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Biomedical subjects

P Kelly

Publications and source records attributed to P Kelly.

At least 91 records · Page 5Linked to original sources

Bacterial infections of the gut (excluding enteric fever).

Bacterial enteric infections are still a major cause of morbidity and mortality, and many challenges lie ahead in understanding and managing these conditions. Clostridium difficile remains the most important nosocomial infection. Antibiotic resistance makes the treatment of shigella infections increasingly difficult. Molecular and cellular techniques are, however, rapidly expanding our understanding of the complexity of the pathogenesis of established and newly recognized pathogens.

Journal Article↗

Variable distribution of Cryptosporidium parvum in the intestine of AIDS patients revealed by polymerase chain reaction.

OBJECTIVE: Cryptosporidium parvum is associated with persistent diarrhoea and malnutrition in children, with large waterborne outbreaks and with the diarrhoea-wasting syndrome in AIDS. However, pathophysiology of infection remains to be defined and the reasons for the variability of clinical features are uncertain. The polymerase chain reaction (PCR) is valuable for the analysis of infections with non-culturable organisms because of its high sensitivity, so we compared PCR and microscopy as tools for the analysis of the distribution of infection. DESIGN: PCR was compared with light microscopy (LM) and electron microscopy (EM) in duodenal biopsies from a well characterized series of 75 Zambian AIDS patients. PCR and LM were then used to define the distribution of infection in biopsies from duodenum, ileum, right colon and left colon in eight South African patients with persistent AIDS-related cryptosporidiosis. RESULTS: PCR specifically detected 10 fg of genomic C. parvum DNA. When applied to duodenal biopsies from 75 Zambian AIDS patients, infection was detected in all seven cases of duodenal cryptosporidiosis that were identified by LM or EM and in six additional cases which appeared to be negative by microscopy. Distribution of infection was defined in six of eight South African AIDS patients. Two had pan-enteric infection, three had small bowel infection and one had purely ileo-colonic infection. In two cases infection could not be localized despite using PCR, suggesting that infection was confined to the inaccessible mid-small intestine. CONCLUSIONS: PCR detection of C. parvum DNA demonstrated that infection is highly variable in distribution, which must be taken into account when designing and interpreting studies of pathophysiology.

Acquired Immunodeficiency Syndrome↗

Irritable bowel syndrome, gastro-oesophageal reflux, and bronchial hyper-responsiveness in the general population.

BACKGROUND: Associations have been shown between irritable bowel syndrome (IBS) and gastro-oesophageal reflux, between gastro-oesophageal reflux and asthma, and more recently between IBS and bronchial hyper-responsiveness (BHR). AIMS: To explore the inter-relations between these conditions. SUBJECTS: A randomly selected community sample of 4432 adults. METHODS: A validated postal symptom questionnaire investigating the associations between IBS, gastro-oesophageal reflux symptoms, and symptomatic BHR. RESULTS: 3169 questionnaires (71.7% response) returned by 1451 men and 1718 women were analysed. One year prevalences, in men and women respectively, of IBS were 10.5% and 22.9%, of dyspepsia 26.3% and 25. 25%, of gastro-oesophageal reflux symptoms 29.4% and 28.2%, of BHR 13.2% and 14.6%, and of chronic bronchitis 8.3% and 4.9%. Logistic regression showed independent associations between IBS and BHR, gastro-oesophageal reflux symptoms, and dyspepsia. There was no significant independent association between IBS and chronic bronchitis. In men and women the odds ratio with 95% confidence interval (CI) for IBS and gastro-oesophageal reflux symptoms was 2.6 (2.1-3.1; p<0.001) and for IBS and BHR 2.1 (1.7-2.7; p<0.001). These associations held on stratifying for sex and consultation behaviour. IBS, gastro-oesophageal reflux symptoms, and bronchial hyper-responsiveness occurred more frequently together than expected, 2.5% (95% CI 2.41-2.57) of the sample having all three conditions compared with an expected prevalence of 0.7% (95% CI 0.66-0.71). The conditions were independently associated with each other. CONCLUSIONS: These observations may indicate the presence of an underlying disorder producing symptoms in gastrointestinal and respiratory systems.

Adult↗

Can academic radiology departments become more efficient and cost less?

