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Biomedical subjects

G Jennings

Publications and source records attributed to G Jennings.

At least 19 recordsLinked to original sources
PubMed2002

Integrating cost-effectiveness evidence into clinical practice guidelines in Australia for acute myocardial infarction.

A teaching hospital is working with the Victorian State Government and universities, integrating cost-effectiveness evidence into clinical practice guidelines (CPGs), protocols and pathways for respiratory and cardiology interventions. Acute myocardial infarction (AMI) findings are reported. Results will stimulate cost-effective practice and inform medical associations, federal and state governments and international organisations developing CPGs. Published CPGs by the American College of Cardiology/American Heart Foundation for AMI in 1999 are reviewed by a large interdisciplinary hospital-based committee given cost-effectiveness evidence. Levels of evidence criteria rating on methodological rigor for effectiveness and costs are applied. National Health and Medical Research Council (NHMRC) grades of recommendation criteria for combinations of relative effectiveness versus relative costs and cut-off points are used. Extrapolating results between countries was addressed by applying the OECD's health purchasing power parity series. Recommendations for revisions to United States guidelines and for local application are formulated. United States Guidelines require updating: Regarding angioplasty, percutaneous transluminal coronary angioplasty (PTCA) is cost-effective for men aged 60 years relative to recombinant tissue plasminogen activator (tPA), with additional cost per life year saved of 274 ecu. PTCA with discharge after 3 days is cost-effective in low-risk AMI. Regarding GP IIb/IIIa drugs, Abciximab during intervention incurred equal mean hospital costs for placebo, abciximab bolus, and abciximab bolus+infusion with incremental 6-month cost for the latter treatment costing 293 US dollars per patient. Agent recouped almost all initial therapy costs with significant benefits. Incremental cost of abciximab per event prevented is 3,258 US dollars. Tirofiban was compared to placebo after high-risk angioplasty for AMI or unstable angina. Tirofiban decreased the rate of hospital deaths, myocardial infarction, revascularisation at 2 days by 36% relative to placebo (8% vs. 12%) without increased cost. Clinical benefits were similar at 30 days. Tirofiban+heparin+aspirin was compared to heparin+aspirin. Tirofiban arm resulted in net savings of 33,418 ecu per 100 patients for the first 7 days of treatment. Regarding thrombolytics, tPA is more cost-effective than streptokinase. Incremental costs for each life saved when streptokinase is substituted by recombinant tissue plasminogen are 31%, 45%, 97% higher in Germany, Italy and the United States than in the United Kingdom. Regarding anticoagulants, enoxaparin is a promising alternative to unfractionated heparin for hospitalised patients with non-Q-wave myocardial infarction or unstable angina, saving 1,485 Canadian dollars per patient over 12 months with 10% reduction in 1 year risk of death, myocardial infarction or recurrent angina. Regarding antiarrhymics, the cost-effectiveness of no amiodarone, amiodarone for patients with depressed heart rate variability (DHRV), and amiodarone for patients with DHRV plus positive programmed ventricular stimulation (PPVS) for high-risk post-AMI was investigated. Amiodarone for DHRV+PPVS patients was dominated by a blend of the two alternatives. Compared to no amiodarone, the incremental cost-effectiveness of amiodarone for DHRV patients was 39,422 US dollars per quality adjusted life year gained. Amiodarone for DHRV is the most appropriate. Other CPG updates concern serum markers, for example, cardiac troponin I assay (c-Tnl), cost advantages of ad hoc angioplasty and secondary prevention through antioxidants and pravastatin. Australian costs are reported later in the paper.

Journal Article↗
PubMed2001

Capturing a photoexcited molecular structure through time-domain x-ray absorption fine structure.

The determination of the structure of transient molecules, such as photoexcited states, in disordered media (such as in solution) usually requires methods with high temporal resolution. The transient molecular structure of a reaction intermediate produced by photoexcitation of NiTPP-L2 (NiTPP, nickeltetraphenylporphyrin; L, piperidine) in solution was determined by x-ray absorption fine structure (XAFS) data obtained on a 14-nanosecond time scale from a third-generation synchrotron source. The XAFS measurements confirm that photoexcitation leads to the rapid removal of both axial ligands to produce a transient square-planar intermediate, NiTPP, with a lifetime of 28 nanoseconds. The transient structure of the photodissociated intermediate is nearly identical to that of the ground state NiTPP, suggesting that the intermediate adopts the same structure as the ground state in a noncoordinating solvent before it recombines with two ligands to form the more stable octahedrally coordinated NiTPP-L2.

