Edward M. Bednarczyk

Global cerebral blood flow, blood volume, and oxygen metabolism in patients with migraine headache

Objective Migraine headaches with and without aura are representative of vascular headache states traditionally thought to be mediated by alterations in vascular tone. Validation of this theory has been hampered in part by technical difficulties inherent in the measurement of cerebral blood flow (CBF). The purpose of this study was to compare CBF measured during migraine and migraine-free states using PET. Methods Patients with a minimum of one migraine headache without aura per month (International Headache Society [IHS] criteria) underwent measurement of CBF, cerebral blood volume (CBV), oxygen extraction, and metabolism during an episode of spontaneous migraine headache. Imaging was repeated during a migraine-free period of at least 48 hours. PET radiotracers used were: CBF, H215O; CBV, C15O; oxygen metabolism, 15O2. Results In nine patients (seven female and two male), global CBF (mL/min/ 100 g [SD]) was measured as 52.70 (6.9) during migraine and 59.65 (10.6) in the migraine-free state; p = 0.028. CBV (mL/100 g [SD]) was 3.6 (0.43) during the symptomatic state and 3.8 (0.55) after the migraine; p = 0.047. Oxygen metabolism (mWmin/100 g [SD]) was 3.68 (0.9) during migraine and 3.38 (1.02) without headache; p = 0.211. The oxygen extraction ratio was 0.48 (0.15) and 0.41 (0.12) during migraine and migraine-free states, respectively; p = 0.132. Conclusions In patients experiencing migraine without aura, CBF and CBV are reduced during the headache phase. Cerebral oxygen metabolism and oxygen extraction are not significantly affected.

Inhibition of Atazanavir Oral Absorption by Lansoprazole Gastric Acid Suppression in Healthy Volunteers

Study Objective. To determine whether the pharmacokinetics of atazanavir, a protease inhibitor used to treat human immunodeficiency virus (HIV) infection, are altered by its coadministration with lansoprazole, a proton pump inhibitor.

Efficacy and Safety of Galantamine in Patients with Dementia with Lewy Bodies: A 12-Week Interim Analysis

Observations on the neurochemistry of dementia with Lewy bodies (DLB) have suggested that cholinesterase inhibitors (ChEIs) might be beneficial in treating some clinical symptoms of DLB. A 24-week, multicenter open-label study was designed to assess the safety and efficacy of the ChEI galantamine in patients with DLB, and an interim analysis of results was performed at 12 weeks. Efficacy analyses were performed on data from 25 patients. Scores on the Neuropsychiatric Inventory (NPI-12) improved (decreased) by 7.52 points over the 12 weeks (marginally significant, p = 0.061). NPI-12 scores decreased by half in 12 of the 25 patients. Highly significant improvement was observed in scores on the NPI-4 subscale (delusions, hallucinations, apathy, and depression: p = 0.003). Scores on the Clinician’s Global Impression of Change (CGIC) improved by 0.95 points (significant, p = 0.02). Improvements also were found in secondary efficacy variables, including cognitive, functional, activities of daily living, sleep and confusion assessments. Motor scores, as measured by the UPDRS motor subscale, showed mild improvement, which demonstrates that galantamine has no adverse effect on parkinsonian symptoms. Adverse events generally were transient and of mild-to-moderate intensity. Two of the 25 patients discontinued galantamine because of nausea and anorexia. One serious adverse event was recorded, but it was judged to be unrelated to the study medication.

Measurement of Human Cerebral Blood Flow with [15O]Butanol and Positron Emission Tomography

Although H215O is widely used for CBF measurement by positron tomography, it underestimates CBF, especially at elevated flow rates. Several tracers, including butanol, overcome this problem, but the short half-life of 15O provides advantages that cause water to remain the tracer of choice. We report the first use and evaluation of 15O–labeled butanol for CBF measurement. Flow measurements made in a similar fashion with water and butanol at 10-min intervals were compared in normal volunteers under resting and hypercapnic conditions. Regional analysis showed good agreement between the tracers at low flows, and significant underestimation of flow by water relative to butanol in regions of elevated flow. The observed relationship between the tracers and the curve-fitted permeability-surface area product for water (133 ml · 100 g−1 · min−1) follow the known relationship between water and true flow. These observations indicate that [15O]-butanol provided accurate measurements of human regional CBF under conditions of elevated perfusion. We conclude that butanol is a convenient and accurate method for routine CBF determination by positron emission tomography.

