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Biomedical subjects

L Kennedy

Publications and source records attributed to L Kennedy.

At least 19 recordsLinked to original sources
PubMed2006

Circulating adiponectin levels, body composition and obesity-related variables in Prader-Willi syndrome: comparison with obese subjects.

BACKGROUND: People with obesity and/or the metabolic syndrome have an increased risk for developing diabetes and cardiovascular disease and may have low adiponectin levels. The obesity associated with Prader-Willi syndrome (PWS) would be expected to have similar complications. However, it was recently reported that, despite their adiposity, people with PWS have reduced visceral fat and are less likely to develop diabetes mellitus or the metabolic syndrome compared with people with simple obesity. OBJECTIVE: To determine if plasma adiponectin levels and other variables relevant to diabetes and cardiovascular risk are different in a cohort of PWS subjects with known genetic subtypes compared with age-, sex- and weight-matched control subjects. RESULTS: Fasting plasma glucose, C-peptide, triglycerides, leptin and cholesterol levels were similar in PWS and obese subjects. Our 20 PWS subjects (mean age = 27.7 years) had higher percent body fat (54.1 vs 48.5%) determined by DEXA measurements and lower percent lean mass (45.9 vs 51.5%) compared with 14 obese controls (mean age = 26.9 year). Plasma adiponectin levels were significantly higher in PWS (15.5 +/- 8.2 microg/ml) than in obese controls (7.5 +/- 2.7 microg/ml). A significant positive correlation was found with insulin sensitivity in PWS subjects (r = 0.75, P = 0.0003) but not in obese controls (r = 0.36, P = 0.20). DISCUSSION: Our study confirmed an earlier observation of higher adiponectin levels in PWS subjects and less insulin resistance proportionate to their obesity status than found in subjects with simple obesity. Furthermore, no differences were seen in PWS subjects with the chromosome 15 deletion or maternal disomy 15. The reported excessive visceral adiposity in subjects with simple obesity compared with PWS may be associated with decreased production and lower circulating levels of adiponectin.

Adiponectin↗
PubMed2005

Effectiveness of antipsychotic treatment for schizophrenia: 6-month results of the Pan-European Schizophrenia Outpatient Health Outcomes (SOHO) study.

OBJECTIVE: To present the 6-month outcomes associated with antipsychotic treatment of patients participating in the Schizophrenia Outpatient Health Outcomes (SOHO) study. METHOD: SOHO is a 3-year, prospective, observational study of the health outcomes associated with antipsychotic treatment in 10 European countries. The study included over 10,000 out-patients who were initiating or changing their antipsychotic medication. RESULTS: Clinical Global Impression (CGI)-severity and quality of life (QOL) scores improved in all treatment cohorts. There was a higher response in the CGI-overall symptoms and in the CGI-schizophrenia positive, negative, cognitive and depressive symptom scales in the olanzapine (Olz) and clozapine (Cloz) cohorts compared with other treatment cohorts. Changes were associated with an improvement in QOL. CONCLUSION: Patients starting Olz and Cloz tend to have better outcomes at 6 months than patients who start other antipsychotics in actual out-patient clinical practice. The results should be interpreted conservatively because of the non-randomized study design.

Adult↗
PubMed2005

Olanzapine vs. other antipsychotics in actual out-patient settings: six months tolerability results from the European Schizophrenia Out-patient Health Outcomes study.

OBJECTIVE: The European Schizophrenia Out-patient Health Outcomes study is an observational study investigating treatment in schizophrenia. We report treatment-emergent adverse events during the first 6 months of treatment. METHOD: The rate of extrapyramidal symptoms (EPS), anticholinergic use, weight gain and sexual related dysfunctions were assessed in 8,400 out-patients. RESULTS: Patients typical antipsychotics and risperidone experienced significantly more EPS and anticholinergic use than patients in the clozapine, olanzapine, and quetiapine cohorts. Patients treated with amisulpride, typical antipsychotics and risperidone were significantly more likely to have sexual related dysfunctions and/or amenorrhea. Increases in weight and body mass index occurred in all cohorts, but were significantly greater in the olanzapine and clozapine cohorts. CONCLUSION: Patients treated with olanzapine, quetiapine and clozapine had better tolerability outcomes regarding EPS and sexual related dysfunctions compared with patients receiving risperidone, amisulpride and typicals. Patients treated with olanzapine and clozapine had higher weight increases than patients treated with risperidone, quetiapine and typicals.

