Protective effect of glucan in experimentally induced candidiasis.
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Biomedical subjects
Publications and source records attributed to J A Cook.
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Control of Schistosoma mansoni transmission solely by treatment of all infected persons was attempted in Marquis Valley (population about 3,100), St. Lucia. Two-year results are reported. Excluding 26 pregnant patients, 709 to 729 persons who were found to be infected received treatment the first year. Most of these, 677, were given a single injection of hycanthone (2.5 mg/kg of body weight), and the same treatment was administered to 159 patients the second year. Side effects were not severe; the major side effect, vomiting, occurred in about 22% on both occasions. In villages with initially high transmission rates, the incidence of new infections in children 0 to 14 years fell from 20.8% before chemotherapy to 7.4% after 1 year and to 3.7% after 2 years. This pattern was significantly different from that in the comparison area where no control scheme exists. Chemotherapy alone appears to be a rapid, effective, and comparatively inexpensive method of controlling S. mansoni transmission in St. Lucia.
In vitro lymphocyte blastogenesis assays were performed using peripheral blood lymphocytes obtained from patients with schistosomiasis mansoni. Their infection was well characterized both clinically and in regard to the duration and intensity of Schistosoma mansoni infection. Subjects who were either not infected with any helminths or who were negative for S. mansoni but infected with other helminths provided two control groups. Cultures were exposed to various concentrations of heterogeneous soluble antigens prepared either from S. mansoni eggs, worms, or cercariae. In this series there was no statistical correlation between the intensity of infection (as determined by eggs/ml of feces) and the degree of cell-mediated reactivity observed by lymphocyte blastogenesis to any of the antigenic preparations. Individual patient lymphocyte responsiveness varied considerably. However, analysis of the data by groups, based upon the longevity of their S. mansoni infection, demonstrated different patterns of reactivity in regard to the antigen preparations. Responses to the egg antigens were only present early in infection. In contrast, reactivities stimulated by either the worm or cercarial preparations increased in a direct relationship to the duration of S. mansoni infection.
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Plasma samples from St. Lucians were tested for the presence of antibodies which cooperate in vitro with normal human leukocytes in causing cytotoxic damage to schistosomula of Schistosoma mansoni. The in vitro antibody activity, which has been previously shown to depend on eosinophil effector cells was detected in 56% of the individuals with known, current S. mansoni infections and in 14% of control subjects from the same endemic area. Quantitatively, eosinophil dependent cytotoxic antibody (EDCA) activity, when expressed as the maximum amount of damage to schistosomula induced at high plasma concentration, correlated significantly with the intensity of S. mansoni infection as determined by fecal egg count, the highest levels of activity occurring in patients with stool counts of 60 eggs/ml or greater. In addition, plasma EDCA activity was found to correlate with the in vitro blastogenic responsiveness of patients' lymphocytes to three different parasite antigen preparations. In contrast, titrations of EDCA activity failed to reveal a relationship between EDCA titer and the most recent egg count performed on each subject. However, a significant correlation was observed when titers were compared to egg counts averaged over a 3-year period. Neither maximal EDCA activity nor titer was found to correlate with the duration of known schistosome infection.
A relatively simple, standardized hatching test was devised, tested and used to estimate the Schistosoma mansoni hatching rate for 88 St Lucian subjects selected by age, sex and intensity of infection. The hatching rate was dependent on the intensity of infection and rose proportionately with it. The rate also decreased with increasing age of the subject. Sex alone had no direct effect but there was a suggestion of an interaction between sex and age. These results suggest that several hatching tests are necessary, before and after treatment in schistosomicidal drug trials, to permit valid conclusions to be drawn. The hatching data are used in conjunction with survey results to calculate the contamination potential of different age groups in a population. School children (5-14 years old) are about twice as important as young adults (15-29 years old) who, nevertheless, contribute over a quarter of the total contamination potential. However, whereas school children are fairly accessible for mass chemotherapy control programmes, young adults often are not and, furthermore, involve problems associated with the treatment of women of child-bearing age.
This report is submitted not to refute the occurrence of any toxicity but to record that in St. Lucia, given reasonable care in administration and careful follow-up, we have not yet encountered jaundice, liver necrosis or other serious side effects.
