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Ronald Brown

Publications and source records attributed to Ronald Brown.

7 recordsLinked to original sources
PubMed2005

Effect of alpha2B-adrenoceptor polymorphism on peripheral vasoconstriction in healthy volunteers.

BACKGROUND: Alpha-2B adrenoceptor is the vasoconstrictive subtype in the mouse. Human alpha2B-AR deletion (D) allele has been associated with loss of short-term agonist-promoted receptor desensitization, which may lead to increased vasoconstriction on alpha2 activation. The goal of this study was to test the hypothesis that alpha2B-adrenoceptor activation induces enhanced vasoconstriction in carriers of the DD genotype, compared with carriers of the insertion/insertion (II) genotype. METHODS: The authors administered increasing doses of dexmedetomidine (targeting plasma concentrations of 0.15, 0.3, 0.6, and 1.2 ng/ml) to 16 healthy young volunteers (8 carrying the alpha2B DD genotype, 8 carrying the II genotype) in whom sympatholytic effects of the drug were attenuated by general anesthesia. Measurements were made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmitted through a finger, finger blood flow by venous occlusion plethysmography, and hemodynamic variables. RESULTS: All concentration of dexmedetomidine increased light transmitted through the finger (vasoconstriction) and systolic blood pressure and decreased heart rate in both groups (P < 0.001 for all). Dexmedetomidine reduced finger arterial inflow only in the DD group (P < 0.001). Dexmedetomidine had no effect on finger venous outflow or venous capacitance. There were no significant differences between the II and DD groups in any of the variables. CONCLUSIONS: The results of this study confirm the alpha2 agonist induced vasomotor and hemodynamic effects in peripheral vasculature. However, the results do not support the hypothesis that alpha2B-adrenoceptor polymorphism has an effect on peripheral vasoconstriction in humans.

Adrenergic alpha-Agonists↗
PubMed2005

Alpha-2B adrenoceptor polymorphism and peripheral vasoconstriction.

OBJECTIVES: Alpha-2B adrenoceptors (AR) mediate vasoconstriction in the mice. A human alpha-2B AR deletion (D) variant has been associated with loss of short-term agonist-promoted receptor desensitization, which may lead to increased vasoconstriction upon alpha-2 AR activation. This study tested the hypothesis that alpha-2 AR activation will induce enhanced vasoconstriction in carriers of the alpha-2B AR DD genotype, compared to carriers of the II or the DI genotypes. METHODS: We administered 1 microg/kg dexmedetomidine (an alpha-2 agonist) intravenously to 80 surgical patients in whom sympatholytic effects of the drug were attenuated by general anesthesia. Measurements were made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmission through a finger (LTF) and of hemodynamic variables. RESULTS: Dexmedetomidine increased LTF (vasoconstriction), induced an initial increase in systolic blood pressure and decreased heart rate in all genotype groups (P<0.0001 for all). Three min after the start of dexmedetomidine infusion, the increase in LTF was more pronounced (P=0.014) in the DD group compared to the DI and II groups. There were no significant differences in LTF values between the groups at the end of or 5 min after dexmedetomidine infusion. There were no differences in systolic blood pressure or heart rate values between the groups during or after the dexmedetomidine infusion. CONCLUSIONS: The results of this study confirm that the alpha-2 agonist dexmedetomidine induced marked peripheral vasoconstriction. Subjects with the alpha 2B DD genotype had an enhanced vasoconstrictive response at the beginning of dexmedetomidine infusion. However, this enhanced vasoconstrictive response was not sustained throughout or after the 15-min dexmedetomidine infusion.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2005

Intraoperative clonidine administration to neurosurgical patients.

The goals of this two-part study were to determine the dose of clonidine to prevent postoperative shivering after mild hypothermia and to evaluate the effect of clonidine on recovery from anesthesia in patients undergoing surgery for intracranial lesions. We enrolled 48 patients undergoing elective supratentorial neurosurgical procedures into one of two studies. In study 1 (n=14) we determined the ED50 of clonidine to prevent postoperative shivering after mild hypothermia (35 degrees C) using Dixon's up-and-down method. Clonidine dose for the first study patient was 3 microg/kg. The dose was then adjusted in 1-microg/kg increments for the following patients. Shivering was assessed for 1 h postoperatively. Study 2 (n=34) was a prospective, randomized, double-blind, placebo controlled study to evaluate the effect of 3 microg/kg clonidine on recovery from anesthesia. At the beginning of dural closure, patients randomly received a 15-min infusion of either clonidine or normal saline. Recovery variables were studied for 2 h after the end of anesthesia. The ED50 of clonidine to prevent shivering was 1.1 +/- 1.5 microg/kg in neurosurgical patients whose target core temperature was 35 degrees C at the end of surgery. Compared with saline, 3 microg/kg of clonidine administered to neurosurgical patients 1 h before the end of anesthesia did not delay emergence from anesthesia nor did it have clinically significant sedative or hemodynamic effects. Our results imply that clonidine may be used in neurosurgical patients to prevent postoperative shivering after mild hypothermia.

