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Biomedical subjects

P Kelly

Publications and source records attributed to P Kelly.

At least 127 records · Page 7Linked to original sources

Jejunal water and electrolyte transport in human cryptosporidiosis.

Cryptosporidiosis may have severe clinical consequences in both immunocompromised and immunocompetent individuals. However, pathophysiological mechanisms that are responsible for diarrhea are poorly understood. We performed jejunal perfusion studies in patients with human immunodeficiency virus-related cryptosporidial diarrhea to measure water and electrolyte transport in vivo. Five patients with human immunodeficiency virus-related cryptosporidiosis and nine healthy volunteers were studied using a triple-lumen steady-state jejunal perfusion technique. Stool volume measurement and distal duodenal biopsy showed that the patients had diarrhea (600-1500 ml/24 hr) and morphological abnormalities of small intestinal mucosa. Net water, sodium, and chloride movement in the jejunum was not significantly different from healthy controls. In these patients with watery diarrhea and morphological mucosal abnormalities, we found no evidence that cryptosporidial diarrhea was due to a secretory state in the proximal small intestine. We conclude that diarrhea may be due to secretion of electrolytes and water efflux more distally or to other abnormalities of gastrointestinal function.

AIDS-Related Opportunistic Infections↗

The prevalence and aetiology of persistent diarrhoea in adults in urban Zambia.

As the AIDS pandemic has spread, diarrhoea in adults has become a major burden on health care institutions in central Africa and on the families of sufferers. In order to assess the magnitude of the problem, we carried out a survey of households in a high population density township of Lusaka to determine the prevalence of persistent diarrhoea in adults. We also carried out a study of the causes of persistent diarrhoea in patients attending the University Teaching Hospital, Lusaka. The community survey assessed 460 households, representing a sample of 1440 adults. 94 adults were reported as having had diarrhoea in the 2 weeks prior to the survey, implying an attack rate of 1.74 per adult per year. Of these 94 cases, six had diarrhoea of between 2 and 4 weeks duration, and ten had diarrhoea of over 4 weeks duration. In the hospital study, 75 (97%) out of 77 patients with diarrhoea of over 1 months' duration were HIV seropositive; potentially pathogenic parasites were found in 61/75 (81%) of seropositives. This information indicates that persistent diarrhoea in adults, mostly related to HIV infection, is likely to be an important and growing reservoir of enteric pathogens and represents a significant burden on hospitals and relatives. This emerging problem in sub-Saharan Africa may foreshadow developments in other continents.

Adult↗

C-erbB-2 in bladder cancer: molecular biology, correlation with epidermal growth factor receptors and prognostic value.

PURPOSE: To study the c-erbB-2 oncogene in primary transitional cell bladder cancer. MATERIALS AND METHODS: Ninety-five patients with known clinical follow-up and epidermal growth factor receptor (EGFr) status were studied for expression of c-erbB-2 by immunostaining. Possible mechanisms underlying increased staining for c-erbB-2 protein were investigated by analyzing DNA and RNA encoding c-erbB-2. RESULTS: Strong positive staining for c-erbB-2 was detected in 20 (21%) tumors, with weaker staining in a further 13 (14%). There was no correlation between increased staining for c-erbB-2 and tumor stage, grade, or EGFr status. There was a low rate of amplification of the c-erbB-2 gene (1 of 24) on Southern blotting with a higher rate of elevated c-erbB-2 mRNA (4 of 44) with dot blot hybridization. For pT1 tumors, the rate of recurrence was higher for those tumors which were positive for c-erbB-2. CONCLUSIONS: c-erbB-2 oncoprotein is expressed by a significant proportion of transitional cell tumors of the bladder. In this study, the prognostic significance of c-erbB-2 expression appears limited.

Blotting, Southern↗

Comprehensive pharmaceutical care in the chain setting.

