Human urotensin II in the plasma of anephric subjects.
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Biomedical subjects
Publications and source records attributed to Raymond R Townsend.
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PURPOSE: BAY 43-9006 (sorafenib) is an inhibitor of Raf kinase, the vascular endothelial growth factor (VEGF) receptor-2, and angiogenesis in tumor xenografts. The current study investigated the incidence, severity, and mechanism of blood pressure (BP) elevation in patients treated with BAY 43-9006. PATIENTS AND METHODS: Twenty patients received BAY 43-9006 400 mg orally twice daily. BP and heart rate were measured at baseline and then every 3 weeks for 18 weeks. VEGF, catecholamines, endothelin I, urotensin II, renin, and aldosterone were measured at baseline and after 3 weeks of therapy. We assessed vascular stiffness at baseline, after 3 to 6 weeks of therapy, and again after 9 to 10 months of therapy. RESULTS: Fifteen (75%) of 20 patients experienced an increase of > or = 10 mmHg in systolic BP (SBP), and 12 (60%) of 20 patients experienced an increase of > or = 20 mmHg in SBP compared with their baseline value, with a mean change of 20.6 mmHg (P < .0001) after 3 weeks of therapy. There were no statistically significant changes in humoral factors, although there was a statistically significant inverse relationship between decreases in catecholamines and increases in SBP, suggesting a secondary response to BP elevation. Measures of vascular stiffness increased significantly during the period of observation. CONCLUSION: Treatment with BAY 43-9006 is associated with a significant and sustained increase in BP. The lack of significant change in circulating factors suggests that these humoral factors had little role in the increase in BP.
Ethanol is a molecule of enduring research interest because its consumption has important social as well as medical implications. With excessive ethanol consumption, there is higher prevalence for hypertension, stroke, cardiomyopathy, and arrhythmias. A principal mechanism by which ethanol exerts these cardiovascular effects is through modulation of blood pressure. In this article, we focus on recent research that pursues information on the effects of alcohol on blood pressure in human subjects, regardless of whether they have hypertension or not. Known means by which alcohol exerts hemodynamic effects are briefly covered, and insights on novel biomediators, such as endothelin and gene-based mechanisms, are presented. Newer tools, such as the Alcohol Use Disorders Identification Test-Consumption Questions (AUDIT-C) survey and carbohydrate-deficient transferrin (CDT) serum test, are also covered. Reducing excessive alcohol intake can produce a reduction in blood pressure of up to 4 mm Hg, on average, which could substantially affect the rates of stroke and ischemic heart disease.
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Pheochromocytoma (Pheo) is a rare cause of hypertension (HTN). Classically, a triad of symptoms includes sweating, palpitations, and headache. HTN is often present and labile. Although a triad of symptoms is cited as the most frequent presenting complaints, our clinical experience leads us to question how often these are present. Thirty-two patients with histologically proven pheo or paraganglionoma were evaluated. Around 84.4% patients had adrenal pheos and 15.6% had extra-adrenal pheos. Two patients had bilateral adrenal tumors, two had a history of prior pheos, and four had a family history of pheo. There were 19 (59.4%) female and 13 (40.6%) male patients. Six (18.7%) patients were black and 26 (81.3%) were white. The mean age at presentation was 43.2+/-13.9 years. Two patients were known to have neurofibromatosis type 1, two had von Hippel-Lindau disease, one had multiple endocrine neoplasia 2A, and one PGL/SDHD genetic mutation. Twenty-six patients had sporadic tumors or had not had genetic testing. Biochemical diagnosis was confirmed with 24-h urine measurements. Urine catecholamine measurements were elevated at least 2 to 4 times above normal levels. Mean SBP readings at presentation were 128+/-19 mmHg. Mean DBP readings were 81+/-13 mmHg. Around 65.6% patients were hypertensive at presentation. Fifty percent of the patients had palpitations, 40.6% had tachycardia, 34.4% had sweating, and 31.3% had headaches. Initial presenting symptoms were diverse. Pheo is a rare clinical entity and remains a huge diagnostic challenge for all clinicians.