Transcranial doppler: An introduction for primary care physicians

Transcranial Doppler (TCD) is a diagnostic tool that can be used at bedside to assess the cerebral vasculature noninvasively. It is inexpensive, safe, and reliable when compared with other techniques. It can be repeated multiple times and can be used for continuous monitoring if needed. Screening of children with sickle cell disease to assess and prevent ischemic strokes and monitoring for vasospasm after subarachnoid hemorrhage are well established, evidenced based utilizations of TCD. It is useful for the evaluation of occlusive intracranial vascular lesions with many emerging indications in the management of ischemic stroke. TCD with micro-bubble enhancement has comparable sensitivity to transesophageal echocardiogram in detecting right-to-left atrial cardiac shunts. TCD is underused as a clinical tool despite well established indications. The pressure to contain increasing medical cost will likely result in increased utilization of this test in future.

Syncope and head CT scans in the emergency department

ContextPatients presenting with syncope to the emergency department (ED) of a community hospital were evaluated.AimThe objective of this study is to examine the use and results of head computerized tomography (CT) scans in patients presenting with syncope to the ED of a community hospital.Settings and designA retrospective chart review of patients presenting with syncope to the emergency room was conducted.Methods and materialsWe reviewed the charts of patients who presented to the ED over a 6-month period with syncope. When performed, head CT scan findings were noted, and their relationship to the clinical presentation was examined.ResultsOne hundred twenty-eight patients were identified. Forty-four patients had their head CT scans performed. In 1 patient, the CT scan showed evidence of infarction in the posterior circulation. In 19 patients, the head CT scan was normal. Twenty-four patients had abnormal findings unrelated to the ED presentation.ConclusionsHead CT scans were commonly used in our series of syncope patients. Abnormal findings pertinent to the syncope were observed in only 1 patient. A prospective study examining yield in a larger series of patients may help define the utility of this neuroimaging modality in syncope.

Assessment of intravenous fenoldopam mesylate in the management of severe systemic hypertension.

To evaluate the acute BP response to iv fenoldopam mesylate (FNP), 14 patients with severe hypertension (diastolic BP 120 to 170 mm Hg) were studied in an open-label trial. Initial infusion rate of FNP was 0.1 microgram/kg.min. Titration to diastolic BP goal (95 to 110 mm Hg) was followed by a constant infusion phase (greater than or equal to 6 h), a detitration phase (2 h), and a postinfusion phase. FNP reduced BP by 27/29 mm Hg (p less than .001) with no significant effect on heart rate. Maintenance of the BP effect was noted through the 6 h of constant rate infusion. Mild, transient vasodilating-associated adverse effects were noted with FNP. We conclude that FNP is an effective, well-tolerated iv antihypertensive agent for acute BP reduction in a severely hypertensive population.

Brain blood flow in the nitroglycerin (GTN) model of migraine: measurement using positron emission tomography and transcranial Doppler.

Nitroglycerin has been widely used as a model of experimental migraine. Studies combining measurement of flow velocity using transcranial Doppler (TCD) concurrently with measures of cerebral blood flow (CBF) are uncommon. We report the results of a study combining TCD and positron emission tomography (PET). Healthy volunteers with no personal or family history of migraine underwent measurement of CBF using H215O PET, and velocity using TCD. Measurements were done at baseline, and following i.v. nitroglycerin at 0.125, 0.25 and 0.5 μg/kg per min. Subcutaneous sumatriptan (6 mg) was injected, with CBF and velocity measured 15, 30, and 60 min later. Nitroglycerin was terminated and measurements obtained 30 min later. Six male and six female subjects were studied. Nitroglycerin increased global CBF while flow velocities decreased. Sumatriptan did not have a significant effect on these values. Regions of increased flow included the anterior cingulate, while regions of decreased flow included the occipital cortex. Our data suggest that nitroglycerin induces regional changes in CBF that are similar to changes reported in spontaneous migraine, but produces distinctly different effects on global CBF and velocity.

