In vivo efficacy of silver-coated (Silzone) infection-resistant polyester fabric against a biofilm-producing bacteria, Staphylococcus epidermidis

OBJECTIVE: To study the characteristics of birthweight and gestational age of third trimester fetal deaths which occurred before the onset of labour. DESIGN: Review of computerised confidential perinatal mortality records. Data originated from the 1992 Trent Region Perinatal Mortality Survey. SAMPLE: One hundred and forty-nine antepartum stillbirths of at least 24 weeks of gestation confirmed by early ultrasound scan. Congenital abnormalities and multiple pregnancies were excluded. MAIN OUTCOME MEASURES: Reported causes of stillbirth; weight-for-gestational age centiles based on a standard derived from normal pregnancies; pregnancy characteristics compared with the local maternity population. RESULTS: Of 149 stillbirths, 83 (56%) were preterm and 66 were at term, and the majority (126; 85%) occurred from 31 weeks. Most of the deaths (97; 65%) were reported as 'unexplained' even though post-mortems had been carried out in 60% of all cases. Using a gestational age-specific fetal weight standard derived from normal, term live births, 41% of all cases of stillborn infants were small-for-gestational age (< 10th centile; OR 6.2; 95% CI 3.3-11.5); 39% of which had been classified as unexplained were small for gestational age (OR 5.6; 2.6-12.0). This excess of small stillbirths was most pronounced between 31 and 33 weeks, where the weights of 63% of all stillbirths and 72% of unexplained fetal deaths were < 10th centile. Overall, a higher proportion of preterm (< 37 weeks) than term stillbirths were small for gestational age: 53% vs 26% (OR 3.3; 1.6-6.5). However, at term there were also more subtle differences in weight deficit, with more fetuses with a weight between the 10th and 50th centiles than between 50th and 90th (36 vs 11; OR 3.3; 1.4-7.8). Mothers of pregnancies ending in stillbirth were similar in age, size, parity and ethnic group to mothers of live born babies, but were more likely to be smokers (37 vs 27%, OR 1.6; 1.2-2.3). CONCLUSIONS: Many stillborn babies are small for gestational age. In the absence of significant differences in physiological pregnancy characteristics, this is unlikely to be a constitutional smallness, but represents a preponderance of intrauterine growth restriction. For a full appreciation of the strength of this association, appropriate weight standards and classifications need to be applied in perinatal mortality surveys. Many antepartum stillbirths which are currently designated as unexplained may be avoidable if slow fetal growth could be recognised as a warning sign.     

MMS2, encoding a ubiquitin-conjugating-enzyme-like protein, is a member of the yeast error-free postreplication repair pathway

Among the three Saccharomyces cerevisiae DNA repair epistasis groups, the RAD6 group is the most complicated and least characterized, primarily because it consists of two separate repair pathways: an error-free postreplication repair pathway, and a mutagenesis pathway. The rad6 and rad18 mutants are defective in both pathways, and the rev3 mutant affects only the mutagenesis pathway, but a yeast gene that is involved only in error-free postreplication repair has not been reported. We cloned the MMS2 gene from a yeast genomic library by functional complementation of the mms2-1 mutant [Prakash, L. & Prakash, S. (1977) Genetics 86, 33-55]. MMS2 encodes a 137-amino acid, 15.2-kDa protein with significant sequence homology to a conserved family of ubiquitin-conjugating (Ubc) proteins. However, Mms2 does not appear to possess Ubc activity. Genetic analyses indicate that the mms2 mutation is hypostatic to rad6 and rad18 but is synergistic with the rev3 mutation, and the mms2 mutant is proficient in UV-induced mutagenesis. These phenotypes are reminiscent of a pol30-46 mutant known to be impaired in postreplication repair. The mms2 mutant also displayed a REV3-dependent mutator phenotype, strongly suggesting that the MMS2 gene functions in the error-free postreplication repair pathway, parallel to the REV3 mutagenesis pathway. Furthermore, with respect to UV sensitivity, mms2 was found to be hypostatic to the rad6Delta1-9 mutation, which results in the absence of the first nine amino acids of Rad6. On the basis of these collective results, we propose that the mms2 null mutation and two other allele-specific mutations, rad6Delta1-9 and pol30-46, define the error-free mode of DNA postreplication repair, and that these mutations may enhance both spontaneous and DNA damage-induced mutagenesis.     

A severe adverse reaction to mefloquine and chloroquine prophylaxis

A 23 year old man with no history of neurological or psychiatric illness ingested three weekly 228 mg doses of mefloquine base (250 mg salt) as malaria prophylaxis while in India. He experienced an increasingly severe adverse reaction after each dose, including symptoms of paranoia, hallucinations, and suicidal ideation. The man discontinued mefloquine and continued malaria prophylaxis with chloroquine. Shortly after the first 300 mg dose of chloroquine base (500 mg chloroquine phosphate salt), symptoms acutely intensified and became debilitating. Severe symptoms persisted for 12 months following the discontinuation of both antimalarial drugs.     