Adult↗
PubMed2004

Left atrioventricular plane displacement but not left ventricular ejection fraction is influenced by the degree of aortic stenosis.

AIMS: To examine how left atrioventricular plane displacement (AVPD), a widely used measure of left ventricular (LV) function, is related to presence and degree of aortic stenosis. METHODS AND RESULTS: Cardiac dimensions, LV filling, left AVPD, LV ejection fraction (LVEF), and valve function were assessed by echocardiography/Doppler in 182 patients with various cardiac diseases (mean (SD) age 69 (12) years, 36% women), 49 consecutive with and 133 consecutive without aortic stenosis. In an analysis of covariance, neither left AVPD nor LVEF was independently correlated with the presence of aortic stenosis. However, looking separately at patients with aortic stenosis, left AVPD (p = 0.03) but not LVEF correlated independently with degree of aortic stenosis in multiple linear regression analysis. In patients with aortic stenosis, an abnormal left AVPD had 94% sensitivity and 90% negative predictive value with regard to severe aortic stenosis, compared with 56% and 62%, respectively, for LVEF. CONCLUSION: In patients with cardiac disease, neither left AVPD nor LVEF correlated independently with presence of aortic stenosis. However, in patients with aortic stenosis, left AVPD but not LVEF correlated with the degree of aortic valve obstruction and left AVPD but not LVEF had high sensitivity and negative predictive value with regard to severe aortic stenosis. Compared with LVEF, left AVPD is an earlier and more sensitive marker of LV haemodynamic load in patients with aortic stenosis.

Aged↗
PubMed2004

Co-occurrence of thyroid binding globulin excess and a pituitary macroadenoma containing thyroid stimulating hormone-producing cells.

A patient is described in whom thyroid binding globulin (TBG) excess was found in association with a pituitary macroadenoma containing thyroid stimulating hormone (TSH)-producing cells, and the potential for diagnostic confusion arising from this unusual combination of endocrine disorders is discussed. The patient presented with visual field disturbance, and magnetic resonance imaging led to the diagnosis of a pituitary tumour. Raised levels of total thyroxine and triiodothyronine along with normal TSH levels suggested the possibility of a TSH-secreting pituitary adenoma. Immunostaining of the tumour removed at transsphenoidal surgery confirmed the presence of TSH-producing cells. When raised total thyroxine and triiodothyronine levels persisted postoperatively, the diagnosis of TBG excess was confirmed. Use of free, rather than total, thyroid hormone assays would almost certainly have prevented the diagnostic confusion concerning possible TSH-secreting pituitary adenoma, but may have resulted in the TBG excess being overlooked entirely.

Adenoma↗
PubMed2001

A randomized, controlled trial of remacemide for motor fluctuations in Parkinson's disease.

BACKGROUND: Preclinical studies suggest that glutamate antagonists help ameliorate motor fluctuations in patients with PD treated with levodopa. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study, the authors assessed the safety, tolerability, and efficacy of the glutamate receptor blocker remacemide hydrochloride in 279 patients with motor fluctuations treated with levodopa. The primary objective was to assess the short-term tolerability and safety of four dosage levels of remacemide during 7 weeks of treatment. Patients were also monitored with home diaries and the Unified PD Rating Scale (UPDRS) to collect preliminary data on treatment efficacy. RESULTS: Remacemide was well tolerated up to a dosage of 300 mg/d on a twice daily schedule and 600 mg/d on a four times daily schedule. The most common dosage-related adverse events were dizziness and nausea, as observed in previous studies of remacemide. The percent "on" time and motor UPDRS scores showed trends toward improvement in the patients treated with 150 and 300 mg/d remacemide compared with placebo-treated patients, although these improvements were not significant. CONCLUSION: Remacemide is a safe and tolerable adjunct to dopaminergic therapy for patients with PD and motor fluctuations. Although this study had limited power to detect therapeutic effects, the observed improvement is consistent with studies of non-human primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian signs and symptoms. Additional studies are warranted to confirm these results over an extended period of observation, and to explore the potential neuroprotective effects of remacemide in slowing the progression of PD.

Acetamides↗
PubMed2000

Dramatic mutation instability in HD mouse striatum: does polyglutamine load contribute to cell-specific vulnerability in Huntington's disease?

