Safety of regadenoson, an adenosine A2A receptor agonist for myocardial perfusion imaging, in mild asthma and moderate asthma patients: A randomized, double-blind, placebo-controlled trial

Background. Patients with reactive airways are at risk for adenosine-induced bronchocon-striction, mediated via A_2B and/or A₃ adenosine receptors. Methods and Results. To examine the effects of regadenoson, a selective adenosine A_2A receptor agonist, on airway resistance, we conducted a randomized, double-blind, placebo-controlled crossover trial in asthmatic patients with a positive adenosine monophosphate challenge test. The mean ratio of the forced expiratory volume in 1 second (FEV₁) at each tested time point relative to the baseline FEV₁ was significantly higher after treatment with regadenoson compared with placebo from 10 to 60 minutes after treatment. One patient had a substantial but asymptomatic FEV₁ reduction (−36.2%) after regadenoson that reversed spontaneously. The most common adverse events with regadenoson were tachycardia (66%), dizziness (53%), headache (45%), and dyspnea (34%). The mean heart rate significantly increased with regadenoson (maximum of +10.4 beats/min) versus placebo. Conclusions. In this pilot safety study of 48 patients with mild or moderate asthma who had bronchial reactivity to adenosine monophosphate, regadenoson was safe and well tolerated. CV Therapeutics provided financial assistance for this study.     

Persistent erythema multiforme: a report of three cases

Three cases of persistent erythema multiforme, two of unknown aetiology and one precipitated by influenza are reported. Lesions were widespread, mostly atypical in appearance and regressed in response to immunosuppressants (systemic steroids and/or azathioprine) or, in one case, to dapsone. One patient developed erythroderma responding eventually to etretinate. Histology in all patients was consistent with the mixed, epidermodermal pattern of erythema multiforme. There were no significant laboratory abnormalities nor marked symptomatology apart from itching. The persistent form appears to belong to the spectrum of erythema multiforme being heterogeneous with respect to inducing stimuli, including viral antigens, neoplastic or inflammatory disease or unknown causes. Whenever it is possible, treatment should be adjusted depending on the causative agent.     

Transcranial Doppler Ultrasound: A New Method of Monitoring Hemispheric Anesthetization During the Intracarotid Amobarbital Procedure

BACKGROUND: Electroencephalography (EEG) is traditionally used to assess the duration of hemispheric anesthetization and to monitor return of function in the anesthetized hemisphere during the intracarotid amobarbital procedure (IAP), but EEG changes are not consistently seen. The authors evaluated the role of continuous transcranial Doppler (TCD) monitoring as an alternative to EEG. METHODS: The authors performed both continuous TCD monitoring and EEG during the IAP in 10 patients with medically intractable partial epilepsy. Mean velocities were monitored continuously in both middle cerebral arteries (MCAs), and changes in MCA velocities on continuous TCD monitoring were time locked with the EEG changes. RESULTS: The average mean MCA velocities were within normal limits bilaterally (50-85 cm/s) in all patients at baseline. Mean MCA velocites increased in all patients to 95-115 cm/s at the start of the test when the patients were asked to raise their hands and start counting. After injection of sodium amobarbital, mean MCA velocities in all patients dropped dramatically on the ipsilateral side to values of 12-39 cm/s and returned to the baseline average value when the hemiparesis recovered. In 8 patients, the duration of delta activity on EEG coincided with the time interval during which the mean MCA velocities were low on TCD monitoring. In 2 patients, despite the presence of hemiparesis clinically and a drop in mean MCA velocities on the ipsilateral side on continuous TCD monitoring, EEG remained normal on the ipsilateral side. CONCLUSIONS: Continuous TCD monitoring may be a more sensitive method than EEG in determining the duration of hemispheric anesthetization during IAP. Because the items for assessment of memory are presented during the period of hemispheric anesthetization, TCD may be useful in more precisely defining the time window for memory testing.     

