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Biomedical subjects

J Simpson

Publications and source records attributed to J Simpson.

At least 55 records · Page 3Linked to original sources

An outbreak of whooping cough in a highly vaccinated urban community.

In 1950 a whole-cell pertussis vaccine was introduced in Cape Town and was followed by a marked decline in reported whooping cough mortality and morbidity. This resulted in reduced awareness of whooping cough as a clinical problem and, in recent years, no routine diagnostic tests for Bordetella pertussis have been performed. An outbreak of whooping cough occurred in Cape Town between 1 June 1988, and 31 May 1989, with 292 children admitted to hospital for whooping cough during this period (hospital admission rate in children under 5 years of age = 187 per 100,000). In an investigation of 239 children attending four pre-primary schools in the city, the whooping cough attack rate was 33 per cent, while pertussis vaccine coverage was 95 per cent. In the latter part of the outbreak nasopharyngeal swabs and serology were performed in patients presenting to a children's hospital with suspected whooping cough. Bordetella pertussis was isolated from 3 out of 34 (9 per cent) children tested and the first isolate was serotyped as type 1,2,4. Available clinical and laboratory evidence indicated that the organism responsible for the outbreak was Bordetella pertussis. Coverage studies for pertussis vaccine in Cape Town indicated that between 81 and 93 per cent of children were fully immunized by 13 months of age. These findings suggest that, since its introduction, the whole-cell pertussis vaccine produced in South Africa has been highly effective in controlling whooping cough. However, it was not able to prevent a moderate scale outbreak, even in the presence of high vaccination levels.

Child

Effects of perinatal stroke on striatal amino acid efflux in rats studied with in vivo microdialysis.

We used in vivo microdialysis to determine the impact of a focal hypoxic-ischemic insult on striatal amino acid efflux in the immature brain. Microdialysis probes were inserted into the right striatum of postnatal day 7 rats. To induce hypoxic-ischemic injury, the right carotid artery was ligated and the animals were exposed to 8% oxygen for 2.5 hours (n = 22). Rats exposed to ligation alone (n = 10) or hypoxia alone (n = 8) and untreated controls (n = 17) were also studied. Two hours after probe insertion, a 30-minute baseline microdialysis sample was obtained. After arterial ligation, two additional baseline samples were collected. Five more samples were collected over the next 2.5 hours (in 8% oxygen or room air). Eight amino acids (glutamate, aspartate, taurine, glutamine, alanine, serine, glycine, and asparagine) were consistently detected in dialysates using a high-performance liquid chromatography assay with electrochemical detection. In untreated controls, amino acid efflux did not change over 4 hours. During hypoxia-ischemia, efflux values fluctuated widely, with marked intra-animal and interanimal variability. Efflux peaks for each amino acid were defined as values greater than the highest control mean value plus two standard deviations. Glutamate efflux peaks (greater than 7 pmol/min compared with 2 pmol/min at baseline) were detected in no controls and in eight hypoxic-ischemic rats (p = 0.006, Fisher's two-tailed exact test). Taurine efflux peaks (greater than 75 pmol/min compared with 10 pmol/min for controls at baseline) were detected in 10 hypoxic-ischemic rats and one control (p = 0.01) and in seven of the eight animals in which glutamate efflux peaks occurred (p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine

Medication-nutrient interactions: hypophosphatemia associated with sucralfate in the intensive care unit.

Clinically significant medication-nutrient interactions are of concern to the nutritional support practitioner. To emphasize the possible effect of the aluminum-containing medication sucralfate on serum phosphorus levels, patients admitted to the intensive care unit of a small private hospital were monitored for a 4-week period. Sixteen patients demonstrated low serum phosphorus levels; eight (50%) of these were receiving sucralfate. Eighteen patients had no low phosphorus levels measured; five (28%) patients in this group were receiving sucralfate. The hypophosphatemia observed in these patients was probably multifactorial; respiratory alkalosis and dextrose feeding as well as sucralfate use are consistent with hypophosphatemia.

Adult

Hypoxia-ischemia stimulates hippocampal glutamate efflux in perinatal rat brain: an in vivo microdialysis study.

