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Biomedical subjects

R A Henderson

Publications and source records attributed to R A Henderson.

At least 19 recordsLinked to original sources
PubMed2006

Interventional versus conservative treatment in acute non-ST elevation coronary syndrome: time course of patient management and disease events over one year in the RITA 3 trial.

OBJECTIVE: To determine whether, in acute non-ST elevation coronary syndrome, the benefit from early invasive coronary intervention compared with a conservative strategy of later symptom-guided intervention varies over time. METHODS: In RITA 3 (Randomised Intervention Trial of unstable Angina 3) patients were randomly assigned to coronary angiography (median 2 days after randomisation) and appropriate intervention (n = 895) or to a symptom-guided conservative strategy (n = 915). RESULTS: In the first week patients in both groups were at highest risk of death, myocardial infarction (MI) or refractory angina (incidence rate 40 times higher than in months 5-12 of follow up). There were 22 MIs and 6 deaths in the intervention group (largely due to procedure-related events, 14 MIs and 3 deaths) versus 17 MIs and 3 deaths in the conservative group. In the rest of the year there were an additional 12 versus 27 MIs, respectively (treatment-time interaction p = 0.021). Over one year in the intervention group there was a 43% reduction in refractory angina; 22% of patients underwent coronary artery bypass surgery and 35% underwent percutaneous coronary intervention only, which reduced refractory angina but provoked some early MIs; and 43% were still treated medically, mostly because of a favourable initial angiogram. CONCLUSION: Any intervention policy needs to recognise the high risk of events in the first week and the substantial minority of patients not needing intervention. Intervention may be best targeted at higher risk patients, as the early hazards of the procedure are then offset by reduced subsequent events.

Adult↗
PubMed2004

Do men benefit more than women from an interventional strategy in patients with unstable angina or non-ST-elevation myocardial infarction? The impact of gender in the RITA 3 trial.

AIMS: The RITA 3 trial randomized patients with non-ST-elevation myocardial infarction or unstable angina to strategies of early intervention (angiography followed by revascularization) or conservative care (ischaemia or symptom driven angiography). The aim of this analysis was to investigate the impact of gender on the effect of these two strategies. METHODS AND RESULTS: In total, 1810 patients (682 women and 1128 men) were randomized. The risk factor profile of women at presentation was markedly different to men. There was evidence that men benefited more from an early intervention strategy for death or non-fatal myocardial infarction at 1 year (adjusted odds ratios 0.63, 95% confidence interval 0.41-0.98 for men and 1.79, 95% confidence interval 0.95-3.35 for women; interaction p-value=0.007). Men who underwent the assigned angiogram were more likely to be put forward for coronary artery bypass surgery, even after allowing for differences in disease severity. CONCLUSION: An early intervention strategy resulted in a beneficial effect in men which was not seen in women although caution is needed in interpretation. Further research is needed to evaluate why women do not appear to benefit from early intervention and to identify treatments that improve the prognosis of women.

Angina, Unstable↗
PubMed2004

Plasma ghrelin response following a period of acute overfeeding in normal weight men.

BACKGROUND: Ghrelin, a 28 amino-acid peptide secreted primarily from the stomach has been identified as the endogenous ligand for the growth hormone secretagogue receptor. Ghrelin is suppressed in the postprandial state and has been linked to both type II diabetes and obesity. AIMS: To investigate the effects of a period of overfeeding with high-fat dietary supplements on plasma ghrelin levels in nonobese men. METHODS: Six healthy males (21-34 y; BMI 21-24 kg/m(2)) underwent the dietary intervention after completing diet and exercise diaries for 7 days. For 3 further weeks subjects followed their own diet diary supplemented with 125 ml single cream and 50 g roasted peanuts (88 g fat, 15 g Protein, 8 g carbohydrate) every day. Oral fat tolerance tests (OFTT) were undertaken at baseline, 7, 14 and 21 days of fat supplementation. The diet was increased in energy by 3.9 MJ/day and from a mean of 29-45% energy intake from fat with a small weight gain noted each week (P=0.009). RESULTS: Ghrelin concentrations were significantly reduced during the baseline OFTT. The postprandial ghrelin response (AUC) was significantly reduced following 2 weeks of dietary supplementation (P=0.005) increasing the suppression of plasma ghrelin by 18% despite only a 3% increase in body weight. Plasma triacylglycerol (P=0.009) and leptin (P=0.035) concentrations were also elevated and postprandial pancreatic polypeptide levels decreased (P=0.038) following dietary-supplementation. CONCLUSIONS: These results suggest that the metabolic profile associated with obesity, including a reduction in plasma ghrelin levels, may be related to recent dietary energy intake and precedes the development of significant adiposity.

