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Biomedical subjects

D Carey

Publications and source records attributed to D Carey.

At least 19 recordsLinked to original sources
PubMed2006

A prospective comparison of multidisciplinary treatment of oesophageal cancer with curative intent in a UK cancer network.

AIMS: Combined modality therapy (with chemotherapy+/-radiotherapy) has become a standard treatment for locally advanced oesophageal cancer. However, there appears to be no compelling evidence for one treatment type or combination to suit all and at this time the clinical multi-disciplinary team (MDT) forms an important role in selecting optimal therapies for the individual. This prospective comparison in one cancer network, looks at the outcomes of this decision making process. METHODS: Over a five year period 1998-2003, data were prospectively collected on all 330 consecutive patients, referred to a tertiary specialised MDT for whom curative treatment was the planned intent. Patients were managed according to an agreed local protocol and allocated to receive one of 5 treatments: surgery alone (S), pre-operative chemotherapy (C+S), pre-operative chemo-radiotherapy (CRT+S), definitive chemo-radiotherapy (CRT) and radiotherapy alone (RT). RESULTS: The 2 and 5 year survival for all patients receiving potentially curative treatment were 49% and 26% respectively. With 2 and 5 year survival for S, CRT+S, C+S, CRT and RT being 53,21; 57,40; 37,27; 50,27; 23,0 months respectively. Of the surgical therapies, mortality was highest in the CRT+S group, versus C+S and S; 12.5%, 1.6%, 4.5% respectively (p=0.025). Non-surgical based therapies had more than double the incidence of local relapses compared to surgical based therapies; however the CRT group had an overall survival comparable with S alone. The commonest sites of distant relapse were liver (56%), lung (38%), bone (32%) and non-regional lymph nodes (24%). CONCLUSION: The results suggest that in patients who are deemed unfit for surgical intervention, definitive chemoradiotherapy remains a viable alternative; they also lend further support to selected case triple modality therapy. These areas should be further examined in the context of randomised controlled phase III trials.

Aged↗
PubMed2006

Virological and immunological outcomes at 3 years after starting antiretroviral therapy with regimens containing non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or both in INITIO: open-label randomised trial.

BACKGROUND: Antiretroviral therapy has greatly reduced HIV mortality and morbidity. However, the best sequence of regimens and implications of initial regimen for long-term therapeutic success are not well defined. METHODS: In INITIO, a large international randomised trial, we compared antiretroviral therapy with two nucleoside analogue reverse transcriptase inhibitors (didanosine+stavudine) plus either a non-nucleoside reverse transcriptase inhibitor (efavirenz, EFV) or a protease inhibitor (nelfinavir, NFV), or both (EFV/NFV), in patients with HIV-1 infection who had not previously received antiretroviral drugs. Primary outcomes were proportion with undetectable HIV RNA in plasma, and change in CD4 count from baseline at 3 years. Analyses were by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN44582462. FINDINGS: We followed up 911 participants (297 EFV, 311 NFV, 303 EFV/NFV). At 3 years, the proportion with HIV RNA less than 50 copies per mL was highest in the EFV group (188 [74%] EFV, 162 [62%] NFV, 155 [62%] EFV/NFV; p=0.004). Mean (95% CI) increases in CD4 count were 316x10(6) cells per L (288-343) for EFV, 289x10(6) cells per L (262-316) for NFV, and 274x10(6) cells per L (231-291) for EFV/NFV (p=0.1). Fewer participants in the EFV group than in the other groups stopped adequate antiretroviral therapy for more than 30 days (p=0.005). Participants in the EFV/NFV group had shorter time to stopping the initial regimen (p<0.0001) and to a treatment modifying adverse event (p=0.04) than those in the other groups. INTERPRETATION: Starting antiretroviral therapy with a three-drug/two-class regimen including efavirenz was better than starting with regimens including nelfinavir or efavirenz plus nelfinavir in terms of virological suppression and durability of the initial regimen. The shorter time on adequate antiretroviral therapy or to a treatment-modifying adverse event might explain the absence of additional benefit for the four-drug regimen.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Effect of orlistat on cardiovascular disease risk in obese adults.

