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Biomedical subjects

P Kelly

Publications and source records attributed to P Kelly.

At least 55 records · Page 3Linked to original sources
PubMed2001

Vitamin A levels in HIV/AIDS.

OBJECTIVE: To study the correlation of vitamin A concentrations in patients with AIDS, HIV positive symptom free and HIV negative symptom free men and women. DESIGN: A cross-sectional study. SUBJECTS: Male and female volunteers aged between 15 and 60 years willing to undergo an HIV-test. SETTING: Participants came from different backgrounds within the city of Ndola. Some were urban while others were peri-urban dwellers. They were included in the study only if they were willing to undergo the HIV test regardless of their place of residence. MAIN OUTCOME MEASURES: After obtaining consent blood samples were taken from the participants using needle and syringe. Whole blood was used to measure haematological indices while serum was used to measure vitamin A concentrations and HIV status. RESULTS: One hundred and thirty five participants were recruited for the study. Vitamin A was analysed in eighty seven HIV negative symptom free, forty one HIV-positive symptom free and seven AIDS cases. There was a significant difference (p < 0.05) in the variance of vitamin A levels in the three groups. Vitamin A deficiency is defined as blood concentrations below 30 micrograms/dl. Using this cut-off point, the Odds Ratio for deficiency if HIV-positive was found to be 6.3 (2.5, 16.7 p < 0.0001). The Odds Ratio for HIV and serum vitamin A deficiency was approximately the same for males and females. There was a modest correlation between vitamin A concentrations and haemoglobin (r = 0.34, 95% CI 0.18, 0.48, p < 0.0001). CONCLUSION: Vitamin A concentration is lowered in HIV infection. The depletion of vitamin A seems to increase with progression of the infection leading to AIDS disease. Whether regular supplementation of vitamin A to the HIV infected individual can lead to a delayed progression to AIDS needs to be explored.

Acquired Immunodeficiency Syndrome↗
PubMed2001

The role of soft tissue reconstruction after melanoma resection in the head and neck

INTRODUCTION: Reconstruction after wide local excision of melanomas in the head and neck can be formidable. Many tumors lie close to vital structures, and excision must carefully balance preservation of form and function. For small defects, primary closure or skin grafting is satisfactory. However, it has become increasingly evident that more advanced reconstructive procedures can improve the outcome in terms of both function and aesthetics. This study was undertaken to determine the effectiveness of flap closure after wide local excision of melanomas in the head and neck and to develop a set of surgical recommendations on the basis of our experience. METHOD: We reviewed 35 patients who underwent 39 flap closures at The University of Texas, M. D. Anderson Cancer Center after wide local excision of head and neck melanomas. Local flaps were primarily used to close defects after the resection of superficial or intermediate-thickness melanomas. Pedicle and free flaps were used to cover larger defects resulting from the excision of extensive tumors. The flap closures were compared with an analogous database of 560 melanoma resections that underwent primary closure or skin grafting. RESULTS: The mean age of the patient population was 57 years. The most common location for tumor presentation was the cheek, followed by the ear, forehead, and lip. Pathologic findings most commonly demonstrated superficial spreading melanoma, and the average defect size was 30.7 cm(2). Local flaps were used most often for reconstruction. The only variable that significantly predicted local recurrence was the depth of the tumor. Local, pedicle, or free flaps did not decrease the ability of detecting local recurrence or increase this number compared with primary closure and skin grafting. Major postoperative complications were detected in seven patients. We found flap closure to achieve excellent functional and aesthetic results. CONCLUSION: Although primary closure is the ideal method of reconstruction for small defects, flap closure provides a versatile and safe alternative when simple closure would yield unsatisfactory results. With careful planning, flap closure offers an exceptional functional and aesthetic result and may even enhance contour defects after extensive neck or parotid dissections. Moreover, our experience with flap closure did not appear to delay the detection of local recurrence and may have even served to decrease the incidence of local failure after wide local excision of head and neck melanomas. Copyright 2000 John Wiley & Sons, Inc. Head Neck 23: 8-15, 2001.