Adult↗
PubMed2002

Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina.

BACKGROUND: Current guidelines suggest that, for patients at moderate risk of death from unstable coronary-artery disease, either an interventional strategy (angiography followed by revascularisation) or a conservative strategy (ischaemia-driven or symptom-driven angiography) is appropriate. We aimed to test the hypothesis that an interventional strategy is better than a conservative strategy in such patients. METHODS: We did a randomised multicentre trial of 1810 patients with non-ST-elevation acute coronary syndromes (mean age 62 years, 38% women). Patients were assigned an early intervention or conservative strategy. The antithrombin agent in both groups was enoxaparin. The co-primary endpoints were a combined rate of death, non-fatal myocardial infarction, or refractory angina at 4 months; and a combined rate of death or non-fatal myocardial infarction at 1 year. Analysis was by intention to treat. FINDINGS: At 4 months, 86 (9.6%) of 895 patients in the intervention group had died or had a myocardial infarction or refractory angina, compared with 133 (14.5%) of 915 patients in the conservative group (risk ratio 0.66, 95% CI 0.51-0.85, p=0.001). This difference was mainly due to a halving of refractory angina in the intervention group. Death or myocardial infarction was similar in both treatment groups at 1 year (68 [7.6%] vs 76 [8.3%], respectively; risk ratio 0.91, 95% CI 0.67-1.25, p=0.58). Symptoms of angina were improved and use of antianginal medications significantly reduced with the interventional strategy (p<0.0001). INTERPRETATION: In patients presenting with unstable coronary-artery disease, an interventional strategy is preferable to a conservative strategy, mainly because of the halving of refractory or severe angina, and with no increased risk of death or myocardial infarction.

Angina Pectoris↗
PubMed2002

Cost effectiveness of eptifibatide in acute coronary syndromes; an economic analysis of Western European patients enrolled in the PURSUIT trial. The Platelet IIa/IIb in unstable Angina: Receptor Suppression Using Integrilin Therapy.

AIMS: To assess the direct medical costs and cost effectiveness of routine eptifibatide use amongst patients with unstable angina and myocardial infarction without persistent ST-segment elevation in the Western European subgroup of the PURSUIT trial. METHODS AND RESULTS: Health care resources were collected for the Western European PURSUIT trial patients (n=3697). Unit costs for major resources were developed within six countries using a consistent bottom-up methodology. Resource consumption from the Western European population was used to calculate the average direct medical costs per patient in the eptifibatide and placebo arms of the trial. Eptifibatide was estimated to cost 524 Euros per treatment. Long-term survival estimated from the 6-month trial survival data and combined with the cost data was used to calculate cost-effectiveness ratios. Additionally, cost per death and non-fatal myocardial infarction at 30 days was calculated. Sensitivity analyses were conducted on the discount rate and resource consumption. Cost-effectiveness ratios ranged from 9603 Euros to 18 115 Euros per year of life saved with 3% discount. Using resource consumption based on countries with low coronary arteriography rates, the cost per year of life saved was between 3329 Euros and 10 079 Euros. Using resource consumption based on high coronary arteriography rate countries, the cost per year of life saved was between 17 089 Euros and 24 099 Euros. Assuming no difference in treatment costs except for the addition of eptifibatide, the incremental cost per year of life saved was 23 818 Euros. CONCLUSIONS: Routine eptifibatide use was associated with a reduction in the combined end-point of death and myocardial infarction at 30 days, which was sustained at 6 months. Long-term projections indicate a modest increase in survival in eptifibatide patients. These data translate into cost-effectiveness ratios that compare favourably with other new technologies that are currently in use.

Acute Disease↗
PubMed2001

Bone mineral content in girls perinatally infected with HIV.

