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Biomedical subjects

L Flint

Publications and source records attributed to L Flint.

At least 19 recordsLinked to original sources
PubMed2001

Impaired coronary tissue plasminogen activator release is associated with coronary atherosclerosis and cigarette smoking: direct link between endothelial dysfunction and atherothrombosis.

BACKGROUND: The aim of the study was to establish the influence of proximal coronary artery atheroma and smoking habit on the stimulated release of tissue plasminogen activator (tPA) from the heart. METHODS AND RESULTS: After diagnostic coronary angiography in 25 patients, the left anterior descending coronary artery (LAD) was instrumented, and the proximal LAD plaque volume was determined by use of intravascular ultrasound (IVUS). Blood flow and fibrinolytic responses to selective LAD infusion of saline, substance P (10 to 40 pmol/min; endothelium-dependent), and sodium nitroprusside (5 to 20 microgram/min; endothelium-independent) were measured by intracoronary IVUS and Doppler, combined with arterial and coronary sinus blood sampling. Mean plaque burden was 5.5+/-0.8 mm(3)/mm vessel (range 0.6 to 13.7 mm(3)/mm vessel). LAD blood flow increased with both substance P and sodium nitroprusside (P<0.001), although coronary sinus plasma tPA antigen and activity concentrations increased only during substance P infusion (P<0.006 for both). There was a strong inverse correlation between the LAD plaque burden and release of active tPA (r=-0.61, P=0.003). Cigarette smoking was associated with impaired coronary release of active tPA (current smokers, 31+/-23 IU/min; ex-smokers, 50+/-33 IU/min; nonsmokers 202+/-73 IU/min; P<0.05). CONCLUSIONS: We found that both the coronary atheromatous plaque burden and smoking habit are associated with a reduced acute local fibrinolytic capacity of the heart. These important findings provide evidence of a direct link between endogenous fibrinolysis, endothelial dysfunction, and atherothrombosis in the coronary circulation and may explain the greater efficacy of thrombolytic therapy for myocardial infarction in cigarette smokers.

Area Under Curve↗
PubMed2001

Drugs, guns, and kids: the association between substance use and injury caused by interpersonal violence.

BACKGROUND: Drug and alcohol uses have been linked to the frequency of injury events, recurrent hospital admission for injury, and interpersonal violence. Data regarding the association of recent substance use and injury type and frequency in children and young adults are not available. Such data probably would be valuable in planning interventions to prevent substance use and reduce the risks of injuries. METHODS: Evidence of substance use was assessed in trauma patients presenting to the authors' level 1 trauma center over a 6-month interval. Demographic data, mechanisms of injury, revised trauma scores (RTS), injury severity scores (ISS), hospital days, and mortality rate were evaluated. Chi square analysis and 2-tailed, paired t tests were used for statistical analysis. Multivariate logistic regression was utilized to determine the influence of individual variables. RESULTS: From a total group of 743 patients with life-threatening injuries, trauma registry records of 186 patients less than 21 years old were eligible for evaluation, and 126 of these had complete blood and urine drug assessments completed on admission to the trauma center. Forty-two percent (53 of 126) patients tested positive for alcohol or drugs. No patients less than 14 years of age (n = 61) had positive drug screen results. However, in the cohort of patients aged 14 and 15 (n = 17), 71% tested positive. Also, 72% of adolescents (age < 18) who were victims of injuries from gunshot wounds had evidence of substance use. Multivariate analysis showed gunshot wounds (P <.003) to be associated independently with positive drug screens. No statistical differences were observed in ethnic distribution, ISS, RTS, hospital days, or mortality rate when patients with positive screen results were compared with those without evidence of substance use. CONCLUSIONS: Trauma victims had evidence of substance use in early teen age years especially in the 14 and 15-year-old age groups. Toxicology screening disclosed that substance use is associated strongly with gunshot wounds. Substance use, along with poverty, inadequate family support, and peer pressure are factors that influence injury risk. Interventions to prevent substance use in young children may reduce the risk of injury.

Adolescent↗
PubMed2000

The influence of heart rate on augmentation index and central arterial pressure in humans.

