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Biomedical subjects

P J Cooper

Publications and source records attributed to P J Cooper.

At least 19 recordsLinked to original sources
PubMed2001

Early human infection with Onchocerca volvulus is associated with an enhanced parasite-specific cellular immune response.

The immune response after early exposure to or infection with Onchocerca volvulus was investigated in an autochthonous focus caused by the migration of infected persons to a previously unaffected area in Ecuador. Peripheral blood mononuclear cell (PBMC) proliferative and cytokine responses (interferon [IFN]-gamma and interleukin [IL]-5) to filarial antigens were measured in 14 subjects with serologic evidence of exposure and in 7 subjects with evidence of dermal microfilarial DNA and were compared with responses in 43 subjects with chronic O. volvulus infections. PBMC proliferative and cytokine responses (IFN-gamma and IL-5) to parasite antigens were elevated in the early exposure/infection group, compared with those in the chronic infection group. Addition of an IL-10-neutralizing antibody to filaria antigen-stimulated cultures resulted in significantly elevated proliferative responses in the chronic infection group. The findings suggest that early exposure and early parasite patency are associated with a vigorous cellular response, but, as infections become chronic, the cellular response becomes down-regulated, partly through an IL-10-dependent mechanism.

Adolescent↗
PubMed2001

Sudden cardiac death by Commotio cordis: role of mechano-electric feedback.

Moderate pre-cordial mechanical impact can cause sudden cardiac death, even in the absence of morphological damage to the heart. This is the most severe expression of a condition termed, in the 19th century, Commotio cordis. Experimental studies performed in the early 1930s showed that sudden cardiac death after chest impact is brought about by an intrinsic cardiac response to the mechanical stimulus. The precise (sub-)cellular mechanisms of this response are still poorly understood. This article summarises experimental findings on the condition and relates them to the more recently established concept of cardiac mechano-electric feedback. As a result, an explanation of the mechanisms that give rise to sudden cardiac death by Commotio cordis and targets for further research are suggested.

Biomechanical Phenomena↗
PubMed2001

Human infection with Ascaris lumbricoides is associated with suppression of the interleukin-2 response to recombinant cholera toxin B subunit following vaccination with the live oral cholera vaccine CVD 103-HgR.

To investigate the potential immunomodulatory effects of concurrent ascariasis on the cytokine response to a live oral vaccine, we measured cytokine responses to cholera toxin B subunit (CT-B) following vaccination with the live oral cholera vaccine CVD 103-HgR in Ascaris lumbricoides-infected subjects randomized in a double-blind study to receive two doses of either albendazole or placebo prior to vaccination and in a group of healthy U.S. controls. Postvaccination cytokine responses to CT-B were characterized by transient increases in the production of interleukin-2 (IL-2; P = 0.02) and gamma interferon (IFN-gamma; P = 0.001) in the three study groups combined; however, postvaccination increases in IFN-gamma were significant only in the albendazole-treated A. lumbricoides infection group (P = 0.008). Postvaccination levels of IL-2 were significantly greater in the albendazole-treated group compared with the placebo group (P = 0.03). No changes in levels of Th1 and Th2 cytokines in response to control ascaris antigens were observed over the same period. These findings indicate that vaccination with CVD 103-HgR is associated with a Th1 cytokine response (IL-2 and IFN-gamma) to CT-B, that infection with A. lumbricoides diminishes the magnitude of this response, and that albendazole treatment prior to vaccination was able to partially reverse the deficit in IL-2. The potential modulation of the immune response to oral vaccines by geohelminth parasites has important implications for the design of vaccination campaigns in geohelminth-endemic areas.

Adult↗
PubMed2001

Metabolic consequences of a species difference in Gibbs free energy of Na+/Ca2+ exchange: rat versus guinea pig.

The Gibbs free energy of the sarcolemmal Na+/Ca2+ exchanger (DeltaG(Na/Ca)) determines its net Ca2+ flux. We tested the hypothesis that a difference of diastolic DeltaG(Na/Ca) exists between rat and guinea pig myocardium. We measured the suprabasal rate of oxygen consumption (VO2) of arrested Langendorff-perfused hearts of both species, manipulating DeltaG(Na/Ca) by reduction of extracellular Na+ concentration, [Na+](o). Hill equations fitted to the resulting VO2-[Na+](o) relationships yielded Michaelis constant (K(m)) values of 67 and 25 mM for rat and guinea pig, respectively. We developed and tested a simple thermodynamic model that attributes this difference of K(m) values to a 7.84 kJ/mol difference of DeltaG(Na/Ca). The model predicts that reversal of Na+/Ca2+ exchange, leading to diastolic Ca2+ influx, should occur at a value of [Na+](o) about three times higher in rat myocardium. We verified this quantitative prediction using fura 2 fluorescence to index intracellular Ca2+ concentration in isolated ventricular trabeculae at 37 degrees C. The postulated difference in free energy of Na+/Ca2+ exchange explains a number of reported disparities of Ca2+ handling at rest between rat and guinea pig myocardia.