Adrenergic alpha-Agonists↗
PubMed2004

Short-term efficacy of methylphenidate: a randomized, double-blind, placebo-controlled trial among survivors of childhood cancer.

PURPOSE: Children surviving acute lymphoblastic leukemia (ALL) and malignant brain tumors (BTs) have a higher incidence of attention and learning problems in school than do their healthy peers. The present study tests the hypothesis that the psychostimulant methylphenidate (MPH) improves cognitive and social functioning among these patients. PATIENTS AND METHODS: We report on 83 long-term survivors of ALL and BT identified as having attentional deficits on behavioral testing and parent or teacher report, and problems with academic achievement. The 47 male and 36 female patients ranged from 0.6 to 14.3 years (median, 5.4 years) of age at diagnosis and 6.7 to 17.9 years (median, 11.9 years) of age at participation. The patients (40 ALL, 43 BT) participated in a randomized, double-blind, 3-week home cross-over trial of placebo (bid), low-dose MPH (0.3 mg/kg; maximum dose, 10 mg bid), and moderate-dose MPH (0.6 mg/kg; maximum dose, 20 mg bid). The primary end points were weekly teacher and parent reports on the Conners' Rating Scales and Social Skills Rating System. RESULTS: Compared to placebo, significant improvement with MPH was reported by teachers and parents on the Conners' Rating Scales and by teachers on the Social Skills Rating System. However, no consistent advantage of moderate dose over low dose was observed. Of those participating, 66 (79.5%) of the 83 patients continued on best clinical management. CONCLUSION: Treatment with MPH can at least temporarily reduce some attentional and social deficits among survivors of childhood ALL and BT. Long-term follow-up will reveal those subsets of patients who are more likely to benefit from MPH.

Adolescent↗
PubMed2003

Systemically administered alpha2-agonist-induced peripheral vasoconstriction in humans.

BACKGROUND: alpha(2)-Adrenoceptors mediate both sympatholytic and vasoconstrictive hemodynamic effects. The goal of this study was to profile the peripheral vasoconstrictive effects of a selective alpha(2)-adrenoceptor agonist in isolation from the sympatholytic effects it also induces. METHODS: The authors administered increasing plasma target concentrations of dexmedetomidine (0.075, 0.15, 0.3, and 0.6 ng/mL) or saline placebo to healthy young volunteers in whom the sympatholytic effects of the drug were attenuated in one of two ways: general anesthesia (propofol-alfentanil-nitrous oxide) or axillary brachial plexus block. Measurements were made of finger blood volume (an indicator of vasoconstriction) by photoplethysmographic determination of light transmitted through a finger (LTF) and hemodynamic variables. Measurements made before and during the four steps of infusion were compared by repeated-measures ANOVA. RESULTS: In anesthetized volunteers, all concentrations of dexmedetomidine increased LTF (vasoconstriction) and systolic blood pressure (P < 0.001 for both), whereas placebo did not. In awake volunteers, all concentrations decreased systolic blood pressure (P < 0.001). Concentrations of 0.15, 0.3, and 0.6 ng/mL decreased LTF (vasodilation) in the neurally intact hand; in contrast, the same concentrations increased LTF (vasoconstriction) in the sympathectomized hand (P < 0.001 for both). CONCLUSIONS: The results of this study are the first to characterize the lower end of the dose-response curve for vasoconstriction induced by dexmedetomidine. By denervating the vascular bed of interest or by decreasing sympathetic nervous system activity, the authors were able to observe vasoconstriction induced by a systemically administered alpha(2)-agonist with minimal interference from the sympatholytic effects of the drug.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2002

A comparison of three anesthetic techniques in patients undergoing craniotomy for supratentorial intracranial surgery.

UNLABELLED: Several anesthetic techniques have been used successfully to provide anesthesia for resection of intracranial supratentorial mass lesions. One technique used to enhance recovery involves changing anesthesia from vapor-based to propofol-based for cranial closure. However, there are no data to support a beneficial effect of this approach in the immediate postoperative period after craniotomy. We evaluated 3 anesthetic techniques in 60 patients undergoing elective surgery for supratentorial mass lesions. Patients were randomly assigned to three anesthesia study groups: propofol infusion, isoflurane inhalation, and these two techniques combined. In the combination group, once the dura was closed, isoflurane was discontinued and propofol infusion simultaneously started. We studied intra- and postoperative hemodynamics and several recovery variables for 2 h after the end of anesthesia. Baseline and average intraoperative blood pressure and heart rate values did not differ among the groups. Heart rate and blood pressure increased similarly in all groups in response to intubation and pin placement and postoperatively. None of the recovery event times (open eyes, extubation, follow commands, oriented, Aldrete score) or psychomotor test performance differed significantly. We conclude that the sequential administration of isoflurane and propofol did not provide earlier recovery and cognition than the intraoperative use of isoflurane alone. IMPLICATIONS: We evaluated three anesthetic techniques with and without propofol in patients undergoing elective surgery for supratentorial mass lesions by using a prospective, randomized clinical study design and found that the three anesthetics did not differ in intra- or postoperative hemodynamic stability or early postoperative recovery variables.

Adult↗