A controlled, randomized study was conducted in two chain pharmacies to determine the clinical value of comprehensive pharmacy services for hypertensive patients in a chain pharmacy setting. Twenty-seven patients were enrolled as intervention participants with 26 control subjects. Monthly services for the intervention group included blood pressure and heart rate assessments and counseling on lifestyle modifications and drug therapy. Control patients received initial and final blood pressure measurements and minimal counseling. Both study and control groups completed quality-of-life questionnaires upon entering and completing the study. Results showed that blood pressure control was significantly improved in the study group. Compliance rates as well as energy/fatigue scores (a quality-of-life scale) improved in the study group compared with the control population. Community pharmacists in chain stores could have a beneficial effect on the health care of large numbers of patients if pharmaceutical care programs were developed.

Adult↗

Codon usage in Cryptosporidium parvum differs from that in other Eimeriorina.

Codon usage of Crytosporidium parvum was compared with those of other Eimeriorina Toxoplasma gondii and Eimeria tenella and revealed a biased use of synonymous codons with a preference for NNU (40.0%) and NNA (33.4%). There was no close resemblance of the codon usage of C. parvum to T. gondii (correlation coefficient, r = 0.14) or E. tenella (r = 0.14) but it was similar to Entamoeba histolytica (r = 0.75) and Plasmodium falciparum (r = 0.5). Analysis of the codon usage in homologous gene sequences (actin, beta-tubulin) also failed to reveal a close relationship between C. parvum and T. gondii or E. tenella. The low usage codons in C. parvum were most frequently used codons in T. gondii and E. tenella. These observations are consistent with 18S rRNA sequence analysis which shows no close relationship of Cryptosporidium with other Eimeriorina (Sarcocystis, Toxoplasma and Eimeria) and questions the validity of the current classification of C. parvum.

Actins↗

Prediction of radiotherapy response of cervical carcinoma through measurement of proliferation rate.

Estimation of tumour proliferation may allow the design of individualised radiotherapy schedules to optimise response. This prospective study correlates the tumour proliferation rate of cervical carcinoma with response to conventional radiotherapy. The potential tumour cell doubling rate (Tpot) was estimated following flash labelling of the tumours in vivo using the DNA precursor, bromodeoxyuridine (BrdUrd); samples were analysed by flow cytometry. Tumour ploidy, DNA index and mitotic count were also assessed as was histological grade and type. Multiple biopsies from each tumour were obtained from 121 women. The median Tpot was 4.0 days, median S-phase duration 12.8 h and median adjusted labelling index 9.8%. Higher BrdUrd labelling was seen in patients who developed pelvic tumour recurrence following radiotherapy. This was the only biological/histological parameter with univariate and multivariate significance in relation to locoregional recurrence (P = 0.006 and P = 0.034 respectively). This study represents the first assessment of Tpot in relation to long-term response of cervical tumours treated by radiotherapy treatment. The association of high BrdUrd labelling and poor pelvic disease-free survival indicates the need for further research into the potential of radiotherapy schedule alteration to reflect tumour proliferation. The predictive value may be enhanced by combination with other biological parameters.

Aged↗

Effect of ageing upon warfarin dose requirements: a longitudinal study.

This longitudinal study was designed to establish the rate of age-related change in warfarin dose requirements. Warfarin dosage was recorded retrospectively in 104 patients who had been stabilized on warfarin for a median period of 10 years (range 6-24 years) for prophylaxis of thromboembolic disease. There was a significant negative correlation between dosage and age at the start of therapy (p = 0.002, r = -0.30). Warfarin requirements fell over time, dosage difference being significantly correlated with age difference (p = 0.01, r = 0.25). Use of regression equation derived from these data suggests a 21% fall in warfarin requirements in this population over a 15-year period. The relationship between change in warfarin dose requirements and ageing established in this longitudinal study is in good agreement with that established by cross-sectional studies, suggesting that no major birth cohort effect is influencing requirements in our warfarin-treated population.

Adult↗

Systemic immune activation as a potential determinant of wasting in Zambians with HIV-related diarrhoea.