An unstable CAG triplet repeat expansion encoding a polyglutamine stretch within the ubiquitously expressed protein huntingtin is responsible for causing Huntington's disease (HD). By quantifying the repeat sizes of individual mutant alleles in tissues derived from an accurate genetic mouse model of HD we show that the mutation becomes very unstable in striatal tissue. The expansion-biased changes increase with age, such that some striatal cells from old HD mice contain mutations that have tripled in size. If this pattern of repeat instability is recapitulated in human striatal tissue, the concomitant increased polyglutamine load may contribute to the patterns of selective neuronal cell death in HD. Our findings also suggest that trinucleotide repeat instability can occur by mechanisms that are not replication-based.

Alleles↗
PubMed2000

Application of neural networks and sensitivity analysis to improved prediction of trauma survival.

The performance of trauma departments is widely audited by applying predictive models that assess probability of survival, and examining the rate of unexpected survivals and deaths. Although the TRISS methodology, a logistic regression modelling technique, is still the de facto standard, it is known that neural network models perform better. A key issue when applying neural network models is the selection of input variables. This paper proposes a novel form of sensitivity analysis, which is simpler to apply than existing techniques, and can be used for both numeric and nominal input variables. The technique is applied to the audit survival problem, and used to analyse the TRISS variables. The conclusions discuss the implications for the design of further improved scoring schemes and predictive models.

Analysis of Variance↗
PubMed2000

Immune reconstitution following high-dose chemotherapy with stem cell rescue in patients with advanced breast cancer.

The present study examines the nature of humoral and cellular immune reconstitution in 28 patients with advanced breast cancer following high-dose chemotherapy with stem cell rescue. Patients underwent testing of T, B, NK and dendritic cell function at serial time points until 1 year post transplant or until the time of disease progression. Abnormalities in T cell phenotype and function were observed following high-dose chemotherapy that persisted for at least 6-12 months. The vast majority of patients experienced an inversion of the CD4/CD8 ratio and demonstrated an anergic response to candida antigen. Mean T cell proliferation in response to PHA and to co-culture with allogeneic monocytes was significantly compromised. In contrast, mean IgG and IgA levels were normal 6 months post transplant and NK cell yields and function were transiently elevated following high-dose chemotherapy. Dendritic cells generated from peripheral blood progenitors displayed a characteristic phenotype and were potent inducers of allogeneic T cell proliferation in the post-transplant period. The study demonstrates that patients undergoing autologous transplantation for breast cancer experience a prolonged period of T cell dysfunction. In contrast, B, NK, and DC recover more rapidly. These findings carry significant implications for the design of post-transplant immunotherapy.

Adult↗
PubMed1999

Costimulation of transduced T lymphocytes via T cell receptor-CD3 complex and CD28 leads to increased transcription of integrated retrovirus.

Primary human T lymphocytes were transduced at high efficiency with the Moloney murine leukemia virus (Mo-MuLV) vector, LNC-mB7-1, in which an internal cytomegalovirus (CMV) promoter drives expression of the murine B7-1 cDNA. Compared with transduced T cells expanded in IL-2 or reactivated with soluble antibodies to CD3 or CD28, transgene expression was significantly increased after activation on immobilized anti-CD3 antibodies (CD3i) or by simultaneous activation on immobilized anti-CD3 and anti-CD28 antibodies (CD3i/CD28i). A similar pattern of transgene expression was observed in T cells transduced with Mo-MuLV LNC-EGFP. Proviral copy number was maintained in LNC-mB7-1-transduced T cells expanded in IL-2 or reactivated on CD3i/CD28i. Substantial increases in LNC-mB7-1 steady state mRNA in reactivated T lymphocytes, compared with those maintained in IL-2, correlated with increased transcription of the LNC-mB7-1 proviral DNA. Furthermore, T cells transduced with the Mo-MuLV ZIPPGK-mADA, in which the mADA cDNA is driven by an internal human phosphoglycerate kinase (PGK) promoter, showed increases in steady state ZIPPGK-mADA RNA on reactivation. High levels of transgene expression were evident irrespective of cell cycle position in both CD4+ and CD8+ lymphocytes. After reactivation, increases in LNC-mB7-1 mRNA were observed in the presence of the protein synthesis inhibitor cycloheximide, indicating that proteins involved in upregulating transgene expression preexisted in transduced lymphocytes. Induction of transgene expression on CD3i/CD28i showed a dose-dependent decrease in transgene expression when incubated with selective protein kinase inhibitors. These data provide new insights into the mechanisms governing transgene expression driven by Mo-MuLV constructs containing internal promoters in transduced primary T lymphocytes.

