Single-pill amlodipine/atorvastatin helps patients of diverse ethnicity attain recommended goals for blood pressure and lipids (the Gemini-AALA study).

The Gemini-AALA (Australia, Asia, Latin America, Africa/Middle East) study evaluated the efficacy and safety of single-pill amlodipine/atorvastatin (Caduet) for the treatment of patients of diverse ethnicity with concomitant hypertension and dyslipidaemia. This was a 14-week, open-label study including patients from 27 countries across the Middle East, Asia-Pacific, Africa and Latin America. Eight dosage strengths of single-pill amlodipine/atorvastatin (5/10, 10/10, 5/20, 10/20, 5/40, 10/40, 5/80 and 10/80 mg) were titrated to improve blood pressure and lipid control. Blood pressure and lipid goals were determined according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) guidelines, respectively (blood pressure, <140/90 or <130/80 mm Hg; low-density lipoprotein cholesterol (LDL-C), <4.1 to <2.6 mmol l(-1) (<160 to <100 mgdl(-1))). Overall, 1649 patients received study medication. Most patients (91.4%) had >or=1 cardiovascular risk factor (as defined by NCEP ATP III guidelines) in addition to hypertension/dyslipidaemia, and 61.7% had coronary heart disease/risk equivalent. At baseline, mean blood pressure was 146.6/88.3 mm Hg and LDL-C was 3.4 mmol l(-1) (130.2 mgdl(-1)). At week 14, 55.2% of patients reached both blood pressure and lipid goals, 61.3% reached blood pressure goal and 87.1% reached lipid goal (34.0% were at lipid goal at baseline). Mean blood pressure reduction was 20.2/11.4 mm Hg. For patients who were lipid-lowering drug naive at baseline, mean reduction in LDL-C was 41.0%. Treatment-related adverse events led to the discontinuation of 3.6% of patients. Single-pill amlodipine/atorvastatin therapy was well tolerated and effective for the reduction of blood pressure and lipids to recommended goals in patients from diverse ethnic backgrounds.

Endothelium and angiogenesis in white coat hypertension.

Hypertensive patients are at particular risk of cardiovascular complications, possibly related to endothelial damage or dysfunction, or to abnormal angiogenesis. The aim of this study was to compare the risk conferred by white coat hypertension (WCH) vs sustained hypertension in the development of the endothelial dysfunction and abnormal angiogenesis by evaluating nitric oxide (NO=NO2+NO3), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and E-selectin levels in plasma. The study group included 102 subjects, 34 with WCH (17 male and 17 female patients) aged 49+/-11 years, 34 sustained hypertensives (HT) (15 male and 19 female patients) aged 47+/-11 years and 34 normotensive control subjects (NT) (16 male and 18 female patients) aged 48+/-10 years. WCH was defined as clinical hypertension and daytime ambulatory blood pressure less than 135/85 mmHg. The subjects were matched for age, gender, body mass index and the patients with smoking habit, dyslipidaemia, and diabetes mellitus were excluded from the study. The NO, ET-1, VEGF and E-selectin levels were analysed by ELISA technique. The WCH subjects had significantly higher levels of NO than the HT (41.68+/-2.23 vs 32.18+/-2.68 micromol/l; P<0.001) and significantly lower values than the NT (48.24+/-4.29 micromol/l; P<0.001). ET-1 levels of the WCH group were significantly higher than the NT (8.10+/-0.92 vs 5.95+/-0.26 ng/ml; P<0.001) and significantly lower than the HT (11.46+/-0.59 ng/ml; P<0.001). Considering with VEGF, the WCH group had significantly higher levels than the NT (195.88+/-11.84 vs 146.26+/-18.67 pg/ml; P<0.001), but the difference from the HT group was not significant (203.35+/-7.48 pg/ml; P=0.062). E-selectin in the WCH group was significantly lower than the HT (4.77+/-0.52 vs 8.49+/-2.85; P<0.001), but the difference from the NT group was not significant (3.86+/-0.67; P=0.077). Our data demonstrate that WCH is associated with endothelial dysfunction and abnormal angiogenesis. The degree of these changes is not as severe as observed in hypertensive population.

[Vertebroplasty]. / Vertebroplasti.

Vertebroplasty is the polymethylmetacrilate (PMMA) injection into a vertebral body. It may be used for patients with compression fractures due to osteoporosis, metastatic tumors, or benign tumors. Vertebroplasty is performed to provide pain relief or to produce bone strengthening. The contraindications of the intervention are lack of patient consent, coagulopathy, infection, radiculopathy and extensive vertebral destruction. Vertebroplasty may be performed with transpedicular or extrapedicular approaches. The main complications are lamina pedicle or rib fractures, pneumothorax, and cement leakage into vessels, epidural space or disc.

Oxidative stress in white coat hypertension; role of paraoxonase.