Journal Article↗
PubMed2001

The role of soft tissue reconstruction after melanoma resection in the head and neck.

INTRODUCTION: Reconstruction after wide local excision of melanomas in the head and neck can be formidable. Many tumors lie close to vital structures, and excision must carefully balance preservation of form and function. For small defects, primary closure or skin grafting is satisfactory. However, it has become increasingly evident that more advanced reconstructive procedures can improve the outcome in terms of both function and aesthetics. This study was undertaken to determine the effectiveness of flap closure after wide local excision of melanomas in the head and neck and to develop a set of surgical recommendations on the basis of our experience. METHOD: We reviewed 35 patients who underwent 39 flap closures at The University of Texas, M. D. Anderson Cancer Center after wide local excision of head and neck melanomas. Local flaps were primarily used to close defects after the resection of superficial or intermediate-thickness melanomas. Pedicle and free flaps were used to cover larger defects resulting from the excision of extensive tumors. The flap closures were compared with an analogous database of 560 melanoma resections that underwent primary closure or skin grafting. RESULTS: The mean age of the patient population was 57 years. The most common location for tumor presentation was the cheek, followed by the ear, forehead, and lip. Pathologic findings most commonly demonstrated superficial spreading melanoma, and the average defect size was 30.7 cm2. Local flaps were used most often for reconstruction. The only variable that significantly predicted local recurrence was the depth of the tumor. Local, pedicle, or free flaps did not decrease the ability of detecting local recurrence or increase this number compared with primary closure and skin grafting. Major postoperative complications were detected in seven patients. We found flap closure to achieve excellent functional and aesthetic results. CONCLUSION: Although primary closure is the ideal method of reconstruction for small defects, flap closure provides a versatile and safe alternative when simple closure would yield unsatisfactory results. With careful planning, flap closure offers an exceptional functional and aesthetic result and may even enhance contour defects after extensive neck or parotid dissections. Moreover, our experience with flap closure did not appear to delay the detection of local recurrence and may have even served to decrease the incidence of local failure after wide local excision of head and neck melanomas.

Adolescent↗
PubMed2000

Genetic influences on F cells and other hematologic variables: a twin heritability study.

To assess the relative contribution of genetic factors in the variation of F cells (FC) and other hematologic variables, we conducted a classical twin study in unselected twins. The sample included 264 identical (monozygotic [MZ]) twin pairs and 511 nonidentical (dizygotic [DZ]) same-sex twin pairs (aged 20 to 80 years) from the St. Thomas' UK Adult Twin Register. The FC values were distributed continuously and positively skewed, with values ranging from 0.6% to 22%. FC values were higher in women than in men and decreased with age, with the variables accounting for 2% of the total FC variance. The intraclass correlations of FC values were higher in MZ (rMZ = 0.89) than in DZ (rDZ = 0.49) twins. The XmnI-(G)gamma polymorphism in the beta-globin gene cluster had a significant effect on FC levels, accounting for approximately 13% of the total FC variance. Variance components analysis showed that the FC values were accounted for predominantly by additive genetic and nonshared environmental influences, with an estimate of heritability of 0.89. Hemoglobin levels and red blood cell, white blood cell, and platelet numbers were also substantially heritable, with heritability estimates of 0.37, 0.42, 0.62, and 0.57, respectively. Previously, studies of sib pairs with sickle cell disease and isolated family studies showed that high levels of Hb F and FC tend to be inherited. Here, our classical twin study demonstrated that the variance of FC levels in healthy adults is largely genetically determined. (Blood. 2000;95:342-346)

Adult↗
PubMed2000

The dangerousness of youth-at-risk: the possibilities of surveillance and intervention in uncertain times.

This paper will explore the dangerous possibilities provoked by the popular and promiscuous construction of the category of "youth-at-risk". In an age of large-scale and profound social changes, narratives of uncertainty and risk dominate popular, political and theoretical discourses about youth. Under these social conditions, the discourse of youth-at-risk is mobilized from a variety of intellectual and political positions in various attempts to regulate the behaviors and dispositions of youth. The paper will argue that these discourses provoke dangerous possibilities for the increased surveillance of, and intervention into, young people's lives by regulatory authorities (schools, police, health services, and juvenile justice systems) and the forms of expertise recruited by these agencies.