Antibodies↗
PubMed1999

Capture ElISA and in vitro cell binding assay for the detection of antibodies to human papillomavirus type 6b virus-like particles in patients with anogenital warts.

To investigate human papillomavirus (HPV) virus-like particle (VLP)-specific antibody responses among anogenital warts patients, a VLP-based capture ELISA was established. Twenty-six percent (35/134) of control subjects and 50.0% (39/78) of patients with current anogenital warts showed IgG seropositivity to HPV 6b VLPs. HPV 6b VLP-specific antibody responses recognised native VLPs only, and had no cross-reaction with HPV type 16 VLPs. No differences in reactivity were observed between L1 and L1 + L2 VLPs, suggesting that L2 contributes little to the total immunogenicity of the papillomavirus virion. A VLP-cell binding assay was also established. Some sera from patients with anogenital warts specifically inhibited VLP binding to the surface of epithelial cells, suggesting that these antibodies might be functionally neutralising. These data show that serological responses to HPV 6b VLPs were induced among some but not all patients with anogenital warts, and give a proportional estimate of infection in the community.

Adolescent↗
PubMed1999

Is whole-lung CT scanning still necessary in all cases of ACTH-dependent Cushing's syndrome in the era of petrosal sinus sampling?

We reviewed 31 patients in whom both bilateral inferior petrosal sinus sampling without CRH stimulation, and a CT scan of the lungs were done. Twenty-five had normal lung CT scans, of whom 23 had a higher inferior petrosal sinus: peripheral ACTH ratio > or = 1.5. After careful follow-up, none was subsequently shown to have ectopic ACTH syndrome. Six had abnormal lung CT scans, of whom two had ratios > or = 1.5. In these two patients, other investigations suggested pituitary disease, and pituitary surgery led to apparent cure. Of the remaining four patients, who had ratios < 1.5, two had incidental lung findings, and pituitary abnormalities were demonstrated at pituitary surgery. The third underwent bilateral adrenalectomy, and no evidence of ectopic ACTH syndrome has emerged as yet after 4 years follow-up. The fourth had a small-cell carcinoma of the lung, confirmed histologically. Our series suggests that whole-lung CT scanning is only necessary in cases of ACTH-dependent Cushing's syndrome where bilateral inferior petrosal sinus sampling has not demonstrated a significant increase in petrosal sinus ACTH levels as compared with the peripheral level. Thus, in our experience the test is now only necessary in those patients (approximately 25%) where the ratio is < or = 1.5.

ACTH Syndrome, Ectopic↗
PubMed1999

Selective in vivo mobilization with granulocyte macrophage colony-stimulating factor (GM-CSF)/granulocyte-CSF as compared to G-CSF alone of dendritic cell progenitors from peripheral blood progenitor cells in patients with advanced breast cancer undergoing autologous transplantation.

Dendritic cells (DCs) are potent antigen-presenting cells that are essential for the initiation of T cell-mediated immunity. DCs develop from myeloid progenitor populations under the influence of granulocyte macrophage colony-stimulating factor (GM-CSF) and pass through an intermediate stage of maturation that is characterized by CD14 expression. Interest has focused on generating human-derived DCs for antigen-specific tumor vaccines to be used as adjuvant immunotherapy in minimal disease settings, such as after autologous transplantation. In the present study, mobilized peripheral blood progenitor cells (PBPCs) were obtained from 18 patients with locally advanced or metastatic breast cancer preparing to undergo autologous stem cell transplantation. PBPCs mobilized in 10 patients with GM-CSF for 1 week, followed by the combination of GM-CSF and G-CSF, were compared with those obtained from patients receiving G-CSF alone with respect to the presence of DC progenitors and the capacity to generate functionally active mature DCs. PBPCs mobilized with GM-CSF/G-CSF were markedly enriched for CD14+ DC progenitor cells as compared with those mobilized with G-CSF alone. Consistent with an immature progenitor population, the CD14+ cells express Ki-67 antigen but not nonspecific esterase. CD14+ cells purified by fluorescence-activated cell sorting from PBPCs mobilized with either regimen and cultured for 1 week in GM-CSF and interleukin-4 generated nearly pure populations of cells with characteristic DC phenotype and function. The addition of GM-CSF to the mobilization regimen resulted in greater yields of functionally active DCs for potential use in posttransplant immunotherapy.

