Development of a Web-based faculty publications database.
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Connecticut↗
Biomedical subjects
P Kelly
Publications and source records attributed to P Kelly.
PCR for Tropheryma whippelii.
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Actinobacteria↗
Efficient transduction of human lymphocytes and CD34+ cells via human immunodeficiency virus-based gene transfer vectors.
The development of gene transfer systems for the efficient transduction of human primary cells including lymphocytes and CD34+ cells is a significant step in the advancement of gene therapy and cell marking protocols. Efficient gene transfer systems also represent useful tools for basic research. Here we show that human primary lymphocytes and CD34+ cells can be efficiently transduced using a VSV-G pseudotyped HIV-1-based gene transfer system. The enhanced green fluorescent protein (EGFP) was chosen as the marker transgene, because it can be easily visualized and quantitated using fluorescence microscopy and flow cytometry, thus eliminating the need for selection or PCR to score transduction. Vectors produced with this system did not generate replication-competent retroviruses (RCRs) and efficiently transduced human cell lines (40-90%), PBMCs (60%), mobilized CD34+ cells (39%), and CD34+ cells from umbilical cord blood (60%) as measured by flow cytometry. Cells treated with AZT prior to infection did not express EGFP, ruling out passive protein or plasmid DNA transfer. This was further confirmed in methylcellulose cultures, where expression in myeloid and erythroid colonies was maintained for at least 3 weeks. In addition, this HIV-based vector was able to efficiently transduce freshly isolated, not-prestimulated CD34+ cells (70% EGFP positive) in serum-free medium. Under these same conditions, a Moloney murine leukemia virus-based vector failed to transduce not-prestimulated CD34+ cells. These characteristics make this gene transfer system an excellent choice for both basic science and possible gene therapy applications.
Antigens, CD34↗
Micronutrient supplementation in the AIDS diarrhoea-wasting syndrome in Zambia: a randomized controlled trial.
OBJECTIVE: As HIV has spread through sub-Saharan Africa, persistent diarrhoea has emerged as a major problem in hospitals and in the community in severely affected areas. We have previously demonstrated that antiprotozoal therapy with albendazole reduces diarrhoea in AIDS patients in urban Zambia. This trial was designed to test the hypothesis that the clinical response to albendazole might be improved by oral micronutrient supplementation. DESIGN: Randomized, placebo-controlled trial. SETTING: Home care service of Ndola Central Hospital, Zambia. PATIENTS: HIV-seropositive patients with persistent diarrhoea. INTERVENTION: Patients were randomized to albendazole plus vitamins A, C and E, selenium and zinc orally or albendazole plus placebo, for 2 weeks. MAIN OUTCOME MEASURES: Time with diarrhoea following completion of treatment; mortality; adverse events. RESULTS: Serum vitamin A and E concentrations before treatment were powerful predictors of early mortality, but supplementation did not reduce time with diarrhoea or mortality during the first month, even after taking into account initial vitamin A or E concentrations, CD4 cell count or clinical markers of illness severity. Serum concentrations of vitamins A and E did not increase significantly in supplemented patients compared with those given placebo, and there were no changes in CD4 cell count or haematological parameters. No adverse events were detected except those attributable to underlying disease. CONCLUSIONS: Although micronutrient deficiency is predictive of early death in Zambian patients with the diarrhoea-wasting syndrome, short-term oral supplementation does not overcome it nor influence morbidity or mortality.
Acquired Immunodeficiency Syndrome↗
Laparoscopic extraperitoneal inguinal hernia repair in the day-care setting.
BACKGROUND: Totally extraperitoneal (TEP) laparoscopic inguinal hernia repair is gaining popularity, and our preference is to perform this procedure as a day case. This study evaluates the suitability of TEP repair in the day-care setting. METHODS: A policy of day-care TEP repair, unless contraindicated, was adopted for inguinal hernia repair, and the outcome was prospectively evaluated. Of 87 consecutive inguinal hernia repairs, day-care TEP was possible in 54 (62%); 17 (20%) were in-patient TEP, 14 (16%) were open repairs, and 2 (2%) were converted from TEP to open repairs. RESULTS: Among day-care TEP repairs, median visual analog pain score at discharge was 2.3/10, and 43% of patients had no pain. Complications included cord hematoma 2 (4%) and seroma 3 (6%). Median times for stopping analgesia, resumption of full activity, and return to work were 3, 3, and 6 days respectively. Complete satisfaction with day-care TEP was expressed by 91% of patients; 9% were moderately satisfied, and none expressed dissatisfaction. CONCLUSIONS: Day-care TEP repair is feasible in the majority of patients with inguinal hernias, and it is associated with minimal complications, excellent recovery, and a high degree of patient satisfaction.
