Biomedical subjects

D Lyons

Publications and source records attributed to D Lyons.

At least 19 recordsLinked to original sources

PubMed1999

Vascular endothelial growth factor is more important than basic fibroblastic growth factor during ischemic wound healing.

OBJECTIVES: To test the influence of vascular endothelial growth factor (VEGF) on normal and ischemic wounds in a noncontractive dermal ulcer standardized model in the rabbit ear and to assay the levels of both VEGF and basic fibroblastic growth factor messenger RNA levels in normal and ischemic wounds at different intervals during the healing process. DESIGN AND INTERVENTIONS: Dermal ulcers were created in the normal and ischemic ears of 20 anesthetized young female New Zealand white rabbits. Either VEGF 121, VEGF 165 (30 microg per wound), or buffered saline solution alone was applied to each wound and covered. Wounds were harvested at day 7 or 10 and evaluated histologically. Twenty-four similar rabbits were wounded in the same manner and their untreated wounds were harvested at 1, 3, 7, and 10 days after wounding. The wounds were analyzed with reverse transcriptase polymerase chain reaction. MAIN OUTCOME MEASURES: Histologic specimens were measured for amount of new epithelium and granulation tissue. Reverse transcriptase polymerase chain reaction was used to determine basic fibroblastic growth factor and VEGF messenger RNA expression. RESULTS: Both isoforms of VEGF improved granulation tissue formation in both normal and ischemic wounds with a magnitude similar to other vulnerary agents tested in the past. Vascular endothelial growth factor application had no effect on new epithelium formation. In contrast to basic fibroblastic growth factor, VEGF messenger RNA levels were induced 4 fold by ischemia alone and 6 fold by wounding in both ischemic and normal wounds. CONCLUSION: Vascular endothelial growth factor seems to be more important than basic fibroblastic growth factor during ischemic wound healing. Treatment of ischemic wounds with VEGF improves the deficit in wound healing produced by ischemia.

Animals↗

PubMed1999

The effect of age on vascular compliance in man: which are the appropriate measures?

Vascular compliance declines rapidly with age and measures of arterial compliance may help understanding of the aging process. Of the different measures of vascular compliance, those more closely related to chronological age need to be identified. These measures may help in the estimation of 'biological age'. We measured pulse wave velocity as the carotid-finger interval, carotid-toe interval and QKD interval (time between the Q wave and the arrival of the diastolic Korotkoff sound (K) over the brachial artery in diastoly (D)); central aortic compliance (CAC) and SV/PP (the stroke volume divided by pulse pressure in the brachial artery). Thirty-six volunteers were studied (30 men), ages 20 to 84, mean 49 years, to give the relationship of these measurements with age. CAC, the QKD interval and the carotid-toe interval were most closely related to age (r = - 0.51, -0.60 and -0.58 respectively). After adjustment for age, the only measure related to blood pressure was the carotid-finger interval; b for diastolic blood pressure = -0.83 (P = 0.01), the higher the pressure the shorter the interval. Measurements of CAC, QKD interval and carotid-toe interval may be employed to assess the impact of age on vascular compliance. Measures of peripheral vascular compliance, such as the carotid-finger interval, may prove useful in assessing the relationship between blood pressure and vascular compliance.

Adult↗

PubMed1998

Brain imaging. Functional consequences of ethanol in the central nervous system.

In recent years, sophisticated methods have been developed to view structure and function within the living brain. Functional imaging methods are used to visualize dynamic chemical processes that are linked to brain activity. Increased neural activity, for example, leads to greater glucose and oxygen consumption and greater regional rates of blood flow to meet elevated energy demands. Mapping these changes provides quantitative visual descriptions of localized changes in brain activity that result from behavioral or pharmacological manipulations. This chapter first describes several current methods and how they are used to study the effects of alcohol on brain function. In the second part, the effects of acute intoxication are discussed with emphasis on the complex nature of alcohol's effects in the central nervous system, which depend on dose, time since administration, and environmental context. In the final part, the functional consequences of long-term exposure to alcohol as well as diseases associated with chronic alcoholism are reviewed.