Clinical trials of hycanthone (single intramuscular dose) were undertaken in schistosomiasis mansoni patients in St. Lucia at five dose levels: 3.0, 2.5, 2.0, 1.5, and 1.0 mg/kg body weight. The most common side effect, vomiting, decreased in frequency from 51% at the highest dose to 3% at the lowest; minor side effects showed a similar trend. Three fecal specimens were examined before and at 6 months after treatment by qualitative, quantitative, and hatching techniques. All dose levels caused reductions in egg excretion of 89 to 98%. Rates of cure (absence of eggs by all three methods) according to dose (descending), pretreatment egg output (0-19, 20-49, 50-399, 400+ eggs/ml feces), and age (0-7, 8-14, 15-29, 30+ years) were analyzed to estimate the effect of each variable if the others had been constant. For dose, the standardized percentage success rates were 53.9%, 62.0%, 51.2% 54.0%, and 27.4%; for egg output, 67.0%, 51.8%, 43.2%, and 21.7%; and for age, 25.2%, 34.5%, 59.3% and 57.4%. Logit regression analysis shows a significant difference in cure rate (a) between the lowest dose and all others, among which latter there was no difference, (b) between patients excreting 0 to 49 eggs/ml before treatment and those excreting 50+ eggs/ml, and (c) between the age groups 0 to 14 and 15+ years. All dose levels caused some regression in enlargement of liver or spleen. A dose of 1.5 to 2.0 mg/kg body weight is considered to be as effective as one of 3.0 mg/kg and more acceptable for a control program because of the marked reduction in side effects.
A mollusciciding campaign was begun in Cul-de-Sac Valley, St Lucia, at the end of 1970, following several years of epidemiological studies in which transmission of Schistosoma mansoni was found to be high in settlements on the valley floor but low in hillside settlements. Postcontrol (1971-73) findings in children, when compared with precontrol data and with data from an adjacent valley having a similar transmission pattern, show significant reductions in prevalence, incidence, and intensity of infection.
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Intravenous administration of an acute dose of lead acetate or cadmium acetate enhanced the susceptibility of rats to intravenous challenge with E. coli by approximately 1000-fold. Since equivalent vulnerability of lead- or cadmium-treated rats to killed E. coli was observed, toxicity is probably due to the endotoxin content of the bacteria. This postulate is further supported by the observation that equal doses of the Gram-positive bacteria, Staphylococci epidermidis, failed to elicit lethality in the acute lead-intoxicated rats. The synthetic glucocorticoid, methylprednisolone, prevented lethality induced by the Gram-negative bacteria in lead-treated rats. It did not, however, afford significant protection in cadmium-treated rats in the presence of E. coli. Marked alterations in hepatic morphology were apparent in both lead- and cadmium-treated rats challenged with E. coli.
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As an experimental control measure to reduce the transmission of S. mansoni, an individual household water supply was provided in 400 houses in 5 rural settlements of the Riche Fond Valley, St Lucia. This population of about 2 000 had previously been dependent for water on infective streams and rivers. Six other settlements in the valley, all provided with limited piped water from public standpipes, served as the comparison area. After 2 years the incidence, prevalence, and intensity of infection with S. mansoni were significantly lower in the household water supply area, whereas all these indices of infection had increased in the comparison area. An adequate, reliable, and convenient supply of water can reduce the transmission of S. mansoni and should be considered as a control measure in other endemic areas.
A single injection of cadmium acetate givenintravenously to rats produced, at 16 hours, liver damage but no observable kidney changes. Ultrastructure of the liver revealed more profound changes in parenchymal cells than in Kupffer cells. The most prominent changes were single parenchymal cell necrosis, deterioration of rough endoplasmic reticulum, proliferation of smooth endoplasmic reticulum, autophagocytosis, and mitochondrial degenerative changes. Lesions of Kupffer cells were not prominent, although occasional areas of cytoplasmic degradation and increased vacuolation were observed. Dewquamation of these cells appears also to be a frequent finding in cadmium intoxication. Accumulation of platelets, cellular debris, inflammatory cells, and fibrin in the sinusoids may be the cause of the occasionally observed focal necrosis. Although the present experiment does not simulate any known clinical situation, these composite studies provide a morphologic basis for hepatic dysfunction following acute cadmium administration as well as an ultrastructural basis for thebetter understanding of the synergistic actionof cadmium with other substances such as endotoxins.
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