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Biomedical subjects

M E Scott

Publications and source records attributed to M E Scott.

At least 19 recordsLinked to original sources
PubMed1992

Factors generating aggregation of Heligmosomoides polygyrus (Nematoda) in laboratory mice.

The importance of host heterogeneity in generating aggregation was investigated using Heligmosomoides polygyrus (Nematoda) in laboratory mice. Parameters of infection were compared between inbred and outbred mice, between primary and challenge infection protocols, and between gavage and natural exposure protocols, to investigate the relative effects of innate resistance, acquired resistance and behaviour, respectively. Heterogeneity in acquired resistance was identified as the most consistent factor leading to variability and aggregation of H. polygyrus numbers in mice. This hypothesis was supported in two experiments where groups of mice did not develop resistance to challenge infection (use of certain inbred strains of mice and immunosuppression with corticosteroids in the drinking water) and where variability in worm numbers after the challenge infection was comparable with that after the primary infection. Heterogeneity in host behaviour, particularly in behaviours enhancing skin contact with larvae, also was associated with increased heterogeneity in worm burden, though not as consistently as heterogeneity in acquired resistance. Surprisingly, worm burdens were not more variable in outbred compared with inbred mice. Our data suggest that the relative contributions of innate resistance, acquired resistance and behaviour in generating variable worm burdens are likely to vary spatially and temporally.

Adrenal Cortex Hormones↗
PubMed1992

Marginal zinc deficiency has no effect on primary or challenge infections in mice with Heligmosomoides polygyrus (Nematoda).

The effect of low dietary zinc on the survival of an intestinal nematode (Heligmosomoides polygyrus) was investigated in two experiments. In experiment 1 (primary infection), outbred CD1 mice were infected once only with 100 H. polygyrus larvae. In Experiment 2 (challenge infection), mice were given a primary infection that was terminated after 9 d using an anthelmintic drug; the mice were reinfected 5 d later. This protocol stimulates host immunity to the second parasitic infection. Three dietary treatments (control, 60 mg Zn/kg diet; zinc-restricted, 5 mg Zn/kg diet; and energy-restricted, 60 mg Zn/kg diet) were used for both experiments. Both infected and uninfected mice were included within each dietary treatment to control for the effect of parasitic infection on host nutritional status. Plasma zinc concentrations were significantly lower in mice fed the zinc-restricted diet, compared with mice fed the control or energy-restricted diets in both experiments; there were no significant differences in plasma alkaline phosphatase activity or tissue zinc concentration. The significant reduction in plasma zinc had no significant effect on worm burden or egg production of H. polygyrus in either experiment, indicating that the 30-40% reduction in plasma zinc was not sufficient to modify parasite numbers. However, the parasite did affect host nutritional status. Spleen weight was significantly higher in infected mice in both experiments. Following the challenge infection, both liver and spleen copper concentrations were significantly higher, and spleen iron concentration significantly lower, in the infected compared with the noninfected mice.

Animals↗
PubMed1992

The biochemistry and pharmacology of PD 116124 (8-amino-2'-nordeoxyguanosine), an inhibitor of purine nucleoside phosphorylase (PNP).