Adolescent↗
PubMed2000

High-level expression of biologically active human prolactin from recombinant baculovirus in insect cells.

We examined the feasibility of high-level production of recombinant human prolactin, a multifunctional protein hormone, in insect cells using a baculovirus expression system. The human prolactin cDNA with and without the secretory signal sequence was cloned into pFastBac1 baculovirus vector under the control of polyhedrin promoter. Prolactin was produced upon infection of either Sf9 or High-Five cells with the recombinant baculovirus containing the human prolactin cDNA. The production of recombinant prolactin varied from 20 to 40 mg/L of monolayer culture, depending on the cell types. The prolactin polypeptide with its own secretory signal was secreted into the medium. N-terminal amino acid sequence analysis of the recombinant polypeptide purified from the culture medium indicated that the protein was processed similar to human pituitary prolactin. Carbohydrate analysis of the purified protein indicated that a fraction of the recombinant prolactin made in insect cells appeared to be glycosylated. Also, both secreted and nonsecreted forms of the recombinant prolactin in insect cells were biologically equivalent to the native human prolactin (pituitary derived) in the Nb2 lymphoma cell proliferation assay.

Animals↗
PubMed2000

Radiology quality and performance metrics on the Web: a management information and communications tool.

RATIONALE AND OBJECTIVES: The purpose of this study was to demonstrate the feasibility of using the World Wide Web to communicate critical radiology quality and performance metrics to departmental and hospital management staff. MATERIALS AND METHODS: Data on report turnaround, appointment access, patient and physician satisfaction, and financial performance were harvested from a variety of sources. These were then standardized and condensed so they could be displayed electronically in a concise, information-dense fashion. RESULTS: The final product was a series of graphic materials on a single Web site. The most informative was a summary "spiderweb chart" that indicated the percentage of specified performance goals achieved for 12 operational parameters. These graphic materials were distributed to management staff monthly by means of e-mail. CONCLUSION: The use of simple Web-based technology facilitates the collection of key departmental performance data and the dissemination of these data to a wide audience.

Humans↗
PubMed2000

Efficient gene transfer into human cord blood CD34+ cells and the CD34+CD38- subset using highly purified recombinant adeno-associated viral vector preparations that are free of helper virus and wild-type AAV.

Recombinant adeno-associated viral (rAAV) vectors have been evaluated for their ability to transduce primitive hematopoietic cells. Early studies documented rAAV-mediated gene expression during progenitor derived colony formation in vitro, but studies examining genome integration and long-term gene expression in hematopoietic cells have yielded conflicting results. Such studies were performed with crude vector preparations. Using improved methodology, we have generated high titer, biologically active preparations of rAAV free of wild-type AAV (less than 1/107particles) and adenovirus. Transduction of CD34+ cells from umbilical cord blood was evaluated with a bicistronic rAAV vector encoding the green fluorescent protein (GFP) and a trimetrexate resistant variant of dihydrofolate reductase (DHFR). Freshly isolated, quiescent CD34+ cells were resistant to transduction (less than 4%), but transduction increased to 23 +/- 2% after 2 days of cytokine stimulation and was further augmented by addition of tumor necrosis factor alpha (51 +/- 4%) at a multiplicity of infection of 106. rAAV-mediated gene expression was transient in that progenitor derived colony formation was inhibited by trimetrexate. Primitive CD34+ and CD34+, CD38- subsets were sequentially transduced with a rAAV vector encoding the murine ecotropic receptor followed by transduction with an ecotropic retroviral vector encoding GFP and DHFR. Under optimal conditions 41 +/- 7% of CD34+ progenitors and 21 +/- 6% of CD34+, CD38- progenitors became trimetrexate resistant. These results document that highly purified rAAV transduce primitive human hematopoietic cells efficiently but gene expression appears to be transient. Gene Therapy (2000) 7, 183-195.