Adolescent↗
Prolactin blocks glucocorticoid induced cell death by inhibiting the disruption of the mitochondrial membrane.
Prolactin (PRL) has been reported to inhibit dexamethasone (Dex) induced cell death. Nevertheless, the mechanism through which PRL exerts its protective effect is still not unravelled. Here, we analyse the effect of PRL at different stages of the glucocorticoid (GC) apoptotic pathway in PRL dependent cells (Nb2 cells). PRL blocks completely the GC induced loss of the mitochondrial transmembrane potential (delta psi(m)) and consequently phosphatidylserine (PS) exposure and loss of DNA content. Although PRL promotes an upregulation of the bcl-2 expression, simultaneous addition of PRL to GC fails to maintain even the normal levels of this anti-apoptotic protein. This finding excludes a critical role for bcl-2 in the PRL protective effect against GC. GC induced delta psi(m) disruption can be inhibited by the ICE-like inhibitor zVAD-fmk but not by ICE inhibitor tetrapeptide acetyl-Tyr-Val-Ala-Asp.chloromethylketone (YVAD-cmk) nor by caspase-3 inhibitor zDEVD. It can be speculated that PRL blocks delta psi(m) disruption by inhibiting an unknown caspase activated by GC.
Animals↗
Ceramide glycanase activities in human cancer cells.
Ceramide glycanase (CGase) activities have been detected in different human tumor cells (colon, carcinoma Colo-205; neuroblastoma, IMR-32; breast cancer lines, SKBr3 and MCF7). However, the level of enzymatic activity is lower in these cells compared to that present in other mammalian tissues reported before (Basu, M., Kelly, P., Girzadas, M. A., Li, Z., and Basu, S. Methods Enzymol. (in press)). The majority of CGase activity was found in the 100,000 g soluble supernatant fraction isolated from all these cell lines and tissues. Using the soluble enzyme, the requirement for optimum CGase activity was found to be consistent with previous observations found for rat and rabbit tissues (Basu, M., Dastgheib, S., Girzadas, M. A., O'Donnell, P. H., Westervelt, C. W., Li, Z., Inokuchi, J. I., and Basu, S. (1998) Acta Pol. Biochim. 42:327). The CGase activities from both Colo-205 and IMR-32 cells are optimum at a protein to detergent ratio of one. All the mammalian CGases, including human cancer cells, show an optimum pH between 5.5 and 5.8 in sodium acetate buffer. The CGase activities from cancer cells are found to be cation-independent; however, mercury, zinc, and copper ions seem to inhibit the enzyme activity substantially in both tumor cells lines. The mercury ion inhibition of CGase activities from all different sources indicates a possible structural homology in the CGase proteins. Radiolabeled substrates, labeled at the sphingosine double bond or at the 3-position of sphingosine without modifying double bond of sphingosine were used in this investigation. Both were active substrates with all enzyme preparations isolated from different cancer cells (apparent Km, 500 microM for nLcOse5[3H-DT]Cer and 350 microM for GgOse4[sph-3-3H]Cer with Colo-205 enzyme). Structural analogues of ceramide and sphingosine (L-PPMP. L-PDMP, alkylamines, and Tamoxifen) inhibited cancer cell CGase activities in vitro.
Antineoplastic Agents↗
Isolation and stigma: the experience of patients with active tuberculosis.
Tuberculosis treatment is an important component of community health programs. Understanding how different groups of patients experience tuberculosis can influence the completion of drug therapy. This study explored how a sample of patients with active tuberculosis experienced their illness. Guided by questions from Kleinman's (1980) explanatory model, 28 semistructured interviews were conducted in public health clinics. The analysis suggested that patients understood tuberculosis through the medical model and perceived themselves as disease vectors. After their diagnosis became known, almost all patients felt that their family and friends avoided or shunned them. Patients responded to these attitudes by isolating themselves and becoming secretive about their illness. An awareness of patients' experiences can help nurses to understand behaviors that may be labeled as noncompliant and design interventions that address these behaviors. Modifying community attitudes and behaviors poses a longer term challenge to the elimination of tuberculosis.
