Biomedical subjects
Publications and source records attributed to R Black.
A prospective study of abdominal and chest films of 212 babies without symptoms of intra-abdominal disease, aged 1 day-12 weeks, showed that the bubbly "fecal pattern" normally seen in older children is rare in young premature babies in the first two weeks of life. When it is seen, it may represent intramural air bubbles and signal the presence of necrotizing enterocolitis.
Enterotoxigenic Escherichia coli (ETEC) of serotype O6:H16, biotype A, bearing colonization factor antigen II (CFA/II) possesses two distinct coli surface antigens, CS1 and CS3, whereas CFA/II-positive ETEC of serotype O8:H9 manifests only CS3. CS1 has been shown to be fimbrial in nature, but heretofore the morphology of CS3 has not been described. Accordingly, by immune electron microscopy we investigated the morphological characteristics of CS3 on bacterial cells and after purification. CS3 was found to consist of thin (2-nm), flexible, wiry, "fibrillar" fimbriae, visible both on bacteria (O6:H16, biotype A, and O8:H9 strains) and in the pure state. In contrast, CS1 exists as wider (6-nm), rigid fimbriae on the surface of O6:H16, biotype A, strains. By the use of antisera to CS1 and CS3 in immune electron microscopy, immunodiffusion in gel, and immunoblotting techniques, CS1 and CS3 were found to be immunologically as well as morphologically distinct. Six of nine volunteers who developed diarrhea after challenge with an O139:H28 ETEC strain bearing CS1 and CS3 had significant serological rises to purified CS1 and CS3 antigens, suggesting that both antigens are elaborated in vivo, play a role in pathogenesis, and stimulate an immune response.
A ganglioside enzyme-linked immunosorbent assay (ELISA) was used to study and attempt to differentiate between antitoxin responses in persons infected with either Vibrio cholerae or Escherichia coli producing heat-labile enterotoxin. In most cases (69%-94%), experimentally infected North Americans and naturally infected Bangladeshis responded to either infection with significant (greater than twofold) increases in serum antibody titer to both heat-labile enterotoxin and cholera toxin. In all but one instance, the response was higher to the homologous than to the heterologous toxin, and for the Americans the homologous antitoxin titers remained significantly higher for at least one year. Determination of levels of antibodies to purified subunits A and B of cholera toxin by an ELISA showed that V. cholerae infection in most instances induced a significant response to subunit B but rarely to subunit A. E. coli infection, on the other hand, induced only slight increases in antibody titer to either subunit.
Ty21a, a stable attenuated mutant of Salmonella typhi, is a safe, protective oral vaccine when 3 doses of 10(9) cells in saline are taken after neutralization of gastric acidity by 1 g NaHCO3. To identify a more convenient method to administer vaccine and to determine the feasibility of immunizing with a single dose, we studied the immune response of children and adults to different formulations of Ty21a with a newly developed, sensitive, enzyme-linked immunosorbent assay (ELISA). In this ELISA, a rise in S. typhi O antibody was defined as a change in net optical density of greater than or equal to 0.15 (more than 3 SD from the mean difference in optical density in a negative control population). Three hundred and thirty-five Chilean children were given 3 doses of 10(9) Ty21a in 150 ml of milk with 0.8 g NaHCO3 or in enteric-coated capsules. In each group, 5% seroconverted by Widal O but 41% by IgG ELISA O antibody titers; mean antibody levels by group were identical. Studies were also carried out in healthy college students in a non-endemic area (U.S.A.) who had no history of prior typhoid immunization. In total, 141 U.S. adults received vaccine formulated in either one of two ways: 1) in gelatin capsules administered with two additional gelatin capsules containing a total of 0.8 gm NaHCO3 or 2) in enteric-coated capsules. Thirty-six persons received one dose, 30 got two doses and 16 ingested three doses of enteric-coated vaccines, while 44 persons receiving one dose and 15 got two doses of vaccine in the gelatin capsule formulation. Rates of seroconversion of ELISA O antibody were similar in all the groups. Ty21a vaccine was not recovered from multiple stool, jejunal fluid or blood cultures of the U.S. vaccine recipients. Based on these observations a large-scale field trial of efficacy has been initiated in 90.000 schoolchildren 6-20 years of age in Santiago, Chile, of whom one-third received one dose of enteric-coated vaccine, one-third got two doses and the remainder received placebo.
One hundred and thirty-seven patients with operable breast cancer have been treated by mastectomy and node sampling. At the time of operation, portions of tumour were taken for determination of oestrogen receptor activity. In 91 cases adjacent tissue was taken for fixation and histological assessment of malignant epithelial cell content ('cellularity index'). The patients were followed for two years or more, or until first recurrence or death. Prognosis (probability of staying disease-free) was significantly better in patients whose tumours contained receptors than in those whose tumours were receptor-negative (p less than 0.03). However, the best prognosis was in patients with low receptor positive tumours. Those with highest values had a prognosis almost as poor as patients with receptor-negative tumours. In addition, a new finding emerged: prognosis was better in patients with tumours of low cellularity than in those with tumours of high cellularity (p less than 0.04). Since, for receptor-positive tumours, receptor level was also significantly correlated with cellularity (R = +0.35, p less than 0.01), the relationship between prognosis and receptor level was re-examined after 'correction' of the latter quantity for differences in cellularity: on this basis, again prognosis was better in patients with receptor-positive tumours (p less than 0.02), but there was no longer a tendency for any one sub-group of patients with receptor-positive tumours to fare better than the rest. It is concluded that prognosis in operable breast cancer is related to oestrogen receptor activity (either per mg weight, or per cell) and to cellularity.
