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Biomedical subjects

G Kenny

Publications and source records attributed to G Kenny.

At least 19 recordsLinked to original sources
PubMed2005

Influence of Pro12Ala peroxisome proliferator-activated receptor gamma2 polymorphism on glucose response to exercise training in type 2 diabetes.

AIMS/HYPOTHESIS: Exercise training improves glycaemic control in some but not all individuals and little research has been done regarding genetic impact on the exercise training response in type 2 diabetes. The purpose of this study was to investigate the influence of the Pro(12)Ala variant of the peroxisome proliferator-activated receptor (PPAR) gamma2 gene on changes in fasting plasma glucose in response to exercise training. METHODS: The study population comprised 139 sedentary type 2 diabetic patients (age: 54.4+/-7.2; HbA(1)c: 7.7+/-0.9%) who completed 3 months of supervised exercise training. The primary outcome variable in our analysis was the post-intervention change in blood glucose. Other assessments included measures of body composition, insulin sensitivity indices and maximal oxygen uptake (VO(2max)). RESULTS: The frequency of the Ala allele was 8.3% and the genotypes were in Hardy-Weinberg equilibrium. At baseline, neither body composition variables (weight, BMI, waist circumference), glucose homeostasis variables (glucose, insulin, HbA(1)c, homeostasis model assessment method) nor VO(2max) were different between genotypes (wild-type: Pro(12)Pro n=117, Ala carriers: X(12)Ala n=22). The exercise-training intervention led to similar improvements in body composition and glucose homeostasis variables in both genotype groups (p<0.05). The change in fasting plasma glucose was significantly different between PPARgamma2 genotypes (-1.66 mmol/l vs -0.54 mmol/l, Ala carriers and wild-type, respectively) (p=0.034 unadjusted and p=0.089 including baseline glucose) and the significant association between genotype and glucose response remained after adjusting for statistically significant predictors (age, changes in insulin and BMI [p=0.015]) and including baseline glucose, insulin and BMI (p=0.031). CONCLUSIONS/INTERPRETATION: These data suggest that the Pro(12)Ala polymorphism may influence the glycaemic response to exercise in type 2 diabetes.

Adult↗
PubMed2005

Understanding obstacles to the recognition of and response to dementia in different European countries: a modified focus group approach using multinational, multi-disciplinary expert groups.

Experts from eight European countries (Belgium, France, The Netherlands, Ireland, Italy, Portugal, Spain and the United Kingdom) and the disciplines of clinical psychology, general practice, geriatric medicine, old age psychiatry, medical sociology, nursing and voluntary body organisation met in 2003 to explore obstacles to recognition of and response to dementia in general practice within Europe. A modified focus group methodology was used in this exploratory process. Groups were conducted over a two-day period, with five sessions lasting 1-1.5 hours each. An adapted nominal group method was used to record themes arising from the group discussion, and these themes were used in a grounded theory approach to generate explanations for delayed recognition of and response to dementia. The overarching theme that arose from the focus groups was movement, which had three different expressions. These were: population movement and its consequences for localities, services and professional experience; the journey of the person with dementia along the disease process; and the referral pathway to access services and support. Change is the core issue in dementia care, with multiple pathways of change that need to be understood at clinical and organisational levels. Practitioners and people with dementia are engaged in managing emotional, social and physical risks, making explicit risk management a potentially important component of dementia care. The boundary between generalist and specialist services is a particular problem, with great potential for dysfunctionality. Stigma and ageism are variably distributed phenomena both within and between countries.

Aged↗
PubMed1998

Dendritic cell-based immunotherapy of prostate cancer.