Arterial stiffness is an important determinant of cardiovascular risk. Augmentation index (AIx) is a measure of systemic arterial stiffness derived from the ascending aortic pressure waveform. The aim of the present study was to assess the effect of heart rate on AIx. We elected to use cardiac pacing rather than chronotropic drugs to minimize confounding effects on the systemic circulation and myocardial contractility. Twenty-two subjects (13 male) with a mean age of 63 years and permanent cardiac pacemakers in situ were studied. Pulse wave analysis was used to determine central arterial pressure waveforms, non-invasively, during incremental pacing (from 60 to 110 beats min-1), from which AIx and central blood pressure were calculated. Peripheral blood pressure was recorded non-invasively from the brachial artery. There was a significant, inverse, linear relationship between AIx and heart rate (r = -0.76; P < 0.001). For a 10 beats min-1 increment, AIx fell by around 4 %. Ejection duration and heart rate were also inversely related (r = -0. 51; P < 0.001). Peripheral systolic, diastolic and mean arterial pressure increased significantly during incremental pacing. Although central diastolic pressure increased significantly with pacing, central systolic pressure did not. There was a significant increase in the ratio of peripheral to central pulse pressure (P < 0.001), which was accounted for by the observed change in central pressure augmentation. These results demonstrate an inverse, linear relationship between AIx and heart rate. This is likely to be due to alterations in the timing of the reflected pressure wave, produced by changes in the absolute duration of systole. Consideration of wave reflection and aortic pressure augmentation may explain the lack of rise in central systolic pressure during incremental pacing despite an increase in peripheral pressure.

Age Factors↗
PubMed2000

Invited Critique.

Explore the source record for details and available documents.

Journal Article↗
PubMed1998

Neither dopamine nor dobutamine corrects mesenteric blood flow depression caused by positive end-expiratory pressure in a rat model of acute lung injury.

OBJECTIVE: To determine if either dopamine or dobutamine would counteract the deleterious effect that positive end-expiratory pressure (PEEP) has on cardiac output and mesenteric blood flow in a rat model of acute lung injury. DESIGN: Prospective, randomized, controlled trial in a clinically relevant model of acute lung injury. SETTING: Microcirculation research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: The animals were anesthetized with pentobarbital (30 mg/kg) by intraperitoneal injection. They underwent tracheostomy, jugular and femoral vein cannulation, femoral artery cannulation, carotid artery thermistor placement, and bowel preparation for in vivo video microscopy. Acute lung injury was created by administering 0.1 N hydrochloric acid (1 mL/kg) via the tracheostomy. Dopamine or dobutamine (2.5 or 12.5 microg/kg/min), followed by two intravenous fluid boluses, was administered to rats ventilated with 5, 10, 15, and 20 cm H2O of PEEP. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, thermodilution cardiac output, mesenteric arteriolar diameter, and red blood cell velocity were measured and mesenteric blood flow was calculated. Cardiac output was depressed in rats exposed to 20 cm H2O of PEEP by 32+/-2%. The corresponding values for cardiac output depression at 20 cm H2O of PEEP in rats receiving 2.5 and 12.5 microg/kg/min of dopamine and 2.5 and 12.5 microg/kg/min of dobutamine were 31+/-1%, 21+/-1%, 29+/-0%, and 24+/-2%, respectively. Mesenteric blood flow was depressed in rats ventilated with 20 cm H2O of PEEP by 74+/-3%, while the corresponding values in rats exposed to 20 cm H2O of PEEP and receiving 2.5 or 12.5 microg/kg/min of dopamine or 2.5 or 12.5 microg/kg/min of dobutamine were 86+/-3%, 77+/-3%, 73+/-3%, and 66+/-3%, respectively. Fluid boluses did not correct the deficits in cardiac output or mesenteric blood flow caused by the combination of acute lung injury and PEEP. CONCLUSIONS: The higher doses of dopamine and dobutamine partially, but insignificantly, corrected the cardiac output depression caused by PEEP in a model of acute lung injury. Neither dose of dopamine nor dobutamine was able to improve PEEP-induced mesenteric blood flow depression.

Animals↗
PubMed1998

Mitral valve replacement in Sickle C disease using intraoperative exchange transfusion.