Journal Article↗
PubMed2001

Tumour necrosis factor inhibitors reduce the acute-phase response in hapten-induced colitis.

BACKGROUND: Tumour necrosis factor (TNF) alpha has been implicated in the pathogenesis of inflammatory bowel disease. The aim of this study was to assess the contribution of TNF to the pathogenesis of hapten-induced colitis. METHODS: Colitis was induced in Wistar rats using intracolonic instillation of the hapten trinitrobenzenesulphonic acid (TNBS) in ethanol. Animals were treated with monoclonal anti-TNF antibody (cTN3), an idiotype control antibody (CB0006) or pentoxifylline. Colonic and systemic inflammation was assessed quantitatively. RESULTS: The use of either TNF inhibitor attenuated the acute-phase response in the early stages of colitis. Median (interquartile range (i.q.r.)) alpha 2-macroglobulin levels were reduced in animals pretreated with cTN3 (421 (279-915) micromol/ml) or pentoxifylline (567 (253-1454) micromol/ml) compared with levels in untreated colitic animals (1552 (1406-1998) micromol/ml) (P < 0.001 and P = 0.006, respectively). In established colitis, administration of anti-TNF antibodies resulted in an increase in median (i.q.r.) weight gain (percentage change in body-weight): colitic animals -2.3 (- 5.5 to 9.2) per cent versus cTN3-treated rats 15 (7.5-16.7) per cent; P < 0.05. CONCLUSION: The systemic response to TNBS-induced colitis appears to be at least partially dependent on TNF. This study did not provide evidence to support a role for TNF in the pathogenesis of colonic inflammation in this model. Presented in part to the 86th meeting of the Surgical Research Society in Nottingham, UK, 9-11 July 1997, and published in abstract form as Br J Surg 1997; 84: 1613

Acute-Phase Reaction↗
PubMed2001

Sympathetic nerve biology in essential hypertension.

1. Although the importance of sympathetic nervous activation in the pathogenesis of essential hypertension is well documented, the exact pathophysiology of the sympathetic nervous dysfunction present remains to be delineated. There are several possible explanations for the increased spillover of noradrenaline from the kidneys and heart to plasma, a key piece of evidence supporting the neurogenic basis of essential hypertension, in addition to the obvious one of an increased rate of sympathetic nerve firing. 2. The possibility that there may be an increase in the density of sympathetic innervation in human hypertension, well documented in the spontaneously hypertensive rat, is currently under investigation by us. 3. Adrenaline cotransmission is present in the cardiac sympathetic nerves of patients with essential hypertension, presumptive evidence of their exposure to high levels of stress and a possible basis for the observed increase in cardiac noradrenaline spillover, through presynaptic augmentation of noradrenaline release. 4. Phenotypic evidence exists also of faulty noradrenaline reuptake into the sympathetic nerves of the heart in essential hypertension, an abnormality that would amplify the sympathetic neural signal by impairing removal of noradrenaline from the synaptic cleft.

Aging↗
PubMed2001

Community health promotion and the randomized controlled trial: approaches to finding common ground.

The randomized controlled trial is the model against which research designs are judged. Concurrent with rising standards of evidence, however, is a trend toward greater inclusiveness in community-based research, exemplified by the Centers for Disease Control and Prevention-funded Prevention Research Centers, a nationwide network of academic-community partnerships engaged in community-based health promotion and disease prevention research. The Yale-Griffin Prevention Research Center developed a replicable process for devising randomized trials in the context of community collaboration. Several examples of trials developed this way and their interim results are provided.

Cardiovascular Diseases↗
PubMed2001

Low-dose estrogen supplementation improves vascular function in hypogonadal men.

