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Biomedical subjects

C Thompson

Publications and source records attributed to C Thompson.

At least 145 records · Page 8Linked to original sources

Maternal immunization with Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in The Gambia.

OBJECTIVE: To evaluate maternal responses to Haemophilus influenzae type b (Hib) polysaccharide-tetanus protein conjugate (polyribosylribitol phosphate-tetanus or PRP-T) given to pregnant Gambian women, the transplacental transfer of antibody, and the effect of maternal immunization on infant responses to the vaccine. DESIGN: An open, randomized immunogenicity study. SETTING: A busy urban health center in The Gambia. STUDY PARTICIPANTS: A total of 451 pregnant women enrolled during the third trimester of pregnancy. INTERVENTION: Study participants were randomized to three groups. In one group, mothers were given PRP-T during the third trimester and their infants were given PRP-T at 2, 3, and 4 months of age. In the second group, mothers received PRP-T and infants were given inactivated poliovirus vaccine. In the third group, mothers received meningococcal A and C vaccine, and their infants received PRP-T. MAIN OUTCOME MEASURES: Anti-PRP antibody measurements of maternal cord, and infant blood. RESULTS: Vaccinated women had a marked increase in total anti-PRP antibody (geometric mean titer 9.0 micrograms/mL), which was greatest in women in their first or second pregnancy. Previous tetanus vaccination during the same pregnancy and high concentrations of antitetanus antibody were associated with lower anti-PRP responses. In infants of PRP-T recipients, cord blood anti-PRP IgG concentrations were 61% of simultaneous maternal concentrations. In vaccinated infants of vaccinated mothers, geometric mean anti-PRP antibody concentrations at birth, 2 months of age, and 5 months of age were 1.92, 0.35 and 2.84 micrograms/mL, respectively, while in vaccinated infants of unvaccinated mothers, the corresponding concentrations were 0.29, 0.12, and 3.91 micrograms/mL. At 2 months of age, 60% of infants of vaccinated mothers and 26% of infants of unvaccinated mothers had anti-PRP antibody concentrations considered to be protective (>0.15 micrograms/mL). CONCLUSIONS: In areas where much invasive Hib disease occurs in infants younger than 6 months, maternal immunization may help to reduce the risk of Hib disease in infants too young for immunization.

Antibodies, Bacterial↗

Comparative analyses of relative ERCC3 and ERCC6 mRNA levels in gliomas and adjacent non-neoplastic brain.

Nucleotide excision repair (NER) is an ordered process in nonmalignant cells, in both human and nonhuman systems. We previously reported that in human brain there is discordant mRNA expression of excision repair cross-complementing (ERCC) 1 and ERCC2 in malignant tissues, concurrent with excellent concordance of these genes in nonmalignant tissues from the same patients. Here we have extended these studies to compare low-grade tumors to high-grade tumors and to include ERCC3 (which links DNA repair with DNA transcription) and ERCC6 (which is essential for gene-specific repair). Glial tumor and adjacent normal brain specimens from 19 individuals were studied. Paired malignant and nonmalignant tissues were obtained from 12 of these patients. For ERCC3, there was excellent concordance of mRNA expression between malignant and nonmalignant tissues from the same individuals (P = 0.003). For ERCC6, no concordance was observed (P = 0.314). Tumor tissue from patients with high-grade gliomas exhibited marked discordance of mRNA expression patterns in situations in which good concordance was observed in tumor tissue from low-grade gliomas. We previously established that malignant brain tumors show increased disorder of genes in the NER process, as compared with nonmalignant tissues. These data suggest that increasing disorder in the NER process may occur as cells move from low-grade to high-grade malignancy.

Astrocytoma↗

The validation of a 7-locus multiplex STR test for use in forensic casework. (I). Mixtures, ageing, degradation and species studies.

We have evaluated a multiplex STR system for routine forensic use, which co-amplifies six short tandem repeat (STR) loci; HUMTH01, D21S11, D18S51, D8S1179, HUMVWF31/A and HUMFIBRA (FGA), in conjunction with the X-Y homologous gene Amelogenin. Analysis of PCR products employs denaturing polyacrylamide gels coupled with fluorescent labelled primers and detection is undertaken on ABD 373A automated sequencers. The technique was shown to be robust and reproducible when samples were analysed under conditions consistent with those encountered in a forensic environment. The system was demonstrated to be human specific and is suitable for use with both aged and degraded material. Somatic stability was proven with a wide range of tissue types and we were able to detect mixtures at ratios between 1:10 and 10:1. During this study no incidence of sample mis-typing due to allelic or locus drop-out was observed. Furthermore, although additional artefact bands were occasionally encountered these did not interfere with the interpretation of results. The performance of the system with poor quality samples demonstrated its suitability as a powerful tool in forensic investigation.