OBJECTIVES: The authors conducted a randomized, double-blind, two-way crossover clinical trial to compare the pharmacokinetics and cardiovascular effects of 11.9 milliliters of 4 percent articaine hydrochloride (HCl) plus 1:100,000 epinephrine (A100) with those of 11.9 mL of 4 percent articaine HCl plus 1:200,000 epinephrine (A200). METHODS: During two testing sessions, the authors administered injections of A100 and A200 over a seven-minute period (in one-cartridge doses unless otherwise noted): maxillary right first molar infiltration, maxillary left first molar infiltration, maxillary right first premolar infiltration, maxillary left first premolar infiltration, right inferior alveolar injection, left inferior alveolar injection, right long buccal infiltration (one-half cartridge) and left long buccal infiltration (one-half cartridge). They analyzed venous blood samples for articaine levels. They used noninvasive acoustic tonometry to measure a variety of cardiovascular parameters over a two-hour period. RESULTS: Plasma concentration curves of articaine over time were similar for both solutions, with peak concentrations and times to maximum concentration being 2,037 nanograms per milliliter and 22 minutes for A100 and 2,145 ng/mL and 22 minutes for A200. At the 10-minute point, the mean systolic blood pressure and heart rate were significantly elevated (P < .05) with A100 versus A200. CONCLUSIONS: Maximum dose recommendations for the A100 solution also can be applied to the A200 solution. A200 produces less cardiovascular stimulation than does A100. CLINICAL IMPLICATIONS: A200 is as safe as A100, and may be preferable to A100 in patients with cardiovascular disease and in those taking drugs that reportedly enhance the systemic effects of epinephrine.
STUDY OBJECTIVE: To measure the effectiveness of a multifaceted educational intervention to improve ambulatory hypertension control. DESIGN: Cluster-randomized trial. SETTING: Academic health system using an ambulatory electronic medical record. SUBJECTS: A total of 10,696 patients with a diagnosis of hypertension cared for by 93 primary care providers. INTERVENTION: Academic detailing, provision of provider-specific data about hypertension control, provision of educational materials to the provider, and provision of educational and motivational materials to patients. MEASUREMENTS AND MAIN RESULTS: The primary outcome was blood pressure control, defined as a blood pressure measurement below 140/90 mm Hg, and was ascertained from electronic medical records over 6 months of follow-up. We determined the adjusted odds ratio for the association between the intervention and the achievement of controlled blood pressure. When we accounted for clustering by provider, this adjusted odds ratio was 1.13 (95% confidence interval 0.87-1.47). Adjusted odds ratios were 1.03 (95% confidence interval 0.78-1.36) in patients whose blood pressure was controlled at baseline and 1.25 (95% confidence interval 0.94-1.65) in those whose blood pressure was not. These odds ratios were not significantly different (p=0.11). CONCLUSIONS: These results were consistent with no effect or, at best, a relatively modest effect of the intervention among patients with hypertension. Had we not included a concurrent control group, the data would have provided an unduly optimistic view of the effectiveness of the program. The effectiveness of future interventions may be improved by focusing on patients whose blood pressure is uncontrolled at baseline.
Hypertension is a common disorder with well-recognized consequences on the heart, brain, and kidney as target organs. Guidelines espouse a treatment goal of blood pressure reduction to <140 mm Hg for the systolic pressure and <90 mm Hg for the diastolic pressure in most hypertensive patients. In this review, the basis for these recommendations, the practical achievement of these goals in various practice settings, and the risk versus the benefit of achieving such goals in most hypertensive patients are examined.
Numerous epidemiologic investigations have found an association between moderate intake of alcohol and increased blood pressure (BP). However, in controlled clinical studies that directly tested the effects of alcohol intake on BP, findings are inconsistent, perhaps because of differences in duration of alcohol use and the timing of BP measurements. In this setting, we performed a systematic review of trials that measured BP after a period of sustained alcohol intake (defined as daily intake of at least one alcoholic drink daily) in one group and that also had a control group of individuals who consumed no alcohol. Nine studies met the entrance criteria. The review demonstrated a significant rise in systolic blood pressure (SBP) and diastolic BP (DBP) of 2.7 mm and 1.4 mm Hg, respectively, after alcohol intake. An early effect of alcohol leading to a reduction BP (in the hours after exposure) and a later effect (next day) of raising BP led to smaller differences in the net effect of alcohol on BP when ambulatory BP monitoring measurements were compared with casual office- or clinic-based measurements. Our findings may have important implications for interpreting studies measuring the effect of alcohol on BP as well as for regular clinical care. These findings indicate that the timing of BP measurements after alcohol intake has a substantial effect on the magnitude and perhaps even the direction of BP change.
BACKGROUND: Hypertension is a frequent medical complication of pregnancy. Renovascular hypertension is present in 5-10% of cases of severe hypertension during pregnancy. CASE: In this report we describe a 36-year-old woman with severe hypertension caused by bilateral renal artery stenosis due to fibromuscular dysplasia. Guided by the patient's ultrasound findings, only 1 side was treated with angioplasty. Continued labile blood pressure resulted in arteriography of the contralateral renal artery, which confirmed renal artery stenosis was present on the other side. CONCLUSION: Clinicians should maintain a high index of suspicion for renovascular hypertension in pregnancy when drug resistance is present. Because the potential for false-negative results with noninvasive testing for renal artery stenosis is present, if clinical suspicion is high, one should consider using invasive testing.
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