Wasting in African AIDS patients is severe, and its aetiology is probably multifactorial: persistent diarrhoea, poverty and tuberculosis may all contribute. We report a cross-sectional study of body composition measured anthropometrically in 75 adult patients with HIV-related persistent diarrhoea in Lusaka, and its relationship to gastrointestinal infection and systemic immune activation assessed using serum neopterin and soluble tumour necrosis factor receptor (sTNF-R55) concentrations. Patients as a group were generally severely wasted (mean body mass index (BMI) 15.8 kg/m2, range 11-22), but the severity of wasting was related neither to oesophageal candidiasis nor to intestinal infection. In men but not women, all measures of nutritional status were negatively related to serum sTNF-R55 concentration (fat-free mass in men, r = -0.64; 95% CI: -0.80, -0.41; p < 0.0001). Some wasted patients had cutaneous features of malnutrition, again associated with higher sTNF55 concentrations, and two had peripheral oedema. The diarrhoea-wasting syndrome in this part of Africa seems to be associated with evidence of high cytokine activity in men, rather than oesophageal candidiasis or any particular intestinal opportunistic infection. This immune activation requires further investigation in the context of the sex difference we have observed.

Adolescent↗

Multifocal remitting-relapsing cerebral demyelination twenty years following allogeneic bone marrow transplantation.

We report a case study of a female who received an allogeneic bone marrow transplantation (BMT) from a sex-mismatched related donor and who, after a twenty-year interval, developed an acute fulminant biopsy-proven demyelinating disorder of cerebral white matter which followed a remitting-relapsing chronic course. In situ hybridization studies using Y-chromosome-specific markers revealed Y-chromosome-positive mononuclear cells in biopsy samples of white matter. Magnetic resonance imaging (MRI) studies of the asymptomatic healthy male donor showed multiple white matter lesions. These observations suggest that donor lymphocytes were sensitized to central nervous system (CNS) antigens prior to or at the time of transplantation but remained dormant for 20 years before becoming activated to cause widespread demyelination.

Adult↗

Developing a new method to record care at home for children with cancer: an example of research and practice collaboration in a regional paediatric oncology unit.

Academics need to address the facilitation of nurses in practice to research and develop the care given to patients if nursing is to move closer towards a research-based profession. This paper describes a project involving collaboration between an academic department of nursing and nurses working in clinical practice providing care at home for children with cancer. The project involved an audit of the nursing care records for the service, and the development of a new style of record-keeping which described and quantified complex nursing care. The authors discuss the method and results of the project, describing the benefits of research and practice collaboration.

Child↗

Paracetamol use, availability, and knowledge of toxicity among British and American adolescents.

Paracetamol is the commonest agent employed in self poisoning, however it is not clear whether adolescents possess insight into the serious complications associated with its misuse. Using a one page questionnaire, the availability, usage, and knowledge of toxicity of paracetamol among 1147 American and British adolescents was assessed. Although 90% of all students recognised that paracetamol could kill, the great majority of students overestimated the lethal dose. In addition, while knowledge regarding side effects of paracetamol was poor the drug was widely available to, and used by, the study population. It is proposed that gross overestimation of the number of tablets required to kill, poor understanding of paracetamol side effects, and wide availability of the drug contribute to its frequent use in adolescent suicidal behaviour. The inclusion of some over-the-counter medications in school drug education programs in addition to tighter control of the availability of paracetamol may help reduce the problem of adolescent self poisoning.

Acetaminophen↗

Effects of nitrogen oxides on natural killer cells in glass craftsmen and braziers.

OBJECTIVES: To assess the effect of exposure to nitrogen oxides on peripheral blood natural killer cells. METHODS: Groups of glass craftsmen and braziers exposed to nitrogen oxides and non-exposed controls were studied. Air concentrations of nitrogen oxides were measured. Mononuclear cells isolated from peripheral blood samples were assayed for natural killer cell activity with K562 target cells in a 51Cr release assay and the percentage of natural killer cells (CD16) was measured by flow cytometry. RESULTS: Braziers were exposed to 1.2 ppm nitrogen dioxide and 8.6 ppm nitric oxide and glass craftsmen to 2.9 ppm nitrogen dioxide and 26.5 ppm nitric oxide. The natural killer cell activity of exposed workers was significantly lower than in non-exposed controls (P < 0.05 ANOVA Scheffe test). The percentage of natural killer cells in glass craftsmen was significantly greater than in controls (P < 0.05 ANOVA Scheffe test). Regression of natural killer cell activity against age, smoking habit, number of years worked and current exposure to nitrogen dioxide and nitric oxide gases was not significant. The percentage of natural killer cells was not significantly correlated with age, smoking habit, or numbers of years worked, but was significantly related to air concentrations of nitrogen dioxide (P < 0.01) and nitric oxide (P < 0.001). CONCLUSION: Natural killer cell activity and the percentage of natural killer cells in peripheral blood cells were altered in workers exposed to nitrogen oxides.