Alcohol Drinking↗

PubMed1998

New, angle-independent, low cost Doppler system to measure blood flow.

BACKGROUND: A new Doppler flowmeter using a special transducer forming two ultrasound beams to insonate vessels was developed. This low-cost flowmeter allows the flow to be measured independently of the angle of insonation. METHODS: Sixty-five flow determinations were made in the carotid arteries of five pigs. The flowmeter measured the flow in an artery bled into a calibrated vessel. Results were compared with the true volume of the blood captured. RESULTS: On average, 13 measurements per animal were made at different flow rates (80 to 600 mL/min). The flowmeter measured flow-volume rates in mL/min were found to be within +/- 15% of the cylinder captured volume. CONCLUSIONS: The accuracy of the angle-independent flowmeter is comparable with that of flowmeters currently used clinically. The small size and portability, low operator dependency, and low cost suggest potential for continuous acute and chronic-flow monitoring and a potential for an implantable flow-monitoring device.

Animals↗

PubMed1998

Multiphasic consequences of the acute administration of ethanol on cerebral glucose metabolism in the rat.

The present study investigated the role of the postinjection interval in determining the functional consequences of acute ethanol administration in the CNS. Local cerebral metabolic rates for glucose (LCMRglc) were determined by the 2[14C]deoxyglucose method in 48 brain structures of ethanol-naive Sprague-Dawley rats. Tracer was injected 1 or 45 min after a 0.8 g/kg intragastric dose of ethanol or water. At the early time point, LCMRglc was increased in a highly restricted portion of the basal ganglia that included the dorsal striatum, globus pallidus, and core of the nucleus accumbens, compared to water controls. No significant decreases were found at this early time point. At the later time point, by contrast, LCMRglc was decreased in a different set of brain structures. These sites were limbic in nature and included the infralimbic and anterior cingulate cortices, dentate gyrus, lateral septum, and the bed nucleus of the stria terminalis. These data indicate that there are multiple phases that can be detected during the time course of an acute dose of ethanol. They further demonstrate the involvement of different neural systems at the two time points. Increased activity in basal ganglia is consistent with stimulated motor activity, whereas diminished activity in limbic sites may correspond to changes in mood and motivation.

Administration, Oral↗

PubMed1998

Time-dependent effects of acute ethanol administration on regional cerebral blood flow in the rat.

The present study investigated the role of the postinjection interval in determining the functional consequences of acute ethanol administration in the CNS. Regional cerebral blood flow (RCBF) was determined by the [14C]iodoantipyrine method in 33 brain structures of ethanol-naive Sprague-Dawley rats. In the first experiment, changes in RCBF were assessed 5 and 15 min after a 0.8 g/kg (i.p.) dose of ethanol or water. Five minutes after treatment, rates of RCBF were increased in the motor cortex, agranular insular cortex, and the olfactory tubercle compared to water controls. No significant differences compared to control were found at the 15-min time point, despite the continued presence of ethanol in the blood. Experiment 2 tested whether blood ethanol level was the sole determinant of this response to ethanol by comparing animals with the same blood ethanol level at the 5- and 15-min time points. Greater rates of RCBF were found at 5 min postinjection compared to 15 min, in the motor cortex, agranular insular cortex, caudate/putamen, cerebellum, and the lateral septum. These data demonstrate that the rates of cerebral blood flow are increased in regionally discrete portions of the rat brain shortly after ethanol administration. Furthermore, blood ethanol level is not the exclusive factor governing this functional response.

Animals↗

PubMed1998

Differences between amlodipine and lisinopril in control of clinic and twenty-four hour ambulatory blood pressures.