BACKGROUND: Early diagnostic efforts and advances in multidrug therapy have considerably prolonged the survival time of children infected perinatally with HIV. Despite these advances, few studies have addressed calcium status and bone growth in HIV-infected children. OBJECTIVE: Our objective was to examine the effect of HIV infection on calcium status and bone growth in children. DESIGN: We measured calcitropic hormones, urinary calcium excretion, bone mineral content, and body composition in 19 young girls aged 9.2 +/- 2.6 y (range: 5.9-15.2 y) who were infected perinatally with HIV. RESULTS: Serum concentrations of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] and parathyroid hormone concentrations were elevated above normal ranges in 25% and 12% of these girls, respectively. Urinary calcium excretion normalized for creatinine excretion was also elevated (Ca/Cr >0.18) in 17% of these children despite suboptimal calcium intakes (679 +/- 437 mg/d). Total-body bone mineral content, measured with the use of dual-energy X-ray absorptiometry, averaged 845.1 +/- 279.0 g and was on average 2.7 z scores below age- and race-matched values reported in non-HIV-infected healthy girls. Significant positive correlations were found between an indirect marker of bone resorption in urine (N:-telopeptide) and 1,25(OH)2D (P < 0.02, r2 = 0.586, n = 9), and between serum N-telopeptide and total alkaline phosphatase (P < 0.001, r2 = 0.541, n = 17), suggesting that calcium insufficiency may be increasing bone resorption in this group. CONCLUSIONS: Young girls with HIV infection had low bone mass and evidence of calcium insufficiency. Nutritional counseling of children with HIV infection should emphasize adequate calcium intakes because of the importance of this age period in bone mineral acquisition.

Absorptiometry, Photon↗
PubMed2001

Oxygen measurements in brain stem slices exposed to normobaric hyperoxia and hyperbaric oxygen.

We previously reported (J Appl Physiol 89: 807-822, 2000) that < or =10 min of hyperbaric oxygen (HBO(2); < or = 2,468 Torr) stimulates solitary complex neurons. To better define the hyperoxic stimulus, we measured PO(2) in the solitary complex of 300-microm-thick rat medullary slices, using polarographic carbon fiber microelectrodes, during perfusion with media having PO(2) values ranging from 156 to 2,468 Torr. Under control conditions, slices equilibrated with 95% O(2) at barometric pressure of 1 atmospheres absolute had minimum PO(2) values at their centers (291 +/- 20 Torr) that were approximately 10-fold greater than PO(2) values measured in the intact central nervous system (10-34 Torr). During HBO(2), PO(2) increased at the center of the slice from 616 +/- 16 to 1,517 +/- 15 Torr. Tissue oxygen consumption tended to decrease at medium PO(2) or = 1,675 Torr to levels not different from values measured at PO(2) found in all media in metabolically poisoned slices (2-deoxy-D-glucose and antimycin A). We conclude that control medium used in most brain slice studies is hyperoxic at normobaric pressure. During HBO(2), slice PO(2) increases to levels that appear to reduce metabolism.

Animals↗
PubMed2000

Quality of life after coronary angioplasty or continued medical treatment for angina: three-year follow-up in the RITA-2 trial. Randomized Intervention Treatment of Angina.

OBJECTIVES: We sought to evaluate the impact of percutaneous transluminal coronary angioplasty (PTCA) and medical treatment on self-perceived quality of life among patients with angina. BACKGROUND: The second Randomized Intervention Treatment of Angina trial (RITA-2) implemented initial policies of PTCA or continued medical treatment in patients with angina, allowing assessment of long-term health consequences. METHODS: A total of 1,018 patients were randomly assigned (504 to PTCA and 514 to medical treatment). The short form 36 (SF-36) self-administered quality-of-life questionnaire was completed at randomization and three months, one year and three years later. To date, 98% of patients reached one year and 67% reached three years. RESULTS: The PTCA group had significantly greater improvements in physical functioning, vitality and general health at both three months and one year, but not at three years. These quality-of-life scores were strongly related to breathlessness, angina grade and treadmill exercise time both at baseline and at one year. The treatment differences in quality of life are explained by the PTCA group's improvements in breathlessness, angina and exercise time. The attenuation of treatment difference at three years is partly attributed to 27% of medically treated patients receiving nonrandomized interventions in the interim. For both groups, there were also improvements in ratings of physical role functioning, emotional role functioning, social functioning, pain and mental health, but for these the superiority of PTCA over medical treatment was less pronounced. After one year, 33% and 22% of the PTCA and medical groups, respectively, rated their health much better. CONCLUSIONS: Coronary angioplasty substantially improves patient-perceived quality of life, especially physical functioning and vitality, as compared with continued medical treatment. These differences are attributed to alleviation of cardiac symptoms (specifically, breathlessness and angina), but must be balanced against the small procedure-related risks of PTCA.

Activities of Daily Living↗
PubMed2000

Hyperbaric oxygen depolarizes solitary complex neurons in tissue slices of rat medulla oblongata.