PD 116124 (8-amino-2'-nordeoxyguanosine; 2,8-diamino-1,9-dihydro-9- ([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)-6H-purin-6-one) is a competitive, reversible inhibitor of human purine nucleoside phosphorylase with an apparent inhibition constant of 0.41 microM. In a cell line system using human MOLT-4 and CEM T lymphoblasts and human MGL-8 and NC-37 B lymphoblasts, PD 116124 failed to inhibit [3H]thymidine uptake at concentrations up to 500 microM. However, in the presence of 10 microM 2'-deoxyguanosine (dGuo), a noninhibitory dGuo concentration by itself, PD 116124 produced potent inhibition of growth of both T cell lines but not of either B cell line. Significant elevation of intracellular 2'-deoxyguanosine triphosphate was observed in both inhibited T cell lines but not in either B cell line. Greater and more sustained accumulation of 2'-deoxyguanosine triphosphate was observed in T lymphoblasts cultured with PD 116124 plus dGuo than with dGuo only. PD 116124 was only weakly inhibitory in human mixed lymphocyte cultures (IC50 approximately equal to 1420 microM), but in the presence of 10 microM dGuo, the IC50 for PD 116124 was reduced to 108.7 microM. Administration of PD 116124 p.o. to normal male Wistar rats caused dose-dependent elevation of plasma inosine up through 500 mg/kg. Maximal inosine elevation occurred at 30 min after dosing, and elevation was significant even 24 hr after dosing. Guanosine was also elevated, although not in a dose-dependent manner. Administration of PD 116124 i.v. produced marked and statistically significant elevation of both inosine and guanosine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Heligmosomoides polygyrus (Nematoda): susceptible and resistant strains of mice are indistinguishable following natural infection.

BALB/c mice were characterized as more resistant to infection with Heligmosomoides polygyrus (Nematoda) than C57BL/6 mice based on lower establishment and survival during a primary infection and stronger protection induced by an immunizing regime. It was hypothesized, therefore, that C57BL/6 mice would be more heavily infected than BALB/c mice when they lived together as a single population in a large indoor arena where transmission occurred through contact between the mice and damp peat trays where parasite eggs developed into larvae. Fifty female mice (including 5 infected mice) of each strain were placed in a 3.2 x 0.8 m arena. Net egg production and numbers of larvae acquired by sentinel mice of each strain were monitored every two weeks. The experiment was replicated twice. The results did not support the hypothesis. No difference was detected between strains of mice in the number of larvae acquired by sentinel mice during 24 h exposure periods, or in the numbers of worms present after 12 or 23 weeks. Net egg production was also comparable between strains. A hypothesis that the unexpected similarity of infection in the two strains was related to differences in rates of contact with the peat trays was not supported by preliminary data on mouse behaviour that revealed equal frequency of contact with peat trays between strains. A second hypothesis that continuous exposure to larvae led to similar infection levels in the two strains (in contrast to the controlled characterization experiments) was also unsupported. Mice were infected weekly with 10, 50 or 100 larvae for 5 or 10 weeks. Net egg production and numbers of worms were consistently higher in C57BL/6 than BALB/c mice. At this time it is not clear why infection in the two strains was virtually identical in the large arenas but clearly distinct in all controlled infection experiments.

Animals↗
PubMed1990

Management of acute coronary occlusion during percutaneous transluminal coronary angioplasty: experience of complications in a hospital without on site facilities for cardiac surgery.

OBJECTIVE: To determine whether percutaneous transluminal coronary angioplasty may be safely performed in cardiology centres in the United Kingdom without immediate on site cardiac surgical cover for complications arising at angioplasty. DESIGN: Retrospective review of coronary angioplasties and complications in a hospital without on site cardiac surgical cover. SETTING: All angioplasties were performed in the catheterisation laboratory of the Belfast City Hospital. Revascularisation surgery for complicated coronary angioplasty was performed in the cardiac surgical unit of the Royal Victoria Hospital, 2.4 km away from the catheterisation laboratory. PATIENTS: 540 Coronary angioplasties were performed on 512 patients between late 1982 and November 1988. Indications included stable angina, unstable rest angina, and suitable coronary disease at coronary arteriography after myocardial infarction. MAIN OUTCOME MEASURES: In hospital mortality after complicated coronary angioplasty and delay to surgical revascularisation after acute coronary occlusion at angioplasty. RESULTS: Coronary angioplasty was successful in 444 cases (82%). Acute coronary occlusion occurred in 35 cases (6.5%). Twelve patients required urgent revascularisation surgery and were transferred safely to the surgical unit; none of these patients died. A mean delay of 268 minutes (range 180-390 minutes) occurred before revascularisation compared with 273 minutes (range 108-420 minutes) in the Royal Victoria Hospital, where on site surgical cover was available. The principal cause of delay was the wait for a cardiac operating theatre to become available and not the transfer time between hospitals. Five deaths occurred after coronary angioplasty, a mortality of 0.9%. Three deaths were related to acute coronary occlusion. The absence of immediate surgical help did not influence the outcome in any patient. CONCLUSION: With careful selection of patients coronary angioplasty may be safely performed in a hospital without on site cardiac surgical facilities, provided that these are available at a nearby centre.