The anti-hypertensive efficacy of once-daily amlodipine (up to 10 mg) and lisinopril (up to 20 mg) were compared in terms of clinic and ambulatory blood pressure (BP) control, in an observer-blind, two-period crossover study. Following a 4-week placebo run-in period, patients underwent two active treatment phases each lasting 12 weeks and separated by a 4-week washout period. Sixty patients with a supine diastolic BP between 90 and 120 mm Hg were included, irrespective of whether or not they had received previous anti-hypertensive medication. Amlodipine reduced supine systolic and diastolic clinic BP significantly more than lisinopril (-20+/-2/-14+/-1 vs -11 3/-7+/-1 mm Hg; P=0.02/ P=0.001) 24 h post-dose. Clinic standing diastolic BP was also significantly reduced with amlodipine compared with lisinopril (P=0.05). Both drugs produced control of mean ambulatory BP relative to baseline over 24 h. Amlodipine showed more consistent control of BP over the 24-h period in contrast to lisinopril which exerted its greatest effect during the daytime.

Adolescent↗

PubMed1998

Ligand recognition by alpha beta T cell receptors.

While still incomplete, the first data concerning the biochemistry of T cell receptor-ligand interactions in cell-free systems seem to have considerable predictive value regarding whether a T cell response is strong or weak or suppressive. This data will help considerably in elucidating the mechanisms behind T cell responsiveness. Also of great interest are the first structures of T cell receptor molecules and, particularly, TCR-ligand complexes. These appear to confirm earlier suggestions of a fixed orientation for TCR engagement with peptide/MHC and should form the basis for understanding higher oligomers, evidence for which has also just emerged. We conclude with an analysis of the highly diverse CDR3 loops found in all antigen receptor molecules and suggest that such regions form the core of both TCR and antibody specificity.

Animals↗

PubMed1997

Impairment and restoration of nitric oxide-dependent vasodilation in cardiovascular disease.

The generation of nitric oxide by the vascular endothelium maintains a continuous vasodilator tone that is essential for the regulation of blood flow and blood pressure. Nitric oxide also contributes to the control of platelet aggregation and has important antiatherogenic effects. These properties are mediated by the action of constitutive nitric oxide synthase and subsequent activation by nitric oxide of soluble guanylate cyclase. Impaired release of nitric oxide occurs in most animal and human models of hypertension, contributing to the increased peripheral resistance and most likely to the development of cardiovascular complications. Antihypertensive medications (angiotensin-converting enzyme [ACE] inhibitors and calcium channel blockers) appear to prevent the impairment of nitric oxide-mediated vasodilation in experimental hypertension, though in humans the data are not as clear. Reduced nitric oxide release appears therefore to be a consequence rather than a cause of high blood pressure, and the reduction in blood pressure per se is most important. In hyperlipidaemia, endothelium-dependent relaxations are reduced probably due to the inhibitory action of oxidized low-density lipoproteins on endothelium-dependent relaxations. Lipid-lowering strategies and, more recently, ACE inhibition have been demonstrated to improve nitric oxide dependent coronary vasodilation in hypercholesterolaemic patients with and without atheromatous coronary disease. Nitric oxide dependent vasodilation is also impaired in insulin- and non-insulin-dependent diabetes as well as in healthy aging. Endothelial dysfunction may be improved in non-insulin-dependent diabetes by administration of the antioxidants, supporting the hypothesis that nitric oxide inactivation by oxygen-derived free radicals contributes to abnormal vascular reactivity in diabetes.

Aging↗

PubMed1997

Identification and characterization of a pro-tumor necrosis factor-alpha-processing enzyme from the ADAM family of zinc metalloproteases.

Tumor necrosis factor-alpha (TNF) is initially expressed as a 26-kDa membrane-bound precusor protein (pro-TNF) that is shed proteolytically from the cell surface, releasing soluble 17-kDa TNF. We have identified human ADAM 10 (HuAD10) from THP-1 membrane extracts as a metalloprotease that specifically clips a peptide substrate spanning the authentic cleavage site between Ala76 and Val77 in pro-TNF. To confirm that HuAD10 has TNF processing activity, we cloned, expressed, and purified an active, truncated form of HuAD10. Characterization of recombinant HuAD10 (rHuAD10) suggests that this enzyme has many of the properties (i.e. substrate specificity, metalloprotease activity, cellular location) expected for a physiologically relevant TNF-processing enzyme.