Adolescent↗
Expression of the ErbB-neuregulin signaling network during human cerebellar development: implications for the biology of medulloblastoma.
The four receptor tyrosine kinase I receptors, ErbB-1, ErbB-2, ErbB-3, and ErbB-4, which have been implicated in the development of a variety of normal and malignant tissues, are activated through ligand mediated homo- and heterodimerization. We have previously reported the frequent coexpression, heterodimerzation, and prognostic significance of ErbB-2 and ErbB-4 in childhood medulloblastoma, an embryonal tumor of the cerebellar external granule cell layer (EGL). In the present study, we have used immunohistochemistry and Western blotting analysis to analyze the expression of the ErbB receptors and neuregulin (NRG) 1-alpha and NRG1-beta ligands during normal human cerebellar development. We demonstrate that ErbB-1, ErbB-3, ErbB-4, and NRG1-beta display specific temporal and topographical distribution in the cerebellum during intrauterine and postnatal life, and that normal ErbB-NRG signaling in the EGL multiplying zone is likely to be mediated by ErbB-4 and NRG1-beta. In contrast, ErbB-2, which is expressed in 86% of medulloblastomas, could not be detected at any stage of cerebellar development. Therefore, we propose that positive deregulation of ErbB-2 expression in the cerebellar EGL, leading to the formation of a NRG41-beta-driven ErbB-2/ErbB-4 autocrine loop, is an important factor in medulloblastoma tumorigenesis. In further support of this hypothesis, we provide evidence using reverse transcription-PCR analysis that expression of the ErbB-2 and ErbB-4 receptors, but not ErbB-1 or ErbB-3, is deregulated in medulloblastoma compared with normal developing cerebellum. We also demonstrate NRG1-beta expression in 87% (n = 46 of 48) of medulloblastoma primary tumors, with the greatest expression levels occurring in tumors with high ErbB-2 and ErbB-4 receptor coexpression. Furthermore, the expression of all three components of the proposed autocrine loop (ie., ErbB-2, ErbB-4, and NRG1-beta) was significantly related to the presence of metastases at diagnosis (P < 0.05).
Blotting, Western↗
High adult mortality in Lusaka.
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Adolescent↗
Does sucrase deficiency in black South Africans protect against colonic disease?
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Black People↗
A randomized controlled trial of extraperitoneal bupivacaine analgesia in laparoscopic hernia repair.
BACKGROUND: The limited space developed in totally extraperitoneal laparoscopic inguinal hernia repair (TEP) provides the ideal setting for direct instillation of local anesthetic. This study evaluates the efficacy of extraperitoneal bupivacaine analgesia in patients undergoing day-care TEP. METHODS: Fifty-six consecutive patients were randomized to intraoperative extraperitoneal instillation of bupivacaine (n = 29) or normal saline control (n = 27). Patients were blindly assessed on discharge from hospital, at 24 hours, 1 week, and 1 month postoperatively. RESULTS: Compared with controls, patients treated with bupivacaine had lower median (range) visual analogue pain scores on discharge (1.5 [0 to 5.9] versus 3.7 [0.2 to 6.9], P = 0.03), and were more frequently pain free (54% versus 31%, P = 0.078). Although this difference had gone by 24 hours, the bupivacaine group continued to recover faster; stopping analgesia earlier (2 [0 to 7] days versus 3 [0 to 21] days, P = 0.01) and returning to full activity earlier (2.5 [1 to 14] days versus 5 [1 to 21] days, P = 0.013). Of bupivacaine patients 100% were completely satisfied with the procedure compared with 81% of controls (P = 0.02). CONCLUSION: Extraperitoneal bupivacaine minimizes pain following day-care TEP repair, facilitates recovery, and increases patient satisfaction. Benefits persist beyond the pharmacological action of bupivacaine.
Adolescent↗
Induction of CYP2E1 activity in liver transplant patients as measured by chlorzoxazone 6-hydroxylation.
