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Biomedical subjects

G O'Driscoll

Publications and source records attributed to G O'Driscoll.

At least 19 recordsLinked to original sources
PubMed2006

Late humoral rejection in a cardiac transplant recipient treated with the anti-CD20 monoclonal antibody rituximab.

Humoral or vascular rejection results from a B cell-mediated production of immunoglobulin (Ig) G antibody against a transplanted organ, producing immune complex deposition on the vascular endothelium, activation of the complement cascade, generation of endothelial dysfunction, and regional ischemic injury. Antibody-mediated rejection, which may be accompanied by hemodynamic compromise, is associated with reduced long-term graft survival. Patients believed to be at an increased risk of developing humoral rejection include women, particularly those with high levels of panel reactive antibodies, cytomegalovirus seropositivity, and positive cross matches, and subjects with prior sensitization to OKT3. Treatment options for humoral rejection include plasmapheresis to lower the circulating immunoglobulin levels followed by high-dose cyclophosphamide to reduce the B-cell population. Other modalities include total lymphoid irradiation, photophoresis, splenectomy, and, for treatment failures, retransplantation. Rituximab is a chimeric humanized monoclonal antibody directed against the pan B-cell surface molecule, CD20. It is approved for the treatment of low-grade B-cell non-Hodgkin's lymphoma. It has also been used successfully for the treatment of posttransplant B-cell lymphoproliferative disease. We report a case of late humoral rejection successfully treated with rituximab.

Antibodies, Monoclonal↗
PubMed2005

Abnormal ventilatory responses to hypoxia in Type 2 diabetes.

AIMS: The incidence of Type 2 diabetes is increasing, along with its associated micro- and macrovascular disease manifestations. Previous studies indicate that patients with Type 2 diabetes exhibit abnormal cardiopulmonary reflex responses to various stimuli, although the impact of hypoxia, a common physiological stimulus, on ventilatory responses has not previously been studied in humans with Type 2 diabetes. METHODS: Minute ventilation (V(E)) breathing pattern responses (total breath time, T(TOT); expiratory time, T(E); inspiratory time, T(I); inspiratory duty cycle, T(I)/T(TOT)) were measured during 5 min each of normoxia and isocapnic hypoxia (arterial O2 saturation approximately 85%) in eight subjects with Type 2 diabetes and seven age- and body mass index-matched healthy subjects. RESULTS: During normoxia, V(E) was similar in control and diabetic subjects (6.4+/-1.2, 6.4+/-1.1 l/min, respectively). In response to hypoxia, V(E) significantly increased in both groups (to 17.0+/-5.0 and 9.5+/-2.0 l/min, respectively, P<0.05), but the magnitude of increase in V(E) was significantly less in diabetic than in control subjects (P<0.05). In addition, the breathing pattern response to hypoxia differed between groups in terms of T(I)/T(TOT) and T(TOT) (P<0.05), with control subjects significantly decreasing T(TOT) and T(E) (P<0.05) while diabetic subjects tended to increase both. CONCLUSIONS: Relative to matched control subjects, Type 2 diabetic subjects exhibit blunted V(E) responses to acute isocapnic hypoxia, suggesting that this group of diabetic subjects possesses a chemoreflex ill-equipped to respond homeostatically to hypoxic challenge.

Diabetes Mellitus, Type 2↗
PubMed2001

The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes.

OBJECTIVES: The purpose of this study was to examine whether exercise training stimulates a generalized improvement in vascular function in patients with type 2 diabetes mellitus. BACKGROUND: Exercise is often recommended for patients with type 2 diabetes to improve physical conditioning and glycemic control. This study examined the effect of eight weeks of exercise training on conduit and resistance vessel function in patients with type 2 diabetes, using a randomized crossover design. METHODS: Both resistance vessel endothelium-dependent and -independent functions were determined by forearm plethysmography and intrabrachial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, in 16 patients with type 2 diabetes. Conduit vessel endothelial function was assessed in 15 of these patients using high-resolution ultrasound and flow-mediated dilation of the brachial artery; glyceryl trinitrate (GTN) was used as an endothelium-independent dilator. RESULTS: Flow-mediated dilation increased from 1.7 +/- 0.5% to 5.0 +/- 0.4% following training (p < 0.001). The forearm blood flow ratio to ACh was significantly improved (analysis of variance, p < 0.05). Responses to SNP and GTN were unchanged. Endothelium-dependent vasodilation was enhanced in both conduit and resistance vessels. CONCLUSIONS: If endothelial dysfunction is an integral component of the pathogenesis of vascular disease, as currently believed, this study supports the value of an exercise program in the management of type 2 diabetes.

