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Biomedical subjects

P J Cooper

Publications and source records attributed to P J Cooper.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Treatment of acute asthma: salbutamol via jet nebuliser vs spacer and metered dose inhaler.

OBJECTIVE: To compare the efficacy of salbutamol delivered by jet nebuliser (JN) with salbutamol via a pressurised metered dose inhaler (PMDI) and a large volume spacer (Volumatic) for management of acute asthma. STUDY POPULATION: A total of 160 children aged from 4 to 12 years presenting to an Emergency Department with acute asthma. METHODS: The study was of multicentre (n=5) randomised, double blind, parallel design. Children weighing less than 25 kg received salbutamol 2.5 mg via the JN or 600 microg (six puffs) from the PMDI. Children over 25 kg received salbutamol 5 mg via the JN or 1200 microg (12 puffs) via the PMDI. Clinical score (range 0-12) and PEF (over 7 years) were recorded at baseline and 15, 30, 45 and 60 mins post administration. RESULTS: The improvement from baseline at 30 min in the clinical score was 1.87 for JN and 1.43 for PMDI (P=0.09) and at 60 min was 2.15 for JN and 1.12 for PMDI (P=0.0001). The improvement in PEF at 30 min was 51 L min(-1) for JN and 27 L min(-1) for PMDI (P=0.0007) and at 60 min was 57 L min(-1) for JN and 31.5 L min(-1) for PMDI (P=0.001). CONCLUSION: Administration of salbutamol via a PMDI and a large volume spacer device provides effective relief in the management of acute asthma in children, but to a lesser extent than a jet nebuliser. This difference may represent a dose response effect.

Acute Disease↗

Pneumocystis carinii pneumonia: pitfalls of prophylaxis.

Pneumocystis carinii pneumonia (PCP) occurs commonly in immunocompromised patients. Sulfamethoxazole-trimethoprim (SMX-TMP) is effective prophylaxis, although PCP may still occur despite apparently adequate use. We report three cases of PCP which highlight some of the pitfalls of prophylaxis.

Anti-Infective Agents↗

Impaired tetanus-specific cellular and humoral responses following tetanus vaccination in human onchocerciasis: a possible role for interleukin-10.

Onchocerca volvulus infection has been associated with impaired cellular responses to parasite antigens, an impairment that may also extend to nonparasite antigens. To investigate the mechanism of this impaired immune response, the effect of concurrent O. volvulus infection on the immune response to tetanus toxoid (TT) following tetanus vaccination was studied. The proliferative, cytokine, and antibody response to TT of O. volvulus-infected subjects (n = 19) and comparable noninfected controls (n = 20) were studied before and 6 months after vaccination with TT. Following vaccination, antibody levels, proliferative responses, and levels of interferon-gamma were significantly greater in noninfected subjects (P < .05, .001, and .05, respectively); however, infected subjects produced interleukin-10, but noninfected controls did not (P < .001). These studies indicate that concurrent infection with O. volvulus can diminish the immune response to an unrelated antigen (TT) by a mechanism that is likely to involve interleukin-10.

Adolescent↗

A randomised controlled trial of two pressure-reducing surfaces.

This randomised controlled trial of two dry-flotation pressure-reducing surfaces evaluates pressure sore incidence, patient comfort and the appropriate use of equipment in 100 orthopaedic patients. The trial involved five full Roho mattresses, five Sofflex mattresses and 10 Roho Quatro cushions to be used to complement the beds. Given the low rate of pressure sore incidence in this high-risk group it is not possible to determine whether there is any difference in effectiveness between the two mattresses. Both appear to provide similar levels of comfort, with the majority of patients finding them either comfortable or very comfortable. The initial setting of the equipment was, however, unsatisfactory.

Activities of Daily Living↗

The pathogenesis of chorioretinal disease in onchocerciasis.

The pathogenesis of onchocercal chorioretinopathy is poorly understood. In this article, Philip Cooper, Ronald Guderian, Roberto Proaño and David Taylor discuss the important clinical, histological and epidemiological features of the resulting lesions that cause blindness, and review the numerous mechanisins that have been put forward to explain its pathogenesis. The pathogenesis of anterior segment disease, particulary sclerosing keratitis, has been reviewed in depth previously(1) and will not be discussed here.

Journal Article↗

Successful control of onchocerciasis with community-based ivermectin distribution in the Rio Santiago focus in Ecuador.

Onchocerciasis is a major blinding disease in equatorial Africa and Central and South America. Ivermectin is a safe and effective drug in the treatment of this disease and now forms the basis of disease control in most endemic areas. We report the findings of long-term control of this infection in the Río Santiago focus in Ecuador, between January 1990 and December 1996, using a strategy of giving ivermectin treatments biannually in hyperendemic communities and annually in meso- and hypoendemic communities. Ivermectin was administered by local health workers from each community. A high level of compliance to ivermectin was achieved, with 81.9% to 98.0% of those eligible receiving the drug at each treatment instance. The impact of ivermectin therapy was monitored using a cohort of 120 randomly selected infected individuals from 8 hyperendemic communities. The geometric mean microfilarial density of this group declined from 19.3 to 0 mf/mg over the 84-month observation period. Ivermectin had a significant impact on anterior segment ocular disease, acute onchodermatitis and sowda. The rate of infection of blackflies declined from 1.1% in 1989-0.08% in 1996, which is below the vectorial capacity of the Simulium vector and, as no new nodules were detected after 1994 and no children under 5 became infected over the observation period, it is likely that the transmission of this infection was interrupted in the study area.

Animals↗

Prevalence and significance of weight and shape concerns in girls aged 11-16 years.

BACKGROUND: The prevalence of the core ideational component of eating disorders among the at-risk population (11-to 16-year-old girls) is not known. METHOD: A community survey of 11- to 16-year-old girls was conducted to establish the prevalence of significant concerns about body weight and shape characteristics of eating disorders. A total of 1068 girls were screened and 368 interviewed using standardised measures. RESULTS: Significant weight and/or shape concerns were estimated to be present in 14.5% of the 11-to 12-year-olds, 14.9% of the 13-to 14-year-olds and 18.9% of the 15-to 16-year-olds. Only among those aged 15 to 16 was the presence of such concerns associated with a significant level of concurrent behavioural and ideational disturbance. CONCLUSIONS: Significant concerns about weight or shape are present in almost one in five 15-to 16-year-old girls, many of whom evidence high levels of ancillary disturbance.

Adolescent↗