Prevention of chronic diseases: a call to action

Chronic (non-communicable) diseases—principally cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes—are leading causes of death and disability but are surprisingly neglected elements of the global-health agenda. They are underappreciated as development issues and underestimated as diseases with profound economic effects. Achievement of the global goal for prevention and control of chronic diseases would avert 36 million deaths by 2015 and would have major economic benefits. The main challenge for achievement of the global goal is to show that it can be reached in a cost-effective manner with existing interventions. This series of papers in The Lancet provides evidence that this goal is not only possible but also realistic with a small set of interventions directed towards whole populations and individuals who are at high risk. The total yearly cost of the interventions in 23 low-income and middle-income countries is about US$5·8 billion (as of 2005). In this final paper in the Series we call for a serious and sustained worldwide effort to prevent and control chronic diseases in the context of a general strengthening of health systems. Urgent action is needed by WHO, the World Bank, regional banks and development agencies, foundations, national governments, civil society, non-governmental organisations, the private sector including the pharmaceutical industry, and academics. We have established the Chronic Disease Action Group to encourage, support, and monitor action on the implementation of evidence-based efforts to promote global, regional, and national action to prevent and control chronic diseases.     

MGB1 Poor Adherence to Hypertension Treatment Guidelines: An Analysis of Therapeutic Choices

The recent Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) reiterated long-standing recommendations that Stage 1 hypertension (BP ≥ 140/90 mm Hg) without comorbidity should be treated initially with diuretics (DI) or beta blockers (BB). Yet market research suggests that many physicians prefer to use other drug classes, such as calcium channel blockers and ACE inhibitors.
OBJECTIVES: To explore the determinants of therapeutic choice in hypertension.
METHODS: We surveyed by mail a stratified random sample of 10,000 U.S. cardiologists, internists, and family/general practitioners. Physicians were queried about their practice environment and their knowledge, attitudes, and practices regarding antihypertensive therapy, including their choice of drugs to treat patients with specified clinical profiles. The probability that physicians would follow JNC guidelines Stage 1 hypertension was analyzed using multiple logistic regression with stepwise backward elimination to select variable with p < 0.001.
RESULTS: Completed surveys were received from 1,023 physicians. 86.7% prescribe drug therapy for Stage 1 hypertension, and 19.5% (22.5% of drug prescribers) limit their choices to DI and BB. Guideline conformity was higher among physicians who: practice in academic medical centrers; are older; are general practitioners (versus general internists); have smaller caseloads; have fewer hypertensive patients; have higher proportions of HMO, Medicaid, and uninsured patients; and experience more formulary restrictions. Cardiologists and family practitioners were less likely than internists to follow guidelines.
CONCLUSION: JNC guidelines are better accepted by academic physicians, older physicians who have more expenence using DI and BB, physicians with smaller caseloads and hence more time for follow-up and therapy adjustment, and physicians who face drug reimbursement constraints.     

Ankle effusions following acute ankle injury.

We prospectively studied 56 patients with an acute ankle injury and an effusion to determine the significance of the ankle effusion to functional outcome. The average size of effusion was 15 mm. Most injuries occurred following a fall (73%) and most (73%) were inversion injuries. At 6 months all but two patients had returned to their normal activities with no further problems. No correlation was found with size of effusion and the functional and clinical outcome. We conclude that an ankle effusion does not reliably distinguish which injuries require further investigations and unless there are clinical indications further investigations are not indicated.     

Peripheral arterial occlusive disease: P-31 MR spectroscopy of calf muscle

The effect of a graded exercise protocol on phosphorus-31 magnetic resonance (MR) spectroscopy of calf skeletal muscle in nine healthy (control) subjects and 16 patients with symptomatic peripheral arterial occlusive disease (PAOD) was assessed. Ankle-brachial pressure indexes were obtained in all 16 patients, and 10 patients underwent peripheral arteriography. Temporal profiles of pH and the inorganic phosphorus (Pi) index were calculated from the spectra. A Pi-index recovery rate constant was calculated for each subject. Arteriograms were graded by calculating the runoff resistance in the limb of interest. The pH profiles during exercise did not differ significantly between the PAOD patients and control subjects. The Pi-index recovery rate constant in the PAOD patients was significantly (P less than .01) smaller than in the control subjects. There was no significant correlation between recovery rate and the ankle-brachial pressure indexes, but there was a strong negative correlation between recovery rates and angiographic resistance grades, with smaller recovery rate constants in patients with increased arterial resistance. It is concluded that P-31 MR spectroscopy shows promise as a direct measure of tissue perfusion.