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The primary tumour and 1-3 invaded, axillary nodes from each of 24 patients were examined both histologically for the proportion of the specimen constituted by malignant epithelial cells ('cellularity index') and biochemically for oestrogen receptor concentration. Both malignant epithelial cell content and oestrogen receptor concentration were significantly higher in the nodal metastases than in the primary tumours, malignant cells constituting approximately half of the former tissue and three quarters of the latter. On average, receptor concentrations were 1.6 x (protein basis) to 2.3 x (wet weight basis) higher in nodes than in the primary tumours, probably due at least in part to the difference in cellularity. When, to eliminate the effect of the latter, receptor concentration in each tumour deposit was 'corrected' using the appropriate 'cellularity index', the difference in receptor concentration between primary and node was significantly diminished, but not quite eliminated. In one patient, progestogen receptor concentrations were also studied and found to be higher in the nodes than in the primary tumour. If the actual quantity of receptor is to be used for predictive/prognostic purposes, then either a different 'cut-off point' should be used for invaded nodes from that used for assessment on the primary tumour, or receptor concentrations should be corrected for differences in cellularity.
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Enteric virus-specific IgA and IgG present in paired human sera and colostrums were measured by the enzyme-linked immunosorbent assay (ELISA). Virus-specific IgA was present in all colostrums, but virus-specific IgG could not be detected. The reverse was true when sera were assayed. Most of these colostrums also neutralized either polio virus or reovirus, as did IgA, which was separated from a pool of colostrums by exclusion chromatography. No correlation could be made between levels of neutralizing and ELISA antibody titers in colostrums.
Until recently confusion has existed concerning the clinical features and surgical treatment of gastroschisis and omphalocele. Since 1971 75 infants with these abdominal wall defects have been treated at our institution. Significant differences (p equal to 0.001 in all instances) were noted between the two diseases. Gastroschisis occurred twice as often as omphalocele and is increasing in frequency. Prematurity was commonly seen with gastroschisis (65%). While the overall incidence of malformations associated with gastroschisis was low (23%), the vast majority of the additional malformations were jejunoileal or colonic atresias. The mortality rate was 12.7% among gastroschisis patients, with only one death attributable to prematurity. All other deaths were preventable, indicating that even lower mortality rates are feasible. Omphalocele was associated with a 23% incidence of premature birth but associated anomalies were present in 66% of the patients. Major cardiac (52%) and chromosomal defects (40%) predominated. In addition, 17% of omphalocele patients had either Cantrell's pentalogy or cloacal/bladder exstrophy. The mortality rate in omphalocele (34%) was nearly three times that of gastroschisis. Nine of ten patients who died from omphalocele died either from major cardiac or chromosomal disease. However, in patients without cardiac or chromosomal defects the survival rate was 94%.
Two brands of thiosulfate citrate bile salts sucrose agar and Monsur taurocholate tellurite gelatin (TTG) agar were compared with two newly developed media, sucrose tellurite teepol agar and Vibrio parahaemolyticus agar for isolation and identification of Vibrio cholerae. The thiosulfate citrate bile salts sucrose and TTG agars were the best selective media, whereas sucrose tellurite teepol agar was the poorest. Both TTG and sucrose tellurite teepol agars were good for use in follow-up serological tests, whereas only TTG agar could be used for follow-up oxidase tests. In our opinion TTG agar has more advantages for cholera research laboratories routinely culturing large numbers of patients for cholera on a daily basis and where media needs can be accurately predicted. In contrast, in smaller clinical laboratories or in laboratories investigating epidemics, thiosulfate citrate bile salts sucrose agar is best because it is commercially available and easy to prepare and can be used to distinguish colonies of suspect V. cholerae from V. parahaemolyticus.
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In our longitudinal study on the influence of nutrition upon health during infancy we found in a cohort of 556 infants in good health, 6.4% of infants at six months with a total serum cholesterol level above 200 mg/100 ml. Because of the known importance of hypercholesterolemia for health we studied the role of the food intake patterns during the first six months in relation to the serum cholesterol. We analysed the 24 hours dietary recalls, the dietary habits and a set of biochemical determinations used for evaluation of nutritional status: 35 infants, 21 girls and 14 boys, were compared with a control group matched for sex and birth date. There were no differences in mean body weight and socio-demographic characteristics. Daily energy and protein intake was higher in the study group. Analysing milk consumption we found that the daily intake was always higher in the high cholesterol group. The solid foods were introduced earlier in the study group, i.e. for 46% of infants in the second week of life. The serum levels of vitamins A, C, and E, and of triglyceride were higher in the high cholesterol groups. At twelve months 33% of infants with the cholesterol level above 200 mg/100 ml we included in the studied group remain still with a high level. This tendency underlines the need of further research.
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