Adolescent↗

Electrical stimulation of the globus pallidus preceding stereotactic posteroventral pallidotomy.

Physiological methods such as microelectrode recording of neuronal activity and electrical stimulation of target structures can improve the safety and efficacy of certain stereotactic surgeries. The globus pallidus (GP) was electrically stimulated in 136 patients with Parkinson's disease prior to unilateral posteroventral pallidotomy to identify functional areas and prevent deficits. We found that electrical stimulation of the GP elicited two principal responses: contractions of the contralateral hand and flashing lights. The mean voltage that evoked motor responses was 4.3 V (range 1.7-9.0 V), while higher intensity was necessary to elicit visual responses (mean 6.8 V; range 3.5-9.9 V). Contralateral tremor, speech impairment, paresthesias, and warm sensations were also elicited.

Adult↗

Dioxinlike properties of a trichloroethylene combustion-generated aerosol.

Conventional chemical analyses of incineration by-products identify compounds of known toxicity but often fail to indicate the presence of other chemicals that may pose health risks. In a previous report, extracts from soot aerosols formed during incomplete combustion of trichloroethylene (TCE) and pyrolysis of plastics exhibited a dioxinlike response when subjected to a keratinocyte assay. To verify this dioxinlike effect, the complete extract, its polar and nonpolar fractions, some containing primarily halogenated aromatic hydrocarbons, were evaluated for toxicity using an embryo assay, for antiestrogenicity using primary liver cell cultures, and for the ability to transform the aryl hydrocarbon receptor into its DNA binding form using liver cytosol in a gel retardation assay. Each of these assays detect dioxinlike effects. Medaka (Oryzias latipes) embryos and primary liver cell cultures of rainbow trout (Oncorhynchus mykiss) were exposed to concentrations of extract ranging from 0.05 to 45 micrograms/l. Cardiotoxicity with pericardial, yolk sac, and adjacent peritoneal edema occurred after exposure of embryos to concentrations of 7 micrograms/l or greater. These same exposure levels were associated with abnormal embryo development and, at the higher concentrations, death. Some of the fractions were toxic but none was as toxic as the whole extract. In liver cells, total cellular protein and cellular lactate dehydrogenase activity were not altered by in vitro exposure to whole extract (0.05-25 micrograms/l). However, induction of cytochrome P4501A1 protein and ethoxyresorufin O-deethylase activity occurred. In the presence of whole extract, estradiol-dependent vitellogenin synthesis was reduced. Of the fractions, only fraction 1 (nonpolar) showed a similar trend, although vitellogenin synthesis inhibition was not significant. The soot extract and fractions bound to the Ah receptor and showed a significantly positive result in the gel retardation/DNA binding test. Chemical analyses using GC-MS with detection limits for 2,3,7,8-tetrachlorodibenzo-p-dioxin and dibenzofuran in the picomole range did not show presence of these compounds. Our results indicate that other chemicals associated with TCE combustion and not originally targeted for analysis may also pose health risks through dioxinlike mechanisms.

Aerosols↗

Measurement of the vestibulo-ocular reflex by magnetometry during active head movement.