Adult↗

Readability of printed sources of diet and health information.

This study surveyed nutrition education materials which are low in cost, brief and the type most used in patient education to determine which might be useful with low literacy clients. Readability of 209 pamphlets from professional health organizations, commercial organizations, government agencies, and educational institutions was assessed using three different tests. Using the Flesch and Raygor tests, materials from educational institutions had significantly lower reading levels than materials from professional organizations and government agencies. No significant differences were seen among the sources using the Fry test. Sixty-eight percent (142) of the publications were written at ninth grade level or higher. Eleven percent (24) scored at sixth grade or below on either the Fry or Raygor scale. Only two publications were written at the third grade level. Many of the publications reviewed can be read and understood by many Americans, but there were few for the millions that have limited literacy skills.

Educational Status↗

Streptozotocin at low doses induces apoptosis and at high doses causes necrosis in a murine pancreatic beta cell line, INS-1.

The ability of beta cells to endure assaults by various environmental agents, including toxins and viruses, may be relevant to the development of diabetes. We have examined the mode of cell death caused by streptozotocin (STZ) in a murine pancreatic beta cell line, INS-1. Apoptosis was identified by detection of initial endonuclease-mediated DNA strand breaks by DNA gel electrophoresis. Apoptosis and necrosis were distinguished morphologically by light and electron microscopy. Higher rates of apoptosis, as compared to necrosis, were observed when cells were exposed to 15 mM STZ for 1 hr followed by a 24 hrs recovery period. Higher doses of STZ (30 mM) caused the cells to undergo necrosis (22%) as well as apoptosis (17%). These results suggest that the cytotoxic effect of STZ, at low doses, on beta cells involves the activation of the apoptotic pathway, whereas, at high doses, the mode of beta cell death is predominantly necrosis.

Animals↗

Diphtheria antitoxin levels in US blood and plasma donors.

Plasma samples from 500 blood donors were titrated for diphtheria antitoxin (DAT) by the toxin neutralization (TN) test. Only 1.6% of donors had <0.01 IU/mL DAT, the minimum protective level against diphtheria; 15% had levels between 0.01 and <0.1 IU/mL, indicating basic protection, and 83.4% had levels > or =0.1 IU, indicating full protection. Three hundred fifty samples were studied by ELISA for diphtheria toxoid IgG antibodies to assess the utility of the assay as a quick, convenient method for evaluating diphtheria immunity. Although the correlation between TN and ELISA titers for the 350 samples was high (r = .80), there was no correlation (r = .07) for samples with antitoxin titers <0.1 IU/mL, the level of special interest for serosurveys for protection. Titration of 62 immune globulin samples (prepared from 1957 to 1994) showed that DAT levels in Massachusetts blood donors increased concurrently with increased use of tetanus-diphtheria vaccine in the state.

Animals↗

Adverse reactions to sedative/hypnotics: three years' experience.

Reported adverse reactions to orally administered sedative/hypnotics were systematically recorded during a 3-year period in a 1,000-bed teaching hospital. Reported cases were reviewed by a multidisciplinary committee and then by a pharmacist, and judgments were made as to type, severity, and outcome of adverse reactions. Probability that the reaction was caused by the medication was recorded in terms of both a global judgment and a systematic scale. The frequency of adverse reactions was calculated as a percentage of total doses of each agent dispensed by the pharmacy during the same time period. The assessment of benzodiazepine sedative/hypnotics indicated that adverse reactions were rare, ranging from frequencies of 0.05% of doses administered (lorazepam) to none (chlorazepate). The median frequency of reported adverse reactions was 0.01%, or 1 in 10,000 doses. The vast majority of reactions could be viewed as extensions of the therapeutic effect, were considered mild, and were without sequelae. All adverse reactions occurred in patients over 55 years old except for four patients under age 50 who received lorazepam. There were no reported cases of violent behavior or global amnesia.

Accidental Falls↗

Nursing orientation: a continuous quality improvement story.

THIS ARTICLE ADDRESSES an orientation process utilizing a collaborative, multidisciplinary approach and principles of continuous quality improvement (CQI). This process successfully transitioned 63 graduate nurses into three different practice specialties, decreased the vacancy rate, and eliminated the need for agency nurses at Georgia Baptist Medical Center in Atlanta, Georgia. CNSs, acting as educators, clinical experts, and consultants, played a key role in developing, implementing, and evaluating this comprehensive program.

Clinical Competence↗

High-dose recombinant endotoxin neutralizing protein improves survival in rabbits, with Escherichia coli sepsis.