Induction of tumor necrosis factor-alpha and apoptosis in gastric mucosal injury by indomethacin: effect of omeprazole and ebrotidine

BACKGROUND: Inhalation of swine dust causes airway inflammation with influx of inflammatory cells, predominantly neutrophils, into the lungs. A study was undertaken to determine whether or not exposure to swine dust induces release of interleukin 8 (IL-8) into upper and lower airways and how this possible release is related to cellular influx. A further aim was to study the relationship between the inflammatory response and swine dust exposure. METHODS: Thirty one healthy, non-smoking, previously unexposed subjects were exposed to swine dust during three hours work in a swine house. Bronchoalveolar lavage (BAL) was performed two weeks before and 24 hours after the exposure (n = 16). Nasal lavage and acoustic rhinometry were carried out 1-2 hours before and seven hours after the start of the exposure (n = 31). Exposure measurements were performed with personal sampling equipment. RESULTS: The exposure led to 19-fold and 70-fold increases in the neutrophil concentrations in nasal lavage and BAL fluid, respectively (p < 0.001). In BAL, fluid macrophages, lymphocytes and eosinophils increased significantly. The IL-8 levels in BAL fluid increased from < 31.3 ng/l to 63 (43-109) ng/l (median (25-75th percentile), p < 0.001), and in nasal lavage fluid the concentrations increased from 144 (97-227) ng/l to 1064 (864-1437) ng/l (p < 0.001). IL-8 levels showed a significant correlation with the increase in neutrophils in the nasal lavage fluid but not in the BAL fluid. Acoustic rhinometry demonstrated significant swelling of the nasal mucosa. The air concentration of inhalable dust was 23.3 (20.0-29.3) mg/m3, endotoxin 1.3 (1.1-1.4) micrograms/m3, and muramic acid 0.99 (0.78-2.1) microgram/m3. CONCLUSIONS: The concentration of IL-8 increases in BAL fluid and nasal lavage fluid following exposure to swine dust and may be one of the chemoattractants contributing to the recruitment of neutrophils to the nasal cavity and the alveolar space.     

Use of monoclonal antibodies in diagnosis of paracoccidioidomycosis: new strategies for detection of circulating antigens

The precise diagnosis of paracoccidioidomycosis, in most cases, is established by direct methods and indirect immunological tests. The latter method is reliant on the identification of the host's humoral responses, which are usually impaired or absent in patients with severe juvenile forms of the disease and in immunocompromised patients. Determining disease activity or assessing treatment responses by measuring antibody levels is difficult, since antibody titer may remain elevated or persist at stationary levels, even in the presence of clinical improvement. Consequently, there is a need for alternative tests aimed at the identification of circulating antigens. A modification of the standard hybridoma production method was used to raise a panel of murine monoclonal antibodies (MAbs) against the yeast form of Paracoccidioides brasiliensis. Of these, MAb PIB, directed against an 87-kDa determinant, was used to develop an inhibition ELISA (inh-ELISA) capable of detecting as little as 5.8 ng of circulating antigen per ml of serum. Sera from 46 patients with paracoccidioidomycosis or other mycoses and sera from healthy individuals were evaluated by the inh-ELISA; overall sensitivity was 80.4% (37 of 46 paracoccidioidomycosis patients tested positive), and specificity compared with that of normal controls from areas of endemicity was 81.4%. The inh-ELISA detected circulating antigen in 100% of patients with the acute form of paracoccidioidomycosis and in 83.3 and 60% of patients with the chronic multifocal and unifocal forms of paracoccidioidomycosis according to the patients' clinical presentation. These results indicate that the inh-ELISA with MAb PIB is effective in the detection of circulating antigen and that this test may be useful for monitoring responses to treatment and establishing disease prognoses.     

Fatty acid composition of black bear (Ursus americanus) milk during and after the period of winter dormancy

Black bears give birth and lactate during the 2–3-mon fast of winter dormancy. Thereafter the female emerges from the den with her cubs and begins to feed. We investigated fatty acid patterns of milk from native Pennsylvania black bears during the period of winter dormancy, as well as after den emergence. Throughout winter dormancy, milk fatty acid composition remained relatively constant. The principal fatty acids at all times were 14∶0, 16∶0, 16∶1, 18∶0, 18∶1, 18∶2n−6, 18∶3n−3 and 20∶4n−6. After den emergence, large changes occurred in almost all the fatty acids, particularly in 18∶2n−6 and 18∶3n−3. Large variability among the active free-ranging animals likely reflected differences in diet. In a carnivore, with apparently limitedde novo synthesis of fatty acids, milk fatty acid composition may be affected by factors such as transition from reliance on stored lipids to feeding, and by temporal changes in dietary intake. Based on a paper presented at the Symposium on Milk Lipids held at the AOCS Annual Meeting, Baltimore, MD, April 1990.     