It is widely accepted that in women, estrogens provide protection against the development of cardiovascular disease. However, the cardiovascular role of estrogens in men remains uncertain, despite preliminary evidence that endogenous estrogens produced by aromatization of androgenic precursors are of physiological importance. Hypogonadal men have very low levels of circulating estrogen. We studied the responsiveness of forearm resistance arteries to vasoconstrictor and vasodilator agents in 12 men (mean+/-SEM age, 68.7+/-2.6 years) rendered hypogonadal as a result of treatment for prostatic cancer, before and after 8 weeks of estrogen supplementation (estradiol valerate 1 mg daily; n=7) or placebo (n=5). Forearm blood flow was measured by venous occlusion plethysmography, and vasoactive agents were infused through a brachial artery cannula in doses that did not affect blood pressure or heart rate. Estrogen supplementation was well tolerated, with no adverse effects. After estrogen treatment, mean estradiol levels increased from <30 to 308+/-65 pmol/L, and both systolic and diastolic blood pressures were reduced. HDL cholesterol levels increased significantly, and vasoconstrictor responses to the NO synthase inhibitor N(G)-monomethyl-L-arginine (1, 2, 4 micromol/min) were enhanced. Vasoconstrictor responses to angiotensin II (8, 16, 32 ng/min) were markedly attenuated by estrogen treatment, as were vasoconstrictor responses to norepinephrine (25, 50, 100 ng/min). Estrogen did not alter the vasodilator responses to acetylcholine (9.25, 18.5, 37 microgram/min) or to the endothelium-independent agent sodium nitroprusside (1.6 microgram/min). Responses to all vasoactive agents were unchanged after administration of placebo. We conclude that low-dose estrogen supplementation in hypogonadal men is well tolerated, lowers blood pressure, and may affect vascular reactivity in a manner that is potentially beneficial, through several mechanisms, including enhancement of basal NO release and attenuation of vasoconstrictor responses to angiotensin II and norepinephrine. These findings suggest the need to consider a possible clinical role for estrogenic compounds in cardiovascular risk reduction in some groups of men.

Acetylcholine↗
PubMed2000

Serial echocardiographic assessment of left ventricular dimensions and function after myocardial infarction in mice.

OBJECTIVE: To test the usage of serial echocardiography in mice with induced myocardial infarct (MI) and to characterize the mouse model of MI. METHODS: C57 mice underwent open-chest surgery to induce left coronary artery occlusion or sham-operation (SH). Echocardiography was performed before and at 1, 2.5, 6 and 9 weeks after surgery. Left ventricular end diastolic and end systolic dimensions (LVEDd, LVESd) and fractional shortening (FS) were measured. Haemodynamics was determined at week 9 by LV catheterization and hearts were examined morphologically. RESULTS: Post-infarct mortality was 46% (10/22), of which, 70% died of acute heart failure or LV rupture within the first week. LV dimensions and FS remained stable in SH group (n = 10) during the study period. In surviving MI mice (n = 12), there was modest LV dilatation and fall in FS at week 1. Compared with week 0 values, there were progressive increase in LVEDd (+50(-)+66%) and LVESd (+124(-)+171%), and decline in FS (-53(-)-73%) during the 2.5-9 week period. Infarcted mice also had lower LV systolic pressure (LVSP), dP/dtmax and dP/dtmin (all P < 0.01 vs. SH group). Infarct size, LVSP and dP/dt significantly correlated with FS and LV dimensions (r = 0.61-0.80, all P < 0.01). CONCLUSIONS: LV remodeling and dysfunction in mice with MI are time-dependent processes and early remodeling seems associated with high risk of rupture and acute pump failure. Our findings provide a baseline description of this murine model and confirm echocardiography as a reliable means to serially assess changes of cardiac structure and function after MI.

Animals↗
PubMed2000

Ultrastructural appearance of renal and other basement membranes in the Bull terrier model of autosomal dominant hereditary nephritis.