OBJECTIVE: To examine the phenotypic expression of CYP2E1 in liver transplant patients, as measured by the in vivo probe chlorzoxazone, and to evaluate CYP2E1 activity over time after transplantation. METHODS: Thirty-three stable liver transplant patients were given 250 mg chlorzoxazone within 1 year after transplantation as part of a multiprobe CYP cocktail; urine and blood were collected for 8 hours. Chlorzoxazone and 6-hydroxychlorzoxazone concentrations were determined by HPLC. Twenty-eight healthy control subjects, eight patients with moderate to severe liver disease, and four patients who had not received liver transplants were also studied for comparison. The chlorzoxazone metabolic ratio, calculated as the plasma concentration of 6-hydroxychlorzoxazone/chlorzoxazone at 4 hours after chlorzoxazone administration, was used as the phenotypic index. In a subgroup of patients and control subjects, additional blood samples were obtained to allow for the calculation of chlorzoxazone pharmacokinetic parameters by noncompartmental methods. RESULTS: The chlorzoxazone metabolic ratio for the liver transplant patients in the first month after transplantation (mean +/- SD, 6.4 +/- 5.1) was significantly higher than that after 1 month after surgery (2.1 +/- 2.0), when the chlorzoxazone metabolic ratio was not different from control subjects (0.8 +/- 0.5). The chlorzoxazone metabolic ratios in the patients who had not received liver transplants (1.1 +/- 0.7) were equivalent to those of healthy control subjects. The maximum observed 6-hydroxychlorzoxazone plasma concentration was 3046 +/- 1848 ng/ml in seven liver transplant patients in the first month after surgery compared with 1618 +/- 320 ng/ml in 16 healthy control subjects (p < 0.05). The maximum observed concentration of chlorzoxazone, the chlorzoxazone apparent oral clearance, and the formation clearance of 6-hydroxychlorzoxazone were also significantly different between the groups. CONCLUSIONS: We conclude that significant induction of CYP2E1, as indicated by the chlorzoxazone metabolic ratio, occurs in the first month after surgery in liver transplant patients and that drugs that are substrates for CYP2E1 may require dosage alteration during that period. Contrary to expectations, drug metabolism is not uniformly depressed after liver transplantation.
Adult↗
Combining the clinical signs improves diagnosis of scaphoid fractures. A prospective study with follow-up.
This is a prospective study evaluating the efficacy of four clinical signs believed to be useful in the diagnosis of scaphoid fracture. Two hundred and fifteen consecutive patients with suspected scaphoid fracture were examined on two separate occasions to evaluate tenderness in the anatomical snuff box (ASB), tenderness over the scaphoid tubercle (ST), pain on longitudinal compression of the thumb (LC) and the range of thumb movement (TM). At the initial examination ASB, ST and LC were all 100% sensitive for detecting scaphoid fracture with specificities of 9%, 30% and 48% respectively. These clinical signs used in combination, within the first 24 hours following injury, produced 100% sensitivity and an improvement in the specificity to 74%. TM had 69% sensitivity and 66% specificity. Our results suggest that these clinical signs are inadequate indicators of scaphoid fracture when used alone and should be combined to achieve a more accurate clinical diagnosis.
Adolescent↗
Comparative study of electric and manual toothbrushes in patients with fixed orthodontic appliances.
The objective of this three treatment, three period, single blind, cross-over trial was to evaluate the efficacy of three toothbrushes in a cohort of children undergoing fixed appliance orthodontic therapy. The brushes used were: (1) Dental Logic HP550 with regular brush head HP5924 (Philips, U.K.); (2) Braun Oral B Plaque Remover (D7) with dedicated orthodontic brush head OD5-1 (Braun AG, Germany); and (3) a manual dedicated orthodontic toothbrush (P35, Oral B Laboratories, Calif.). Sixty orthodontic patients, aged 10 to 16 years and wearing upper and lower fixed appliances, were screened and recruited with parental consent. After an oral soft tissue examination at baseline, the percentage of plaque-covered tooth surfaces and gingival bleeding sites were recorded using visible plaque and gingival bleeding indexes. Each subject was randomly allocated to one of three groups (n = 20) with brushing sequences 1-2-3, 2-1-3, 3-2-1. The first brush was given 2 weeks after baseline (visit 1). The time interval for using each brush was 4 weeks at the end of which visible plaque and gingival bleeding indexes were recorded and a further prophylaxis given. Statistical analysis was undertaken with analysis of variance. Data were analyzed on a site-specific basis; buccal smooth and interproximal surfaces, lingual smooth and interproximal surfaces. At baseline the mean visible plaque index for all subjects were; buccal smooth, 52.5% (+/- 22.5%); buccal interproximal, 70.5% (+/- 18.5%); lingual smooth, 68.5% (+/- 21%); lingual interproximal, 76% (+/- 16%). At visit 1, the plaque scores at all surfaces had reduced significantly compared to baseline, but there had been no active treatment. This was attributed to a Hawthorne effect. Subsequently, there were no significant effects on visible plaque (or gingival bleeding) indexes with any toothbrush at any tooth surfaces. This suggests that the new HP550 is equally effective as specifically designed orthodontic toothbrushes in removing plaque from patients with fixed orthodontic appliances.