The immunotherapy of cancer, based on eliciting or enhancing the body's own capacity to mount an effective antitumor response, has produced encouraging early results in the areas of melanoma and renal-cell carcinoma. Such treatments utilizing dendritic cells (DC), immune cells that are excellent antigen presenters, are especially promising. We performed a phase I clinical trial assessing the administration of autologous DC pulsed with HLA-A0201-specific prostate-specific membrane antigen (PSMA) for the treatment of 51 men with hormone-refractory prostate cancer. Participants were divided into five groups receiving four or five infusions of peptides alone (PSM-P1 or PSM-P2; group 1 and 2, respectively), autologous DC (group 3), or DC pulsed with PSM-P1 or P2 (group 4 and 5, respectively). No significant toxicity was observed. Immune reactivity against PSM-P2 was detected in HLA-A2+ patients infused with DC pulsed with PSM-P1 or -P2 (group 4 and 5). An average decrease in PSA was observed only in group 5. Seven partial responders were identified based on NPCP criteria + PSA. The excellent tolerance of this treatment approach, as well as the enhanced cellular responses, decreased PSA levels, and partial clinical responses in some patients suggests that it holds great potential in prostate cancer therapy.

Dendritic Cells↗
PubMed1996

Presentation of prostate tumor antigens by dendritic cells stimulates T-cell proliferation and cytotoxicity.

Dendritic cells (DCs) are "professional" antigen-presenting cells capable of stimulating T-cell proliferation and cytotoxicity when loaded with and presenting specific antigens, including tumor antigens. We demonstrated the stimulation of an autologous cytotoxic T-cell response elicited by DC loaded with autologous tumor cell lysate derived from primary prostate tumor. A candidate tumor antigen is prostate-specific membrane antigen (PSMA), which is overexpressed in prostate cancer patients. We identified a HLA-A2 motif in PSMA, isolated patient DC, loaded peptide into DC, and stimulated autologous T cells to proliferate. The ability to use DC for presentation of either tumor or peptide antigen in an HLA-restricted fashion in order to stimulate T-cell proliferation and cytotoxicity demonstrates the potential of this technology for development of a prostate cancer vaccine.

Amino Acid Sequence↗
PubMed1996

Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen.

BACKGROUND: Conventional treatment for metastatic prostate cancer have failed to demonstrate curative potential in all patients. Investigations involving the role of T-cell immunity in the clearance of neoplastic cells are now available. Development of T-cell immunotherapy may give a new approach to the treatment of advanced metastatic prostate cancer. METHODS: A phase I clinical trial assessing the administration of autologous dendritic cells (DC) pulsed with HLA-A0201-specific prostate-specific membrane antigen (PSMA) peptides were conducted. Participants were divided into five groups receiving four or five infusions of peptides alone (PSM-P1 or PSM-P2; groups 1 and 2, respectively), autologous DC (group 3), or DC pulsed with PSM-P1 or P2 (groups 4 and 5, respectively). RESULTS: No significant toxicity was observed in all five groups. Cellular response against PSM-P1 and -P2 was observed in HLA-A2+ patients infused with DC pulsed with PSM-P1 or -P2 (groups 4 and 5), respectively. An average decrease in PSA was detected only in group 5. Seven partial responders were identified based on NPCP criteria + PSA. CONCLUSIONS: Infusions of test substances were well tolerated by all study participants. Detection of cellular response and decrease in PSA level in some patients who received DC pulsed with PSM-P2 indicate this method's potential in prostate cancer therapy.

Dendritic Cells↗
PubMed1995

In vitro propagated dendritic cells from prostate cancer patients as a component of prostate cancer immunotherapy.

T cell-mediated cancer immunotherapy requires efficient antigen-presenting cells. Dendritic cells (DCs) are arguably the most efficient antigen-presenting cells studied to date. Individuals with prostate cancer often undergo various therapies which may compromise their immune system, including the state of their DC precursors. We report the in vitro propagation of DCs from peripheral blood of patients with prostate cancer, most of whom are in clinical stages D1 or D2 and have undergone radiation therapy. After 7 days in culture, the number of DCs recovered were 20-50-fold higher than those isolated directly from peripheral blood. This number is comparable to findings of previous studies with healthy individuals. Cultured patients' DCs were capable of presenting tetanus toxoid to autologous T cells in vitro. Furthermore, T cells from 2 of 4 patients proliferated when cultured with their DCs and the lysate of a human prostate cancer cell line (LNCaP), demonstrating the potential role of autologous DCs in prostate cancer immunotherapy studies.

