Twenty-four-hour activity of felodipine extended release in chronic stable angina pectoris

To investigate the antiischemic efficacy and duration of action of the dihydropyridine calcium antagonist felodipine, 15 patients with stable exertional angina were enrolled in a double-blind, crossover study comparing 2 doses (5 and 10 mg) of felodipine extended release (ER) and placebo given once daily for 1 week. Bicycle exercise tests were repeated at the end of each treatment period 4 and 24 hours after dosing. Four hours after dosing with both felodipine doses, only 5 patients discontinued the exercise test because of greater than 2 mm of ST-segment depression, whereas 10 continued until exhaustion (p less than 0.01 vs placebo). Compared with placebo, total exercise time was increased by 19% (p less than 0.001), with no difference between doses. After 24 hours, exercise duration was prolonged up to physical exhaustion in 6 patients taking felodipine 10 mg (p less than 0.05 vs both placebo and felodipine 5 mg); moreover, 11 patients taking 10 mg and 5 taking 5 mg increased time to 1 mm of ST depression greater than or equal to 15% compared with exercise time during the placebo test. Mean time to 1 mm of ST depression at 24 hours was increased by 8% with 5 mg and by 18% with 10 mg (p less than 0.001 vs placebo; p less than 0.01 between doses). Total exercise time at 24 hours was increased with both doses (p less than 0.001), with greater efficacy with the 10-mg dose (p less than 0.05 vs 5 mg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Adrenal gland hypofunction in active polymyalgia rheumatica. effect of glucocorticoid treatment on adrenal hormones and interleukin 6

OBJECTIVE: To evaluate hypothalamic-pituitary-adrenal (HPA) axis function in patients with recent onset polymyalgia rheumatica (PMR) not previously treated with glucocorticoids; and to detect possible correlations between adrenal hormone levels, interleukin 6 (IL-6), and other acute phase reactants at baseline and during 12 months of glucocorticoid treatment. METHODS: Forty-one PMR patients of both sexes with recent onset disease and healthy sex and age matched controls were enrolled into a longitudinal study. Patients were monitored for serum cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione (ASD), and clinical and laboratory measures of disease activity such as C-reactive protein and IL-6 concentrations at baseline and after 1, 3, 6, 9 and 12 months of glucocorticoid treatment. To assess dynamic HPA axis function, serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were evaluated in another 8 patients with recent onset PMR not treated with glucocorticoid in comparison to controls after challenge with ovine corticotropin releasing hormone (oCRH) test. In addition, serum cortisol and 17-hydroxyprogesterone (17-OHP) levels were evaluated after stimulation with low dose (1 microg) intravenous ACTH. RESULTS: Serum cortisol and ASD levels of all PMR patients at baseline did not differ from controls. During followup, cortisol levels dipped at one and 3 months. Serum DHEAS levels in all patients were significantly lower than in controls at baseline. In female PMR patients a significant correlation was found at baseline between cortisol levels and duration of disease. Serum concentrations of IL-6 at baseline were significantly higher in PMR patients than in controls. During 12 months of glucocorticoid treatment IL-6 levels dropped significantly at one month; thereafter they remained stable and did not increase again despite tapering of the glucocorticoid dose. After oCRH stimulation, a similar cortisol response was found in patients and controls. After ACTH administration, a significant cortisol peak was detected in patients and controls, whereas no significant difference in cortisol area-under-the-curve (AUC) was found between the groups. In contrast, ACTH induced a significantly higher (p < 0.05) peak of 17-OHP and AUC in PMR patients than in controls. CONCLUSION: This study found reduced production of adrenal hormones (cortisol, DHEAS) at baseline in patients with active and untreated PMR. The defect seems mainly related to altered adrenal responsiveness to the ACTH stimulation (i.e., increased 17-OHP), at least in untreated patients. The 12 month glucocorticoid treatment of patients reduced the production of inflammatory mediators (i.e., IL-6) in a stable manner that persisted after glucocorticoids were tapered.     

Diagnostic accuracy of peak exercise echocardiography in coronary artery disease: comparison with thallium-201 myocardial scintigraphy

To evaluate the accuracy of exercise two-dimensional echocardiography for the recognition of coronary artery disease, 53 patients (46 men and 7 women, age range 35 to 69 years) without either previous myocardial infarction or resting wall motion abnormalities, were studied. According to coronary angiography 26 had normal coronary arteries, 14 had one-vessel, seven had two-vessel, and six had three-vessel disease. After withdrawal of any therapy, all patients underwent a single exercise stress test with a stress table during which cine-loop digitized echocardiography was acquired and 74 MBq of thallium-201 (TI-201) were injected. Echocardiographic images were evaluated at rest and at peak exercise. Three-view planar scintigraphic images were collected immediately after exercise and 4 hours later. For the overall recognition of coronary artery disease, exercise electrocardiography had 77.8% sensitivity and 65.4% specificity; myocardial scintigraphy had 100% sensitivity and 92.3% specificity; and exercise echocardiography had 92.6% sensitivity and 96.2% specificity (both NS versus myocardial scintigraphy). Global accuracy was 71.7% for exercise electrocardiography, 94.3% for stress echocardiography, and 96.2% for myocardial scintigraphy. For the classification of the individual involved coronary arteries, the sensitivity of myocardial scintigraphy was 84.8% and that of exercise echocardiography was 63% (p less than 0.01); the related specificities were 98% and 98.2% respectively (NS). It may be concluded that exercise echocardiography is highly accurate for the recognition of coronary artery disease, whereas it appears less sensitive in the identification of the involved vessels, particularly in patients with multivessel disease.     