Acute Disease↗
PubMed1990

Measurement of Ascaris lumbricoides infection intensity and the dynamics of expulsion following treatment with mebendazole.

Intensity of Ascaris lumbricoides infection was measured in terms of egg counts and worm burden in children 2-10 years of age. The expulsion of A. lumbricoides with a 3-day treatment of mebendazole occurred over 8 days, beginning on the second day of treatment. Ninety-seven percent of the worms were expelled between the second and seventh days. A rapid means of estimating eggs per gram (epg) by the Kato Katz technique correlated well with the method described by Martin & Beaver (1968). In spite of apparent density dependence in egg production, A. lumbricoides egg counts correlated well with worm burdens. It is concluded that, within the context of community surveys, epg is a reasonable means of identifying heavily infected individuals and that epg can be estimated rapidly by a slight modification to the standard Kato Katz technique.

Animals↗
PubMed1990

Effect of selection pressure for thiabendazole resistance on fitness of Haemonchus contortus in sheep.

A strain of Haemonchus contortus showing moderate levels of resistance to thiabendazole (TBZ) (egg hatch assay LC50 2.1 microM) was subjected, in alternating sequence, to 5 in vitro and 4 in vivo selections with TBZ. This resulted in a significant increase in resistance (egg hatch assay LC50 2.8 microM). The isolates obtained after each combined in vitro and in vivo selection were compared in terms of egg hatch assay, establishment, net egg output, per capita egg output and degree of pathology caused in infected hosts. The increase in resistance was accompanied by a significant increase in larval establishment in sheep (22.8-39.2%) and was associated with more severe pathology, higher egg count and worm recovery 3 months post-infection. The resistant strains were also compared with a TBZ-susceptible strain (egg hatch assay LC50 1.0 microM). The TBZ-susceptible strain had the highest net egg output, it caused the most severe pathology and it resulted in higher worm recovery than any of the TBZ-resistant strains, although the most resistant strain was very similar to the TBZ-susceptible strain. Neither the per capita egg output nor biological features of the free-living stages were significantly affected by the degree of resistance. The implications of these observations for anthelmintic use and for management of nematode anthelmintic resistance in the field are discussed.

Animals↗
PubMed1990

An experimental and theoretical study of the dynamics of a mouse-nematode (Heligmosomoides polygyrus) interaction.

The population dynamics of outbred laboratory mice in indoor enclosures in the absence and presence of a naturally transmitted direct life-cycle nematode Heligmosomoides polygyrus Dujardin 1845 were reported previously. This manuscript presents further information on the age and sex structure of the populations, results of experiments designed to estimate the density-dependent effect of the parasite on host survival and reproduction, and a mathematical model of both uninfected and infected mouse populations. In the uninfected mouse population, survival of female mice was age- and density-independent, survival of male mice was age-dependent and density-independent, and recruitment was density-dependent. Independent experiments revealed that the parasite had no density-dependent effect on mouse reproduction, but had density-dependent effects on both acute and chronic survival of mice. An age-structured Leslie matrix model captured the exponential growth and plateau of the uninfected mouse population. Modification of the model to incorporate the effects of the parasite provided a good fit to the data from the infected populations, supporting the hypothesis that density-dependent effects of the parasite on host survival could lead to regulation of host abundance.

Age Factors↗
PubMed1990

Intravenous streptokinase for acute myocardial infarction reduces the occurrence of ventricular late potentials.