ADAM Proteins↗

PubMed1997

ACE inhibition: postsynaptic adrenergic sympatholytic action in men.

BACKGROUND: The mechanisms by which ACE inhibitors produce a sustained clinical benefit are not entirely clear but may involve the sympathetic nervous system. We compared the effect of local brachial artery infusions of an ACE inhibitor (perindoprilat) with the effect of placebo (0.9% NaCl) on endogenously mediated (lower body negative pressure [LBNP]) and exogenously mediated (brachial artery infusions of norepinephrine) sympathetic vasoconstriction. METHODS AND RESULTS: Eight healthy, normotensive male volunteers (20 to 32 years) were studied on one occasion. Forearm blood flow (FABF; mL x dL forearm(-1) x min(-1)) responses to LBNP (-20 cm H2O) and increasing increments of norepinephrine (60, 120, and 240 pmol/min) were compared when coinfused with placebo and perindoprilat (5 nmol/mL). FABF was measured simultaneously in both arms by venous occlusion plethysmography with mercury-in-Silastic strain gauges with drugs infused locally at the left brachial artery. The right arm served as a control. Baseline FABFs did not differ between the infused and control arms (3.04+/-0.52 versus 3.05+/-0.42 mL x dL forearm(-1) x min(-1); P=.98). Perindoprilat did not alter FABF when infused alone, but the FABF response to LBNP in the infused arm was attenuated during the perindoprilat infusion compared with placebo (-17.8+/-4.3% versus -33.8+/-3.1%, respectively; P=.015). The FABF response to the maximum dose of norepinephrine was also attenuated during the perindoprilat infusion compared with placebo (-28.3+/-1.4% versus -36.9+/-2.8%, respectively; P=.015). The mean slope of the FABF (log transformed) versus norepinephrine dose-response curve was significantly attenuated by perindoprilat compared with placebo (-0.11+/-0.019 versus -0.02+/-0.02; P=.001). CONCLUSIONS: We conclude that ACE inhibition has a significant postsynaptic sympatholytic effect in the forearm circulation of men.

Adult↗

PubMed1997

Dopamine depletion in the rostral nucleus accumbens alters the cerebral metabolic response to cocaine in the rat.

The functional consequences of dopamine depletion in the rostral nucleus accumbens were examined using the quantitative 2-[14C]deoxyglucose method for determining rates of local cerebral glucose utilization. Cerebral metabolism was determined in 35 brain structures of Sprague-Dawley rats with unilateral 6-hydroxydopamine or sham lesions of the rostral accumbens. The effect of the lesion was assessed in cocaine-naive animals treated systemically with cocaine or saline. In saline-treated animals, the lesion increased cerebral metabolism in typical basal ganglia regions, such as the globus pallidus and entopeduncular nucleus, as well as portions of the extended amygdala that included the bed nucleus of the stria terminalis and the hypothalamic preoptic area. Cerebral metabolism was affected bilaterally in a subset of all affected structures which demonstrated that the functional consequences of the lesion extended beyond the primary monosynaptic output zones of the rostral accumbens. The lesion also changed the topography of the normal cocaine response such that cocaine effects were blunted in the shell of the nucleus accumbens, globus pallidus and the medial ventral pallidum. Thus, the present study describes functional evidence of the link between the rostral accumbens and the extended amygdala and demonstrates that dopamine in the rostral accumbens plays an important role in the central response to cocaine.

Animals↗

PubMed1997

Partnership nursing home care for dementia: the Glasgow experience--one-year follow-up.

The outcome of the transfer of 60 elderly patients suffering from dementia from hospital to nursing home care under a partnership contract was reviewed at 6 and 12 months following transfer. The nursing home population had fared badly compared with patients remaining in hospital during the first 3 months. This difference was less evident at 6 months follow-up and had disappeared at 12 months follow-up. It seems that a partnership agreement such as this can deliver a quality of health care at least as good as hospital treatment as long as the transfer is handled carefully.

