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Biomedical subjects

M A James

Publications and source records attributed to M A James.

At least 19 recordsLinked to original sources
PubMed1992

The paradoxical role of left ventricular hypertrophy in wall stress-related arrhythmia.

OBJECTIVE: To investigate the interrelationship between arrhythmias provoked by acute pressure changes, and the presence of left ventricular hypertrophy and electrolyte imbalances. DESIGN: An isolated working rat heart model was used in a prospective comparison of the effects of acute pressure changes in hypertensive and normotensive hearts during perfusion with perfusate containing differing electrolyte compositions. SETTING: An experimental laboratory study. STUDY MATERIALS: Forty-four rat hearts (20 hypertensive, 24 normotensive). INTERVENTIONS: Hearts were subjected to sudden pressure changes of varying sizes during perfusion with two different electrolyte solutions and the arrhythmias provoked were recorded. MAIN OUTCOME MEASURES: The size of the pressure change necessary to provoke arrhythmias, and the amount and severity of arrhythmias provoked by equivalent-sized pressure changes. RESULTS: During perfusion with normal electrolyte concentrations, no hypertrophied hearts developed arrhythmia compared with more than half of the normal hearts during equivalent-sized pressure changes, and a much larger pressure increase was necessary to produce any arrhythmia in the hypertrophied hearts. During perfusion with cation-depleted perfusate, arrhythmias significantly increased in both groups of hearts, but the pattern was reversed; more than half of the hypertrophied hearts compared with none of the normal hearts developed ventricular tachycardia during equivalent-sized pressure increases, whilst the minimum pressure change necessary to provoke arrhythmia became significantly smaller in the hypertrophied hearts compared with the normal hearts. CONCLUSIONS: Left ventricular hypertrophy plays a paradoxical role in the development of arrhythmias in this model. It appears to protect the heart from developing arrhythmias in response to sudden pressure changes when electrolyte concentrations are normal. However, it also seems to lead to a marked increase in the sensitivity of the myocardium to pressure changes during perfusion with low levels of potassium and magnesium. Under these conditions, potentially fatal arrhythmias can be readily provoked by relatively small pressure changes. These results may be of importance for the management of hypertension and may provide insight into some of the mechanisms underlying sudden death in hypertension. The findings may also be of relevance to other cardiac diseases associated with ventricular hypertrophy or abnormal wall stress.

Animals↗
PubMed1992

Platelet kinetics and other hematological profiles in experimental Plasmodium falciparum infection: a comparative study between Saimiri and Aotus monkeys.

Levels of platelets and other hematological values were monitored in 21 Saimiri and 12 Aotus monkeys over a period of three weeks post-infection with monkey-adapted Indochina CDC-1 strain of Plasmodium falciparum. In both Saimiri sciureus boliviensis and Aotus nancymai karyotype-1 monkeys the severest thrombocytopenia was observed at 14 days post-infection coinciding with peak parasitemia, neutropenia, lymphocytosis, and anemia associated with severe hemoglobinemia and elevated fibrinogen degeneration products(FDP's). MCH and MCV profiles in Aotus monkeys decreased with ascending parasitemia. In contrast, these parameters in Saimiri were characterized by a significant compensatory increase correlating with parasitemia. In general, thrombocytopenia was one of the earliest clinical manifestations of the infection with the platelets returning to normal levels shortly after peak parasitemia at 14 days. Platelet kinetics had a strong correlation with hematologic and parasitologic values in the Aotus model. No consistent associations were observed between platelet kinetics and other parameters in the Saimiri model. These data indicate that the Aotus model for malaria is more predictable than the Saimiri. Further, platelet turnover rates and recovery provide a useful prognostic parameter during malaria infection. The results are discussed in relation to the value of the two species of monkeys as models for the pathogenesis of human malaria.

Animals↗
PubMed1992

Malaria and pregnancy in Cameroonian women. Effect of pregnancy on Plasmodium falciparum parasitemia and the response to chloroquine.

The interaction between malaria and pregnancy was investigated in an epidemiologic study conducted in Mfou, a rural community in Cameroon. The study consisted of both cross-sectional and longitudinal analyses involving 225 pregnant women and 75 nonpregnant controls. Information was obtained by a standardized questionnaire to determine the pattern of antimalarial drug use. The parasitologic response to chloroquine was also determined. A dosage of chloroquine base (25 mg/kg of body weight) was given to women over a 3-day period, followed by 5 mg/kg doses administered weekly for 4 weeks. The results showed that Plasmodium falciparum infections occurred more frequently in pregnant (45%) than in nonpregnant (31%) women in terms of parasite rates (p = 0.03) and density (p less than 0.003), especially in primigravidae as compared with multigravidae matched for parity and age. Levels of parasitemia were also higher in the second trimester than in the first trimester of pregnancy (p less than 0.01). Failure to clear parasitemia after a chloroquine regimen was more frequent in pregnant than in nonpregnant women (p less than 0.01), particularly in primigravidae. Higher parasitemia and a lower parasitologic response to chloroquine in pregnant women, especially in primigravidae, suggest a relatively low level of clinical immunity and emphasize the need to target this group of women for malaria control strategies.