Diabetes Mellitus, Type 2↗
PubMed2001

Exercise training, vascular function, and functional capacity in middle-aged subjects.

PURPOSE: The aim of this study was to investigate the effect of 8 wk of exercise training on functional capacity, muscular strength, body composition, and vascular function in sedentary but healthy subjects by using a randomized, crossover protocol. METHODS: After familiarization sessions, 19 subjects aged 47 +/- 2 yr (mean +/- SE) undertook a randomized, crossover design study of the effect of 8 wk of supervised circuit training consisting of combined aerobic and resistance exercise. Peak oxygen uptake (.VO(2peak)), sum of 7 maximal voluntary contractions and the sum of 8 skinfolds and 5 segment girths were determined at entry, crossover, and 16 wk. Endothelium-dependent and -independent vascular function were determined by forearm strain-gauge plethysmography and intrabrachial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP) in 16 subjects. RESULTS: Training did not alter ACh or SNP responses. .VO(2peak), (28.6 +/- 1.1 to 32.6 +/- 1.3 mL.kg(-1).min(-1), P < 0.001), exercise test duration (17.4 +/- 1.1 to 22.1 +/- 1.2 min, P < 0.001), and muscular strength (465 +/- 27 to 535 +/- 27 kg, P < 0.001) significantly increased after the exercise program, whereas skinfolds decreased (144 +/- 10 vs 134 +/- 9 mm, P < 0.001). CONCLUSION: These results suggest that moderate intensity circuit training designed to minimize the involvement of the arms improves functional capacity, body composition, and strength in healthy, middle-aged subjects without significantly influencing upper limb vascular function. This finding contrasts with previous studies in subjects with type 2 diabetes and heart failure that employed an identical training program.

Anthropometry↗
PubMed2001

Losartan, an angiotensin type I receptor antagonist, improves conduit vessel endothelial function in Type II diabetes.

We have demonstrated previously that inhibition of angiotensin-converting enzyme (ACE) with enalapril and angiotensin II blockade with losartan improve acetylcholine-dependent endothelial function in resistance vessels of patients with Type II diabetes. It was therefore of interest to examine the effect of losartan on conduit vessel function in this group. The influence of losartan (50 mg daily for 4 weeks) on endothelium-dependent and -independent vasodilator function was determined in 12 subjects with Type II diabetes using a randomized, double-blind, placebo-controlled crossover protocol. Conduit vessel endothelial function was assessed using high-resolution ultrasound and the brachial artery response to reactive hyperaemia (flow-mediated dilation; FMD); glyceryl trinitrate (GTN) was used as a non-endothelium-dependent dilator. Losartan administration significantly increased the FMD response from 5.2+/-0.7% (mean+/-S.E.M.) to 7.4+/-0.6% of vessel diameter (P<0.05; paired t-test). There was no effect of losartan on the endothelium-independent responses to GTN (17.8+/-1.8% to 17.6+/-1.2%). Consistent with our previous findings in resistance vessels, administration of 50 mg of losartan daily improves NO-mediated dilation in the conduit vessels of subjects with Type II diabetes. Together with the findings that both ACE inhibition and angiotensin II blockade improve resistance vessel function in this group, it is likely that at least some of the beneficial effect is mediated through the angiotensin II/type I receptor pathway. A type I receptor antagonist seems a reasonable alternative to an ACE inhibitor to maintain conduit vessel endothelial function in Type II diabetic subjects.

Angiotensin I↗
PubMed2000

Losartan, an angiotensin type 1 receptor antagonist, improves endothelial function in non-insulin-dependent diabetes.