Aged↗

PubMed1997

Partnership nursing home care for dementia: the Glasgow experience--one-year follow-up.

Aged↗

PubMed1997

Effect of enalapril and quinapril on forearm vascular ACE in man.

OBJECTIVE: Different ACE inhibitors can be distinguished in vitro by their affinity for converting enzyme in vascular and other tissues. Quinapril appears to be amongst the more effective inhibitors of vascular tissue ACE in vitro. This study assesses the in vivo effect of single oral doses of quinapril and enalapril, in attenuating the vasoconstrictive action of angiotensin I (AI) (which we have previously shown depends on its conversion to angiotensin II (AII) by vascular ACE) in the forearm resistance vessels of man. METHODS: The design was of randomized, open, placebo controlled, two way crossover type, Forearm blood flow (FABF) was measured simultaneously in both forearms by mercury in silastic strain gauge plethysmography. AI infusion were via a fine bore cannula in the left brachial artery with the right arm serving as a control. RESULTS: Mean plasma ACE on placebo was 34.3 U.l-1. Both quinapril and enalapril produced a similar degree of plasma ACE inhibition reducing concentrations to 2.8 U.l-1 and 2.6 U.l-1 respectively. Quinapril caused a significantly greater inhibition of AI induced vasoconstriction with a 30.0% reduction compared with 67.0% and 85.0% for enalapril and placebo respectively. Enalapril attenuated AI induced vasoconstriction to a greater degree than placebo but the difference was not significantly different. CONCLUSION: These results indicate that when quinapril and enalapril are administered as single 20 mg doses, each of which produces the same degree of plasma ACE inhibition and blood pressure reduction- quinapril inhibits vascular ACE to a greater degree than both enalapril and placebo.

Adult↗

PubMed1997

Impaired nitric oxide-mediated vasodilatation and total body nitric oxide production in healthy old age.

1. Basal release of nitric oxide from the vascular endothelium maintains a constant vasodilating tone. Impaired nitric oxide-mediated vasodilatation has been described in hypertension and atheromatous disease. Circulatory diseases account for considerable morbidity and almost half of all deaths in people over the age of 75 years. 2. We have therefore compared nitric oxide-dependent vasorelaxation in 12 healthy elderly subjects with 12 young volunteers matched for blood pressure, cholesterol and glucose, using forearm occlusion venous plethysmography combined with brachial artery infusions of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA; 1, 2 and 4 mumol/min) with noradrenaline (60, 120 and 240 pmol/min) as a control vasoconstrictor. We also measured urinary nitrate excretion after a controlled 48 h low nitrate diet as an index of total body nitric oxide production and correlated these changes with forearm blood flow responses to L-NMMA and noradrenaline in both groups. 3. The mean age and blood pressure of the elderly subjects was 76 (range 66-82) years and 132/76 (SEM 4/3) mmHg respectively, while in the young these were 27 (20-35) years and 131/72 (4/3) mmHg respectively. L-NMMA and noradrenaline produced dose-dependent reductions in forearm blood flow in both groups. L-NMMA (4 mumol/min) produced less vasoconstriction in the elderly than in the young (-37.7 +/- 2.6 versus -48.3 +/- 4.2%; P = 0.017). The mean slope of the L-NMMA dose-response curves in the elderly was significantly less than the younger group (-35.2 +/- 3.1 versus -63.7 +/- 10.6; P = 0.041). Noradrenaline, 240 pmol/min, also produced less vasoconstriction in the elderly compared with the young (-22.8 +/- 2.9 versus -35.3 +/- 5.0%; P = 0.029) although the slopes of the dose-response curves did not differ significantly. 4. Urinary nitrate adjusted for creatinine clearance was also significantly higher in the younger group (460.6 +/- 97.7 versus 205.9 +/- 64.8 mumol/day; P = 0.042) and showed a significant correlation with the percentage change in forearm blood flow in response to the maximum dose of L-NMMA (r = 0.5, P = 0.046). 5. We conclude that nitric oxide-mediated vasodilatation in the forearm vascular bed is diminished in old age and this reflects a more generalized reduction in nitric oxide production (as measured by urinary nitrate) in the circulation of older people. The blunted response to noradrenaline points to a more generalized reduction in vascular reactivity in the elderly.