The occurrence of ventricular late potentials in survivors of acute myocardial infarction treated with intravenous streptokinase was compared with that in a conservatively treated group and the relation between ventricular late potentials and patency of the infarct related artery was examined. Of 115 patients admitted with a first infarct, 55 were treated with intravenous streptokinase (streptokinase group) and 60 were treated conservatively (non-streptokinase group). A signal averaged electrocardiogram was recorded in all patients and coronary angiography was performed in 45 (81.8%) of the streptokinase group and in 21 (35%) of the non-streptokinase group. At a 40 Hz filter setting ventricular late potentials were significantly less common in patients treated with streptokinase (9 (16.4%) of 55) than in those who were not (26 (43.3%) of 60). A total of 66 patients underwent angiography. Of the 26 who had closed infarct-related arteries, 17 had ventricular late potentials at a 40 Hz filter setting (sensitivity 65.4%, specificity 95%) and 38 of the 40 patients with a patent infarct-related artery did not have ventricular late potentials (sensitivity 80.9%, specificity 89.5%). Patients with acute myocardial infarction treated with intravenous streptokinase were significantly less likely to have ventricular late potentials than conservatively treated patients and the absence of ventricular late potentials at 40 Hz filter setting was a good non-invasive predictor that the infarct-related artery was patent.

Arrhythmias, Cardiac↗
PubMed1989

Pathological changes after intravenous streptokinase treatment in eight patients with acute myocardial infarction.

At necropsy five of eight patients (mean age 57 years) who died after intravenous streptokinase treatment for severe acute myocardial infarction (mean Peel index = 18) were found to have a patent infarct related coronary artery. Coronary artery stenoses were caused by fibrofatty atheromatous plaques; there were no residual thrombi in the lumen or acute intimal lesions. Three of these infarcts were of partial thickness (less than two thirds wall width) with sparing of the outer third of the myocardium and subendocardial zones. In the other three patients the infarct related coronary arteries remained histologically closed with residual lumen thrombi and underlying intimal lesions. Two infarcts were transmural. Six of the eight infarcts were noticeably haemorrhagic. Myocardial haemorrhage was confined to areas of necrotic myocardium and did not affect viable regions. These findings suggest that thrombus overlying a complex lesion may be more difficult to lyse than thrombus overlying a simple fibrofatty plaque. They also suggest that myocardial haemorrhage outside the infarct area, which might lead to cardiac rupture or delayed healing, does not usually occur.

Acute Disease↗
PubMed1988

Relation of coronary arterial patency and left ventricular function to electrocardiographic changes after streptokinase treatment during acute myocardial infarction.

One hundred and eighty-eight patients with evolving acute myocardial infarction were treated with intravenous streptokinase. Serial 12-lead electrocardiograms were recorded for 3 hours after treatment and inspected for rapid repolarization changes of the ST segment and T wave. Abrupt electrocardiographic repolarization changes were observed in 106 patients (56%) and were strongly predictive for an open infarct-related coronary artery at a mean of 6 days after treatment (predictive value = 0.92, sensitivity = 0.67). Abrupt electrocardiographic changes were not observed in 82 patients (44%). This absence was not a good predictor of an occluded infarct-related coronary artery (predictive value = 0.4). There was no relation between the presence or absence of abrupt electrocardiographic changes and global or regional left ventricular function after streptokinase treatment. Abrupt repolarization changes after thrombolytic treatment indicate a high probability of an open infarct-related artery. When abrupt repolarization changes do not occur, the patency of the infarct-related coronary artery cannot be predicted with accuracy. Serial electrocardiographic recordings do not provide sufficient information about coronary patency to eliminate the need for coronary arteriography.

Aged↗
PubMed1988

Clustering of Ascaris lumbricoides and Trichuris trichiura infections within households.