ADP-ribosyl Cyclase↗
PubMed2000

Mannose-binding lectin is a component of innate mucosal defense against Cryptosporidium parvum in AIDS.

BACKGROUND & AIMS: Nonimmune mechanisms of mucosal defense seem to be biologically important and might explain the observed variability in the course of enteric infection in immunodeficiency. Mannose-binding lectin (MBL) deficiency is associated with persistent diarrhea in children. We found that genetic determinants of MBL deficiency appear to predispose to cryptosporidiosis in patients with the acquired immunodeficiency syndrome (AIDS), and went on to study interactions of MBL and complement on Cryptosporidium parvum sporozoites. METHODS: This study involved cross-sectional study of MBL genotype and enteric infection in 72 Zambian AIDS patients with diarrhea, immunofluorescence analysis of MBL and C4 binding to C. parvum, and immunoblotting for MBL and complement in small intestinal fluid. RESULTS: Individuals homozygous for MBL structural gene mutations were at increased risk of cryptosporidiosis (odds ratio, 8.2; 95% confidence interval, 1. 5-42; P = 0.02). Lectin-mediated and concentration-dependent binding of purified MBL was detected on sporozoites but not oocysts, and MBL activated C4 on sporozoites. MBL, C3, C4, and albumin were detected in small intestinal fluid in half the patients tested, suggesting transudation of serum components into the enteropathic gut. CONCLUSIONS: The increased risk of cryptosporidiosis in MBL deficiency appears to include patients with AIDS. It may operate through MBL-mediated complement activation on sporozoites.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Microvascular decompression for trigeminal neuralgia: report of outcome in patients over 65 years of age.

Microvascular decompression (MVD) is now recognized as an effective operation for the cure of trigeminal neuralgia (TN), and is far superior to the other surgical procedures utilized in the treatment of TN. TN is common in the elderly, but there is debate concerning MVD in 'elderly' patients. Some clinicians have a policy of not offering patients over a certain age the choice of MVD, yet the recurrence rate is inversely related to the age of the patient. Previous failed procedures and a long period of pain before MVD, also affect the outcome negatively. This study is a retrospective review of the outcome in elderly patients following MVD. Forty-two patients over the age of 65 years are reviewed after undergoing MVD for TN. The results indicate that there was no serious morbidity or mortality that could be ascribed to old age and the length of stay in the hospital was not influenced by the age of the patient. The results are compared with the outcome in a younger age group and the literature on MVD for TN reviewed.

Adult↗
PubMed2000

Assessing payback from NHS reactive research programmes.

Aims to assess retrospectively the payback from NHS reactive research programmes in the Northern and Yorkshire region. A questionnaire was sent to all recipients of regional reactive research programme funding (biomedical, health services research (HSR), and primary and community care programmes) between 1 April 1991 and 31 March 1996. The sample available for analysis involved 174 respondents covering 119 projects, with a total financial value of 2.2 million Pounds. The main outcome measures used were peer-reviewed publications, changes in individual practice, changes in NHS service delivery and organisation, and impact on the careers of researchers. Overall, 119 projects produced 230 peer-reviewed publications: this was achieved at an average cost of 10,673 Pounds, 6,386 Pounds and 22,310 Pounds per publication for the biomedical, HSR, and primary and community care programmes respectively. From the qualitative data analysis, important changes in individual practice and NHS service delivery were identified by respondents. The researchers in our sample appeared to have attracted over 6 million Pounds in R&D funding related to the initial regional grant. Although based on self-report, there is evidence to suggest that the return on investment from NHS R&D can be substantial, taking a broad view of benefits to the NHS and to researchers. The findings also confirm the need for more effective dissemination and implementation of research findings.

Efficiency, Organizational↗
PubMed2000

Permanent transfemoral pacemaker implantation is the technique of choice for patients in whom the superior vena cava is inaccessible.