Bull terrier hereditary nephritis may represent a model for autosomal dominant Alport's syndrome because affected dogs have the typically lamellated glomerular basement membrane (GBM) and father-to-son disease transmission occurs. This study examined the ultrastructural appearance of the renal and extrarenal basement membranes and their composition in affected Bull terriers. Affected stillborn animals and puppies had subepithelial frilling and vacuolation of the GBM. In adult dogs, lamellation was common, and subepithelial frilling and vacuolation were less prominent. Foot-process effacement and mesangial matrix expansion occurred frequently. Basement membranes in the glomeruli, tubules, and Bowman's capsule were significantly thickened and often mineralized. Immunohistochemical examination showed alpha 1(IV) and alpha 2(IV) collagen chains in all renal basement membranes; alpha 3(IV), alpha 4(IV), and alpha 5(IV) chains in the GBM, distal tubular basement membrane, and Bowman's capsule; and the alpha 6(IV) chain in Bowman's capsule. Conversely, the basement membranes from the affected Bull terrier cornea, lens capsule, retina, skin, lung, and muscle had a normal ultrastructural appearance and were not thickened compared with membranes in normal age-matched dogs. The distribution of basement membrane abnormalities in Bull terrier hereditary nephritis may occur because the defective protein is present exclusively or more abundantly in the kidney and is structurally more important in the kidney or because of local intrarenal stresses.

Age Factors↗
PubMed2000

Comparison of recoveries in breath carbon dioxide of H13CO-3 and H14CO-3 administered simultaneously by single 6 h constant unprimed intravenous infusion.

The aim of this study was to assess the bioequivalence of H13CO-3 and H14CO-3, by administering both labels simultaneously by single infusion and comparing their recovery in breath CO2 and urinary urea. Six healthy male subjects (age range 24-41 years; weight 76.7 (sd, 18.6) kg; height 1.79 (sd 0.05) m) were infused with unprimed solutions of HCO3- (110.0 mmol/kg) labelled with 13C (0.76 mmol 13C/h) and 14C (48 Bq/h) at a constant rate for 6 h, in a whole-body calorimeter (1400 litres) for measurement of CO2 production. Samples of breath were collected hourly in a Douglas bag and all urine was collected into two batches (0-4 h and 4-6 h) for estimating recovery of infused label by measurement of enrichment or specific activity. Recovery in breath CO2 of both labels increased from about 25 % for the first hour to 88 % and above for hours 3-4 onwards. Mean recovery of 13C in breath CO2 was slightly higher than that of 14C for all periods (mean difference always less than 1 % of infused label) but was significant only for the first 3 h (P < 0.05). Recovery of 14C in urea was significantly higher (P < 0.01) than 13C, but was confounded by substantial variability and uncertainties concerning 13CO2 background enrichments. These results suggest that there is no compelling need to alter factors currently used for recovery of 14C in breath when using 13C instead, and vice versa.

Adult↗
PubMed1999

Impact of tuberculosis on the body composition of HIV-infected men in Brazil.

OBJECTIVE: Tuberculosis (TB) is the commonest HIV-related opportunistic infection in many developing countries and is thought to be a frequent underlying cause of HIV-associated wasting. We have used reference water dilution methods to examine the body composition changes associated with TB and to assess the severity and pattern of wasting. METHODS: The study was conducted at a charitable support house for poor and homeless HIV-infected people in Rio de Janeiro, Brazil. Male patients who were HIV-positive and receiving treatment for active TB (HIVTB+) and HIV-infected controls without TB (HIVTB-) were studied. Total body water (TBW) and extracellular water (ECW) were measured by giving oral doses of deuterium oxide and sodium bromide, respectively, and determining enrichment in plasma after 4 hours. Intracellular water (ICW), body cell mass (BCM), lean body mass (LBM) and fat mass were calculated from these parameters using standard equations. RESULTS: HIVTB+ (n = 11) and HIVTB- (n = 12) groups were similar in age, height, CD4 count and HIV risk factors. HIVTB+ men had significantly lower mean ICW (13.2 versus 16.6 kg; p = .02) and BCM (18.4 versus 23.0 kg; p = .02), a relative expansion of ECW (35.0 versus 30.0 L/kg body weight; p = .04), and small and nonsignificant reductions in total body weight (58.0 versus 62.1 kg; p = .26), LBM (45.5 versus 47.7 kg; p = .33) and fat mass (12.5 versus 14.4 kg; p = .51) compared with HIVTB- controls. BCM in the HIVTB+ group was similar to reference values for severe malnutrition. The relative depletion of BCM appeared excessive in comparison with reference values for uncomplicated starvation. CONCLUSION: The nutritional status of HIVTB+ patients was significantly worse than HIVTB- patients. Body weight and LBM underestimated the nutritional deficit, and measurement of BCM is therefore necessary to appreciate the extent of malnutrition in such patients. Malnutrition in HIVTB+ patients is severe and may therefore contribute to decreased survival. Hypermetabolism appears to play a role in the wasting process in patients coinfected with HIV and TB.