A survey of 428 households in a shanty town in Coatzacoalcos, Mexico, revealed high prevalences of Ascaris lumbricoides and Trichuris trichiura. The data were analysed separately for A. lumbricoides and T. trichiura in order to investigate the spatial distribution of heavy infections through the town. Within each age class, those individuals with egg counts in the upper 20% of the range for that age were classified as "heavily infected". When the data were stratified by household size, it was found that the distribution of "heavily-infected" individuals was not random in the community. "Heavily-infected" individuals were found together in households; fewer household units had a single heavily-infected individual than would be expected by chance. Such a pattern could result either from genetic similarities among family members influencing their ability to mount an effective immunological response to infection, or focal transmission in the vicinity of the home, or both. This result may have important implications for the development of community control programmes.

Adolescent↗
PubMed1988

Effect of repeated anthelmintic treatment on ability to detect predisposition of mice to Heligmosomoides polygyrus and Aspiculuris tetraptera (Nematoda) infections.

Several recent studies have demonstrated predisposition of certain humans to heavy gastro-intestinal nematode infections. This finding has been used to support the concept of community control of nematodes based on selective treatment of the few heavily infected individuals in the community. A mouse model has been used in this study to determine whether those individuals found to be 'predisposed' to heavy infection continue to regain heavy nematode infections following repeated anthelmintic treatments. Re-infection was examined over 3 intervals of 8 weeks in 52 mice and individual worm burdens attained following drug-induced expulsion were analysed. In the case of Heligmosomoides polygyrus, parasite numbers obtained after first treatment were only significantly correlated with those obtained after the second treatment. Re-infection levels in mice during the second and third re-infection periods did not correlate with parasite loads at the beginning of the study. In the case of Aspiculuris tetraptera, correlations after each re-infection period remained significant, although the magnitude of the correlation coefficient decreased with successive re-infection intervals. The data suggest that a selective control programme based on repeated screening to identify heavily infected individuals prior to each treatment would reduce the number of H. polygyrus in the host population 17.6% more than a single screening at the beginning of the control programme, and would reduce the number of A. tetraptera by 14% more than a single screening. Re-infection rates for H. polygyrus were shown to decrease with increasing mouse age whereas re-infection rates for A. tetraptera increased with increasing mouse age.

Age Factors↗
PubMed1988

Predisposition of mice to Heligmosomoides polygyrus and Aspiculuris tetraptera (Nematoda).

The purpose of this study was to determine whether predisposition to Heligmosomoides polygyrus and Aspiculuris tetraptera (Nematoda) exists within a naturally infected population of mice. A breeding mouse population was housed in a spacious arena in which endemic infections of H. polygyrus and A. tetraptera were present. H. polygyrus were over-dispersed in the mouse population. Prevalence reached 100% by the age of 3 weeks; intensity of infection increased to a peak in the 10 to 15-week-old mice, and remained high throughout life. A group of 73 mice was treated with pyrantel pamoate, and the expelled worms were counted. Mice were returned to the arena. Daily egg production was monitored 4, 8, 12 and 14 weeks after treatment. Mice were then killed and numbers of H. polygyrus and A. tetraptera were counted. Significant positive correlations were detected between numbers of H. polygyrus at first treatment and at necropsy, indicating the existence of predisposition. Similar results were obtained for A. tetraptera. Correlations improved when data were analysed by age class of mice. Analyses based on egg-count data during reinfection did not support the hypothesis of predisposition, however. A. tetraptera and H. polygyrus burdens were significantly correlated only in 3 to 4-week-old mice at the time of the treatment.

Animals↗
PubMed1988

Ecological studies on Cyathocotyle bushiensis (Digenea) and Sphaeridiotrema globulus (Digenea), possible pathogens of dabbling ducks in southern Québec.