Cameroon↗
PubMed1991

Efficacy of purified Anaplasma marginale initial bodies as a vaccine against anaplasmosis.

Anaplasma marginale initial bodies of the Florida strain were purified from infected erythrocytes using a combination of ultrasonic disruption, nonionic detergent and differential centrifugation. Immunochemical analysis revealed at least 12 A. marginale proteins in the molecular mass (m) range 81-15 kDa with a prominent band at 38 kDa. Several of these proteins remained insoluble in the presence of nonionic detergent. Preparations of purified Anaplasma initial bodies contained negligible erythrocytic contamination, as confirmed by the minimal induction of isoantibodies against bovine blood group antigens and the absence of delayed-type hypersensitivity to erythrocytic antigens in immunized animals. A total of 33 crossbred and purebred Holstein cattle were vaccinated with either 1.5, 1.0, or 0.1 mg protein of intact initial bodies, or with 1.0 mg of solubilized Anaplasma protein. The immunogens were supplemented with 3.0 mg Quil-A saponin adjuvant and administered in 2 subcutaneous injections given at a 4-week interval. A similar number of nonvaccinated cattle served as controls. Three months after vaccination, all cattle were challenged by inoculation of 10(9) virulent A. marginale of either the homologous (Florida) or heterologous (Venezuelan) strains. Vaccinated cattle showed solid protection after homologous and heterologous challenge, characterized by parasite clearance and minimal hematocrit reductions. Initial data from four field vaccine trials revealed a reduced incidence of clinical anaplasmosis among immunized animals. Use of immunogens consisting of purified A. marginale initial bodies offers a potential immunoprophylactic approach to control of bovine anaplasmosis.

Anaplasma↗
PubMed1991

Effect of different levels of briefly sustained ventricular pressure on arrhythmia in the isolated working rat heart.

1. The effect of different levels of ventricular pressure upon the prevalence of ventricular arrhythmias has been studied in 42 rat hearts by using the isolated working heart model. 2. The results have shown that there is an increased prevalence of arrhythmia at the highest levels of pressure tested in hearts from both normal and hypertensive rats. In hearts from normal rats total ectopic counts were 304 at 140 mmHg and 150 at 60 mmHg (P less than 0.05). In hearts from hypertensive rats total ectopic counts were 4217 at 180 mmHg and 2179 at 100 mmHg (P less than 0.05). 3. Hearts from hypertensive rats demonstrated significantly more ectopic activity than hearts from normal rats at all test pressures. Median values for ectopic counts for each study period were 68 in hearts from hypertensive rats and seven in hearts from normotensive rats (P less than 0.001). 4. There was evidence that the increased arrhythmia observed was not due to ischaemia or fatigue, and it seems likely that these effects of raised pressure are due to its effect on ventricular wall stress. The differences between various pressures were relatively small, but do suggest that a sustained increase in ventricular wall stress is arrhythmogenic. 5. This small arrhythmogenic effect over the relatively short period of these studies may be of much greater significance when considered in the context of the prolonged periods for which the diseased heart may be subjected to raised wall stress.

Animals↗
PubMed1991

Attenuation of nitrate effect during an intermittent treatment regimen and the time course of nitrate tolerance.

The long-term efficacy of transdermal nitrate therapy, in particular the ability of a single patch to provide 24 h prophylaxis against angina, has been questioned. Two mechanisms have been suggested for this loss of effect: the development of pharmacological tolerance, and premature patch exhaustion. This study was designed to investigate this problem, and in particular to investigate the time course of treatment failure. It comprised a randomized, double-blind, cross-over comparison of transdermal glyceryl trinitrate and matching placebo transdermal patches. Significant treatment effects were demonstrated by several criteria for 8 h of continuous therapy, with some limited effect persisting for 15 h. Loss of effect began to develop very soon after treatment was initiated and progressed in a steady, linear fashion so that there was virtually no treatment effect after 24 h. In contrast, during intermittent therapy, treatment effects were maintained on the second day following a nitrate-free interval. Significant benefit was demonstrated for up to 32 h (i.e. 8 h of treatment on day 2). Both nitrate-free intervals (12 and 16 h) seemed to be equally effective in maintaining efficacy after 3 h of treatment on the second day, although this was still somewhat attenuated compared with day 1. These results confirm that loss of therapeutic efficacy of transdermal nitrate is due to the development of tolerance and not premature patch exhaustion. In contrast to previous studies, however, they suggest that tolerance can only partly be reversed by intermittent therapy and also that the onset of tolerance is so rapid that it is well established in less than a day's treatment.