PURPOSE: To determine how successful two large academic radiology departments have been in responding to market-driven pressures to reduce costs and improve productivity by downsizing their technical and support staffs while maintaining or increasing volume. MATERIALS AND METHODS: A longitudinal study was performed in which benchmarking techniques were used to assess the changes in cost and productivity of the two departments for 5 years (fiscal years 1992-1996). Cost per relative value unit and relative value units per full-time equivalent employee were tracked. RESULTS: Substantial cost reduction and productivity enhancement were realized as linear improvements in two key metrics, namely, cost per relative value unit (decline of 19.0% [decline of $7.60 on a base year cost of $40.00] to 28.8% [$12.18 of $42.21]; P < or = .001) and relative value unit per full-time equivalent employee (increase of 46.0% [increase of 759.55 units over a base year productivity of 1,651.45 units] to 55.8% [968.28 of 1,733.97 units]; P < .001), during the 5 years of study. CONCLUSION: Academic radiology departments have proved that they can "do more with less" over a sustained period.

Academic Medical Centers↗

Predictors of quality of life and adjustment after lung transplantation.

STUDY OBJECTIVE: Few studies have examined predictors of quality of life and adjustment after lung transplantation. This study determined whether pretransplant psychological measures predicted physical health, quality of life, and overall adjustment posttransplant. Cross-sectional analyses also examined differences in adjustment and quality of life for lung transplant candidates and recipients. DESIGN AND PARTICIPANTS: Seventeen transplant candidates and 60 transplant recipients completed questionnaires measuring adjustment and quality of life. In addition, we examined archival data on 107 transplant candidates who had received pretransplant psychological assessments, and posttransplant physical health status data were collected on these patients. Of the 107 patients who provided a pretransplant psychological assessment, 32 completed the questionnaires measuring posttransplant adjustment and quality of life. SETTING: University medical center transplant service. RESULTS: Cross-sectional analyses indicated significantly better adjustment and quality of life posttransplant. Pretransplant psychological variables were not associated with measures of posttransplant physical health. Hierarchical multiple regression analyses found that pretransplant anxiety and psychopathology predicted posttransplant adjustment (beta's ranging from 0.32 to 0.68) and greater pretransplant anxiety also predicted worse posttransplant quality of life (beta's ranging from 0.29 to 0.62). Subjective sleep disturbances were associated with poorer adjustment and quality of life (beta's ranging from 0.36 to 0.75), and were found to mediate the relationship between presurgical anxiety and posttransplant adjustment and quality of life. CONCLUSIONS: This study found that psychological status pretransplant predicted adjustment and quality of life posttransplant. Moreover, increased anxiety levels pretransplant predicted subsequent subjective sleep disturbances, which were, in turn, associated with poorer adjustment and quality of life. The benefits of pretransplant stress management interventions are discussed.

Adaptation, Psychological↗

Cryptosporidiosis in urban Zambian children: an analysis of risk factors.

In four crowded townships of Lusaka, Zambia, the prevalence of cryptosporidiosis in 222 children with diarrhea was 18%, with marked temporal and geographic variation over the course of one rainy season. Using data on the finding of oocysts of Cryptosporidium parvum in urban water supplies, the areas under study were categorized as high or low risk. Prevalence of cryptosporidiosis in children with diarrhea was higher in high risk areas after stratification by early/late stage of the rains (Mantel-Haenszel odds ratio [OR] = 2.9, 95% confidence interval [CI] = 1.3, 6.7; P = 0.008). Cryptosporidiosis was not associated with keeping animals, nutritional status, or parental education, but was apparently more common in breast fed children (OR = 2.7, 95% CI = 1.1, 6.9; P = 0.01), although the proportion of exclusively breast fed children was not measured. Since most of these infections were of short duration, we conclude that transmission of C. parvum can vary dynamically within one city and over short periods of time, and that water-borne contamination may be a substantial influence.

Age Distribution↗

HIV-related diarrhoea.

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Acquired Immunodeficiency Syndrome↗

Recovery rates, serotypes, and antimicrobial susceptibility patterns of salmonellae isolated from cloacal swabs of wild Nile crocodiles (Crocodylus niloticus) in Zimbabwe.

Samples from the cloaca and the ventral skin surface of 67 Nile crocodiles (Crocodylus niloticus) captured in four uninhabited areas at Lake Kariba, Zimbabwe, were cultured for Salmonella. All the skin samples tested negative for Salmonella, whereas 18 of 67 (26.9%) cloacal samples grew Salmonella. Significantly more males than females yielded Salmonella, but no statistically significant correlation among salmonella carriage, body size, and age was recorded. Ten different serotypes of S. enterica belonging to the subspecies enterica, salamae, and diarizonae were isolated. All isolates belonging to subspecies enterica displayed invasive properties in an experimental mouse model and thus exhibited pathogenic potential, whereas none of the other isolates were invasive. In general, isolates were sensitive to a number of commonly used antimicrobials, except for three isolates that were resistant to streptomycin.