Hyperbaric oxygen (HBO2) at approximately 3 atmospheres absolute (ATA) pressure is toxic to the mammalian CNS due to excessive O2 free radical production. No study has ever determined the effects of < or = 3 ATA of O2 on the membrane potential and firing rate of neurons in the mammalian brainstem. Likewise, no study has ever determined the effects of < or = 3 ATA pressure per se on brainstem neurons. Accordingly, we initiated intracellular recordings at 1 ATA in solitary complex neurons in slices (300 microns) of rat caudal medulla oblongata that were maintained inside a 72 liter hyperbaric chamber. Helium, which is inert and without narcotic effect at moderate levels of hyperbaria, was used to hydrostatically compress the submerged brain slice to determine the effects of pressure per se. Tissue oxygen tension and extracellular pH were also measured during exposure to hyperbaric gases. Six of 19 neurons were affected by hyperbaric helium; 5 cells were depolarized and 1 cell was hyperpolarized. Input resistance (Rin) either increased (n = 1) or decreased (n = 3). When control perfusate (0.95 ATA O2) was switched to perfusate saturated with 98% O2 (balance CO2, pH = 7.3-7.4, pO2 = 2.5-3.4 ATA; 2-18 minutes of exposure) in a separate pressure vessel, 8 of 13 neurons were depolarized and 5 neurons were insensitive. In the 8 O2-responsive neurons, Rin either increased (n = 5), decreased (n = 2) or was unchanged (n = 1). Three of 8 neurons depolarized by HBO2 were also depolarized by hyperbaric helium, usually with an additional change in Rin. We conclude that hydrostatic (helium) pressure and HBO2 independently increase excitability in certain solitary complex neurons. We hypothesize that these responses contribute, in part, to neural events that either precede or occur during CNS O2 toxicity.

Animals↗
PubMed2000

Reduced metabolic rate accompanies the hemorrhage-induced hypothermia in conscious rats.

The mechanism for the hemorrhage-induced drop in body temperature is unknown. This study determined the alterations in cutaneous heat exchange and metabolic heat production caused by a moderate hemorrhage in conscious rats. Chronically instrumented rats were subjected to a 16 ml/kg hemorrhage, followed by a 4-h recovery period, while monitoring body core temperature and cutaneous temperature. Cutaneous heat transfer was disrupted by housing the animals at an elevated (28 degrees C) ambient temperature. A separate group of experiments measured the change in oxygen consumption in the post-hemorrhage period. Moderate hemorrhage caused a drop in body core temperature which stabilized at 0.7+/-0.3 degrees C below control in the second hour following hemorrhage. Disruption of cutaneous heat exchange by reducing the thermal gradient did not diminish the hemorrhage-induced hypothermia. Hemorrhage caused a significant decline of oxygen consumption (-0. 21+/-0.05 ml O(2)/g per h). This 16% drop in resting oxygen consumption was prevented by immediately retransfusing the aspirated blood back into the rat. These data indicate that a decrease in metabolic heat production mediates the drop in body core temperature caused by moderate hemorrhage in conscious rats.

Animals↗
PubMed2000

Reduced oxygen consumption precedes the drop in body core temperature caused by hemorrhage in rats.

This study examines the early time course in core temperature change and oxygen consumption at 4 levels of hemorrhage. Chronically instrumented rats were acclimatized to a respirometry chamber for 30 min. The rats were briefly (10 min) removed from the chamber for a fixed volume hemorrhage of 0 mL/kg (sham), 8 mL/kg, 16 mL/kg, 24 mL/kg, or 32 mL/kg. Rats were then returned to the chamber, and oxygen consumption and body core temperature were monitored for the next 2 h. Oxygen consumption (control 1.26 mL O2/g/h) fell significantly 5 min after hemorrhage in all but the sham and 8 mL/kg hemorrhage groups, with the decrease proportional to the hemorrhage volume. The 32 mL/kg hemorrhage group showed the greatest decrease, to 0.47 mL O2/g/h. Body core temperature (control 37.5 degrees C) fell more gradually, declining to 35.6 degrees C 110 min after the 24 mL/kg hemorrhage, and to 33.2 degrees C at 6 h after the 32 mL/kg hemorrhage. In the 16 mL/kg hemorrhage group, oxygen consumption fell significantly by 5 min after hemorrhage, but a drop in body temperature was not seen until 25 min after hemorrhage. The data from this study indicate that the drop in core temperature does not cause the observed decrease in oxygen consumption. In fact, the timing and magnitude of the drop in oxygen consumption indicate that the reduced metabolic rate may mediate the hemorrhage-induced drop in body core temperature in conscious rats.