Adolescent↗
Plasma leptin in chronic inflammatory bowel disease and HIV: implications for the pathogenesis of anorexia and weight loss.
1. Leptin inhibits food intake and is an important regulator of long-term energy balance. In rodents, plasma concentrations of leptin are increased by administration of interleukin-1 and tumour necrosis factor. Hyperleptinaemia may mediate the anorexia and weight loss which is observed in chronic infections and inflammatory conditions. 2. Plasma leptin and soluble tumour necrosis factor receptor (sTNF-r55) concentrations were measured in patients with inflammatory bowel disease and acquired immunodeficiency syndrome (AIDS), and healthy controls. 3. The patients with AIDS were severely wasted [% body fat 12 (9-16); median (interquartile range)] compared with those with inflammatory bowel disease [25.1 (19-31.5)] and control subjects [29.4 (23.6-37.8)]. Leptin concentrations were highly correlated with percentage body fat in controls (r = 0.74, P < 0.001) and patients with IBD (r = 0.73, P < 0.001) but not in the patients with AIDS (r = -0.024). Leptin concentrations were similar in the inflammatory bowel disease [4.8 (2.6-10.1) ng/ml] and control groups [8.0 (3.1-14.1) ng/ml] but were significantly lower (P < 0.05) in patients with AIDS [1.8 (1.5-2.3) ng/ml] after 23 patients were matched for sex and percentage body fat in patients with inflammatory bowel disease [2.4 (1.8-4.1) ng/ml]. Plasma concentrations of sTNF-r55 were higher in both the patients with inflammatory bowel disease [0.19 (0.16-0.23) ng/ml] and those with AIDS [4.8 (2.8-7.3) ng/ml] compared with controls [0.14 (0.09-0.16) ng/ml] but were not correlated with either percentage body fat or plasma leptin concentrations. 4. Hyperleptinaemia does not appear to mediate the anorexia and weight loss associated with inflammatory bowel disease and AIDS. In patients with AIDS with extreme wasting there was no relationship between body fat and leptin and this may be related to the rapid weight loss which occurs in these patients.
Acquired Immunodeficiency Syndrome↗
An update on British medical students' lifestyles.
Information about medical students' lifestyles was obtained from 785 second-year students from seven medical schools in Great Britain by a personally administered questionnaire. Fifteen per cent of the students were non-drinkers. Among those who drank, 48% of the men and 38% of the women exceeded sensible weekly limits of alcohol consumption, and high-risk levels of consumption were reported by 12% of men and 7% of women. Cannabis had been used at least once or twice by more than half the men and 40% of the women, and 10% reported regular use (weekly or more often). Experience with other illicit drugs was also reported: amphetamines (8% of students), LSD (7%), ecstasy (4%), amyl/butyl nitrate (10%) and magic mushrooms (7%). Nineteen per cent of the students had used two or more different drugs. Experience with illicit drugs started before entering university in more than a third of those who used them. Comparison of the results with other student surveys suggests that the lifestyles of medical students differ little from those of other student groups, but that alcohol and illicit drug consumption is increasing in university students generally. Prospective studies are under way to establish whether medical students change their lifestyles at later stages of their course and after qualification.
Anxiety↗
Local understandings of adult diarrhoeal disease and its treatment in an area of high HIV-seroprevalence in Zambia.
We set out to investigate the extent to which cultural constructs might determine treatment-seeking for diarrhoea in the poorer populations of Lusaka, Zambia. This paper describes these concepts and perceptions and outlines a classification of such illnesses, together with an analysis of its implications for understanding treatment choice. Data were derived from focus group discussions, a household survey, a survey of practitioners of traditional medicine and interviews with local residents attending an urban health centre with persistent diarrhoea. The classification is based on symptoms and perceptions of aetiology. While resulting categories convey imperatives for treatment choice, it is clear that individuals with diarrhoeal illnesses seek treatment from multiple sources. This may be because any single illness may fit more than once category, or because unrelenting ill-health engenders desperate behaviour. The cultural constructs do not fully explain treatment choice and attitudes to prevention, but could be used to improve communication regarding public health and treatment strategies.
Adult↗