Administration, Cutaneous↗
PubMed1991

Anti-arrhythmic properties of the alpha-adrenoceptor blocking drug indoramin.

1. The anti-arrhythmic properties of the alpha-adrenoceptor blocking drug indoramin were compared with the effect of disopyramide and placebo in a randomised, single-blind, cross-over study. Two doses of indoramin were tested, 25 mg and 50 mg and the dose of disopyramide was 150 mg. All treatments were administered three times daily. 2. Forty patients with benign ventricular arrhythmia were studied. 3. Assessment was by 24 h ambulatory electrocardiography at entry and at the end of each 2 week treatment period. 4. Indoramin was found to have a significant anti-arrhythmic effect compared with placebo, but only at the higher dose tested. 5. The anti-arrhythmic effect was less than that achieved with disopyramide. 6. The mechanism for this anti-arrhythmic effect is unknown but these results suggest that alpha-adrenoceptor blockade may merit further attention as an anti-arrhythmic treatment.

Adrenergic alpha-Antagonists↗
PubMed1991

Left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) may be physiological or pathological. Only pathological LVH has been shown to be a risk factor for cardiovascular events. LVH may not be homogeneous. It seems to progress from muscle hypertrophy to eventual cell death and myocardial fibrosis. Potential for reversal of LVH may therefore depend on the stage at which it has been attempted. An interaction between LVH and serum potassium levels could have important therapeutic implications, particularly with regard to the use of thiazide diuretics as long-term treatment for hypertension.

Animals↗
PubMed1991

Immunogenicity and protective efficacy of affinity-purified Plasmodium falciparum exoantigens in Aotus nancymai monkeys.

Soluble Plasmodium falciparum polypeptides, affinity-purified from culture supernatant fluids using sequential immunoadsorptions employing both monoclonal and polyclonal antibodies, induced protective immunity against experimental falciparum malaria in Peruvian Aotus nancymai monkeys. Susceptible monkeys were vaccinated with polypeptides affinity-purified from supernatant fluids of P. falciparum Indochina I/CDC cultures. Eighteen animals (6 immunized with purified antigens plus adjuvants, 6 injected with only the adjuvant preparation, and 6 untreated) were challenged with whole blood containing monkey-adapted virulent organisms of the Indochina I/CDC strain. Selected hematologic, serologic and parasitologic profiles served as potential indicators of protection. This immunogen, when fortified with an aluminum hydroxide/Quil-A saponin adjuvant combination, elicited good antibody responses to major P. falciparum antigens. Protection in vaccinated animals was evidenced by a significantly limited reduction in hematocrit and hemoglobin levels and a relatively moderate course of infection after homologous needle-challenge with Aotus monkey-adapted P. falciparum parasites.

Animals↗
PubMed1990

Systolic wall stress and ventricular arrhythmia: the role of acute change in blood pressure in the isolated working rat heart.

1. The effect of a sudden acute change in blood pressure upon arrhythmia provocation has been studied in an isolated working heart model from the Wistar-Kyoto strain of rat. Twenty-four hearts were studied. 2. They were perfused with two different, modified, Krebs-Henseleit solutions at a fixed left atrial pressure. 3. Acute changes in pressure, both increases and decreases, were arrhythmogenic. Whilst ectopic activity was more predictably produced by pressure reductions, this consisted of simple ventricular ectopics only. Pressure increases, in contrast, were capable of provoking more complex and sustained arrhythmias. 4. The effect of pressure changes were highly dependent upon electrolyte concentrations in the perfusate. Low potassium and magnesium concentrations increased the amount of arrhythmia provoked by pressure increases but tended to reduce that provoked by pressure reductions. 5. We conclude that the direct effect of an acute change in pressure upon the myocardium is arrhythmogenic. However, the myocardial response to a pressure change is interdependent upon prevailing electrolyte concentrations.

Animals↗
PubMed1990

The effect of oral dosing of xamoterol on systolic time intervals in man and xamoterol plasma concentrations in heart failure patients.