Animals↗
PubMed1999

Whole body protein turnover in children with human immunodeficiency virus (HIV) infection.

The purpose of this study was to determine the rate of whole body protein turnover (WBPT) in human immunodeficiency virus (HIV)-infected children, and to determine the relationship between WBPT and growth. The rate of WBPT was calculated from the cumulative excretion of labeled urinary ammonia after a single intravenous dose of 15N-glycine in three groups of children: 1) HIV+ with growth retardation (HIV+ Gr); 2) HIV+ with normal growth (HIV+); and 3) HIV-uninfected with normal growth (HIV-). Twenty-six children between 2 and 11 y of age were studied (10 HIV+ Gr, 12 HIV+, 4 HIV-). All children were afebrile and free of acute infection during the study. Rates of WBPT (mean +/- SD) for the study groups were: HIV+ Gr, 12.2 +/- 4.8; HIV+, 10.7 +/- 5.1; and HIV-, 8.6 +/- 2.1 g.protein.kg-1.d-1 (NS, P > 0.05). Although not statistically significant, mean WBPT was 42% greater in HIV+ Gr, and 24% greater in HIV+ compared to HIV-. Statistically significant correlations were found between WBPT and Z scores for height (r = -0.39, P = 0.05) and weight-for-age (r = -0.51, P = 0.01) and dietary intake of protein (r = 0.39, P = 0.05), and between protein balance (synthesis-catabolism) and intakes of energy (r = 0.47, P = 0.02) and protein (r = 0.40, P = 0.04). There was no statistically significant correlation between WBPT and resting energy expenditure (r = 0.27, P = 0.19), or CD4 cell number (r = 0.05, P = 0.82). These data suggest an association between increased rates of protein turnover and low weight and height-for-age Z scores, and that it may be possible to achieve positive protein balance given an adequate intake of nutrients.

Ammonia↗
PubMed1999

A qualitative process system for modeling NF-kappaB and AP-1 gene regulation in immune cell biology research.

An experiment-oriented integrated model of the regulation of the biologically ubiquitous NF-kappaB and AP-1 gene transcription promoters was built by extending a previously developed qualitative process system for simulating cell behavior in the immune system. The core knowledge base (KB) implemented a deep biological ontology including molecular, ultrastructural, cytological, histological, and organismic definitions. KB states, relationships, predicates, and heuristics also represented process interactions between reactive oxygen species, growth factors, and a variety of kinases phosphorylating intermediate molecules in the NF-kappaB and AP-1 regulatory signaling pathways. The system successfully simulated the molecular process steps underlying outcomes of eight different molecular genetics laboratory experiments, including those dealing with NF-kappaB and AP-1 regulation in immunodeficiency virus infection and tumor necrosis factor responses.

Antibody Formation↗
PubMed1999

Use of hazard analysis critical control point and alternative treatments in the production of apple cider.

The purpose of this study was to evaluate the practices of Maryland cider producers and determine whether implementing hazard analysis critical control point (HACCP) would reduce the microbial contamination of cider. Cider producers (n = 11) were surveyed to determine existing manufacturing practices and sanitation. A training program was then conducted to inform operators of safety issues, including contamination with Escherichia coli O157:H7, and teach HACCP concepts and principles, sanitation procedures, and good manufacturing practice (GMP). Although all operators used a control strategy from one of the model HACCP plans provided, only one developed a written HACCP plan. None developed specific GMP, sanitation standard operating procedures, or sanitation monitoring records. Six operators changed or added production controls, including the exclusion of windfall apples, sanitizing apples chemically and by hot dip, and cider treatment with UV light or pasteurization. Facility inspections indicated improved sanitation and hazard control but identified ongoing problems. Microbiological evaluation of bottled cider before and after training, in-line apples, pomace, cider, and inoculated apples was conducted. E. coli O157:H7, Salmonella, or Staphylococcus aureus were not found in samples of in-line apple, pomace, and cider, or bottled cider. Generic E. coli was not isolated on in-coming apples but was found in 4 of 32 (13%) in-line samples and 3 of 17 (18%) bottled fresh cider samples, suggesting that E. coli was introduced during in-plant processing. To produce pathogen-free cider, operators must strictly conform to GMP and sanitation procedures in addition to HACCP controls. Controls aimed at preventing or eliminating pathogens on source apples are critical but alone may not be sufficient for product safety.

Beverages↗