Mechanisms of electrical coupling between pyramidal cells

Direct electrical coupling between neurons can be the result of both electrotonic current transfer through gap junctions and extracellular fields. Intracellular recordings from CA1 pyramidal neurons of rat hippocampal slices showed two different types of small-amplitude coupling potentials: short-duration (5 ms) biphasic spikelets, which resembled differentiated action potentials and long-duration (>20 ms) monophasic potentials. A three-dimensional morphological model of a pyramidal cell was employed to determine the extracellular field produced by a neuron and its effect on a nearby neuron resulting from both gap junctional and electric field coupling. Computations were performed with a novel formulation of the boundary element method that employs triangular elements to discretize the soma and cylindrical elements to discretize the dendrites. An analytic formula was derived to aid in computations involving cylindrical elements. Simulation results were compared with biological recordings of intracellular potentials and spikelets. Field effects produced waveforms resembling spikelets although of smaller magnitude than those recorded in vitro. Gap junctional electrotonic connections produced waveforms resembling small-amplitude excitatory postsynaptic potentials. Intracellular electrode measurements were found inadequate for ascertaining membrane events because of externally applied electric fields. The transmembrane voltage induced by the electric field was highly spatially dependent in polarity and wave shape, as well as being an order of magnitude larger than activity measured at the electrode. Membrane voltages because of electrotonic current injection across gap junctions were essentially constant over the cell and were accurately depicted by the electrode. The effects of several parameters were investigated: 1) decreasing the ratio of intra to extracellular conductivity reduced the field effects; 2) the tree structure had a major impact on the intracellular potential; 3) placing the gap junction in the dendrites introduced a time delay in the gap junctional mediated electrotonic potential, as well as deceasing the potential recorded by the somatic electrode; and 4) field effects decayed to one-half of their maximum strength at a cell separation of approximately 20 micron. Results indicate that the in vitro measured spikelets are unlikely to be mediated by gap junctions and that a spikelet produced by the electric field of a single source cell has the same waveshape as the measured spikelet but with a much smaller amplitude. It is hypothesized that spikelets are a manifestation of the simultaneous electric field effects from several local cells whose action potential firing is synchronized.     

Effects of mitomycin C on delayed adjustment in experimental strabismus surgery

We used C3-deficient (C3D) guinea pigs to evaluate the role of C3 in an active model of experimental nephritis. Normal strain 2 (C3N, n = 13) and C3D (n = 6) guinea pigs were immunized with cationized bovine gamma-globulin (CBGG). Fourteen days later (Day 0), daily intravenous injections of CBGG were given for 3 to 7 days and the animals were sacrificed on Day 10 or 21. Immunofluorescence (IF) microscopy of renal tissue revealed two patterns of glomerular IgG deposition: granular loop (11/13 C3N, 3/6 C3D), and predominantly mesangial (2/13 C3N, 3/6 C3D). Codeposited C3 was seen in all C3N and in no C3D animals. Electron microscopy showed subepithelial deposits in all. A significant correlation (P < 0.005) was seen between an animal's IF pattern and its level of serum antibodies to CBGG; those with lower antibody levels exhibited the mesangial pattern. C3D animals had lower mean antibody levels than C3N (P < 0.01), but both IF patterns were represented. Urine protein concentration, which was increased relative to controls, did not differ between C3N and C3D groups, but was significantly greater in those with loop IF. Serum albumin was significantly reduced in animals with loop IF. C3N animals showed a significant reduction in mean serum C3. In this model, immune deposit location and degree of proteinuria are independent of C3 deposition and dependent upon the level of antibody response to CBGG. Induction of antibody to CBGG is impaired in the absence of C3.     

Evidence for the involvement of the Gli gene family in embryonic mouse lung development

Murine Gli, Gli2, and Gli3 are zinc finger genes related to Drosophila cubitus interuptus, a component of the hedgehog signal transduction pathway. In the embryonic lung, all three Gli genes are strongly expressed at the pseudoglandular stage, in distinct but overlapping domains of the mesoderm. Expression of Gli and Gli3, but not of Gli2, is subsequently downregulated at the canalicular stage, coincident with a decline in the expression of sonic hedgehog (Shh) and the hedgehog receptor gene, patched (Ptc). Overexpression of Shh in the lung results in increased levels of Ptc mRNA. Gli, but not Gli2, is also upregulated, suggesting a differential involvement of the Gli genes in the regulation of Ptc by SHH during lung development. Gli3 is not upregulated by Shh overexpression. However, its importance for lung development is shown by the finding that Gli3XtJ embryos, homozygous for a mutation involving a deletion of the Gli3 gene, have a stereotypic pattern of abnormalities in lung morphogenesis. The pulmonary defects in these embryos, consisting of localized shape changes and size reductions, correlate with normal Gli3 expression. Thus, our data indicate that one of the Gli genes, Gli3, is essential for normal lung development, and that another, Gli, can be placed downstream of Shh signaling in the lung.