Alligators and Crocodiles↗

Purification and characterization of avian glycolipid: beta-galactosyltransferases (GalT-4 and GalT-3): cloning and expression of truncated betaGalT-4.

Acidic glycolipid of ganglio-(containing sialic acid) and sialyl-lactofucosyl-type, SA-Lex (containing sialic acid and fucose) are developmentally regulated and appear to be ubiquitous on neuronal and cancer cell surfaces of animals. Two glycolipid: beta-galactosyltransferases, GalT-3 and GalT-4, were characterized in embryonic chicken brain (ECB). Based on substrate competition experiments, these two activities were believed to be due to expression of two gene products. A cDNA fragments (about 600 bp) encoding the catalytic domain of the GalT-4 (UDP-Gal:LcOse3Cer beta1,4galactosyltransferase) from ECB and human Colo-204 were isolated. These cDNAs were expressed as a soluble glutathione-S-transferase fusion protein (48 kDa) in Escherichia coli. Interactions between GlcNAc-, UDP-hexanolamine-, and alpha-lactalbumin were studied with the purified fusion protein (recombinant and truncated). Functionally it was similar to that of native GalT-4 purified (40000-fold) from 11-day-old ECB. GalT-3 (UDP-Gal:GM2beta1,3galactosyltransferase) was purified from 19-day-old ECB, and a polyclonal antibody was produced against the peptide backbone for immunoscreening of a lambdaZAP ECB cDNA expression library. Each of the GalT-3 peptides (62 and 65 kDa was analyzed by protein fingerprinting analysis indicating a similar peptide mapping pattern.

Animals↗

Patterns of alcohol consumption, smoking and illicit drug use in British university students: interfaculty comparisons.

The use of tobacco, alcohol and illicit drugs was investigated by questionnaire in 3699 second year students in ten UK universities. Patterns of use varied considerably between different faculty groups. Tobacco use was most prevalent in arts, social science and biological science students, among whom 36-39% of men and nearly one third of women were regular smokers, and least in female veterinary students (5%). Alcohol consumption was greatest in biological science students: 23% of those who drank exceeded 'hazardous' levels compared with 10-16% in all other faculties. Prevalence of cannabis use was highest in arts and social science students of whom 27% reported regular weekly use compared with 9-22% in other faculties. Experience with other illicit drugs was greatest among arts, social science and physical science students, of whom 64-71% reported experience at least once or twice, and least among veterinary students (42%). Identification of different lifestyles may help to direct appropriate health information to particular student groups.

Alcohol Drinking↗

Medulloepithelioma of the optic nerve head.

Medulloepithelioma of the optic nerve is a rare developmental tumor. We describe a 2-year-old boy with profound loss of vision associated with a visible tumor of the optic nerve head in his left eye. A clinically diagnosed retinoblastoma necessitated left eye enucleation. The histopathological diagnosis was malignant medulloepithelioma that was incompletely resected. Further tumor resection was required, and the patient received adjunctive chemotherapy and radiotherapy. Four years after treatment, the patient has neither clinical nor radiological evidence of tumor.

Chemotherapy, Adjuvant↗

The pathological and biological nature of screen-detected breast carcinomas: a morphological and immunohistochemical study.

Traditional and immunohistochemical markers of prognosis were examined in 455 mammary carcinomas derived from breast cancer screening and compared with those of 277 carcinomas presenting symptomatically over the same period. Tumours detected by population screening under the U.K. National Health Service Programme do not differ from those detected by other screening projects, but compared with symptomatic cancers, screen-detected cancers are more likely to be in situ and if invasive, to be smaller, of lower grade, and to have invaded vessels, perineural spaces, and lymph nodes less frequently. Tubular and cribriform types are more often represented in screened patients. Immunohistochemical markers which have been proposed as being related to likely tumour behaviour (epidermal growth factor receptor, c-erbB-2 protein, oestrogen and progesterone receptors, cathepsin D, p53, and retinoblastoma protein) do not distinguish screen-detected from 'clinical' cancers. It is concluded that cancers diagnosed at screening do not differ biologically from those presenting clinically, but are the same lesions detected at an earlier stage of their natural history.