We describe transfemoral pacemaker implantation in three patients in whom pacing via the superior vena cava was not possible or suboptimal. The first was an 88-year-old man with superior vena cava obstruction presenting with fractured epicardial pacing leads. Recent pneumonia increased the risks of a general anesthetic. The second patient was a 57-year-old man who was intolerant of a pectorally sited pacemaker because of the thinness of his anterior chest wall. The third patient was a 69-year-old woman who presented with an infected eroding pectorally sited pacemaker. Scarring secondary to a previous pacemaker infection rendered the contralateral pectoral site inaccessible. Since the subclavian route was inaccessible (case 1) or suboptimal (case 2 and 3), we implanted transvenous pacemakers via the femoral route, which was safe, and effective, during a 6-month follow-up period.

Aged↗
PubMed2000

Technical cost of radiologic examinations: analysis across imaging modalities.

PURPOSE: To determine the individual technical costs of general diagnostic radiographic, ultrasonographic (US), computed tomographic (CT), magnetic resonance (MR) imaging, and scintigraphic examinations and interventional radiology. MATERIALS AND METHODS: The Radiology Cost and Productivity Benchmarking Study method of the University HealthSystem Consortium, a cooperative group of academic medical centers, was modified and extended to the six imaging modalities in a tertiary care academic setting. Hospital billing and cost records were analyzed for fiscal year 1996. Costs were divided into labor and nonlabor categories and were allocated to individual imaging modalities on the basis of resources consumed. Physician cost and hospital overhead were not included. Unit costs were analyzed per technical relative value unit (RVU) and per examination. RESULTS: The costs per technical RVU for diagnostic radiography, US, CT, MR imaging, scintigraphy, and interventional radiology were $65. 06, $28.74, $20.95, $17.69, $42.19, and $89.03, respectively. The technical costs per examination for diagnostic radiography, US, CT, MR imaging, scintigraphy, and interventional radiology were $41.92, $50.28, $112.32, $266.96, $196.88, and $692.60, respectively. CONCLUSION: The method of unit cost analysis for individual imaging modalities was successfully tested in a tertiary care setting. The method should be adopted to allow cost comparison across many institutions, which will permit the promotion of best practices.

Costs and Cost Analysis↗
PubMed2000

Bizarre parosteal osteochondromatous proliferation (Nora's lesion) of the sesamoid: a case report.

We report the a case of Nora's lesion (Bizarre Parosteal Osteochondromatous Proliferation) of the sesamoid. A 32-year-old woman presented with a painless, enlarging mass of two years duration on the plantar aspect of the first metatarsophalangeal joint of the left foot. Radiographs, Computerized Tomographs and Magnetic Resonance images, initially suggested a parosteal osteosarcoma arising from the tibial sesamoid. The mass was excised, and a histological diagnosis of Bizarre Parosteal Osteochondromatous Proliferation of bone (Nora's lesion) was made. The aggressive growth of this lesion may suggest a neoplasm clinically. Histological features, however, are those of a reactive lesion.

Adult↗
PubMed2000

Improved indices of insulin resistance and insulin secretion for use in genetic and population studies of type 2 diabetes mellitus.

Homeostasis model assessment (HOMA) provides indices of insulin secretion (beta) and insulin resistance (R) derived from fasting plasma glucose (FPG) and fasting plasma insulin (FPI) levels. However, these indices could not account for a significant heritability of fasting plasma glucose (FPG) (h2 = 0.75, P<0.01) in a group of 214 female twins. This result is consistent with a misclassification between effects due to insulin secretion and resistance in the HOMA indices. We report here evidence of such misclassification in the HOMA indices and describe a minor modification to the model which corrects it. Direct measures of insulin resistance (euglycaemic clamp) and secretion (i.v. glucose bolus) were obtained in 43 non-diabetic subjects. Heritability was estimated by statistical modelling of genetic and environmental influences in data from 214 non-diabetic female subjects. Modified HOMA (HOMA') indices were obtained from beta' = (Ln(FPI) - c)/FPG and R' = (Ln(FPI) - c)*FPG where c is a constant derived from regression analysis of Ln(FPI) vs FPG. Indices from both models correlated with the direct measures similarly (r = 0.63 (R), 0.49 (R'), 0.45 (beta), 0.39 (beta'), all P< 0.01). Directly measured insulin resistance and secretion were not significantly correlated (r = 0.13, P = 0.21). However, unmodified HOMA-beta and R were strongly related (r = 0.78, P<0.0001 vs. 0.13) demonstrating substantial misclassification. The relationship between beta' and R' (r = 0.13) was not different from that between the two direct measures and significant heritability of beta' (h2 = 0.68, P<0.01) and R' (h2 = 0.59, P<0.05) was evident in the twin data. The proposed modification to HOMA significantly reduces misclassification and reveals separate components of insulin resistance and insulin secretion in the heritability of FPG.