AIDS-Related Opportunistic Infections↗
PubMed1999

Leptin is released from the human brain: influence of adiposity and gender.

Leptin, a 16-kDa circulating protein primarily derived from adipocytes, is an important factor in the regulation of appetite and energy expenditure. Using simultaneous arterio-venous blood sampling, several organs were assessed with regard to their individual roles in leptin metabolism in healthy male and female subjects constituting a range of body mass indices. Plasma leptin levels were unchanged after passage through the hepatosplanchnic and forearm circulations. In contrast, concentrations in the renal vein were consistently lower than those in the renal artery (-15%; P<0.005), indicating net extraction, whereas the brain was observed to be a net leptin releaser. Concentrations in the internal jugular vein were significantly higher than arterial levels in lean females (change, 3.0+/-1.2 ng/mL; P<0.02) and in obese males (body mass index, >28 kg/m2), but not lean (change, 2.3+/-2.3 vs. 0.1+/-0.1 ng/mL, respectively; P<0.05), indicating a probable influence of both gender and adiposity on brain leptin release. An attempt to grossly localize the site of brain release by using cerebral venous scans to distinguish between jugular venous drainage from cortical and subcortical brain areas revealed no region-specific secretion. These data raise the possibility that the brain is a nonadipose source of leptin. In addition, the higher level of brain release observed in females may contribute to the well documented gender differences in overall plasma leptin levels.

Adipose Tissue↗
PubMed1999

The use of infrared spectrophotometry for measuring body water spaces.

BACKGROUND: The conventional method of measuring total body water by the deuterium isotope dilution method uses gas isotope ratio mass spectrometry (IRMS), which is both expensive and time-consuming. We investigated an alternative method, using Fourier transform infrared spectrophotometry (FTIR), which uses less expensive instrumentation and requires little sample preparation. METHOD: Total body water measurements in human subjects were made by obtaining plasma, saliva, and urine samples before and after oral dosing with 1.5 mol of deuterium oxide. The enrichments of the body fluids were determined from the FTIR spectra in the range 1800-2800 cm-1, using a novel algorithm for estimation of instrumental response, and by IRMS for comparison. RESULTS: The CV (n = 5) for repeat determinations of deuterium oxide in biological fluids and calibrator solutions (400-1000 micromol/mol) was found to be in the range 0.1-0.9%. The use of the novel algorithm instead of the integration routines supplied with the instrument gave at least a threefold increase in precision, and there was no significant difference between the results obtained with FTIR and those obtained with IRMS. CONCLUSION: This improved infrared method for measuring deuterium enrichment in plasma and saliva requires no sample preparation, is rapid, and has potential value to the clinician.

Body Water↗
PubMed1999

Effect of mixed meal ingestion on fuel utilization in the whole body and in superficial and deep forearm tissues.

Six healthy lean male adults, given a mixed meal containing 3190 kJ (16% from protein, 44% from carbohydrate and 40% from fat) were studied for the next 370 min using arteriovenous cannulation techniques across superficial and deep forearm tissues. The meal produced no significant change in forearm blood flow or skin temperature. The major differences between superficial and deep forearm tissues were (a) creatinine release by deep tissues but not superficial tissues; (b) the release of non-esterified fatty acids (NEFA) by superficial tissues and uptake by deep tissues; and (c) the more prolonged large positive arteriovenous concentration difference for glucose across deep than superficial tissues. The similarities were (a) general pattern of individual amino acid exchanges and transient positive amino acid N balance after meal ingestion; (b) consistent uptake of glutamate and release of glutamine (the main carrier of N out of superficial and deep forearm tissues); (c) the magnitude of the arteriovenous concentration differences for glucose, NEFA and total amino acids were related to the changes in their circulating concentrations and to the oxidation of carbohydrate, fat, and protein in the whole body; and (d) increases in the arterio-deep venous and arterio-superficial venous differences for glucose did not result in increased release of lactate, alanine or pyruvate, implying no increase in the activity of glucose-lactate and glucose-alanine cycles between forearm tissues and the liver. This study suggests that in a number of ways superficial and deep tissues can be regarded, at least qualitatively, as behaving as a 'single metabolic unit'.