Biomarkers, Tumor↗

Selection criteria for unilateral posteroventral pallidotomy.

In an attempt to refine the indications for posteroventral pallidotomy (PVP) the authors instituted strict selection criteria which are based on the experience gained from the first 60 pallidotomy patients treated at their institution. In addition to clinical evaluation, all pallidotomy candidates undergo neuropsychological testing and 18F-fluoro-deoxyglucose utilization positron emission tomography (FDG/PET). The data from which these criteria were developed are presented as are early clinical results. The authors demonstrate that these criteria enhance the efficacy of the procedure by assuring therapeutic response and reducing the incidence of post-operative dementia. Their indications and contraindications for pallidotomy are discussed.

Antiparkinson Agents↗

Microcirculatory compensation to progressive atherosclerotic disease.

The precapillary resistance in the skin of the foot increases with standing. This mechanism, termed the venoarterial reflex (VAR) restricts arterial inflow, and avoids an excessive rise in capillary pressure. This study tests the hypothesis that there is microcirculatory compensation to atherosclerotic disease of increasing severity. Foot skin perfusion (FSP) was measured in 100 limbs with a laser Doppler placed on the plantar aspect of the great toe. Limbs were categorized as normal (n = 31) with an ankle brackial index (ABI) > or = 0.96, claudicants (n = 42) ABI 0.5-0.86, and critical ischemia (n = 27) with an ABI < or = 0.49 or a pulse volume recording consistent with severe peripheral vascular disease and symptoms of rest pain or tissue loss. Segmental Doppler pressures and pulse volume recordings were performed prior to laser Doppler measurements. Subjects with clinical signs or symptoms of chronic venous insufficiency were excluded. The resting foot skin perfusion was measured in the horizontal and dependent position, with the patient supine and sitting. Comparisons within categories were done using Wilcoxon matched pairs signed rank test and between groups with Mann-Whitney U test for unpaired data. Differences were considered significant if they exceeded the 95% confidence level (p value < or = 0.05). Resting supine skin perfusion was similar between nondiabetic normals and claudicants and diabetic normals and claudicants. There was a significant decrease in the foot skin perfusion (mean FSP +/- SEM) in the normal limb with a change from the supine (7.8 +/- 2.2 ml/min/100 g) to the dependent (2.8 +/- 0.6 ml/min/100 g) position indicating an intact VAR. This was absent in 33% of the limbs with claudication. Limbs with critical ischemia demonstrated an increase in FSP with dependency (supine 4.0 +/- 1.0 ml/min/100 g) versus dependent (8.4 +/- 1.8 ml/min/100 g) and was present in both diabetic and nondiabetic limbs. Microcirculatory compensation occurs early in atherosclerotic limbs. Although supine FSP is similar in normals and claudicants, a greater percentage of claudicants demonstrate a loss of the VAR. Critically ischemic limbs have increased FSP in the dependent position. These observations indicate that there are microcirculatory alterations in limbs with claudication and assist in explaining why patients with ischemic rest pain obtain relief and develop edema with dependency.

Arteriosclerosis↗

Umbilical cord blood stem cells: application for the treatment of patients with hemoglobinopathies.

Even though there is recognized morbidity and death associated with bone marrow transplantation, this procedure has been performed successfully in a substantial number of patients with hemoglobinopathies. However, finding a suitable related donor is often difficult and the morbidity associated with the use of unrelated donors is high. Several reports indicate that fewer than 30% of patients with thalassemia major and fewer than 20% of patients with sickle cell anemia have histocompatible siblings. Human umbilical cord blood (UCB) contains hematopoietic stem cells capable of reconstituting bone marrow. To date, approximately 200 transplantations have been performed with UCBs. Early results suggest that, even with substantial human leukocyte antigen (HLA) incompatibility, a decrease in the incidence of graft-versus-host disease occurs with cord blood. The extent to which HLA incompatibility can be tolerated when cord blood is used has not been determined. These results raise the possibility that UCB obtained from unrelated donors could be used for transplantation in patients with hemoglobinopathies. This review summarizes current data on UCB stem cells used for transplantation in hematologic diseases. The review contains a discussion of the potential uses of UCB for patients with hemoglobinopathies and the value of programs designed to collect UCB from newborn infants with hemoglobinopathies, from siblings of patients with hemoglobinopathies, and from groups of ethnic minorities similar to those in which hemoglobinopathies are found.

Blood Banks↗