Sickle C (SC) disease is a relatively uncommon hematologic disorder that poses special challenges when the patient requires a major surgical procedure. In particular, those who have a history of hemolytic crises require some type of intervention, usually homologous transfusion, to decrease the level of circulating hemoglobin S (HbS) and prevent intraoperative sickle crisis. We describe a 25-year-old man with SC disease and a history of multiple sickle cell crises who underwent mitral valve replacement using intraoperative exchange transfusion to decrease his HbS level from 53% to 7%.

Adult↗
PubMed1996

Dopexamine prevents depression of mesenteric blood flow caused by positive end-expiratory pressure in rats.

BACKGROUND: The purpose of this study was to investigate the effects of two vasoactive agents, dopamine and dopexamine, on the depression of mesenteric blood flow caused by positive end-expiratory pressure (PEEP) during mechanical ventilation. METHODS: Sprague-Dawley rats were mechanically ventilated with either no PEEP (control group) or increasing levels of PEEP (PEEP group) up to 20 cm H2O pressure. We evaluated PEEP's effect on blood pressure, cardiac output (CO), and the mesenteric microcirculation with a continuous infusion of 2.5 or 12.5 micrograms/kg/min dopamine or 1, 3, or 5 micrograms/kg/min dopexamine. RESULTS: PEEP caused a 20% to 25% decrease in mean arterial pressure and a 30% decrease in CO at both 15 and 20 cm H2O of PEEP (all p < 0.05 versus baseline). Low dose dopamine partially corrected the decrease in CO to 16% and 21% below baseline at 15 and 20 cm H2O of PEEP, respectively (both p < 0.05 versus PEEP group) and partially ameliorated the depression of mesenteric blood flow associated with the application of PEEP. High dose dopamine did not positively affect either CO or mesenteric blood flow. Dopexamine had little effect on CO compared with dopamine. All three doses of dopexamine blocked the effect of PEEP on mesenteric blood flow (p < 0.05 compared with the PEEP group at all levels of PEEP, p < 0.05 compared with the low dose dopamine group at 15 and 20 cm H2O of PEEP). CONCLUSIONS: Dopexamine is superior to dopamine in protecting mesenteric blood flow in the face of increasing levels of PEEP.

Animals↗
PubMed1996

Neither dopamine nor dobutamine reverses the depression in mesenteric blood flow caused by positive end-expiratory pressure.

UNLABELLED: Positive end-expiratory pressure (PEEP) has been shown to cause a depression of mesenteric blood flow (MBF) and redistribution of blood flow away from the mesenteric vascular bed. OBJECTIVE: We sought to determine whether two commonly used vasoactive agents, dopamine, a known mesenteric vasodilator and inotrope, and dobutamine, with its inotropic properties, would correct the MBF depression caused by PEEP. DESIGN, MATERIAL, AND METHODS: Sprague-Dawley rats, 180 to 250 g, were treated with mechanical ventilation and either no PEEP (control group) or increasing levels (0, 10, 15, and 20 cm of H2O pressure) of PEEP (PEEP group). Also, we evaluated PEEP's effect on MBF and cardiac output (CO) under the influence of a continuous infusion of 2.5 or 12.5 microgram/kg/min of dopamine or 2.5 or 12.5 microgram/kg/min of dobutamine. Cardiac output and, using in vivo videomicroscopy, mesenteric A1, A2, and A3 arteriolar intraluminal radii and A1 arteriolar optical Doppler velocities were measured. After 20 cm of H2O pressure PEEP was attained, two boluses of 2 mL of 0.9 normal saline were given. The MBF was calculated from vessel radius and red blood cell velocity. MEASUREMENTS AND MAIN RESULTS: There were no significant changes from baseline in mean arterial pressure or A2 or A3 diameters in any of the groups. Both MBF and CO were unchanged over time in the control group. The MBF was reduced 78% (p < 0.05) and the CO was reduced 31% (p < 0.05) from baseline at 20 cm of H2O pressure PEEP. After 4 mL of normal saline, the MBF was still 53% below baseline (p < 0.05), while the CO had returned to baseline in the PEEP group. Low-dose dopamine partially ameliorated both the decrease in CO and MBF caused by PEEP, but 4 mL of normal saline was required in addition to the low-dose dopamine to return MBF to baseline levels while on 20 cm of H2O pressure PEEP. High-dose dopamine with the addition of 4 mL of normal saline returned CO to baseline on 20 cm of H2O pressure PEEP, but MBF remained approximately 46% below baseline despite fluid boluses. Neither low-dose nor high-dose dobutamine, with or without fluid boluses, had an appreciable positive effect on CO or MBF. CONCLUSIONS: It is clear that inotropes are not a replacement for adequate fluid loading to correct the depression in cardiac output and mesenteric blood flow associated with the use of mechanical ventilation and PEEP. Low-dose dopamine may serve as an adjunct to adequate fluid resuscitation to improve MBF.