OBJECTIVES: The present study examined the effect on forearm endothelial function of an angiotensin II type 1 receptor antagonist, losartan, in subjects with non-insulin-dependent diabetes mellitus (NIDDM). BACKGROUND: Angiotensin-converting enzyme (ACE) inhibition with enalapril improves acetylcholine (ACh)-dependent endothelial function in patients with NIDDM. This could be mediated through angiotensin II and the type 1 receptor or could be due to inhibition of kininase II and a bradykinin preserving effect. It is therefore relevant to determine whether a type 1 receptor antagonist improves endothelial function. METHODS: The influence of losartan (50 mg daily for four weeks) on endothelium-dependent and independent vasodilator function was determined in 9 NIDDM subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gauge plethysmography. RESULTS: Losartan significantly decreased infused arm vascular resistance in response to three incremental doses of intrabrachial acetylcholine (p < 0.05, ANOVA). The forearm blood flow ratio (flow in infused to noninfused arm) was also increased (p < 0.01). Responses to sodium nitroprusside and monomethyl arginine were not significantly changed. CONCLUSIONS: Losartan administration at 50 mg per day improved endothelium-dependent dilation of resistance vessels in patients with NIDDM. That is, blockade of the angiotensin II type 1 receptors improves endothelial function in NIDDM. At least some of the similarly beneficial effect of ACE inhibition is probably mediated also through the angiotensin II-type 1 receptor pathway. The use of a type 1 receptor antagonist seems a reasonable alternative to an ACE inhibitor to maintain endothelial function in NIDDM subjects.

Angiotensin Receptor Antagonists↗
PubMed2000

Effect of aerobic and resistance exercise training on vascular function in heart failure.

Exercise training of a muscle group improves local vascular function in subjects with chronic heart failure (CHF). We studied forearm resistance vessel function in 12 patients with CHF in response to an 8-wk exercise program, which specifically excluded forearm exercise, using a crossover design. Forearm blood flow (FBF) was measured using strain-gauge plethysmography. Responses to three dose levels of intra-arterial acetylcholine were significantly augmented after exercise training when analyzed in terms of absolute flows (7.0 +/- 1.8 to 10.9 +/- 2.1 ml x 100 ml(-1) x min(-1) for the highest dose, P < 0.05 by ANOVA), forearm vascular resistance (21.5 +/- 5.0 to 15.3 +/- 3.9 ml x 100 ml forearm(-1) x min(-1), P < 0.01), or FBF ratios (P < 0.01, ANOVA). FBF ratio responses to sodium nitroprusside were also significantly increased after training (P < 0.05, ANOVA). Reactive hyperemic flow significantly increased in both upper limbs after training (27.9 +/- 2.7 to 33.5 +/- 3.1 ml x 100 ml(-1) x min(-1), infused limb; P < 0.05 by paired t-test). Exercise training improves endothelium-dependent and -independent vascular function and peak vasodilator capacity in patients with CHF. These effects on the vasculature are generalized, as they were evident in a vascular bed not directly involved in the exercise stimulus.

Acetylcholine↗
PubMed2000

Combined aerobic and resistance exercise training improves functional capacity and strength in CHF.

This study examined the effect of a novel circuit weight training (CWT) program on cardiorespiratory fitness, muscular strength, and body composition in 13 patients with chronic heart failure (CHF), using a prospective randomized crossover protocol. Peak exercise oxygen uptake (VO(2 peak)) increased after the 8-wk CWT program (19. 5 +/- 1.2 vs. 22.0 +/- 1.5 ml. kg(-1). min(-1), P < 0.01), as did exercise test duration (15.2 +/- 0.9 vs. 18.0 +/- 1.1 min, P < 0. 001). Submaximal exercise heart rate was lower after training at 60 and 80 W (121 +/- 3 vs. 134 +/- 5 beats/min, P < 0.01) as was rate pressure product, whereas ventilatory threshold increased, from 52 +/- 3 to 58 +/- 3% of VO(2 peak) (P < 0.05). CWT also increased maximal isotonic voluntary contractile strength for seven different muscle groups, from 392 to 462 kg (P = 0.001). CWT, an exercise prescription specifically targeting peripheral abnormalities in CHF, improves functional capacity and muscular strength in these patients.

