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Biomedical subjects

P Jordan

Publications and source records attributed to P Jordan.

At least 145 records · Page 8Linked to original sources

Control of Schistosoma mansoni transmission by chemotherapy in St. Lucia. I. Results in man.

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.

Adolescent↗

Immune responses during human schistosomiasis mansoni. I. In vitro lymphocyte blastogenic responses to heterogeneous antigenic preparations from schistosome eggs, worms and cercariae.

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.

Antigens, Heterophile↗

Immune responses during human schistosomiasis mansoni. II. Occurrence of eosinophil-dependent cytotoxic antibodies in relation to intensity and duration of infection.

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.

Antibodies↗

Mechanism and stereochemistry of enzymic reactions involved in porphyrin biosynthesis.

5-Aminolaevulinate synthetase cataylses the condensation of glycine and succinyl-CoA to give 5-aminolaevulinic acid. At least two broad pathways may be considered for the initial C--C bond forming step in the reaction. In pathway A the Schiff base of glycine and enzyme bound pyridoxal phosphate (a) undergoes decarboxylation to give the carbanion (b) which then condenses with succinyl-CoA with the retention of both the original C2 hydrogen atoms of glycine. In pathway B, loss of a C2 hydrogen atom gives another type of carbanion (c) that reacts with succinyl-CoA. Evidence has been presented to show that the initial C--C bond forming event occurs via pathway B which involves the removal of the pro R hydrogen atom of glycine. Subsequent mechanistic and stereochemical events occurring at the carbon atom destined to become C5 of 5-aminolaevulinate have also been delineated.(Carticle) Several mechanistic alternatices for the formation of the two vinyl groups of haem from the propionate residues of the precursor, coproporphyrinogen III, have been examined. (see article). It is shown that during the biosynthesis both the hydrogen atoms resident at the alpha positions of the propionate side chains remain undisturbed thus eliminating mechanisms which predict the involvement of acrylic acid intermediates. Biosynthetic experiments performed with precursors containing stereospecific labels have shown that the two vinyl groups of haem are formed through the loss of pro S hydrogen atoms from the beta-positions of the propionate side chains. In the light of these results, three related mechanisms for the conversion, propionate leads to vinyl, have been considered. In order to study the mechanism of porphyrinogen carboxy-lyase reaction, stereo-specifically deuterated, tritiated-succinate was incorporated into the acetate residues of uroporphyrinogen III which on decarboxylation generated asymmetric methyl groups in coproporphyrinogen III and then in haem. Degradation of the latter yielded chiral acetate deriving from C and D rings of haem. Configurational analysis of this derivate acetate shows that the carboxy-lyase reaction proceeds with a retention of configuration.

5-Aminolevulinate Synthetase↗

Hycanthone dose-response in treatment of schistosomiasis mansoni in St. Lucia.

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.

Adolescent↗

Preliminary parasitological results of a pilot mollusciciding campaign to control transmission of Schistosoma mansoni in St Lucia.

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.

Adolescent↗

Control of Schistosoma mansoni transmission by provision of domestic water supplies. A preliminary report of a study in St Lucia.

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.

Adolescent↗

Two-year follow-up of hycanthone-treated schistosomiasis mansoni patients in St. Lucia.

Of 433 schistosomiasis mansoni patients in St. Lucia who were treated with hycanthone (3 mg/kg of body weight), 190 were seen 2 years after treatment and 143 of these had attended all follow-up examinations at 6 weeks, 6 months, 1 year and 2 years. Viable eggs were not detected in 86% at 1 year nor in 76% at 2 years. The reinfection rate, as judged by a significant increase in egg excretion, was 15% and was related to the geographic area to which the patient returned. Extremely high total reduction in egg excretion (98%) was achieved through 1 year, and even with reinfections this fell only to 87% at 2 years. Liver and spleen enlargement was related to intensity of infection and responded to treatment in 92% and 83% of instances, respectively. Among patients with hepatosplenomegaly, those 15 years or older showed less clinical response than younger patients but were too few for statistical comparison.

Adolescent↗