Adipose Tissue↗
PubMed1998

CdZnTe array detectors for synchrotron radiation applications.

An X-ray linear-array detector was fabricated using high-pressure Bridgman-grown CdZnTe. The detector area was 175 x 800 microm and the pitch size was 250 microm. The measured dark current for the test 16-element detector was as low as 0.1 pA at 800 V cm(-1) with excellent uniformity. Energy spectra were measured using a 57Co radiation source. Both a small-pixel effect and charge sharing were observed. For the arrays, an average 5.8% full width at half-maximum (FWHM) at the 122 keV photopeak was obtained with a standard deviation of 0.2%. A large-area detector (1 x 1 cm) of the same material before fabrication exhibited a low-energy tail at the photopeak, which limits the photopeak FWHM to 8%, typically due to hole trapping. At energies below 60 keV, charge sharing between elements was observed. The charge sharing was greatly reduced by providing a path to ground for unwanted charges. A prototype readout electronic system for an eight-channel array detector was developed. A readout system intended for a multielement solid-state detector system was also used. The array detector will be used for high-energy diffraction and Compton scattering measurements at the Advanced Photon Source.

Journal Article↗
PubMed1998

Vascular types I and II transforming growth factor-beta receptor expression: differential dependency on tyrosine kinases during induction by TGF-beta.

Recent evidence indicates that the type II transforming growth factor-beta (TGF-beta) receptor (TbetaRII) is a serine-threonine-tyrosine kinase. However, the significance of its tyrosine kinase is unclear. We investigated in vascular smooth muscle cells the effects of tyrosine kinase inhibition on the expression of TGF-beta receptor types I (ALK-5) and II (TbetaRII) mRNA, induced by TGF-beta1. TGF-beta1 elevated ALK-5 mRNA levels 5-fold; essentially similar TGF-beta1-dependent elevations were observed with growth factors, PDGF-BB and FGF-2. The tyrosine kinase inhibitor genistein abolished these TGF-beta1 and growth factor responses. TGF-beta1 also elevated TbetaRII mRNA levels which were not inhibited by genistein. We conclude that tyrosine kinases participate in defining how cells respond to TGF-beta.

Activin Receptors, Type I↗
PubMed1998

Immune response to a single bout of exercise in young and elderly subjects.

The purpose of this investigation was to examine alterations in lymphocyte proliferation activity and T cell subsets following an acute bout of exercise in young and old subjects. Six young (26+/-3 years) and nine old (69+/-5 years) male subjects were tested at rest and immediately after 20 min of submaximal exercise at 50% peak work capacity. Arterial blood was sampled from an indwelling catheter for catecholamine and immunology assays. Peripheral blood lymphocytes were isolated for mitogen-induced phytohemagglutinin (PHA) proliferation capacity. Lymphocyte subsets were analyzed by dual-labeled flow cytometry. As has been shown in previous studies, baseline proliferative responsiveness was significantly lower in the old (down 22%) compared to the young subjects. In response to submaximal exercise, proliferative responsiveness to PHA increased significantly in the young subjects (up 55%), however, for the old subjects this response did not differ significantly from resting values (up 18%). The number of total lymphocytes, as well as CD4+ and CD8+ T cell subsets, at rest were lower for old subjects compared with young. Exercise-induced increases in T cell subset populations were similar across age groups. It was concluded that, while having lower initial T cell numbers and PHA responsiveness, immunoresponsiveness during a single bout of exercise is, in general, maintained in old when compared to young individuals.

Adult↗