AIM: The aim of this study is to compare the effect of orlistat vs. placebo on the predicted 10-year cardiovascular disease (CVD) risk in obese people with one or more cardiovascular risk factors treated for 12 months, in conjunction with a fat-reduced, but otherwise ad libitum, diet. METHODS: A double-blind, randomized, placebo-controlled, parallel study was performed in conjunction with a fat-reduced diet and physical activity advice for 1 year. Participants (n = 339) from eight centres in Australia and New Zealand were randomized to either orlistat (120 mg) three times daily (n = 104 women, 66 men; mean +/- s.d. age = 52.0 +/- 7.5 years, body mass index (BMI) = 37.6 +/- 5.1 kg/m(2)) or placebo three times daily (n = 89 women, 80 men; age = 52.5 +/- 7.4 years, BMI = 38.0 +/- 4.9 kg/m(2)). The primary efficacy criterion was the 10-year risk of developing CVD calculated from the Framingham equation. Secondary efficacy criteria were body weight, waist circumference, blood pressure and serum concentrations of triglycerides, cholesterol (total, LDL and HDL), glucose, insulin and glycated haemoglobin and quality of life. RESULTS: There was no difference in the change in 10-year CVD risk between orlistat and placebo groups over 1 year. The orlistat group, however, had significant favourable changes in many of the individual CVD risk factors (total cholesterol, LDL-cholesterol, glucose, glycated haemoglobin, insulin, body weight and waist circumference) and one of the domains of quality of life measured by means of the SF-36 questionnaire (vitality), compared to the placebo group. Significant reductions in medication use for hypertension and diabetes were observed in the orlistat group, compared to those in placebo, but there were no significant differences in medication use for blood lipids. CONCLUSIONS: Orlistat may have reduced CVD risk, as judged by the favourable changes in individual risk factors and reductions in medication use, but the method used in order to measure absolute CVD risk in this study (Framingham CVD equation) was not sensitive enough to detect the changes in this relatively low-risk group (approximately 10% of risk of a CVD event over 10 years).

Adult↗
PubMed2005

Hospitalisations due to falls in older persons.

This paper describes hospitalisations due to falls among people aged 65 years and over resident in the Eastern Region of Ireland. Of the 2,029 hospitalisations recorded for 2002, 78% were female and 68% were aged 75 years and over. Fractures accounted for 1,697 or 84% of cases with nearly half of them (841) sustained to the hip. Females were more likely to have a limb fracture whereas males were more likely to have a head injury. The total inpatient costs of the 2,029 hospitalisations were estimated at 10.6 million euros. Hip fractures were the costliest injuries as they accounted for 7.4 million euros (70%) of inpatient costs. There are also substantial additional costs implications for hip fractures as they constituted the majority (56%) of cases transferred to nursing/convalescent homes or long-stay health facilities. In keeping with an ageing population, the problem of injuries in older people is likely to increase over time and as falls are the dominant cause of those injuries, all acute and long-stay health facilities need to develop and implement fall prevention strategies for older people.

Accidental Falls↗
PubMed2003

Effect of intensive dietetic interventions on weight and glycaemic control in overweight men with Type II diabetes: a randomised trial.

OBJECTIVE: To investigate the effectiveness of intensive innovative methods for implementing dietary prescriptions on weight management and glycaemic control in overweight men with Type II diabetes. DESIGN: A randomised clinical trial with a 12-week intervention period - three isocaloric dietary intervention groups (intermittent energy restriction, pre-portioned meals and self-selected meals) each with weekly dietitian contact - and a follow-up visit after 18 months. SUBJECTS: A total of 51 men with Type II diabetes (mean age 54 y, mean body mass index (BMI) 31.7 kg/m(2)). MEASUREMENTS: Weight, body composition, waist circumference, glycaemic control (HbA(1c)) and blood lipids. RESULTS: For all subjects, intensive diet therapy over the 12-week intervention period resulted in a mean reduction in energy intake of 2360+/-2780 kJ/day (564+/-665 kcal/day) and significant reductions in weight (6.4+/-4.6 kg), waist circumference (8.1+/-4.6 cm), percent body fat (1.9+/-1.5%), HbA(1c) (1.0+/-1.4%) and triglyceride levels (0.3+/-0.6 mmol/l) compared to baseline levels. Intervention group did not affect clinical outcomes, with the exception of percent body fat. A total of 27 (52.9%) subjects attended the 18-month follow-up visit. At this visit, none of the improvements in clinical parameters was maintained, with all parameters returning to preintervention levels. CONCLUSIONS: : A dietary prescription of 6000-7000 kJ/day (1400-1700 kcal/day) was effective in achieving a 6% weight loss and improving glycaemic control. The method of implementation made no difference to the outcomes between groups at 12 weeks or 18 months. Thus, we propose that it was the intensive weekly contact with a health professional in combination with moderate energy restriction that facilitated the successful short-term results seen.