Oxidative stress in sustained hypertension was shown with several biochemical parameters. Oxidized low-density lipoprotein (oxLDL) plays an important role during the atherosclerosis process and paraoxonase (PON1) can significantly inhibit lipid peroxidation. Serum PON1 activity, oxLDL and malondialdehyde (MDA) concentrations and their relationship with serum lipid parameters and systolic and diastolic blood pressures (SBP and DBP) were determined in subjects with white coat hypertension (WCH), sustained hypertension (HT) and normotension (NT). The study group consisted of a total of 86 subjects, 30 with WCH (14 male, 16 female subjects), 30 with HT (13 male, 17 female subjects) and 26 with NT (12 male, 14 female subjects). Both white coat hypertensive and hypertensive subjects had significantly higher levels of MDA than normotensives (P<0.026 and P<0.001, respectively). The oxLDL level of the HT group was significantly higher than the NT group (P<0.023). The WCH group had an oxLDL level similar to both hypertensive and normotensive groups. HT and WCH groups had significantly lower PON1 levels than the normotensive group (P<0.001). oxLDL correlated with MDA positively (P=0.008), and PON1 negatively (P=0.008). A negative correlation between MDA and PON1 (P=0.014) was detected. MDA correlated positively with both SBP and DBP (P=0.001), while PON1 correlated with both of them negatively (P=0.01 and P=0.008, respectively). OxLDL correlated with diastolic blood pressure positively (P=0.008). Our data demonstrate that oxidative stress increase in WCH is associated with a decrease in PON1 activity. The reduction in PON1 activity may be one of the factors leading to an increase in oxidative status in WCH.

Target organ damage and changes in arterial compliance in white coat hypertension. Is white coat innocent?

The aim of this study was to perform an extensive evaluation of target organ status, metabolic abnormalities and hemodynamic alterations in white coat hypertension (WCH). Fifty normotensive (NT), 90 WCH (ambulatory daytime blood pressure < 135/85 mmHg) and 101 hypertensive (HT) subjects underwent extensive biochemical, echocardiographic, fundoscopic examination. In a subgroup study, arterial compliance and intima-media thickness (IMT) were measured by Doppler ultrasound in left common carotid artery. WCH subjects were found to have higher body mass index (BMI) than the NTs (p = 0.042). Left ventricle mass index (LVMI) was greater in the WCHs than the NTs (p < 0.001), but significantly less than the HTs (p < 0.001). Hypertensive retinopathy was observed in the WCHs, but was less severe and rare compared to the HTs (13% vs 27%). Both WCHs and HTs had high levels of urinary albumin excretion (UAE) (p = not significant). Total cholesterol was higher in WCHs than in the NTs (p = 0.04) The distensibility coefficient (DC) of the WCHs was significantly greater than the HTs (p < 0.01), while significantly smaller than the NTs (p < 0.01). The compliance coefficient (CC) of the WCHs was significantly higher than the HTs (p < 0.01), and significantly less than the NTs (p < 0.01). The IMT in the HTs was significantly higher than the WCHs (0.81 +/- 0.05 vs 0.70 +/- 0.04 mm; p < 0.001) and the NTs (p < 0.001). The difference between the NTs and the WCHs was not significant. Our data indicate that patients with WCH represent an intermediate group between NTs and sustained HTs where target organ damage and cardiovascular risk is concerned.

Application of radiofrequency treatment in practical pain management: state of the art.

Many therapeutic interventions for chronic pain are available, and decisions about optimal management are not easy to make. Radiofrequency (RF) treatment is classified as a percutaneous minimal invasive procedure for patients who do not respond to appropriate medical and physical therapy. Although RF treatment is widely used differences in current practice exist due to ongoing controversies.

Characteristics of patients with coronary artery disease and hypertension: a report from INVEST.

In all, 22,599 patients with coexisting hypertension and coronary artery disease (CAD) from around the world are enrolled in the INternational VErapamil SR/trandolapril STudy (INVEST). As a result, much will be learned regarding the use of treatment strategies using verapamil SR and atenolol with and without trandolapril and/or hydrochlororthiazide in patients with hypertension and CAD, all of whom are at high risk for adverse cardiovascular outcomes. This trial will provide meaningful data on optimal treatment strategies for hypertension, especially among patients who are elderly, have diabetes, have left ventricular hypertrophy, or who are dyslipidemic. This trial will be the first to use Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) guidelines as blood pressure goals to determine the relative benefits of a calcium antagonist versus a beta-blocker strategy in reducing morbidity and mortality. In addition, women and Hispanic patients participating in INVEST will provide the largest controlled experience in the management of hypertensive patients with CAD, facilitating the development of future guidelines.

Neurotoxicity of midazolam in the rabbit.

