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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

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

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

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

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

The use of the eating disorder examination with children: a pilot study.

OBJECTIVE: This article describes the use of a slightly modified version of the Eating Disorders Examination (EDE) in children. METHODS: Sixteen children aged between 7 and 14 years attending an eating disorders clinic over a 5-month period were recruited to the study. The two main modifications to the EDE were (A) the inclusion of a sort task to assess overvalued ideas about weight and shape and (B) the reformulation of certain items to assess intent rather than actual behavior. The existing EDE scoring system was used, resulting in item, subscale, and global scores. RESULTS: Of the 16 children (10 F 6 M), 11 had a diagnosis of anorexia nervosa, and 5 of eating disorder not otherwise specified (EDNOS). There were interesting differences in responses on items assessing core overvalued ideas, with weight and/or shape concerns emerging as of great importance in terms of self-evaluation in the majority of children with anorexia nervosa. DISCUSSION: Results suggest that this may be a useful assessment tool in children, with some children obtaining global and subscale scores consistent with adult norms for females with eating disorders. Problems of the administration of the EDE to this patient group are discussed and details of the modifications used are outlined.

Adolescent

An evaluation of the efficacy of supervised cognitive behavioral self-help bulimia nervosa.

Eighty two patients with bulimia nervosa were managed by providing them with supervision in the use of a highly structured cognitive behavioral self-help manual. Their progress was assessed in an open clinical trial. The 67 patients who completed the course of self-help experienced considerable benefit; the frequency of bulimic episodes and self-induced vomiting decreasing by 80% and 79%, respectively. Compared to those who benefited, those who had a poor outcome or dropped out of treatment were more than twice as likely to have had anorexia nervosa in the past and were somewhat more likely to have a personality disorder. Three-quarters of those who persisted with the programme of supervised self-help were followed up a year after commencing treatment. Clinical gains were well maintained: almost two thirds were abstinent with respect to both bulimic episodes and self-induced vomiting. It would seem appropriate that, as part of a stepped care approach to the management of bulimia nervosa, supervised cognitive behavioral self-help should routinely be the first line treatment.

Adolescent

Direct in situ reverse transcriptase polymerase chain reaction for detection of measles virus.

New methods are described for combined intracellular reverse transcription (RT) and polymerase chain reaction (PCR) using single primer pairs, with direct incorporation of digoxigenin-11-dUTP into amplificants (direct in situ RT/PCR). Routinely used fixatives and minimal pre-treatments were employed. Target sequences of measles virus nucleocapsid (N) and phosphoprotein genes were detected within measles virus infected Vero cells, both in suspension and in formalin-fixed sections, that had been treated by in situ reverse transcription and 30 cycles of direct in situ PCR. Uninfected cells, omission of Taq polymerase, and irrelevant primers were used as controls. Distribution of measles virus within infected cells was determined by in situ hybridisation and immunocytochemistry for measles virus N gene and protein, respectively. Confirmation of amplification within sections was by gel electrophoresis, Southern blotting and sequencing of extracted amplicons. In the majority of cases, measles-infected cells exhibited intense cytoplasmic signal after direct in situ PCR; this was not seen in uninfected cells or infected cells reacted either with irrelevant primers or without Taq polymerase. Unfixed cells in suspension required nested reaction. Measles-specific in situ hybridisation and immunocytochemistry gave an identical signal distribution in sections. Nuclear artifact occurred in some sections and was unpredictable, although it was greatest either in areas of cellular damage, following DNase predigestion, or with vigorous protease pre-treatment. In situ RT-PCR is feasible for measles virus in acutely infected cells both in sections and in suspension. Further work is required to improve the procedure and to eliminate artefactual nuclear signal.

Animals

The development and validation of a predictive index for postpartum depression.

A sample of over 6000 women was recruited in the last trimester of pregnancy and administered a 40-item self-report questionnaire designed to detect the presence of factors that were likely to increase the risk of postpartum depression. The mental state of almost 5000 of these women was determined at around 6 to 8 weeks postpartum. By conducting a series of logistic regressions on two-thirds of this sample the original set of variables was reduced to a predictive index of 17 items with weighted scores calculated for each. This index was then applied to the remaining one-third of the sample as a validating procedure and specificity and sensitivity calculated. The index offers a system for the prediction of postpartum depression that could be of use in both research and clinical practice.

Adult

RANTES in onchocerciasis: changes with ivermectin treatment.

Adverse reactions are seen relatively frequently after treatment of onchocerciasis patients with ivermectin. The chemokines RANTES and IL-8, which have both chemotactic and activation properties for eosinophils and neutrophils, respectively, may have a role in the pathogenesis of post-treatment reactions. Circulating levels of the chemokines and the cytokines tumour necrosis factor-alpha (TNF-alpha) and IL-6 were measured in the plasma of 22 Onchocerca volvulus-infected subjects. Peaks of mean circulating levels of RANTES and TNF-alpha were seen at 6 h after ivermectin administration. Peripheral eosinophil counts declined at 36 h post-treatment and an early peak in RANTES levels was associated with a delay in peripheral eosinopenia. RANTES levels were negatively correlated with severity of rash (P < 0.001) and lymphoedema (P < 0.05), suggesting that high circulating levels of RANTES may inhibit eosinophil sequestration. No changes in circulating levels of IL-8 were seen. These findings suggest a possible role of circulating RANTES in modulating eosinophil sequestration in vivo.

Adolescent