Adult↗
PubMed2001

Phase I study of anti--epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer.

PURPOSE: To evaluate the safety, pharmacokinetics, and efficacy of a chimeric anti-epidermal growth factor receptor monoclonal antibody, cetuximab, in combination with radiation therapy (RT) in patients with advanced squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: We treated 16 patients in five successive treatment schedules. A standard dose escalation procedure was used; three patients entered onto the study at each dose level of cetuximab received conventional RT (70 Gy, 2 Gy/d), and the final three patients received hyperfractionated RT (76.8 Gy, 1.2 Gy bid). Cetuximab was delivered as a loading dose of 100 to 500 mg/m(2), followed by weekly infusions of 100 to 250 mg/m(2) for 7 to 8 weeks. Circulating levels of cetuximab during therapy were determined using a biomolecular interaction analysis core instrument. Human antichimeric antibody response was evaluated with a double-antigen radiometric assay. The recommended phase II/III dose was defined as the optimal cetuximab dose level based on the pharmacologic parameters and adverse events. RESULTS: The most commonly reported adverse events were fever, asthenia, transaminase elevation, nausea, and skin toxicities (grade 1 to 2 in most patients). Skin toxicity outside of the RT field was not strictly dose-dependent; however, grade 2 or higher events were observed in patients treated with higher dose regimens. There was one grade 4 allergic reaction. Most acute adverse effects were associated with RT (xerostomia, mucositis, and local skin toxicity). No antibodies against cetuximab were detected. All patients achieved an objective response (13 complete and two partial remissions). CONCLUSION: Cetuximab can be safely administered with RT. The recommended dose for phase II/III studies is a loading dose of 400 to 500 mg/m(2) and a maintenance weekly dose of 250 mg/m(2).

Adult↗
PubMed2001

Complications of femoral artery closure devices.

We have examined our prospectively collected experience with femoral artery closure devices. Vasoseal (n = 937), Angioseal (N-742), and Techstar (n = 1001) were utilized consecutively in our laboratory for diagnostic and interventional femoral artery closures. Complications were compared to a similar number of closures with manual compression (MC; n = 1019) before closure devices were utilized. The incidence of surgical repair, acute femoral closure, transfusion due to groin complications, readmission for groin complications, infection, and total complications were examined. We found that the Vasoseal and Angioseal devices were associated with higher rates of total complications than manual compression. The Techstar and manual compression had similar total complication rates. Acute femoral artery occlusion was a potentially serious complication with the Angioseal device. Groin infection occurred with each of the closure devices but not with manual compression.

Adult↗
PubMed2001

Adenovirus-mediated soluble FLT-1 gene therapy for ovarian carcinoma.