Aged↗
PubMed1994

Helium pneumoperitoneum for laparoscopic cholecystectomy: ventilatory and blood gas changes.

Laparoscopic cholecystectomy with carbon dioxide pneumoperitoneum may result in hypercarbia and acidosis in patients with cardiorespiratory disease. The aim of the present study was to assess helium as an alternative to carbon dioxide for creating the pneumoperitoneum. Ventilation requirements and carbon dioxide levels were assessed at the beginning and end of laparoscopic cholecystectomy using helium (n = 30) and carbon dioxide (n = 30) pneumoperitoneum. Insufflation with helium did not result in an increase in ventilation requirement although, like carbon dioxide pneumoperitoneum, it was associated with a mean rise in peak airway pressure (of 7 cmH2O; P < 0.001). There was also a 3.2-kPa increase in the alveolar-arterial oxygen gradient with helium (P = 0.006). Carbon dioxide pneumoperitoneum was associated with a significant rise in arterial carbon dioxide levels, despite increasing ventilation. Four patients with helium pneumoperitoneum had surgical emphysema for 5 days. Helium may be a suitable alternative to carbon dioxide for creating pneumoperitoneum in patients with severe cardiorespiratory disease. However, because of its low water solubility helium has a lower safety margin than carbon dioxide in the rare event of gas embolism.

Adult↗
PubMed1994

Disturbance of thermal homeostasis during post-exercise hyperthermia.

The response of core temperature to exercise was investigated during recovery in order to avoid the antagonistic competition between exercise and thermal reflexes for the same effector systems which control skin blood flow. Five healthy, non-training males [mean (SD) age, 23.8 (2.04) years] were habituated to 29 degrees C at relative 50% humidity for more than 2 h and then exercised by treadmill running at about 75% maximum oxygen uptake for 18 min. They then remained at 29 degrees C for up to 65 min of recovery. Oesophageal (T(es)), rectal (Tre) and skin temperatures (Tsk) were recorded at 5-s intervals throughout. The abrupt fall of temperature gradient from the forearm to finger was used to identify the T(es) for skin vessel dilatation (Tdil) during exercise. Mean (SE) Tes rose from a resting value of 36.67 (0.15) degrees C to 38.22 (0.24) degrees C, mean Tre rose from 37.09 (0.25) degrees C to 38.23 (0.15) degrees C, and Tdil occurred at 37.39 (0.32) degrees C. Within 10 min of recovery mean T(es) fell to 37.31 (0.24) degrees C, where it remained a significant 0.64 degrees C above its pre-exercise (PrEx) level (P < or = 0.018) but insignificantly different from Tdil for the remaining 55 min of recovery. Meanwhile, Tre fell gradually throughout recovery to 37.64 (0.18) degrees C. The Tsk at all non-acral sites except the thigh had recovered to PrEx levels by 20-30 min post-exercise (PoEx).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Evaluation of the optimal hand-scrub duration prior to total hip arthroplasty.

Orthopaedic surgeons in many major arthroplasty centres advocate the use of a prolonged surgical hand-scrub prior to total joint replacement. In this study we evaluated the antimicrobial efficacy of a 5 compared with a 10 min scrub before both long (> 90 min) and short (< 90 min) operations for total hip arthroplasty. Surgical hand disinfection was performed on one occasion for 5 min and on a second for 10 min by 41 surgeons and theatre nurses using 4% chlorhexidine gluconate as a detergent formulation ('Hibiscrub', ICI Pharmaceuticals). None of the subjects had previously scrubbed on the day of each test. Bacterial colony counts on the fingers were measured using the method described by Rotter (vide infra) before scrubbing, immediately after scrubbing, and at the end of each operation. Our results showed that for arthroplasty procedures lasting less than 90 min (35 operations) a 5 min hand-scrub was equally as effective as one of 10 min. However, following longer procedures (36 operations) colony counts were significantly higher on subjects who had scrubbed for 10 min than on those who only scrubbed for 5 (P < 0.05, Mann-Whitney U-Test). This study suggests that the practice of a prolonged scrub before total joint replacement does not have a scientific basis and that such a policy should be discontinued where it is still practised.