Anthropometry↗
PubMed2000

Chronic heart failure. A guide for practical management.

BACKGROUND: Chronic heart failure is an increasingly common problem in Australia and most management occurs in the outpatient setting. OBJECTIVE: To review the options available in the management of chronic heart failure. DISCUSSION: Appropriate management can dramatically improve the prognosis, symptoms and quality of life of chronic heart failure patients.

Arrhythmias, Cardiac↗
PubMed1999

Improvement in endothelial function by angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus.

OBJECTIVES: The aim of this study was to assess the effect of angiotensin-converting enzyme (ACE) inhibition with enalapril on forearm endothelial function in subjects with type II diabetes mellitus. BACKGROUND: Endothelial function is depressed in the presence of conventional risk factors for atherosclerosis, and various therapies, such as lipid-lowering therapy in hypercholesterolemia, can improve endothelial-mediated vasodilation. ACE inhibition has improved such function in several conditions including type I diabetes, but there is no evidence for a beneficial effect in type II diabetes. METHODS: The influence of enalapril (10 mg twice daily for 4 weeks) on endothelium-dependent and -independent vasodilator function was determined in 10 type II diabetic subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gage plethysmography and graded intrabrachial infusion of acetylcholine (ACh), N(G)-monomethyl-L-arginine (LNMMA) and sodium nitroprusside (SNP). RESULTS: Enalapril increased the response to the endothelium-dependent vasodilator, ACh (p < 0.02) and the vasoconstrictor response to the nitric oxide (NO) synthase inhibitor, LNMMA (p < 0.002). No difference was evident in the response to SNP. CONCLUSIONS: In type II diabetic subjects without evidence of vascular disease, the ACE inhibitor enalapril improved stimulated and basal NO-dependent endothelial function. The study extends the spectrum of beneficial effects demonstrated to result from ACE inhibition in diabetes.

Acetylcholine↗
PubMed1998

Beneficial effect of vitamin E administration on nitric oxide function in subjects with hypercholesterolaemia.

1. Vitamin E administration improves endothelial function in hypercholesterolaemic animals but, generally, has not been found to do so in man. The aim of this study was to determine whether vitamin E administration improves basal or stimulated function of the nitric oxide (NO) dilator system in patients with hypercholesterolaemia. 2. Seven subjects aged 47+/-3 (+/-S.E.M.) years with moderately elevated serum cholesterol concentrations (6.0+/-0.1 mmol/l) were given 4 weeks of placebo therapy followed by 500 i.u. of vitamin E twice daily for 4 weeks. Endothelium-dependent and -independent vasodilatation were assessed by intrabrachial infusion of acetylcholine and sodium nitroprusside, and forearm blood flow was measured by strain-gauge plethysmography. Basal NO function was assessed by infusion of NG-monomethyl-L-arginine. 3. Plasma alpha-tocopherol concentration was enhanced after administration of vitamin E (34.6+/-1.8 to 86.9+/-9.6 micromol/l; P<0.001). In addition, vitamin E administration significantly increased acetylcholine-mediated vasodilatation whether the results were expressed in terms of changes in absolute forearm blood flow (P<0. 01), forearm vascular resistance (P<0.05) or forearm blood flow ratios (P<0.001). Similarly, absolute forearm blood flow (P<0.05), forearm vascular resistance (P<0.01) and forearm blood flow ratio (P<0.01) responses to NG-monomethyl-L-arginine were augmented by vitamin E therapy. Sodium nitroprusside responses were unaltered. 4. These results indicate that 4 weeks therapy with 1000 i.u. of vitamin E daily improves basal and stimulated NO-related endothelial function in subjects with hypercholesterolaemia.

Acetylcholine↗
PubMed1997

Improvement in endothelial function by angiotensin converting enzyme inhibition in insulin-dependent diabetes mellitus.