We used in vivo microdialysis to determine the impact of a focal hypoxic-ischemic insult on hippocampal amino acid efflux in the immature brain. Microdialysis probes were inserted into the right hippocampus of postnatal d 7 rats. To induce hypoxic-ischemic injury, the right carotid artery was ligated and animals were exposed to 8% oxygen for 2 h (n = 6, histologically verified). Ten 20-min dialysis fractions were collected from each animal: three sequential 20-min baseline samples, six samples during hypoxia, and a recovery sample in room air. Eight amino acids were detected in dialysates with a HPLC assay. There was marked intra- and interanimal variation in glutamate efflux; mean glutamate efflux increased from 17 pmol/min in baseline samples to 51 in the 2nd h of hypoxia (p = 0.002, Kruskal Wallis test). There was a concurrent decline in glutamine efflux (310 to 207 pmol/min, p = 0.0005). Alanine efflux doubled during hypoxia (p = 0.015). There were no changes in efflux of the other five amino acids analyzed. In this experimental model of perinatal stroke, during the acute evolution of hypoxic-ischemic brain injury, transient large increases in glutamate efflux and corresponding declines in glutamine efflux were detected. These data support the hypothesis that synaptic concentrations of the endogenous excitatory amino acid glutamate increase during the evolution of hippocampal ischemic injury.

Amino Acids

Hypoglycemia alters striatal amino acid efflux in perinatal rats: an in vivo microdialysis study.

In adult brain, during insulin-induced hypoglycemia, striatal extracellular fluid concentrations of the excitatory amino acids glutamate and aspartate rise markedly (fourfold to tenfold). In this study, we used in vivo microdialysis to determine if insulin-induced hypoglycemia altered striatal amino acid efflux in similar fashion in the immature brain. Microdialysis probes were inserted into the right striatum of rats on postnatal day 7. After a 2-hour recovery period, in each animal a 30-minute baseline sample was obtained. Then insulin (0.6 mu/kg, intraperitoneal injection) was administered (n = 6) and dialysate sampling was continued over the next 210 minutes (terminal blood glucose level less than 5 mg/dl). Untreated control rats (n = 6) were sampled over the same time interval. After pre-column derivatization with o-phthaldialdehyde, dialysate samples were assayed by high-pressure liquid chromatography with electrochemical detection to measure their amino acid content; eight amino acids (glutamate, aspartate, taurine, glutamine, alanine, serine, glycine, and asparagine) were consistently detected. In controls, amino acid efflux did not change over 4 hours. In hypoglycemic animals, glutamate efflux increased (peak: 238 +/- 85% of baseline, p = 0.02, repeated measures analysis of variance [ANOVA]), glutamine efflux declined (to 44 +/- 5% of baseline, p = 0.002, ANOVA), and taurine efflux increased (up to 310 +/- 120% of baseline; p less than 0.06, ANOVA). In contrast with 9- to 12-fold increases in aspartate efflux reported in adult striatum, aspartate efflux increased only slightly (to 174 +/- 69% of baseline; not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

Nosocomial bacteremias in measles.

The purpose of this study was to determine whether nosocomial bacteremias occurred more frequently in patients admitted with severe measles compared with general pediatric admissions. In a retrospective survey of 977 blood culture reports during a 4-year period, 1985 to 1988, the incidence of nosocomial bacteremias in patients with measles was found to be on the average of 3.37/100 admissions/year, approximately 6 times that of general pediatric patients (0.57). Gram-negative organisms (predominantly Klebsiella and Salmonella species) accounted for 86.5% of all isolates from measles patients, with 23% of these being multiply antibiotic-resistant. All the isolates from the general patients were fully susceptible to antibiotics. The duration of hospitalization was more than doubled in both groups of affected patients. The onset of hospital-acquired bacteremias occurred on an average of 11.2 days after admission in the patients with measles and 20.5 days in the general patients. Our findings revealed that nosocomial bacteremias occurred with greater frequency in patients with measles and contributed to the morbidity of these patients.

Adolescent

An antiserum to the extracellular domain of the Alzheimer amyloid precursor recognizes 70 and 88 kDa brain proteins.

An antiserum raised to the extracellular domain (residues 556-566) of the Alzheimer amyloid precursor protein recognized 70 and 88 kDa proteins in Western blots of rat, Alzheimer, Down's syndrome and control human brain separated by SDS-PAGE. The 70 kDa protein band was resolved into 5 spots by two-dimensional electrophoresis. The findings provide further evidence that a 70 kDa protein is a metabolite of the amyloid precursor protein and reveal an 88 kDa protein which was reduced in 3 out of 6 brains with Alzheimer pathology.

Alzheimer Disease

Normal or early development of puberty despite gonadal damage in children treated for acute lymphoblastic leukemia.