Hyperventilation-Induced Reduction in Cerebral Blood Flow: Assessment by Positron Emission Tomography

The use of positron emission tomography (PET) has been well documented as a relatively noninvasive method of measuring cerebral blood flow (CBF), both globally and regionally. The utility of readily detecting alterations in CBF is apparent, particularly when applied to the evaluation of therapeutic interventions thought to influence CBF. We report the effects of hypocapnia, an experimental condition of known cerebral vasoconstriction, in ten normal volunteers. Subjects had brain blood flow evaluated utilizing H2 15O as the positron emitter before and after approximately five minutes of hyperventilation. Baseline CBF was measured as a mean ± SD of 61.2 ± 16.3 mL/min/100 g of tissue. Mean baseline arterial blood gas values were PaO2 107.4 ± 14 mm Hg, PaCO2 37.7 ± 0.89 mm Hg, and pH 7.39 (calculated from mean [H+]). Post hyperventilation, global CBF was measured as 31.1 ± 10.8 mL/min/100 g. Mean arterial blood gas values were PaO2 141.7 ± 21 mm Hg, PaCO2 19.7 ± 5 mm Hg, and pH 7.63 (calculated from mean [H+]). CBF decreased by a mean of 49.5 ± 11 percent. Data analysis using the Students t-est showed a significant change over baseline in PaCO2 (p<0.001) and CBF (p<0.001), in the hyperventilated state. Correlations were noted between the decrease in CBF and change in PaCO2 (r = 0.81) as well as between hyperventilation PaCO2 and the change in CBF (r=0.97). We conclude that, as measured by PET, CBF decreases significantly during a state of artificial hyperventilation to a degree consistent with results seen using other methods. PET appears to be a valuable tool in the assessment of interventions that could influence CBF.

Comparative acute blood pressure reduction from intravenous fenoldopam mesylate versus sodium nitroprusside in severe systemic hypertension

Fenoldopam mesylate (SK&F 82526J) (FNP) is a specific postsynaptic dopamine-1 receptor agonist,1 with weak α2-antagonistic properties.2 The agent is devoid of dopamine-2, α-1 or β-adrenergic activity.3 Fenoldopam functions as an arteriolar vasodilator with dilation in the renal, mesenteric, skeletal muscle and lumbar beds.4,5 Although a primary effect is through renal vasodilation with consequent increases in renal blood flow,1–2,4–6 reduction in total peripheral resistance appears to be the mechanism of blood pressure (BP) reduction.7,8 Furthermore, fenoldopam improves renal blood flow, fractional sodium and free water clearance while lowering BP.4,9,10 Fenoldopam has a rapid onset (4 minutes) and a short duration of action (<10 minutes) with intravenous administration,11 and has been reported to be an effective parenteral agent in severely hypertensive patients.9 The agent undergoes sulfate, methylate and glucuronide conjugation, and produces no accumulation of toxic metabolic or degradation products.12 Sodium nitroprusside (sodium nitroferricyanide) (NTP) has potent venodilating and arteriolar-dilating properties13 and in many respects is an ideal antihypertensive agent when rapid reduction of BP is required. NTP quickly and reliably reduces BP in most patients and its short half-life aids in rapid titration of the drug. One major drawback associated with the use of NTP is that the very potency that gives it utility has often led to restrictions on its use. Restrictions include invasive monitoring requirements or use in an intensive care setting, thus dramatically escalating the cost associated with NTPs use.14 A second drawback is that the formation of thiocyanate degradation products resulting in toxicity has limited its utility.14 While thiocyanate toxicity has been primarily associated with impaired renal or hepatic function, in which the typical 4-day half-life of thiocyanate is prolonged, reports of toxicity in patients with normal renal function have also occurred.14 Herein, we compared and evaluated the effects of sodium nitroprusside and intravenous fenoldopam mesylate in an open-label, randomized, multicenter trial of patients with severe systemic hypertension.