Adult↗

PubMed1997

Do trandolapril and indomethacin influence renal function and renal functional reserve in hypertensive patients?

AIMS: To assess the effect of trandolapril (2 mg once daily) and indomethacin (25 mg three times daily), alone and in combination, on renal function and renal functional reserve in hypertensive patients (DBP 95-115 mmHg) requiring regular non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Randomized, double-blind, placebo-controlled, four way crossover design. After 3 weeks treatment renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured using the p-aminohippurate (PAH) and inulin methods. Renal functional reserve was estimated by measuring RPF and GFR at the end of an intravenous infusion of dopamine 2 microg kg(-1) and 10% amino acid solution. RESULTS: There was no significant difference in RPF between treatments: -22.79 ml min(-1) (95% CI -54.82, 9.24) for placebo and trandolapril, -10.37 ml min(-1) (95% CI -30.7, 9.96) for placebo and indomethacin, -14.78 ml min(-1) (95% CI -50.33, 20.77) for placebo and trandolapril with indomethacin. There was no significant difference in functional reserve RPF between treatments: -34.96 ml min(-1) (95% CI -119.8, 49.88) for placebo and trandolapril, 29.78 ml min(-1), -15.18, 74.74) for placebo and indomethacin, and -25.84 ml min(-1) (95% CI -87.62, 35.94) for placebo and trandolapril with indomethacin. There was no significant difference in GFR between treatments: -1.01 ml min(-1) (95% CI -7.45, 5.42) for placebo and trandolapril, -7.88 ml min(-1) (95% CI -15.08, -0.68) for placebo and indomethacin, and -0.36 ml min(-1) (95% CI -7.58, 6.86) for placebo and trandolapril with indomethacin. There was no significant difference in functional reserve GFR between treatments: 5.13 ml min(-1) (95% CI -4.97, 15.23) for placebo and trandolapril, 6.31 ml min(-1) (95% CI -1.88, 14.5) for placebo and indomethacin, 7.21 ml min(-1) (95% CI 1.26, 13.16) for placebo and trandolapril with indomethacin. CONCLUSION: In hypertensives chronic treatment with NSAIDs or ACEI alone or in combination did not change RPF or GFR and did not change renal functional reserve capacity of RPF or GFR.

Adult↗

PubMed1997

The contractile properties of the elderly human diaphragm.

It has previously been reported that aging is associated with a substantial decrease in diaphragm strength. To test this hypothesis we studied 15 (10 male, 5 female) subjects with a mean age of 29 (range 21 to 40) and 15 elderly (10 male, 5 female) subjects, mean age 73 (range 67 to 81). We measured transdiaphragmatic pressure (Pdi) during a maximal sniff (Sniff Pdi) and during bilateral cervical magnetic stimulation (CMS) of the phrenic nerve roots (Tw Pdi). Additionally in 17 subjects (9 elderly and 8 young) the Pdi elicited by paired CMS (pTw Pdi) was obtained at interstimulus intervals ranging from 10 to 999 ms (1 to 100 Hz). There was considerable overlap between groups. Mean Sniff Pdi in the elderly was 119 cm H2O compared with 136 cm H2O for the young subjects; this represented a median reduction of 18 cm H2O or 13% (p = 0.05, 95% Cl of difference 0 to 33 cm H2O). Mean Twitch Pdi in the elderly was 26.8 cm H2O compared with 35.2 cm H2O, a median reduction of 8 cm H2O or 23% (p = 0.004, 95% Cl 3 to 13 cm H2O). At 10 Hz the elderly tended to generate a higher fraction of the Pdi obtained at 100 Hz than the young, but this trend did not achieve statistical significance (p = 0.11). We conclude that aging is associated with a reduction in diaphragm strength. However the magnitude of the reduction is small and may be offset by a leftward shift of the force-frequency relationship.

Adult↗