1. Six healthy male human volunteers of mean age 30.8 years (range 23-37) were given single oral doses of xamoterol (20, 50, 100 or 250 mg) and placebo with a 1 week interval between each dose. Xamoterol produced a significant decrease in systolic time intervals (QS2I, LVETI and PEPI) and a significant increase in systolic blood pressure indicating a positive inotropic effect on the heart at rest. The changes in QS2I were dose-related. Maximum decreases in QS2I were noted 1 to 2 h after dosing and were achieved with a dose of 100 mg. 2. In a second study, oral administration of xamoterol at 3 doses (100, 200 or 300 mg) and placebo were studied in 12 patients of mean age 60.4 years (range 52-73) with mild to moderate heart failure. Each dose was given twice daily for 7 days in a random order. Each dose of xamoterol produced a significant decrease in systolic time intervals indicating a positive inotropic effect on the heart at rest in patients with heart failure. It was not possible to distinguish between the effects of the three doses of xamoterol. 3. In heart failure patients, peak plasma concentrations of xamoterol occurred 1 to 2 h after dosing at all dosage levels and there was a linear relationship between dose and plasma concentration. 4. In both studies xamoterol was well tolerated and only minor adverse experiences were reported. 5. We conclude that, at rest, xamoterol has a positive inotropic effect on the heart when given orally to healthy volunteers or patients with mild to moderate heart failure.

Adult↗
PubMed1990

ACE inhibitors and the heart: hypertrophy reversal and antiarrhythmic effects.

Sudden death has been shown to be due in the majority of cases to ventricular arrhythmia. Left ventricular hypertrophy (LVH) may be implicated in the aetiology of some arrhythmia and sudden death. Recent evidence suggests that the relationship between LVH and arrhythmia may be complex and that there may be an interaction with serum potassium levels. ACE inhibitors have been shown to be anti-arrhythmic in heart failure. Although other vasodilators have been shown to be anti-arrhythmic, ACE inhibitors also raise serum potassium levels and this may therefore be of importance to their anti-arrhythmic activity. In LVH, their antiarrhythmic potential may be greatest in those who are potassium depleted.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Distribution of aflatoxins in tissues of growing pigs fed an aflatoxin-contaminated diet amended with a high affinity aluminosilicate sorbent.

The effect of hydrated sodium calcium aluminosilicate (HSCAS) added to the diet of swine fed an aflatoxin-contaminated diet on tissue aflatoxin levels was investigated. Pigs were fed control (less than 10 ng/g B1 + B2), contaminated (500-600 ng/g B1 + B2), and contaminated +0.5% HSCAS diets. Tissues analyzed for the presence of aflatoxin B1, B2, and M1 residues included liver, muscle, kidney, and adipose. Addition of HSCAS to the contaminated diet significantly reduced the amount of M1 in liver, kidney, and muscle tissue. Aflatoxin B1 was not reduced in liver or kidney, but was decreased in muscle.

Aflatoxins↗
PubMed1989

Application of exoantigens of Babesia and Plasmodium in vaccine development.

The University of Illinois malaria vaccine programme uses culture-derived soluble exoantigens of Plasmodium falciparum and the squirrel monkey as an experimental model. Exoantigens are soluble polypeptides naturally released into the blood plasma of animals infected with Babesia or Plasmodium species, or into the supernatant medium of in vitro cultures of these organisms. Immunization with soluble B. bovis and B. bigemina exoantigens prepared from culture supernatant fluids protected cattle against homologous and heterologous challenge. Similarly, vaccination of squirrel monkeys with supernatant fluids from P. falciparum cultures containing exoantigen induced protective immunity against acute clinical malaria. Susceptible monkeys have been vaccinated with an aluminium hydroxide-fortified antigenic fraction partially purified from supernatants of P. falciparum strains Indochina I and Genève/SGE-1; this conferred significant clinical protection against needle challenge with the homologous Indochina I strain, and a moderate degree of immunity to the heterologous strain. Following sequential purification by high performance liquid chromatography, the N-terminal amino acid sequences of P. falciparum 100 kDa, 83 kDa and 70 kDa exoantigens were determined. A 29 amino acid peptide constructed from the N-terminal sequence of the P. falciparum (Genève strain) 83 kDa exoantigen has been synthesized. When coupled to a carrier protein, the peptide was immunogenic in rabbits, mice and squirrel monkeys, inducing antibodies which were trophozoite-specific, reactive to native parasite proteins in a two-site enzyme immunoassay (EIA) and in Western blots, and which inhibited P. falciparum growth in vitro. Using this synthetic peptide, EIAs are being developed for the detection of antibodies to P. falciparum blood-phase parasites in individuals living in malaria-endemic areas of Africa, Asia and South America.

Animals↗