Animals↗
PubMed2000

Human infection with Ascaris lumbricoides is associated with a polarized cytokine response.

To define the cytokine response to Ascaris lumbricoides infection, the cellular immune response to adult and larval-stage Ascaris antigens in young adults with moderate infection intensities (n=73) was compared with that of a group of uninfected control subjects (n=40). A. lumbricoides-infected subjects had significantly greater lymphoproliferative responses to adult and larval-stage antigens, compared with uninfected control subjects (P<.01). The frequencies of parasite antigen-stimulated peripheral blood mononuclear cell (PBMC)-expressing interleukin (IL)-4 and IL-5 were significantly greater in the infected group (P<.001), whereas the frequencies of IL-10- and interferon-gamma-expressing PBMC were similar in the 2 groups studied. The ratios of Th2 to Th1 cytokine frequencies were significantly elevated in the infected group, compared with those in uninfected subjects, as was IL-5 protein production by PBMC stimulated with adult (P<.05) and L3/L4 stage (P<.001) antigens. Analysis of these data indicates that A. lumbricoides infections in endemic regions are associated with a highly polarized type 2 cytokine response.

Adolescent↗
PubMed2000

Albendazole treatment of children with ascariasis enhances the vibriocidal antibody response to the live attenuated oral cholera vaccine CVD 103-HgR.

Because concurrent infections with geohelminth parasites might impair the immune response to oral vaccines, we studied the vibriocidal antibody response to the oral cholera vaccine CVD 103-HgR in children infected with Ascaris lumbricoides and investigated the effect of albendazole pretreatment on the postvaccination response. Children with ascariasis were randomized to receive either 2 sequential doses of 400 mg of albendazole or placebo. After the second dose, CVD 103-HgR was given, and serum vibriocidal antibody levels were measured before and 10 days after vaccination. Postvaccination rates of seroconversion were greater in the treatment group that received albendazole (P=.06). Significantly greater rates of seroconversion and geometric mean titer were observed in the albendazole group in subjects with non-O ABO blood groups. A significant association was observed between vibriocidal seroconversion rates and treatment group, suggesting that A. lumbricoides infections impair the immune response to oral cholera vaccine, particularly in subjects of non-O blood groups.

Adolescent↗
PubMed2000

Eotaxin and RANTES expression by the dermal endothelium is associated with eosinophil infiltration after ivermectin treatment of onchocerciasis.

The roles of eotaxin, RANTES, and MCP-3 expression in eosinophil recruitment to the site of parasite killing that occurs following ivermectin treatment of onchocerciasis were assessed in the skin of 13 Onchocerca volvulus-infected subjects and two noninfected controls before and after ivermectin treatment. Adverse reactions in infected subjects were associated with the appearance of eosinophils in the dermis as part of a perivascular inflammatory infiltrate. Although no expression of RANTES and eotaxin was seen in dermal vascular endothelial cells in biopsies taken before treatment (nor at any time in the skin of uninfected controls), endothelial expression of both eotaxin and RANTES was noted by 24 h following treatment. While RANTES expression was transient, eotaxin expression increased in parallel with increasing eosinophil recruitment up to 60 h posttreatment. These observations indicate that endothelial expression of eotaxin and RANTES may have an important role in eosinophil recruitment into the skin during helminth-killing reactions.

Adult↗
PubMed2000

The association between childhood feeding problems and maternal eating disorder: a community study.

BACKGROUND: A possible association between childhood feeding problems and maternal eating disorder has been suggested by a clinic-based self-report questionnaire study. A community study was conducted, using standardized psychiatric interviews, to investigate the strength and specificity of this putative association. METHODS: Four-year-old children were screened using a self-report version of the Behaviour Screening Questionnaire, completed by mothers, and the Pre-School Behaviour Checklist, completed by teachers. Three groups of children were identified for follow-up: children with feeding problems (N = 42), children with a non-feeding form of disturbance (i.e. shyness, fearfulness or behavioural disturbance; N = 79), and a random sample of children with no disturbance (N = 29). The presence of feeding problems was confirmed by assessment of a filmed family meal, with ratings made blind to child group and maternal mental state. Maternal current and past affective disorder and current and past eating disorder were systematically assessed, blind to child status, using the Anxiety Disorders Interview Schedule and the Eating Disorder Examination respectively. RESULTS: Compared with the mothers of the two comparison groups of children, the mothers of the children with feeding problems had no raised rate of any affective disorder, either current or past, but they did have a markedly raised rate of both current and past DSM-IV eating disorder. The odds ratio of maternal eating disorder for the children with feeding problems was significantly raised at 11.1 (CI 1.4-91.8). CONCLUSION: There is a strong and specific association between childhood feeding problems and maternal eating disorder.