Breast Neoplasms↗
PubMed1998

[Volunteerism and the reorientation of health services].

UNLABELLED: Volunteers are increasingly viewed as health agents. This seems to be linked to the reorientation towards primary health care and the current reforms in the health services. Seen as a way of breaking down social and cultural barriers between the formal health care system and the client community it also claims to cut the cost of services. OBJECTIVE: To know the roles of volunteers in promoting health and the practical aspects of implementation and evaluation. DESIGN: This paper is based on a review of published and sentinel papers from the bibliographic databases, MEDLINE (1991-1995), ERIC (1982-1995) and ERIC INTERNATIONAL (1965-1995). We have also reviewed the IME (until 1997) and the Spanish journals in MEDLINE to know the Spanish context (from 1995-98). RESULTS: The practical experiences from developing countries, the USA and the UK were reviewed within the framework of health promotion. A wide variety of experiences exist. There is a striking difference between activities in these countries, depending of the health service provision. In developing countries the aim is to bring primary health care services to areas with few professional resources. In developed countries, however, experiences have developed in response to failings in the formal health care system, to facilitate illness prevention and health promotion. The settings are different but the process is the same, factors fundamental to performance have therefore been identified in: recruitment, training, monitoring, continuing support and evaluation. The impact on health improvements and the quality of services in both systems, developed and developing countries, seems to be positive. We haven't found too much details from the Spanish experience, then, it emphasizes the need to know abroad experiences. CONCLUSIONS: Finally, the benefits and constraints derived from this type of voluntary action in the health field have been raised. Some specific social changes and health care system reforms contribute to establish volunteering in the health system, but we have to remark organization, coordination and community participation.

Community Health Services↗
PubMed1997

Macrovascular disease and hyperglycaemia: 10-year survival analysis in Type 2 diabetes mellitus: the Belfast Diet Study.

The relationship between macrovascular disease and blood glucose control in long-term follow-up of Type 2 (non-insulin-dependent) diabetes mellitus is difficult to study because of the gradual rise in fasting plasma glucose due to ongoing beta-cell failure. We used time-dependent covariates in Cox's proportional hazards model to allow variables measured annually during a 10-year prospective follow-up to be related to risk of myocardial infarction or cerebrovascular accident. Data for 432 newly diagnosed diabetic patients were available, 112 of whom suffered myocardial infarction (fatal or non-fatal). Analysis of baseline measurements only gave relative hazards (95% CL) of 1.04 (0.99, 1.09) per mmol l(-1) increase in fasting plasma glucose, 1.43 (1.12, 1.83) per decade increase in age and 1.07 (0.98, 1.17) per 10 % increase in percentage of ideal weight. Analysis incorporating ongoing measurements gave corresponding figures of 1.07 (1.02, 1.12) for fasting plasma glucose, 1.64 (1.23, 2.20) for age and 1.06 (0.95, 1.18) for percentage of ideal weight. The risk of myocardial infarction while on insulin treatment 1.09 (0.58, 2.06) or oral agents 1.41 (0.86, 2.31) was not significantly elevated relative to dietary treatment. Baseline smoking status, systolic blood pressure, and previous myocardial infarction were also significant predictors of myocardial infarction. Similar relationships were found for cerebrovascular accident and total mortality. Increasing fasting plasma glucose is a significant independent predictor of macrovascular disease in diabetes.

Adult↗
PubMed1997

Assessment and management of chemotherapy-induced mucositis in children.

Oral mucositis is one of the most common side effects of cancer treatment. The oral mucosa is comprised of membranes of a high mitotic index with rapid epithelial turnover and maturation rates. This causes the mucosa to be vulnerable to the adverse effects of chemotherapy. Chemotherapy alters the integrity of the mucosa, the microbial flora which normally inhabit the oral cavity, salivary quantity and composition, as well as the epithelial maturation. As a result, the child receiving chemotherapy may experience significant pain, dysphagia, alteration in nutritional status, and risk of infection. Severe mucositis can also delay therapy that may compromise the child's treatment and chance for cure. Not all chemotherapy-induced mucositis can be prevented. However, with proper management, the severity and duration of oral complications can be minimized.

Antineoplastic Agents↗