OBJECTIVE: To assess the benefit of a recombinant endotoxin neutralizing protein from Limulus polyphemus in treating Gram-negative bacterial sepsis in rabbits. DESIGN: Prospective, blinded, controlled, laboratory trial. SETTING: Animal research laboratory. SUBJECTS: New Zealand White rabbits. INTERVENTIONS: We established a rabbit model of Escherichia coli peritonitis and bacteremia, with high mortality rate, despite treatment with gentamicin and ceftriaxone. Twenty-five pairs of male New Zealand White rabbits were challenged intraperitoneally with E. coli O18ac K1 in 5% porcine mucin (mean 7 x 10(1) colony-forming units). All animals were treated with intravenous gentamicin (2.5 mg/kg) and ceftriaxone (100 mg/kg), and with either intravenous endotoxin neutralizing protein (50 mg/kg) or saline 1 hr after E. coli challenge. MEASUREMENTS AND MAIN RESULTS: All animals were bacteremic 1 hr after challenge (mean 3.6 x 10(5) colony-forming units/mL). Animals in both groups developed tachycardia, hypotension, and acidosis (NS). Geometric mean serum endotoxin and tumor necrosis factor (TNF) concentrations were significantly ( p < .001) higher 1 hr after challenge compared with baseline prechallenge concentrations in both groups. From 1 to 2 hrs after challenge, endotoxin concentrations increased 2.5-fold in control animals (95% confidence interval = 13.1 to 32.9 endotoxin units/mL, p = .024), whereas endotoxin concentrations increased only 1.2-fold in endotoxin neutralizing protein-treated animals (95% confidence interval = 20.4 to 23.6 endotoxin units/mL, NS). TNF concentrations increased significantly (p < .001) in both groups from 1 to 2 hrs after challenge. Eighteen (72%) of 25 endotoxin neutralizing protein-treated animals vs. 11 (44%) of 25 controls survived 24 hrs (p = .032). CONCLUSIONS: Treatment with endotoxin neutralizing protein had the following effects: a) the increase in serum endotoxin was blunted, but not TNF concentrations measured 1 hr after antibiotic treatment; and b) survival in rabbits with E. Coli sepsis was improved.

Animals↗

A sensitive and specific PCR method to detect Helicobacter felis in a conventional mouse model.

Although many detection methods have been used to determine Helicobacter colonization in small animal models, the sensitivity and specificity of these detection methods are limited. To improve the Helicobacter felis conventional mouse model for accurate evaluation of therapeutic regimens, we developed a PCR for detection of, and a competitive PCR for quantitation of, H. felis in viral antibody-free (VAF) mice. The PCR was based on the H. felis 16S rRNA gene. An internal control DNA was used for competitive quantitation of the PCR. VAF conventional Swiss-Webster mice were infected with an H. felis culture by oral gavage. At various times after H. felis challenge and therapy, stomach mucosa was collected and evaluated by PCR. PCR detected approximately 50 to 100 H. felis cells per mouse stomach and showed no cross-reaction with other bacteria commonly found in mouse stomachs. Colonization of H. felis in the mouse stomach was confirmed by culture isolation from germfree mice and histological examination of VAF mice. Response to therapy in this H. felis model correlated well with results seen in human clinical trials with H. pylori. A model utilizing PCR detection which may be useful for discovering new antibiotics and/or vaccines against Helicobacter ulcer disease has been developed.

Animals↗

An Aplysia cell adhesion molecule associated with site-directed actin filament assembly in neuronal growth cones.

During neuronal growth cone-target interactions, a programmed sequence of cytoskeletal remodeling has been described, involving increased actin assembly at the target site and directed microtubule extension into it. The cell adhesion protein apCAM rapidly accumulates at such interaction sites, suggesting a possible role in regulating cytoskeletal remodeling. To test this hypothesis we crosslinked apCAM to varying degrees with antibodies. Secondary immunocomplexes exhibited a classical patching and capping response; in contrast, high density crosslinking of apCAM by antibody coated beads triggered localized actin assembly accompanied by formation of tail-like actin structures referred to as inductopodia. When beads were derivatized with increasing amounts of anti-apCAM they displayed three sequential dose-dependent kinetic states after binding: (1) lateral diffusion in the plane of the membrane; (2) restricted diffusion due to coupling with underlying F-actin; and (3) translocation in the plane of the membrane driven by de novo actin filament assembly local to bead binding sites, i.e. inductopodia formation. In contrast, lectin coated beads were far less efficient in triggering inductopodia formation despite demonstrated membrane protein binding. This work provides evidence that crosslinking of a diffusable membrane protein, apCAM, to threshold levels, can trigger highly localized actin filament assembly and rapid remodeling of neuronal cytoarchitecture.

Actins↗