Adult↗
PubMed2000

Recombinant human interleukin-10 fails to alter proinflammatory cytokine production or physiologic changes associated with the Jarisch-Herxheimer reaction.

Interleukin (IL)-10 may have a role in the treatment of cytokine-associated inflammatory syndromes. The Jarisch-Herxheimer reaction (J-HR), which follows antibiotic treatment of Borrelia recurrentis infection, is a useful model of acute systemic inflammation associated with a cytokine surge and characteristic pathophysiologic changes. In a double-blind, placebo-controlled study, 49 Ethiopian men with B. recurrentis infection were randomized to receive a single intravenous bolus of either 25 microg/kg of recombinant human (rh) IL-10 or vehicle control shortly before receiving intramuscular penicillin. Patients were monitored for physiologic changes, and plasma samples were taken repeatedly for 24 h after treatment. rhIL-10 had no impact on changes in any of the physiologic parameters of J-HR, plasma cytokine levels, or the rate of spirochete clearance. A single intravenous bolus of 25 microgram/kg of rhIL-10 does not seem to have a useful role in the treatment of the J-HR associated with B. recurrentis infection.

Adolescent↗
PubMed2000

Selected contribution: axial stretch increases spontaneous pacemaker activity in rabbit isolated sinoatrial node cells.

Isolated, spontaneously beating rabbit sinoatrial node cells were subjected to longitudinal stretch, using carbon fibers attached to both ends of the cell. Their electrical behavior was studied simultaneously in current-clamp or voltage-clamp mode using the perforated patch configuration. Moderate stretch ( approximately 7%) caused an increase in spontaneous beating rate (by approximately 5%) and a reduction in maximum diastolic and systolic potentials (by approximately 2.5%), as seen in multicellular preparations. Mathematical modeling of the stretch intervention showed the experimental results to be compatible with stretch activation of cation nonselective ion channels, similar to those found in other cardiac cell populations. Voltage-clamp experiments validated the presence of a stretch-induced current component with a reversal potential near -11 mV. These data confirm, for the first time, that the positive chronotropic response of the heart to stretch is, at least in part, encoded on the level of individual sinoatrial node pacemaker cells; all reported data are in agreement with a major contribution of stretch-activated cation nonselective channels to this response.

Animals↗
PubMed1999

Eosinophil sequestration and activation are associated with the onset and severity of systemic adverse reactions following the treatment of onchocerciasis with ivermectin.

To investigate the role of eosinophil activation and sequestration in the development and severity of adverse reactions after the treatment of Onchocerca volvulus infection, 40 O. volvulus-infected Ghanaians were randomized to receive placebo or standard- or high-dose ivermectin. Subjects were examined for typical physiologic and clinical events before and up to 48 h after treatment. Plasma samples were tested for interleukin (IL)-5 and eosinophil degranulation products (e.g., eosinophil-derived neurotoxin, EDN). After treatment, peripheral eosinophil counts declined in ivermectin-treated groups (P<.001), whereas circulating levels of IL-5 (P<.01) and EDN (P<.05) increased. Cumulative levels of IL-5 and EDN correlated with reaction scores (P<.01). High-dose ivermectin was associated with more-severe reactions, more-profound eosinopenia, and higher circulating levels of IL-5 and EDN, compared with the standard dose. These results suggest that eosinophil sequestration and activation/degranulation are associated with the initiation and severity of ivermectin-associated adverse reactions.

Agranulocytosis↗
PubMed1999

Human onchocerciasis and tetanus vaccination: impact on the postvaccination antitetanus antibody response.

To investigate whether helminth infections may affect the efficacy of vaccines by impairing the immune response to nonparasite vaccine antigens, we compared the antibody responses to tetanus toxoid (TT) after tetanus vaccination in 193 subjects with Onchocerca volvulus infection with 85 comparable noninfected controls. After vaccination, the proportions of subjects in each group attaining protective levels of antitetanus antibodies were similar (96.9% infected versus 97.6% noninfected). Postvaccination increases in antitetanus immunoglobulin G (IgG) and the predominant IgG isotype, IgG1, were equivalent in both groups, as were increases in specific IgG4 and IgE; however, significantly greater increases in specific IgG2 (P < 0.05) and IgG3 (P < 0.001) were observed in the noninfected group. Stratification of the O. volvulus-infected group into two groups representing light and heavy infections revealed a significantly impaired antitetanus IgG response in those with heavy infections compared to those with light infections (P < 0.01) or no infection (P < 0.05). The impact of concurrent intestinal helminth infections on the antitetanus response was also examined; an increased IgG4/IgE ratio was seen in those infected with Strongyloides stercoralis (P < 0.05) and when all helminth infections were combined as a single group (P < 0.05). These findings indicate that concurrent infection with O. volvulus does not prevent the development of a protective antitetanus response, although heavier O. volvulus infections are able to alter the magnitude of this response, and concurrent helminth infections (O. volvulus and intestinal helminths) may alter TT-specific antibody isotype responses.