Over the past 20 yr, recurrent late-summer mortality of dabbling ducks in southern Québec has been attributed to the digenean parasite Cyathocotyle bushiensis. This study attempted to determine whether this parasite was still implicated in the epizootics, and examined aspects of the ecology of the parasite in the definitive host. Comparison of prevalence and mean intensity of infection of all species of Digenea between salvaged carcasses and hunter-shot ducks revealed that C. bushiensis and a second digenean Sphaeridiotrema globulus were both significantly more prevalent in salvaged ducks. Mean intensity of infection was consistently higher for S. globulus in the salvaged carcasses than in hunter-shot ducks. These data provide strong circumstantial support for the hypothesis that C. bushiensis continues to contribute to the annual mortality, but also strongly suggest that S. globulus may be involved. Comparison of the relative numbers of each species of duck between the salvaged carcass sample and the hunter-shot sample revealed that blue-winged teal (Anas discors) occurred significantly more frequently in the salvaged carcass sample whereas wood ducks (Aix sponsa) were common in the hunter-shot sample but were never found in the salvaged carcass sample. A comparison of susceptibility to experimental infection with C. bushiensis revealed that mallards (Anas platyrhynchos), black ducks (Anas rubripes), blue-winged teal, pintail (Anas acuta) and lesser scaup (Aythya affinis) had similar susceptibilities but that wood ducks were significantly less susceptible to infection. Experimental infections also showed that age of mallards significantly influenced the number of parasites obtained 7 days postinfection; ducklings were most heavily infected. Significant differences were detected in the gross pathology caused by C. bushiensis among duck species. Data obtained from sentinel ducks placed in the field for 24 hr revealed that transmission of both C. bushiensis and S. globulus occurs at least between mid-May and mid-September and that large, potentially lethal, infections can be acquired in as little as 24 hr. Finally evidence is presented to suggest that ducks acquire resistance to challenge infections of C. bushiensis.

Age Factors↗
PubMed1987

8-Amino-9-substituted guanines: potent purine nucleoside phosphorylase (PNP) inhibitors.

A series of 8-amino-9-substituted guanines was synthesized and their activity evaluated against human purine nucleoside phosphorylase (PNP). All compounds were found to be potent inhibitors of human PNP (IC50s: 0.17-126 microM). They were also selectively cytotoxic to MOLT-4 lymphoblasts in the presence of a nontoxic amount (10 microM) of the PNP substrate, 2'-deoxyguanosine (GdR). The most potent of these analogs, 2,8-diamino-1,9-dihydro-9-(2-thienylmethyl)-6H-purin-6-one (8-amino-9-(2-thienylmethyl)guanine; PD 119,229) has an IC50 of 0.17 microM (Ki = 0.067 microM), significantly more potent than the known standard, 8-aminoguanosine (IC50 = 1.40 microM). Thus it represents the most potent PNP inhibitor known to date when tested without limiting the concentration of inorganic phosphate.

Cell Line↗
PubMed1987

Preliminary report on 8-amino-9-(2-thienylmethyl)guanine (PD 119,229), a novel and potent purine nucleoside phosphorylase inhibitor.

PD 119,229 [8-amino-9-(2-thienylmethyl)guanine] is a novel and potent inhibitor of human erythrocyte purine nucleoside phosphorylase (PNP) with a Ki of 0.067 microM. In a cell line assay using human MOLT-4 (T cell) and MGL-8 (B cell) lymphoblasts, PD 119,229 alone had no effect on the growth of either cell line at the highest concentration tested (100 microM). However, in the presence of a nontoxic concentration of 2'-deoxyguanosine (10 microM), the IC50 values of PD 119,229 for MOLT-4 and MGI-8 40-fold either cell line at the highest concentration tested (100 microM). However, in the presence of a nontoxic concentration of 2'-deoxyguanosine (10 microM), the IC50 values of PD 119,229 for MOLT-4 and MGI-8 were 0.9 and greater than 100 microM, respectively. The inhibition of growth of MOLT-4 was accompanied by a 40-fold increase in dGTP and a two-fold reduction in GTP, while no alteration in nucleotide profile was noted in MGL-8. Both the inhibition of growth of MOLT-4 and the accumulation of dGTP were substantially prevented by coaddition of 2'-deoxycytidine.

Cell Division↗