We postulated that nitric oxide (NO)-mediated endothelial function would be improved by acute and short-term treatment with an angiotensin converting enzyme (ACE) inhibitor in patients with type I diabetes mellitus, in whom endothelial function is depressed. Nine type I diabetic patients and eight healthy subjects underwent forearm blood flow measurement using strain gauge plethysmography during intraarterial infusion of incremental doses of endothelium-dependent (acetylcholine [ACh]) and endothelium-independent (sodium nitroprusside [SNP]) vasodilators. Pretreatment ACh responses were depressed in diabetic patients relative to the normal subjects (P < 0.05). No difference between the groups was evident in response to SNP. Acute ACE inhibition (with intrabrachial enalaprilat) enhanced ACh responses in the diabetic patients (P < 0.005), with a further improvement evident after 1 mo of oral therapy with enalapril (P < 0.001) when ACh responses were normalized. ACE inhibition did not affect SNP responses. We conclude that acute administration of the ACE inhibitor, enalaprilat, enhances NO-mediated endothelial function in type I diabetic patients, with further improvement evident after 4 wk of enalapril therapy.

Administration, Oral↗
PubMed1997

Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month.

BACKGROUND: Cholesterol-lowering therapy can improve cardiovascular morbidity and mortality in patients with atherosclerosis. Although the mechanisms responsible are unclear, these benefits precede macroscopic changes in the vasculature. Emerging evidence that improvement in endothelial function may occur requires substantiation; in particular, it is unclear how early any such improvement would be detectable after initiation of therapy. METHODS AND RESULTS: This randomized, double-blind, placebo-controlled crossover study evaluated the effect of simvastatin (20 mg daily for 4 weeks) on endothelium-dependent and endothelium-independent vasodilation and on the response to the inhibitor of nitric oxide synthesis, NG-monomethyl-L-arginine (L-NMMA), in the forearm vasculature of subjects with moderate elevation of total serum cholesterol (6.0 to 10.0 mmol/L) by use of strain-gauge plethysmography. Studies were repeated after 3 more months of open therapy. When the results are expressed as percentage changes in flow in the infused arm relative to the noninfused arm, the vasodilator response to acetylcholine was significantly increased after 4 weeks of treatment with simvastatin (P < .0005), and this improvement was further enhanced after 3 months (P < .005). Concurrently, simvastatin augmented the vasoconstrictor response to L-NMMA, an effect that was maintained at 3 months (P < .0005). The response to the endothelium-independent vasodilator sodium nitroprusside was unaltered. CONCLUSIONS: These observations indicate that within 1 month of treatment with simvastatin, both the stimulated and basal nitric oxide dilator functions of the endothelium are augmented, and the benefits of this HMG-coenzyme A reductase inhibitor persist with continued therapy.

Acetylcholine↗
PubMed1996

Control of skeletal muscle blood flow during dynamic exercise: contribution of endothelium-derived nitric oxide.

Traditional explanations for the hyperaemia which accompanies exercise have invoked the 'metabolic theory' of vasodilation, whereby contractile activity in the active muscle gives rise to metabolic by-products which dilate vessels bathed in interstitial fluid. Whilst metabolites with vasodilator properties have been identified, this theory does not adequately explain the magnitude of hyperaemia observed in active skeletal muscle, principally because large increases in flow are dependent on dilation of 'feed' arteries which lie outside the tissue parenchyma and are not subjected to changes in the interstitial milieu. Coordinated resistance vessel dilation during exercise is therefore dependent on a signal which 'ascends' from the microvessels to the feed arteries located upstream. Recent studies of ascending vasodilation have concentrated on the possible contribution of the endothelium, a monolayer of flattened squamous cells which lie at the interface between the circulating blood and vascular wall. These cells are uniquely positioned to respond to changes in rheological and humoral conditions within the cardiovascular system, and to transduce these changes into vasoactive signals which regulate blood flow, vascular tone and arterial pressure. Endothelial cells produce nitric oxide (NO), a rapidly diffusing labile substance which relaxes adjacent vascular smooth muscle. NO is released basally and contributes to the regulation of vascular tone by acting as a functional antagonist to sympathetic neural constriction. In addition, NO is spontaneously released in response to deformation of the endothelial cell membrane, indicating that changes in pulsatile flow and wall shear stress are likely physiological stimuli. Since the dilation of microvessels in response to exercise increases blood flow through the upstream feed arteries, which subsequently dilate, one explanation for ascending vasodilation is that NO release is stimulated by flow-induced shear stress. Evidence that NO contributes to ascending vasodilation is reviewed, along with studies which indicate that NO mediates exercise hyperaemia, that physical conditioning upregulates NO production and that NO controls blood flow by modifying other physiological mechanisms.