Adolescent↗
PubMed1999

Childhood shyness and maternal social phobia: a community study.

BACKGROUND: Family history data suggest the possibility of an association between childhood shyness and parental social phobia. AIMS: To examine the prevalence of maternal affective disorder in a community sample of four-year-old shy and non-shy children. METHOD: By screening 867 children, 43 shy children, 59 children with another form of disturbance (i.e. fearfulness, feeding problem or conduct problem) and 26 children with no disturbance were identified. Interviewers who were unaware of child status used a standardised mental state assessment to determine the rate of affective disorder in the mothers of these children. RESULTS: Compared with the mothers of the children in both comparison groups, the mothers of the children who were purely shy (i.e. shy children with no comorbid condition) had a significantly raised lifetime rate of anxiety disorder in general, and social phobia in particular. The odds ratio of a social phobia in the mothers of the purely shy children was raised over the normal control group by a factor of more than seven. CONCLUSIONS: These findings suggest a specific association between childhood shyness and maternal social phobia.

Adult↗
PubMed1999

Post-partum depression and the mother-infant relationship in a South African peri-urban settlement.

BACKGROUND: Post-partum depression in the developing world has received little research attention, and its association with disturbances in the mother-infant relationship is unknown. AIMS: To determine the prevalence of post-partum depression and associated disturbances in the mother-infant relationship in Khayelitsha, a South African peri-urban settlement. METHOD: The mental state of 147 women who had delivered two months previously was assessed, and the quality of their engagement with their infants was determined. RESULTS: The point prevalence of DSM-IV major depression was found to be 34.7%. Maternal depression was associated with poor emotional and practical support from the partner. It was also associated with insensitive engagement with the infants. CONCLUSIONS: The rate of post-partum depression in Khayelitsha was around three times that found in British post-partum samples, and these depressions were strongly associated with disturbances in the mother-infant relationship.

Adult↗
PubMed1998

The disorder-salient stroop effect as a measure of psychopathology in eating disorders.

OBJECTIVES: The aim was to assess, using sophisticated experimental methods, the amount of interference on a Stroop task in patients with eating disorders, under conditions of blocked and mixed stimulus presentation. METHODS: Patients with eating disorders and non-patients named the color in which a word was displayed. Words came from an experimental category (food/eating, weight/shape, "emotion," or affectively neutral word) or from a matched set of unrelated control words. Color-naming latencies were compared in a blocked condition, with words from just one set in each block, and in a mixed condition, with a mixture of word types in each block. RESULTS: In the mixed condition, patients took longer to color-name food/eating and weight/shape words than control words. With blocked presentation this effect was magnified; and patients with bulimia nervosa also showed increased naming-latency for "emotion" words. Non-patients showed neither effect and no group showed interference for the affectively neutral category. Patients' interference effects correlated reliably with self-reported depression and anxiety. DISCUSSION: Sources of interference and methodological and diagnostic implications are discussed.

Adolescent↗
PubMed1998

A study of the performance of a pressure reducing foam mattress after three years of use.

This paper details the follow up clinical evaluation of a pressure reducing foam mattress (PRFM) three years after a randomised controlled trial. The PRFMs involved in the 1993 randomised controlled trial were used constantly for three years and recalled in 1996. In the original trial the control group had consisted of 18 standard NHS mattresses. In 1996 none of these mattresses were still in use which made it impossible to replicate the 1993 randomised controlled trial. Instead a clinical evaluation using the 1993 methods was carried out using the PRFMs only. Recruitment to the evaluation proved difficult because changes in clinical practice between the two studies had resulted in shorter lengths of stay in hospital for the target population. Comparison of the two outcome measures namely pressure sore incidence and the subjects' perception of comfort showed no statistically significant change between 1993 and 1996. With the exception of two damaged mattress covers all of the original foam components and covers remained in working order in 1996. During the time between the two studies, a pressure sore prevention programme was implemented within the research area. This programme has resulted in a year by year drop in the Directorate incidence rate. It is therefore not possible to attribute the low pressure sore incidence rate to the PRFMs alone. The results obtained suggest that the PRFMs appear to be providing a similar level of performance after three years of use.

Aged↗