Analysis of Variance↗
PubMed1996

Adrenomedullin is inactivated in the lungs of neonatal piglets.

Adrenomedullin, a novel 52 amino acid peptide normally present in adult human plasma, has been shown to induce systemic hypotension in the adult rat, pig and cat, and in the new-born piglet. Little is known about the site (s) of adrenomedullin inactivation in adults or neonates. Groups of five 0-2-day old and 2-week old anaesthetized piglets were prepared to enable continuous monitoring of cardiac output, mean systemic arterial pressure, mean pulmonary artery pressure, mean systemic vascular resistance and mean pulmonary vascular resistance. In both age groups, injections of human adrenomedullin1-52 into the left atrium produced significant (P < 0.05) reductions in mean systemic arterial pressure and mean pulmonary artery pressure. Although injections of similar doses of human adrenomedullin1-52 into the right atrium produced significant (P < 0.05) decreases in mean pulmonary artery pressure, there were no appreciable alterations in mean systemic arterial pressure in either age group. These results suggest that the systemic vasodilator properties of human adrenomedullin1-52 are reduced upon first pass through the pulmonary circulation in 2-week old piglets, a phenomenon that is present at birth.

Adrenomedullin↗
PubMed1995

Autonomic control of the regional hemodynamic response to scald.

Ultrasonic flow probes were placed around the ascending aorta and each femoral artery of dogs to record cardiac index and femoral blood flow, respectively. Intravenous hexamethonium (n = 5) produced 30% decreases in systemic mean arterial pressure and in cardiac index, and a 14% increase in femoral blood flow, effects that waned over time, consistent with the half-life of the agent. Without hexamethonium, hind paw scalding with boiling water for 5 sec (n = 5) caused a marked increase in ipsilateral femoral artery blood flow (70.7 +/- 8.9 ml/min pre-burn vs 243.7 +/- 23.7 ml/min 5 min post-burn) that persisted for the 3 hr observation period. Contralateral femoral blood flow, systemic mean arterial pressure, and cardiac index were unchanged. Compared to burn only dogs, pre-burn treatment with hexamethonium (n = 6) blunted the femoral vasodilator response to burn (78.8 +/- 9.7 ml/min pre-burn vs 116.5 +/- 7.5 ml/min 5 min post-burn). These data suggest that postganglionic autonomic nerves are at least partially responsible for mediation of the regional vasodilator response to thermal injury.

Animals↗
PubMed1995

Positive end-expiratory pressure decreases mesenteric blood flow despite normalization of cardiac output.

Positive end-expiratory pressure (PEEP) is a commonly used adjunct to mechanical ventilation and is known to have deleterious effects on cardiac output (CO). Its effects on regional blood flow are not well known. We evaluated the effect of PEEP on the mesenteric microcirculation and CO. Sprague-Dawley rats were treated with mechanical ventilation and either no PEEP (Control) or increasing levels of PEEP (PEEP). Using in vivo video-microscopy, mesenteric A1 arteriolar optical Doppler velocities and A1 and A3 (the first- and third-order arterioles branching off the feeding mesenteric arcade) intraluminal diameters were measured (n = 6/group). In a separate set of experimental animals, CO was determined by thermodilution technique (n = 5/group). Additionally, after the PEEP group attained a PEEP level of 20-cm H2O PEEP, two boluses of 2 mL 0.9 normal saline (NS) were given intravenously. The Control groups had the same determinations performed over the same time course as the PEEP group but were not exposed to any PEEP. Mesenteric blood flow (MBF) was calculated from vessel diameter and red blood cell velocity. The MBF and CO fell progressively as PEEP was increased from 10- to 15- to 20-cm H2O pressure. MBF was reduced 75% (p < 0.05) and the CO was reduced 31% (p < 0.05) from baseline at 20-cm H2O pressure PEEP. After 4 mL normal saline, the MBF was still 45% below baseline (p < 0.05) while the CO had returned to baseline. In conclusion, both MBF and CO are decreased significantly with increasing PEEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Femoral vasodilation to cromakalim is blocked by U37883A, a non-sulphonylurea that selectively inhibits KATP channels.