PURPOSE: We hypothesized that adenovirus-mediated soluble fms-like tyrosine kinase receptor (sFLT-1) gene therapy can inhibit the ovarian tumor growth and increase survival of mice in the context of ovarian carcinoma. EXPERIMENTAL DESIGN: We constructed an infectivity-enhanced recombinant adenovirus (AdRGDGFPsFLT-1) expressing soluble FLT-1 and green fluorescent protein (GFP). An adenovirus AdRGDGFP expressing GFP alone was used as control. The functional validation of adenovirus-mediated sFLT-1 was determined by an in vitro human umbilical vein endothelial cell proliferation inhibition assay. To evaluate the therapeutic potential of adenovirus-expressed sFLT-1 to inhibit the growth of ovarian tumors and to increase the survival duration of mice with ovarian tumors, two tumor models were used. First, SKOV3.ip1 ovarian carcinoma cells were infected ex vivo with either AdRGDGFPsFLT-1 or AdRGDGFP or uninfected and then inoculated s.c. into BALB/c nude mice, and tumor growth was monitored. Second, SKOV3.ip1 cells were inoculated i.p. into CB17 SCID mice and then treated with two doses of either AdRGDGFPsFLT-1 or AdRGDGFP or with PBS on days 1 and 14 after inoculation of cells, and the survival duration was monitored. RESULTS: Treatment with adenovirus-expressed sFLT-1 significantly inhibited the proliferation of human umbilical vein endothelial cells. The s.c. tumor nodules in mice derived from cells infected with AdRGDGFPsFLT-1 were significantly smaller than those infected with either AdRGDGFP or uninfected. In addition, i.p. administration of the AdRGDGFPsFLT-1 resulted in a significant increase in the survival times of mice compared with AdRGDGFP- or PBS-treated mice. CONCLUSIONS: Our results suggest that adenovirus-mediated sFLT-1 gene therapy can effectively inhibit ovarian tumor growth and increase survival in a murine model of ovarian carcinoma.

Adenoviridae↗
PubMed2001

Preventing accidental falls among older people in long stay units.

A fall prevention programme for older long-stay patients in a 95 bedded District Hospital was undertaken. Data on falls and resulting injuries for the year prior to the intervention were compared with equivalent data after one year (Year 1) and after two years (Year 2) of the intervention. In the pre-intervention year 25% of patients had at least one fall compared with 20.9% and 17.4% in Year 1 and Year 2 respectively. This difference was not statistically significant. However, there were 21% fewer falls in Year 1 and 49.3% fewer in Year 2 than in the pre-intervention year. This difference was significant in Year 2. In both intervention years there was a significant reduction in the incidence of fracture from 20.5% of falls (pre-intervention) to 2.8% in Year 1 and no fractures occurred in Year 2. Significant reductions in soft tissue injuries occurred in Year 2 but not in Year 1, dropping from 38.5% (pre-intervention) to 36.1% and 15.4% respectively. The percentage of patients uninjured after a fall increased from 41% to 61.1% to 84.6%. This intervention reduced falls and their adverse consequences for older people living in the long stay unit. The effect of the intervention escalated in Year 2. The intervention cost IR4,800 pounds. Fall prevention should be part of the routine care of older people in all types of long stay care.

Accidental Falls↗
PubMed2001

Percutaneous endoscopic gastroscopy tube migration: a rare cause of a common surgical problem.

Percutaneous endoscopic gastroscopy (PEG) is now the preferred method for long-term enteral nutrition for patients with inadequate oral intake. It is usually replaced by a Foley catheter when it becomes non-functional because of blockage or wear and tear. PEG tube migration is an unusual complication which may not be noticed by the patient or the medical staff and may present as delayed small bowel obstruction. We report on a patient who developed such a complication and the missing PEG tube was replaced by a Foley catheter when it was thought the original tube had fallen out. The use of catheters with an external stop device is recommended to prevent this rare complication.

Aged↗
PubMed2000

Epidemiology of herpesvirus papio infection in a large captive baboon colony: similarities to Epstein-Barr virus infection in humans.

The epidemiology of herpesvirus papio, a lymphocryptovirus similar to Epstein-Barr virus (EBV), was studied in a captive colony of >1900 baboons. Herpesvirus papio IgG antibody titers were measured by IFA. In total, 438 specimens from 296 baboons were assessed, including 116 serial specimens from 52 juveniles and 6 infants studied monthly for 1 year following birth and at age 18 months. Maternally derived antibody reached a nadir at 4 months of age. About 75% of animals at 12 months of age and >95% of animals after age 24 months demonstrated serologic evidence of herpesvirus papio infection. After age 3 years, the geometric mean titer was 1:60-75. The epidemiology of herpesvirus papio infection in baboons closely parallels that of EBV infection in humans. An animal model of lymphocryptovirus infection will facilitate investigations of human lymphocryptovirus biology.

Animals↗
PubMed2000

Multiple advantages of alpha-fetoprotein as a marker for in vivo gene transfer.