Animals↗
PubMed1995

Lack of effect of vitamin E administration on basal nitric oxide function in male smokers and non-smokers.

1. The antioxidant properties of vitamin E (alpha-tocopherol) have been proposed to account for a possible protective effect in coronary artery disease. Coronary risk factors are associated with depressed endothelium-derived nitric oxide responses, and some evidence suggests increased quenching of the vasodilator effect of nitric oxide by oxygen free radicals. This study examined the possibility that vitamin E supplementation would improve basal function of the nitric oxide dilator system in long-term smokers and non-smokers. 2. Nine healthy male life-long non-smoking subjects and eight smokers (36 +/- 6 cigarettes per day, > 7 years) were given 1000 i.u. of vitamin E per day for a 4-week period, while five additional non-smokers received placebo. Forearm blood flow responses to intra-arterial infusion of noradrenaline (60, 120 and 240 rho mol/min) and the competitive inhibitor of nitric oxide synthesis, NG-monomethyl-L-arginine (1, 2 and 4 mumol/min) were measured before and after therapy. 3. No changes were evident in the constrictor responses to noradrenaline or NG-monomethyl-L-arginine in any group. These results indicate that vitamin E supplementation does not influence basal activity of the nitric oxide-dilator system in vivo.

Adult↗
PubMed1993

The contribution of calcitonin gene-related peptide (CGRP) to neurogenic vasodilator responses.

The neuropeptide calcitonin gene-related peptide (CGRP) is a potent vasodilator in the microcirculation of many tissues including the skin and joint. In order to elucidate the mechanism of endogenous CGRP release, we have used a multiple site 133Xe clearance technique to measure local blood flow changes in response to agents injected intradermally in the rabbit. Capsaicin (100 nmol/site) and human alpha CGRP (3 pmol/site) stimulated similar increases in blood flow and, in both cases, the effect was totally abolished by the CGRP antagonist, CGRP8-37 (1 nmol/site). By contrast, the nitric oxide synthase inhibitor L-nitro arginine methyl ester (L-NAME, 30 nmol/site) had little effect on human alpha CGRP-induced vasodilation, but caused significant inhibition of the response to capsaicin (p < 0.05). These results show that increased blood flow in rabbit skin caused by exogenous CGRP is independent of nitric oxide. In addition, however, they suggest that nitric oxide is required for either the release of endogenous CGRP from capsaicin-sensitive nerves or its subsequent activity.

Animals↗
PubMed1992

A psychoanalytic study of eating disorders: I. A developmental profile of 67 index cases.

Much has been written in both the professional literature and lay press regarding the sociocultural basis for the current increase in eating disorders. The typical victims of these afflictions appear to be intelligent adolescent girls from middle and upper class families (Garfinkel and Garner, 1982). Although the general pressure for thinness, mastery, and achievement among women in our culture undoubtedly help shape the course of illness, these social mores do not appear to be its root causes. The data presented here suggest strongly that the truly eating-disordered individual has a history of disturbances in early relationships, leading to a lack of security and pronounced difficulties in trusting others, and in simply being an authentic individual in the presence of others. As such these individuals share many characteristics of others with severe personality disorders such as inner emptiness, problems with identity, fear of abandonment, and peer relationships (Clarkin et al., in press), but differ in the expression of these basic defects or in solutions found to compensate pathologically for these core deficiencies. Therefore, although contemporary cultural ideals and values may supply the shape of the disorder, these individuals would have fared badly in any social climate although their presentation of illness may have differed (Bemporad et al., 1988). It is this profound underlying personality pathology that necessitates prolonged treatment for any hope of amelioration. Later reports will address this indication with a description of the results of therapy.

Adult↗