risk of positive SPT to aeroallergens, particularly house dust mite, atopic asthma (ever and recent), atopic rhinitis (ever and recent) and increased atopy-related bronchial hyper-responsiveness. In children with negative TST (<10 mm), elevated Ascaris-sIgE was associated with significantly increased risk of atopic symptoms (adjusted odds ratio (OR(adj)) 6.5; 95% confidence interval (CI) 1.9-22.4), whereas in those with positive TST (>/=10 mm) this association disappeared (OR(adj) 0.96; 95% CI 0.4-2.8). CONCLUSIONS: These results suggest that immune response to Ascaris (Ascaris-sIgE) may be a risk factor of atopic disease in populations exposed to mild Ascaris infection and that MTB infection may be protective against this risk, probably by stimulation of anti-inflammatory networks.     

The effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity

The integrity of sperm DNA is crucial for the maintenance of genetic health. A major source of damage is reactive oxygen species (ROS) generation; therefore, antioxidants may afford protection to sperm DNA. The objectives of the study were, first, to measure the effects of antioxidant supplementation in vitro on endogenous DNA damage in spermatozoa using the single cell gel electrophoresis (comet) assay and, second, to assess the effect of antioxidant supplementation given prior to X-ray irradiation on induced DNA damage. Spermatozoa from 150 patients were prepared by Percoll centrifugation in the presence of ascorbic acid (300, 600 microM), alpha tocopherol (30, 60 microM), urate (200, 400 microM), or acetyl cysteine (5, 10 microM). DNA damage was induced by 30 Gy X-irradiation. DNA strand breakage was measured using the comet assay. Sperm DNA was protected from DNA damage by ascorbic acid (600 microM), alpha tocopherol (30 and 60 microM) and urate (400 microM). These antioxidants provided protection from subsequent DNA damage by X-ray irradiation. In contrast, acetyl cysteine or ascorbate and alpha tocopherol together induced further DNA damage. Supplementation in vitro with the antioxidants ascorbate, urate and alpha tocopherol separately has beneficial effects for sperm DNA integrity.      

Pathologic features of the femoral head in Mseleni disease

Severe but atypical osteoarthritic deformities were found in each of 12 femoral heads removed during total hip arthroplasty for Mseleni disease. Although degenerative and regenerative changes were present throughout the cartilage, there was a paucity of eburnation. Histomorphometric analysis of bone at the line of excision indicated that mild osteomalacia was present in four of the 12 specimens. The percentage of the endosteum occupied by osteoid was 9.7 +/- 7.96 (SD) in the patients with Mseleni disease, compared with 5.6 +/- 4.33 in seven African black and 4.1 +/- 2.13 in 13 American white control subjects. The mean thickness of the osteoid seams was not increased. The findings suggest that osteomalacia is not a major pathogenetic factor in Mseleni disease.     

How to use Chlamydia antibody testing in subfertility patients

Screening for tubal factor subfertility by means of Chlamydia antibody testing (CAT) was introduced into the initial work-up of subfertile couples several years ago. The results reported, however, are heterogeneous, and no uniformity exists in cut-off levels of titres, or in definitions of tubal factor subfertility. We performed a prospective cohort study to evaluate the implications of varying the definitions of tubal pathology and of modifying the cut-off levels on the clinical impact of CAT in predicting tubal factor subfertility. In 227 consecutive patients who attended our fertility clinic, the Chlamydia IgG antibody titre was determined and related to tuboperitoneal abnormalities at laparoscopy as a reference standard. According to received operating characteristic (ROC) curve analysis, a titre of 16 is the optimum cut-off level. Increasing the cut-off level improves specificity and positive likelihood ratio (LR+), at the expense of sensitivity and negative LR (LR-). Changing the definition of tubal factor subfertility from unspecified tuboperitoneal abnormalities into extensive adhesions and/or bilateral distal tubal occlusion improves LR+, LR- and kappa significantly. We conclude that CAT is more accurate in predicting severe distal tubal pathology than unspecified tuboperitoneal abnormalities. Although from a statistical point of view a titre of 16 is the optimum cut-off level, from a clinical point of view 32 or 64 may be preferable, depending on the aim of screening and the inception cohort.      

The pH dependent amelogenin solubility and its biological significance

Amelogenins are a group of extracellular enamel matrix proteins which are believed to be involved in the regulation of the size and habit of enamel crystals. The aim of this study was to compare the solubility properties of several amelogenins in various pH (4.0-9.0) solutions with an ionic strength (IS) of 0.15 M using the Micro BCA protein assay at 25 degrees C or 37 degrees C. The solubility of the recombinant amelogenin rM179 was lowest (0.7 mg/ml) close to its isoelectric point and it increased below and above this point. The solubility of the recombinant amelogenin rM166 remained almost the same (1-2 mg/ml) as the pH rose from 6.0 to 9.0 and it increased as the solution became more acidic. Synthetic "tyrosine-rich amelogenin polypeptide" (TRAP) was extremely insoluble (<0.2 mg/ml) in the pH range studied while synthetic "leucine-rich amelogenin polypeptide" (LRAP) was readily soluble (>3.3 mg/ml). The native porcine amelogenin with apparent molecular weight 25 kDa shared similar solubility behavior to rM179. The porcine 23 kDa amelogenin was only sparingly soluble (0.3-0.8 mg/ml) over a wide range of pH. Interestingly, the porcine 20 kDa amelogenin was remarkably soluble in the pH range of 4.0 to 6.0 (approximately 12 mg/ml), but the solubility dropped strikingly to only approximately 0.2 mg/ml at pH larger than approximately 7.0. The strong dependence of amelogenin solubility on solution pH may be involved in the regulation of aggregation, enzymatic degradation and the binding properties of amelogenins, thus playing an important role in enamel biomineralization.