The development of improved gene transfer vectors has been hampered by the lack of a nonimmunogenic reporter gene that can be serially quantified in the serum or from other sites. In response to the need to develop a new reporter protein, we have evaluated alpha-fetoprotein (AFP) as a potential candidate. A first-generation E1/E3-deleted adenoviral vector expressing human AFP (hAFP) was generated as a preliminary tool to evaluate AFP as a reporter. Using both mouse and baboon models, hAFP expression was evaluated in serum after intravenous delivery and in serum and bronchioalveolar lavage (BAL) fluid after delivery to the lung. In immunocompetent animals, intravenous delivery of the hAFP adenoviral vector resulted in hAFP expression in the serum early after injection, which declined rapidly over time. Disappearance of hAFP from the serum was complete by 3-4 weeks after administration and was accompanied by robust antibody responses to hAFP and loss of infected cells. After lung delivery, hAFP could be detected in both serum and BAL. This allowed the analysis of the kinetics of gene expression in the lung without sacrificing the animals. In both liver and lung, immunohistochemical analysis correlated well with hAFP levels as detected in serum or BAL, indicating that serum levels were a reliable marker of tissue expression. Preliminary results with a mouse AFP expressed in a helper-dependent adenoviral vector indicate that use of a species-specific version of AFP will eliminate the complication of antibody development. These initial evaluations suggest that AFP is useful as a reporter gene to evaluate gene expression of therapeutic cassettes in multiple tissues, and it should be considered for use in human subjects.

Animals↗
PubMed2000

Plasma esterase activities in young and old patients undergoing open inguinal hernia repair.

Previous research has shown substantial decrements in enzymes of drug metabolism (esterases) in older patients following fracture neck of femur and hip replacement surgery. The main aim of this study was to examine the effect of open inguinal hernia repair on the activities of four plasma esterases in old and young patients. Seventeen older patients (mean age+/-S.E.M. was 67.6+/-1.8) and 12 young patients (mean age+/-S.E.M. was 38+/-3.3) undergoing open hernia repair for clinical reasons were recruited. The activities of plasma benzoylcholinesterase, butyrylcholinesterase, acetylcholinesterase, and aspirin esterase were determined spectrophotometrically, before the operation, 1 day post operatively and 1 week later. There was no significant effect of hernia repair surgery on any of the four enzymes measured in young or old patients. Neither was there any significant difference in enzyme activity between young and old at any of the three time points. Hernia repair surgery is not associated with decrements in enzymes of drug metabolism in man. This contrasts with the previous findings in hip replacement surgery.

Journal Article↗
PubMed2000

The validity of anthropometric regression equations in predicting percent body fat in collegiate wrestlers.

BACKGROUND: This study was designed to assess the validity of previously-developed anthropometric regression equations in determination of percent body fat in collegiate wrestlers (N=22). METHODS: Means (M) standard deviations (SD), correlation coefficients, standard errors of estimate (SEE) and total errors (TE) were compared to the criterion test of hydrostatic weighing (HW), (M=12.49%, SD=4.67%). RESULTS: Repeated measures analysis of variance revealed the equations of Lohman (M=12.94%, SD=3.59%, R=0.743, SEE=3.13%, TE=3.58%), Katch and McArdle (M=12.41%, SD=3.41 %, R=0.750, SEE=3.10%, TE=3.18%), and Tipton and Oppliger (M= 11.89%, SD=3.01%, R=0.763, SEE=3.03%, TE=3.63%) to be valid. The equations of Thorland et al. (M=14.11%, SD=5.12%, R=0.711, SEE=3.27%, TE=4.89%), Durning and Wommersley (M=14.075, SD=4.45%, R=0.741, SEE=3.13%, TE=4.71%), Jackson and Pollock (M=9.76%, SD=3.13%, R=0.737, SEE=3.17%, TE=5.90%), and Sinning (M=10.84%, SD=4.19%, R=0.741, SEE=3.13%, TE=4.78%) were significantly different from HW. CONCLUSIONS: It is concluded that the above-validated formulas have acceptably low SEE's and TE's to be of practical value in determination of appropriate weight classes for collegiate wrestlers.

Adipose Tissue↗
PubMed1998

Obesity: genes, glands or gluttony?