A new method of measuring the vestibulo-ocular reflex (VOR) during active head movements is presented. Subjects sat and attempted to maintain their gaze upon a fixed point whilst turning their heads from side to side in response to an auditory cue, to attain frequencies of head rotation that increased from 1 Hz to 4 Hz during a 24 s period. Head movements were monitored by a small magnetic field detector worn on the subject's forehead and positioned a set distance from a magnetic field transmitter coil. Eye movements were monitored using the corneo-retinal potential. Gain (eye angle/head angle) and phase difference (eye phase-head phase) were calculated to define the VOR. Three repeat measurements were made on 20 normal subjects. Gain decreased significantly (P < 0.0001) with increasing frequency whilst the phase difference remained unchanged. The 95% prediction intervals were narrow for both gain (+/- 0.28) and phase (+/- 11 degrees). These data, together with the speed and ease of performance of the test, suggest that the test can provide valuable information on the performance of the vestibular system.

Adult↗

Needle wire localization for nonpalpable breast lesions: sensations, anxiety levels, and informational needs.

PURPOSES: To determine the sensations that women most frequently report during needle wire localization (NWL) for nonpalpable breast lesions, to rate preprocedure anxiety, and to describe what preparation women consider desirable for the procedure. SETTING: Outpatient breast center in a large, not-for-profit hospital in a major city in Texas. DESIGN: Prospective, descriptive design. SAMPLE: Nonprobability sample of 56 women who were an average of 57 years old (range = 30-87 years). Forty-three (77%) underwent single wire localization. Nine (16%) of the women were subsequently diagnosed with breast cancer. METHODS: Subjects provided demographic information preprocedure. Postprocedure, subjects described and rated intensity of sensations on a 0-10 verbal, numeric rating scale. Preprocedure anxiety was also rated. Subjects responded to the question "What would you have liked to have been told before NWL to best prepare you for the procedure?" FINDINGS: Most frequently reported sensations were pressure, stinging, and pain, which averaged 6, 4, and 7, respectively, in intensity. Mean anxiety score was 5.3 on a scale of 10 with 10 subjects rating their anxiety as 10. Five (9%) subjects fainted during the procedure. Subjects provided valuable suggestions about how to prepare patients for this procedure, such as providing brochures and pictures about the procedure. CONCLUSIONS: Subjects are moderately or highly anxious before NWL of the breast and describe a variety of sensations. Risk factors for fainting during this procedure and strategies to prevent fainting must be determined. IMPLICATIONS FOR NURSING PRACTICE: Sensory information should be used to prepare women for NWL. Subjects' suggestions about how to prepare women for the procedure can be used to develop educational and sensory approaches to enhance preparation for the procedure and perhaps reduce anxiety.

Adult↗

Genetic influences on central abdominal fat: a twin study.

INTRODUCTION: Recent studies of regional fat distribution have focused on the clinical importance of central abdominal obesity. Central adiposity is strongly related to insulin resistance, non-insulin dependent diabetes mellitus (NIDDM), dyslipidaemia and cardiovascular disease. While significant genetic influences on body mass index (BMI), total body and subcutaneous fat have been demonstrated, the inheritance of central abdominal obesity, has not been studied. OBJECTIVE: To assess genetic effects on regional fat distribution and associated metabolic parameters. DESIGN AND SUBJECTS: We directly measured total body, central abdominal (C-abd) and non-abdominal fat using dual energy X-ray absorptiometry in 50 monozygotic (MZ) and 36 dizygotic (DZ) female twins, of age (mean +/- SD), 44 +/- 12 and 47 +/- 14 y; BMI 24 +/- 5 and 24 +/- 3 kg/m2; C-abd fat 33 +/- 9 and 32 +/- 9%, respectively. Total variance in all parameters was independent of zygosity and genetic analyses of regional adiposity were performed before and after adjusting for age and percentage total body fat. RESULTS: A genetic influence was observed on the population variance in total fat, C-abd fat (C-abd fat rMZ = 0.66 vs rDZ = 0.20, p = 0.03) and non abdominal fat. After adjusting C-abd fat for age and total body fat there was a independent genetic influence on C-abd fat accounting for approximately 70% of the population variance (rMZ = 0.61 vs rDZ = 0.40, p = 0.001). CONCLUSION: The majority of inter-subject variance in central abdominal fat in non-obese individuals is due to genetic factors. The inheritance of abdominal obesity, with its associated metabolic consequences, may contribute to the familial aggregation of insulin resistance, diabetes and cardiovascular disease.

Abdomen↗