Aerosols↗
PubMed1993

Ventilatory and blood gas changes during laparoscopic and open cholecystectomy.

As part of a randomized trial, ventilatory and arterial blood gas changes were assessed during open (n = 30) and laparoscopic (n = 30) cholecystectomy. Measurements were made during anaesthesia before the start of surgery and at the time of removal of the gallbladder. Despite an increase in minute ventilation from a mean(s.d.) of 5.7(1.4) to 6.1(1.2) litres, mean(s.d.) arterial carbon dioxide tension (PaCO2) rose from 5.3(0.9) to 6.0(0.9) kPa during laparoscopic cholecystectomy. End-tidal carbon dioxide tension (PE'CO2) had poor precision in predicting PaCO2 (95 per cent interval of agreement -0.61 to 1.93 kPa). Mean(s.d.) peak airway pressure increased from 17(4) to 23(4) cmH2O. The mean PaCO2--PE'CO2 value did not change significantly, although there was significant within-patient variation. Arterial oxygen levels did not change significantly. By comparison, no clinically significant changes in ventilation or blood gas values occurred during open cholecystectomy. In conclusion, laparoscopic cholecystectomy requires a substantial but variable increase in minute ventilation to compensate for carbon dioxide absorption from the peritoneum.

Adult↗
PubMed1990

A superior method of tattoo removal using the Q-switched ruby laser.

The Q-switched ruby laser was used to treat 101 amateur and 62 professional tattoos in 80 patients over a period of 22 months. Using a 5- to 8-mm spot size and energy fluences of 2-4 joules/cm2, an average of three retreatments resulted in complete pigment removal in four, nearly complete pigment removal in 84, significant pigment removal in 11, and minimal pigment removal in two amateur tattoos. Using identical parameters for professional tattoos, there was complete pigment removal in two, nearly complete pigment removal in five, significant pigment removal in 18, minimal pigment removal in 25, and very little pigment removal in 12. Professional tattoos with red, yellow, and green pigments faded, but required multiple retreatments. While transient hypopigmentation occurred in many patients, skin texture and hair growth returned to normal in all cases and no hypertrophic scarring was seen.

Adolescent↗
PubMed1984

The role of the major histocompatibility complex in in vitro antibody responses; MHC restriction in responses involving linked recognition of antigenic determinants is not solely consequent to T cell-accessory cell restrictions.

Major histocompatibility complex (MHC) restrictions in the secondary antibody response in vitro to the soluble protein antigen trinitrophenyl keyhole limpet haemocyanin (TNP-KLH) were investigated. Experimental conditions were employed which ensured that co-operation between KLH-primed T cells and TNP-primed B cells was possible only through linked recognition of carrier and haptenic determinants. Under such conditions co-operation between T and B cells appears to be MHC-restricted. These experiments were designed to distinguish between two possible reasons for such MHC restrictions: (i) interaction between T and B cells is directly restricted by the MHC; or (ii) MHC-restricted T cell-antigen-presenting cell (APC) interactions limit generation of antibody responses and thus impose a pseudo-MHC restriction on T-B interactions. The ability of F1 APC to circumvent MHC restrictions was determined. The capacity of KLH-primed T cells from (P X Q)F1 leads to parent P and parent P leads to F1 X-irradiation bone marrow chimaeras to help TNP-primed parent P and parent Q B cells was assayed. Such T cells preferentially co-operate with parent P B cells. Addition of F1 APC from the spleen and the peritoneum did not alter the MHC restriction. Antibody responses stimulated by either high or low antigen concentrations were similarly MHC-restricted. Stimulation with antigen-pulsed F1 APC also failed to circumvent MHC restrictions. These results suggest that in this system involving linked recognition of antigenic determinants, the MHC directly restricts interactions between T and B cells.

Animals↗