Cardiac damage due to nonpenetrating trauma. Report of four cases

Four examples of cardiac damage secondary to nonpenetrating trauma in road accidents are described. Two patients had interventricular septal defect and other two had tricuspid insufficiency. In all four cases the lesion was not recognized at the time of the accident but became clinically important later. The time interval between trauma and surgery was one month to thirteen years. After surgical treatment, all four patients have continued to be asymptomatic.     

The epidemiology of hepatitis delta infection in Italy. Promoting Group.

The epidemiology of HDV infection in Italy was assessed in a retrospective study involving 1556 HBsAg chronic carriers on their first presentation at one of the 35 Liver Units in 1987. Total anti-HD was detected in 23.4% of HBsAg carriers and was significantly more frequent in southern than in northern Italy (26.6% vs. 19.1%, p less than 0.01). Age distribution showed that 73% of the anti-HD-positive subjects, but only 56% of the anti-HD-negative subjects, were under 40 years of age (p less than 0.01). Anti-HD prevalence increased with the severity of the liver disease from 3.8% in healthy carriers to 42.5% in cirrhosis. No geographical statistical difference was found among HBsAg healthy carriers or subjects with chronic persistent hepatitis (CPH), while among patients with chronic active hepatitis (CAH) or cirrhosis anti-HD prevalence was much higher in the south (p less than 0.01). The various potential risk factors were evaluated by multiple logistic regression analysis. HDV infection was independently related to young age, residence in the south, i.v. drug abuse, a large family and household contact with an anti-HD-positive carrier. No association was found with blood transfusion or male homosexuality. These findings confirm that HDV infection is endemic in Italy, particularly in some southern areas, where intrafamily contact probably at a young age may favour the spread of the infection.     

Virus Detection and Semiquantitation in Explanted Heart Tissues of Idiopathic Dilated Cardiomyopathy Adult Patients by Use of PCR Coupled with Mass Spectrometry Analysis

Viral detection in heart tissues has become a central issue for the diagnosis and exploration of the pathogenesis of idiopathic dilated cardiomyopathy (IDCM). In the present study, common cardiotropic viruses in 67 explanted heart samples of 31 IDCM adult patients were detected and semiquantified by using for the first time a new technology based on PCR assay coupled to electrospray ionization-time of flight mass spectrometry analysis (PCR-MS), with comparison to reference quantitative real-time PCR (RT-qPCR) assay. PCR-MS identified single or mixed enterovirus (EV) and parvovirus B19 (PVB19) infections in 27 (40.2%) of 67 samples, corresponding to 15 (48.3%) of the 31 patients, whereas RT-qPCR identified viral infections in 26 (38.8%) samples, corresponding to 16 (51.6%) of the patients. The PCR-MS results correlated well with EV and PVB19 detection by RT-qPCR (kappa = 0.85 [95% confidence interval {CI}, 0.72 to 1.00] and kappa = 0.82 [95% CI, 0.66 to 0.99], respectively). The levels of EV RNA (median, 550 [range, 178 to 3,200] copies/μg of total extracted nucleic acids) and of PVB19 DNA (median, 486 [range, 80 to 1,157] copies/μg of total extracted nucleic acids) were measured using PCR-MS and correlated with those obtained by RT-qPCR (r² = 0.57, P = 0.002 and r² = 0.64, P < 0.001 for EV and PVB19, respectively). No viruses other than EV and PVB19 strains were detected using the new PCR-MS technology, which is capable of simultaneously identifying 84 known human viruses in one assay. In conclusion, we identified single or mixed EV and PVB19 cardiac infections as potential causes of IDCM. The PCR-MS analysis appeared to be a valuable tool to rapidly detect and semiquantify common viruses in cardiac tissues and may be of major interest to better understand the role of viruses in unexplained cardiomyopathies.     

Mast Cells as a Potential Prognostic Marker in Prostate Cancer

Despite years of intensive investigation that has been made in understanding prostate cancer, it remains one of the major men''s health issues and the leading cause of death worldwide. It is now ascertained that prostate cancer emerges from multiple spontaneous and/or inherited alterations that induce changes in expression patterns of genes and proteins that function in complex networks controlling critical cellular events. It is now accepted that several innate and adaptive immune cells, including T- and B-lymphocytes, macrophages, natural killer cells, dendritic cells, neutrophils, eosinophils, and mast cells (MCs), infiltrate the prostate cancer. All of these cells are irregularly scattered within the tumor and loaded with an assorted array of cytokines, chemokines, and inflammatory and cytotoxic mediators. This complex framework reflects the diversity in tumor biology and tumor-host interactions. MCs are well-established effector cells in Immunoglobulin-E (Ig-E) associated immune responses and potent effector cells of the innate immune system; however, their clinical significance in prostate cancer is still debated. Here, these controversies are summarized, focusing on the implications of these findings in understanding the roles of MCs in primary prostate cancer.     

Plasma PCSK9 levels and sepsis severity: an early assessment in the emergency department

Clinical and Experimental Medicine - The aim of the study is to evaluate the prognostic value of early PCSK9 levels in non-intubated septic patients admitted to the emergency department. This...