Safe and efficient use of spinal drugs requires neurotoxicologic animal studies before ethical application. We have evaluated the neurotoxicologic interruptions of intrathecal administration of midazolam in rabbits. Eighteen white New Zealand rabbits were randomly assigned into three groups consisting of six rabbits each. In conscious animals, 0.3 ml 0.9% normal saline solution, 0.3 ml 0.1% midazolam (Roche, Dormicum) or 0.3 ml preservative free midazolam were intrathecally administered. Light and fluorescence microscopy evaluations were performed on transverse spinal cord sections by a neurohistopathologist in a blind fashion. Midazolam and preservative free midazolam treated rabbits showed significant histologic changes in light and fluorescence microscopy. The histologic and vascular lesions with the use of midazolam and preservative free midazolam suggested neurotoxic effects; thus chronic intrathecal administration of midazolam should be avoided in humans.

Intravenous administration of caffeine sodium benzoate for postdural puncture headache.

BACKGROUND AND OBJECTIVES: In this study, we evaluated the efficacy and safety of prophylactic administration of intravenous caffeine sodium benzoate for postdural puncture headaches (PDPH) on patients administered spinal anesthesia. METHODS: Sixty ASA I and II patients undergoing lower abdominal or lower extremity surgery were included in this study. Patients were randomized by double-blind, placebo-controlled design to receive either 1,000 mL normal saline with 500 mg caffeine sodium benzoate (group C) or 1,000 mL normal saline (group S) during the first 90 minutes after spinal anesthesia administration. The patient's electrocardiogram, non-invasive blood pressure, and pulse oximetry were monitored and recorded. The patients' headaches were evaluated by using the visual analog scale (VAS). At the end of the fifth day, the severity of the headache was classified as follows: no headache = 0; mild headache = 1; moderate headache = 2; severe headache = 3. Analgesic requirements were recorded for 5 days. RESULTS: Visual analog scale scores were significantly lower in group C than in group S. The incidence of moderate and severe headache was significantly higher in group S (11 patients) when compared with group C (3 patients). Analgesic demand was significantly lower in group C than in group S for 4 days. CONCLUSION: Intravenous caffeine sodium benzoate administration during spinal anesthesia is a simple and safe way to minimize PDPH.

Intrathecal therapy for cancer and nonmalignant pain: patient selection and patient management.

Intrathecal drug delivery improves pain relief, reduces suffering, and enhances quality of life in the small proportion of patients who do not respond well to oral analgesics, including oral morphine. Although morphine is the "gold standard," and the only drug approved for intrathecal pain therapy in the United States, off-label use of alternative agents appears promising, particularly in patients with neuropathic pain. Careful patient selection and management are significant determinants of successful treatment outcomes. Patient selection criteria for cancer and nonmalignant pain are similar; however, a more comprehensive psychological and social assessment is required for patients with nonmalignant pain. In addition, all patients (those with cancer or nonmalignant pain) must exhibit a positive response to an epidural or intrathecal screening test. A multidisciplinary team approach, involving psychologists, nurses, physical therapists, social workers, and spiritual leaders should be used to manage patients. Current practices for patient selection and management, screening tests, and dosing guidelines for intrathecal drug delivery systems are discussed.

Drug adverse events and system complications of intrathecal opioid delivery for pain: origins, detection, manifestations, and management.

Intrathecal drug delivery is effective for the treatment of cancer and nonmalignant pain in patients who do not respond well to oral opioids, in patients who cannot tolerate the side effects associated with opioids, or in patients who show a large, permanent increase in dosage. Although intrathecal drug delivery is associated with pharmacological side effects and complications, its benefits far outweigh its risks. There are three main categories of potential adverse events associated with intrathecal drug delivery: pharmacologic side effects, surgical complications, and device-related complications. Prevention, early recognition, and prompt management of adverse events will optimize patient outcomes. Many adverse events either resolve on their own or can be managed with dosage or device adjustment. More serious complications may require surgical intervention or discontinuation of therapy. This paper will provide an overview of adverse events and complications, their origins, detection, manifestations, and management.

Long-term results of peridural morphine in 225 patients.

The long-term results of peridural morphine in 225 cancer patients have been evaluated. Two methods were employed: percutaneously implanted catheter (175 patients) and subcutaneous reservoirs (50 patients). In the 225 patients, the mean duration of implantation of the peridural catheter was 47.3 days (7-420 days), the mean daily dose of morphine was 13.4 +/- 6.9 (5-80 mg) delivered by 2.6 +/- 0.7 (1-8) injections. The mean duration of action was calculated to be 9.3 +/- 3.8 h (3-32 h). Satisfactory analgesia was achieved in 133 patients (59.1%) in whom peridural morphine was the sole analgesic treatment. Peridural morphine appeared to be especially effective in patients with pain arising in the abdominal region. Complications due to morphine and the catheter were evaluated.