The purpose of the present study was to determine the effects of U37883A, a non-sulphonylurea inhibitor of KATP channels, in the femoral vascular bed of the anaesthetized dog. Administration of U37883A, 4-morpholinecarboxamidine-N-1-adamentyl-N"-cyclohexyl hydrochloride (2.5 mg kg-1, i.v.), significantly inhibited the femoral vasodilator response to intra-femoral arterial injection of cromakalim, an activator of KATP channels. In contrast, U37883A had no effect on the femoral vasodilator responses to nitroglycerin, isoprenaline, 5-HT, or 5-carboxamidotryptamine, suggesting this agent is a novel and selective inhibitor of hindlimb vasodilation induced by KATP-channel activation. Since U37883A did not significantly alter baseline femoral blood flow and femoral vascular resistance, the present data suggest that KATP channels do not contribute, in large measure, to regulating the canine femoral vascular bed under resting conditions in-vivo.

Adamantane↗
PubMed1994

Academic surgical group practices at the dawn of health reform.

OBJECTIVE: The authors collected, analyzed, and interpreted baseline data concerning academic surgical group practices as they function in the contemporary medical marketplace. SUMMARY AND BACKGROUND DATA: Health care reform officially began with President Clinton's recent address to Congress. Features of reform, such as universal coverage, managed competition, and regulation of graduate medical education (GME) challenge academic surgery. Data relevant to the governance, financial status, and market positions of academic surgical practices are not available. A current analysis of revenue sources and uses has not been published. METHODS: The authors used a 158-question survey to obtain information, for 1992, on adaptation to current market conditions, financial performance, and revenue uses in a sample of 100 academic surgical group practices. RESULTS: The response rate was 83%. Seventy-four selected group surveys were analyzed. Twenty-three groups are affiliated with private medical schools; 51 are affiliated with public medical schools. Fifty-seven per cent of the groups have satellite clinic networks, and 78% own or contract with managed-care entities. Eighty-six per cent of the groups derive more than 50% of referrals from outside the academic medical center. Gross revenue median was $35 million (range $10-$101 million). Revenue growth was reported by 66%. Payer mix trends show growth in government and health maintenance organization (HMO) payers. An average of 71% of faculty salaries come from practice. Practice revenues provide 68% of department expenses and 40% of research funds. Graduate medical education is supported directly by 69% of practice groups. CONCLUSIONS: Academic surgical group practices are vulnerable in the current marketplace. Revenue growth will be limited in the future because of weak payer mix and broad support of academic programs, including GME, using clinical income.

Academic Medical Centers↗
PubMed1994

Hyperinsulinaemia in ischaemic heart disease: the importance of myocardial infarction and left ventricular function.

Elevated circulating insulin levels have been reported in ischaemic heart disease, and may be of aetiological importance. Previous studies have not considered the potential influence of heart failure or of previous myocardial infarction, as opposed to stable angina. We therefore measured the insulin response to a 75 g oral glucose tolerance test in five groups with normal glucose tolerance, comparing normal male controls to men with chronic stable angina, men with recent myocardial infarction (two groups, 3 weeks and 3 months post infarction), and men with chronic severe heart failure. Only patients with chronic heart failure had fasting hyperinsulinaemia, probably reflecting associated neuroendocrine abnormalities. Stimulated hyperinsulinaemia was present in all patient groups, but was less pronounced and of shorter duration in patients with angina. At 120 min, only patients with heart failure or previous myocardial infarction were hyperinsulinaemic. The degree of stimulated hyperinsulinaemia was not influenced by the presence of heart failure or by the length of time from infarction. Hyperinsulinaemia is associated with impaired peripheral muscle glucose uptake and metabolism, and might contribute to muscular fatigue on exertion in patients with previous myocardial infarction or heart failure.

Administration, Oral↗