Distribution as well as amount of fat has health implications; central abdominal fat seems to be the major contributor to insulin resistance and risk of diabetes, hypertension and cardiovascular disease. Physical activity and diet affect overall adiposity; moreover, exercise specifically reduces visceral fat. The sexes differ in fat distribution; in particular, pre-menopausal women, despite greater overall adiposity, have much less visceral fat than men. There is a strong genetic determination of overall obesity and central abdominal adiposity. Genes regulating obesity (e.g. Ob) could modulate appetite, satiety, metabolic rate or physical activity. Moderate obesity probably results from interaction between genetic predisposition and an environment of abundant calories and reduced physical activity. Single gene mutations are being identified in a few morbidly obese people; however, the common genetic predisposition for obesity may relate to more subtle variations in regulatory controls. Diet and exercise are effective for some, but the response is often disappointing. Definition of pathways controlling appetite, metabolic rate and lipid metabolism may generate improved pharmacological compounds. Education and availability of lower-energy foods may help, but more radical approaches may be needed, such as environmental restructuring to increase physical activity. The problem is great, but failure will mean intolerably increased health costs.

Adipose Tissue↗
PubMed1998

Competence of pheasants as reservoirs for Lyme disease spirochetes.

Pheasants, Phasianus colchicus L., constitute a major part of the ground-feeding avifauna of England and Wales and are important hosts to immature stages of Ixodes ricinus L., the principal tick vector of Lyme borreliosis spirochetes in Europe. Therefore, their competence as hosts for Borrelia burgdorferi Johnson, Schmid, Steigerwalt & Brenner sensu lato was investigated. One group of pheasants was inoculated by needle with 1 x 10(6) cultured B. burgdorferi s.s. organisms, and a 2nd group of birds was infested with I. ricinus nymphs collected from a focus of Lyme borreliosis in southern England. Both bird groups were subjected to xenodiagnoses using uninfected I. ricinus nymphs. All recovered engorged ticks, as well as pheasant skin biopsies, were analyzed by a nested polymerase chain reaction targeting the 5S-23S rRNA genes of B. burgdorferi s.l. Both groups proved to be infective for ticks. The birds that were infected by tick bites proved to be significantly more infective for ticks (23% of the xenodiagnostic ticks positive) than those infected by needle (5%). The results show that pheasants can be infected experimentally with B. burgdorferi s.l., that they can pass the spirochetes to ticks and that their infectivity for ticks may persist as long as 3 mo. We conclude that pheasants are reservoir competent for Lyme borreliosis spirochetes and potentially play an important role in the maintenance of B. burgdorferi s.l. in England and Wales.

Animals↗
PubMed1998

Histamine receptor antagonists, cyclooxygenase blockade, and tumor necrosis factor during acute septic insult.

Tumor necrosis factor (TNF) may be a major endogenous mediator of sepsis-induced acute organ injury. We proposed that treatment of septic pigs with the combined agents ibuprofen, a cyclooxygenase inhibitor, and histamine receptor antagonists, cimetidine (H2 antagonist) and diphenhydramine (H1 antagonist) would result in lower circulating levels of TNF and decreased parameters of sepsis-induced injury in these animals. To test this, plasma TNF activity, cardiac index, systemic and pulmonary arterial pressures, arterial PO2 and bronchoalveolar lavage protein content were monitored for 300 min in four groups of anesthetized pigs: saline-infused control pigs (n = 4); pigs infused for 60 min with Pseudomonas aeruginosa (5 x 10(8) organisms/mL, .3 mL/20 kg/min) (n = 5) and pigs infused for 60 min with P. aeruginosa plus ibuprofen (12.5 mg/kg) alone (n = 4) or ibuprofen plus cimetidine (150 mg) and diphenhydramine (30 mg/kg) at 0 and 120 min (CID, n = 4). Within 60 min, pigs infused with P. aeruginosa exhibited increased plasma TNF activity (>8-fold increase in ng/mL TNF; L929 cytolysis assay) and showed alterations in all hemodynamic and pulmonary parameters. Ibuprofen or CID administration in the septic pigs decreased peak TNF activity by 4.6 and 10.2 ng/mL, respectively, and CID treatment was correlated with better attenuation of certain sepsis-induced alterations. These results show that CID treatment attenuates sepsis-induced injury and that this is correlated with reduced plasma TNF activity in a porcine model of sepsis-induced acute organ injury.

Animals↗