Adult↗
PubMed2000

Transgenic approaches to model Alzheimer's disease.

Two transgenic mouse lines were generated which express human APP751 containing familial Alzheimer's disease (AD) mutations in brain neurons. These mice develop pathological features reminiscent of AD. The degree of pathology depends on both expression levels and specific mutations. In mice with more advanced pathology (APP 23), typical plaques appear at six months which increase with age and are Congo Red positive at first detection. These congophilic plaques are accompanied by neuritic changes and dystrophic cholinergic fibers. Furthermore, inflammatory processes indicated by a massive glial reaction are apparent. Most notably, plaques are immunoreactive for hyperphosphorylated tau, reminiscent of early tau pathology. A quantitative analysis of degenerative changes by state-of-the-art unbiased stereological methods revealed a significant reduction in neuronal cell bodies of the CA1 field of the hippocampus when compared to controls. This reduction is directly related to plaque load. When subjected to analysis in the Morris water maze, 18 month old APP 23 mice show a significant increase in platform finding latency throughout the entire trial when compared to non-transgenic littermates.

Alzheimer Disease↗
PubMed2000

The quantitative measurement of autoantibodies to thyroglobulin and thyroid peroxidase by automated microparticle based immunoassays in Hashimoto's disease, Graves' disease and a follow-up study on postpartum thyroid disease.

The aim of this study was to investigate the association between various autoimmune thyroid diseases and the presence of anti-TPO and anti-Tg antibodies using two novel automated microparticle based immunoassays developed for the AxSYM analyzer. Serum samples from 65 individuals with Hashimoto's Disease, 38 with Graves' Disease and 80 UK blood donors were assayed. In addition, samples were taken from 50 women known to be positive for TPO antibodies, for up to 24 weeks following delivery. Precision for both assays ranges from 5.7-9.1% CV, while analytical sensitivity was determined to be 1.0 IU/ml for Anti-Tg and 0.3 IU/ml for Anti-TPO. The Anti-TPO test showed positive results in 86% of Hashimoto's Disease and 87% of Graves' Disease. The figures obtained for Anti-Tg were 58% and 73% respectively. Specificity was 94% with Anti-TPO and 99% with Anti-Tg. The postpartum women were divided into 2 groups, group A remained symptomless while group B developed thyroid dysfunction. Within the 2 groups, medians calculated at each time point were compared between and within groups using the Mann-Whitney Rank Sum Test or the Kruskal-Wallis One Way ANOVA on Ranks. Anti-TPO baseline levels (week 6) were statistically different between both groups (median 36 vs. 167 IU/ml, p = 0.002). In group A, the median values increased from 36 to 87 IU/ml within the observation period, although the difference was not statistically significant. In group B, antibody titres showed a statistically significant increase from 168 IU/ml (week 6) up to 676 IU/ml after 20 weeks (p < 0.001). Anti-Tg baseline levels were not statistically different between the two groups. In group A, the median values did not change significantly over time (range: 47-86 IU/ml) whereas antibody titres in group B showed a statistically significant increase from 79 IU/ml (week 6) to 276 IU/ml after 24 weeks (p = 0.002). Results obtained indicate that these assays provide useful tools for the quantitative determination of autoantibodies in both primary diagnosis as shown with the Hashimoto's disease and Graves' disease samples and patient follow-up as demonstrated with the postpartum samples. The automation and high precision of the assays make them perfectly suited to routine diagnostic use.

Autoanalysis↗