To determine the timing of pubertal development and the frequency of gonadal dysfunction in children who survive acute lymphoblastic leukemia, we assessed pubertal status and the plasma levels of sex steroids, gonadotropin, and inhibin in 45 children (20 girls and 25 boys) who had received combination chemotherapy along with 24 Gy of irradiation to the cranium (modified LSA2L2 protocol). We also reexamined testicular biopsy specimens, obtained at the time of the cessation of chemotherapy, for the presence of germ cells. Germ-cell damage, indicated by marked elevations in the plasma level of follicle-stimulating hormone (P less than 0.001 for the comparison with normal children), was evident in both sexes and was confirmed in the boys by the absence of germ cells in the testicular biopsy specimens and by the small size of the testes for pubic-hair stage. Only 44 percent of the pubertal girls had measurable plasma inhibin levels, as compared with more than 93 percent of normal pubertal girls. Although plasma sex-steroid levels were normal, the secretion of luteinizing hormone in response to stimulation with gonadotropin-releasing hormone was elevated in the pubertal children (P less than 0.01 for the comparison with normal controls)--a finding that suggests compensation for decreased gonadal function. Despite clear evidence of gonadal damage, girls had early menarche at a mean age (+/- SD) of 11.95 +/- 0.91 years, as compared with the Australian standard of 12.98 +/- 1.11 years (P less than 0.01). Thus, in girls, puberty was early despite primary gonadal damage. Thirteen of 23 boys reached puberty at a mean age of 12.36 +/- 0.73 years. We conclude that treatment for acute lymphoblastic leukemia may lead to primary gonadal damage in both sexes, regardless of the age at treatment, but that the secondary characteristics of puberty develop at a normal age or, in girls, relatively early.

Adolescent

Cholinergic enzymes in the spinal cord in Alzheimer-type dementia.

Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were measured in anterior and posterior grey matter of the lumbar spinal cord and in temporal and frontal cortex from six cases of Alzheimer-type dementia (ATD), one case of Down's syndrome, three cases of schizophrenia (SZ) and six controls. Compared with control and SZ values, ChAT and AChE were reduced in ATD cerebral cortex. ChAT was reduced, and AChE unaltered, in ATD spinal cord. Decreased cord ChAT may be related to electrophysiological abnormalities which have been reported in motor nerves of patients with Alzheimer's disease.

Acetylcholinesterase

Studies concerning the effect of external irradiation on localization of radiolabeled monoclonal antibody B72.3 to human colon carcinoma xenografts.

Recent studies in animal models involving antibody tumor targeting of hepatoma and melanoma and clinical trials involving hepatoma patients have suggested that preirradiation of tumors may enhance antibody tumor targeting. These reports led us to study the effect of external irradiation on monoclonal antibody (MAb) targeting of human carcinomas; as a model system, we used MAb B72.3 and the LS-174T human colon carcinoma xenograft in athymic mice. LS-174T tumors exposed to 300 cGy grew to approximately 93% the size of non-irradiated tumors, while those exposed to 600, 900, or 2,000 cGy were approximately 41% the size of control tumors. Splitting the 900 cGy into three 300-cGy fractions yielded a two-fold lower tumor volume compared with a single 900-cGy fraction. Histochemical evaluation of the carcinomas revealed a decrease in the number of mitoses per high power field consistent with early effects of radiation exposure. Using the avidin-biotin complex immunoperoxidase technique, carcinomas were assayed for expression of the tumor associated glycoprotein (TAG)-72, the high-molecular-weight mucin detected by MAb B72.3. No discernable variation was observed in the staining intensity among tumors in both the control and radiation treated group; that is, differences among tumors within each group were compatible with the known heterogeneous expression of TAG-72. Exposure of carcinomas to 300 or 900 cGy in a single fraction or 900 cGy split in three 300-cGy fractions did not yield a consistent or substantial enhanced localization of radiolabeled MAb B72.3 IgG or F(ab')2 to tumors. A 1.5-fold augmentation of MAb binding to tumors was observed in preirradiated mice; however, these results were not statistically significant. Inherent differences in tumors such as cell type of origin, size, spatial configuration, extent of vascularization and volume of interstitial space may contribute to variability of the effect of preirradiation of tumors on antibody binding. Our results suggest that consistent augmentation of radiolabeled antibody localization to tumors is not a universal phenomenon.

Animals

Union election activity in the hospital industry.

In the past five years, there has been a dramatic decrease in the number of representation elections in the hospital industry. Once a union is in place, however, decertification is less likely to occur than in other industries.

Collective Bargaining

A large multicentre, parallel group, double-blind study comparing tenoxicam and piroxicam in the treatment of osteoarthritis and rheumatoid arthritis.

A total of 1,328 patients with osteoarthritis or rheumatoid arthritis were entered into this double-blind, parallel group study of tenoxicam and piroxicam. The patient populations were well matched. An improvement was seen in pain on moving and at night in both groups and in both indications. Stiffness was also improved by both drugs, being most marked in the rheumatoid arthritis group. The primary efficacy variable was global assessment, and this showed tenoxicam to have slightly greater effect in osteoarthritis and the reverse in rheumatoid arthritis. There were no statistically significant differences in any of these findings. There were no significant differences in tolerance ratings, although the more serious gastrointestinal events occurred in the piroxicam group.

Adult