Antihypertensive utility of perindopril in a large, general practice-based clinical trial

The authors evaluated, in a community-based open-label trial, the effectiveness and safety of perindopril in 13,220 US hypertensive patients and studied how physicians adhere to hypertension treatment guidelines. Patients received perindopril 4 mg q.d. for 6 weeks. Based on physicians' perception of blood pressure response, the patient was either maintained on 4 mg or the dose was increased to 8 mg for an additional 6 weeks. From baseline to week 12, the mean sitting blood pressure significantly declined from 156.9/94.5 mm Hg to 139.2/84.0 mm Hg. Further dose titration resulted in a clinically significant reduction in blood pressure in all patients with inadequate response on 4 mg at week 6. Blood pressure control (<140/<90 mm Hg) was achieved at 12 weeks in 48.8% patients. The subpopulation analyses demonstrated that perindopril monotherapy was effective in both men and women, in patients of all ethnicities, and in patients <65 and ≤65 years of age. Perindopril was safe and well tolerated in all hypertensive subgroups including high-risk patients. Physicians were more attuned to controlling diastolic than systolic blood pressure, and their adherence to the treatment guidelines was found to be not optimal.     

A systemic type I 5 alpha-reductase inhibitor is ineffective in the treatment of acne vulgaris

Excessive sebum production is a central aspect of the pathophysiology of acne vulgaris. Sebaceous gland function is under androgen control and it is hypothesized that dihydrotestosterone is formed by the action of 5 alpha-reductase. Type I is the controlling isoenzyme. This study describes a 3-month, multicenter, randomized, placebo-controlled clinical trial with a potent, selective inhibitor of type I 5 alpha-reductase used alone and in combination with systemic minocycline. Inhibition of type I 5 alpha-reductase was not associated with clinical improvement of acne when used alone and did not enhance the clinical benefit of systemic minocycline. These results indicate the need for further work at the molecular level to better understand the action of androgens on sebaceous gland function.     

Point-of-care ecarin clotting time versus activated clotting time in correlation with bivalirudin concentration

INTRODUCTION: A thrombin inhibitor management (TIM) point-of-care test based upon the ecarin clotting time (ECT) has been developed. The ECT has been suggested to more accurately reflect the anti-coagulant effect of direct thrombin inhibitors compared with the activated clotting time (ACT). We sought to examine the correlation of the TIM-ECT test with bivalirudin concentration in patients undergoing percutaneous coronary intervention (PCI), and to compare the performance of this test with the current standard (i.e., ACT). MATERIALS AND METHODS: In a multicenter study, blood samples were obtained at six pre-defined time-points in 170 consecutive patients undergoing PCI using bivalirudin. For each sample, the TIM-ECT (citrated and non-citrated), ACT, and bivalirudin concentration was determined. RESULTS: Considering samples from all time-points (n=784), the correlations of TIM-ECT citrated, TIM-ECT non-citrated, and ACT with bivalirudin concentration were 0.96, 0.93, and 0.90, respectively. For samples collected at therapeutic levels of bivalirudin (n=353), the correlations of TIM-ECT citrated, TIM-ECT non-citrated, and ACT with bivalirudin concentration were lower, and showed a greater disparity between methods, with correlation coefficients of 0.75, 0.59, and 0.37, respectively. Prediction models based on the measured bivalirudin concentration were developed for TIM-ECT and ACT, and the coefficients of determination (r(2)) of actual versus predicted TIM-ECT and ACT were 0.91 and 0.81, respectively. CONCLUSIONS: In this PCI population, the TIM-ECT point-of-care test and ACT demonstrated a strong correlation with bivalirudin concentration. The TIM-ECT test had a higher correlation with bivalirudin concentration at therapeutic levels of the drug, and for individual samples appears to more consistently reflect the bivalirudin concentration compared with the ACT.     

Neurobiological correlates of diagnosis and underlying traits in patients with borderline personality disorder compared with normal controls

The purpose of the study was to test the hypothesis that borderline personality disorder (BPD) and its underlying traits are associated with abnormalities in neurotransmitter systems. Subjects were 30 women with BPD and 22 normal controls, assessed using the Diagnostic Interview for Borderlines, revised, the Hamilton Depression Scale (HAM-A) and the Hamilton Anxiety Scale (HAM-A), the Diagnostic Assessment of Personality Pathology, the Buss-Durkee Guilt-Hostility Inventory, the Barratt Impulsivity Scale (BIS), and challenge tests to measure serotonergic, cholinergic and noradrenergic activity. Borderline subjects with high HAM-A and HAM-D scores showed a faster time to peak in prolactin response to meta-chlorphenylpiperazine (m-CPP) challenge. Borderline subjects with high BIS scores showed prolactin blunting. There were no differences in cortisol response to m-CPP, or on the cholinergic and noradrenergic challenges. The results suggest that impulsive traits in borderline patients are associated with abnormalities in serotonergic systems.     

Process irregularity of cortisol and adrenocorticotropin secretion in men with major depressive disorder

Although evidence suggests that major depressive disorder (MDD) is associated with hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, research on basal HPA axis hormone levels in MDD patients has been inconclusive. Definitive characterization of basal cortisol and adrenocorticotropin (ACTH) secretion may be important for understanding the pathophysiology of this disorder. In recent years, a new approach to the analysis of basal hormone secretion has been developed involving the approximate entropy (ApEn) statistic, which represents the degree of disorderliness or serial irregularity in a time series of hormone levels. ApEn has been shown to reflect the degree of coordination in integrated network systems and has provided new insights into the pathophysiology of a number of endocrine conditions. In the study reported here, 15 medication-free men with MDD and 15 healthy control men were admitted to a General Clinical Research Center and had blood sampled for cortisol and ACTH determinations every hour over a 24-h period. The cortisol and ACTH time series were characterized with a cosinor analysis and with analysis of ApEn. Depressed patients and control subjects did not differ significantly on any parameter derived from the cosinor analysis or on several other standard indices of basal hormone secretion. However, the depressed men had significantly increased cortisol ApEn and significantly decreased ACTH ApEn compared with the healthy subjects. The ApEn findings suggest a loss of regulatory control over cortisol secretion, and possibly increased cortisol feedback on the pituitary in the depressed patients. Together, these results are most consistent with a primary abnormality of the adrenal gland and suggest that further investigation of adrenal gland physiology may be informative for the pathophysiology of depression.     

Novel haplotypes in 17q21 are associated with progressive supranuclear palsy

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are sporadic neurodegenerative diseases presenting as atypical parkinsonian disorders, characterized by the presence of tau-positive neurofibrillary tangles. Recently, an extended haplotype (H1E) of 787.6 kb that comprises several genes including MAPT showed increased association with PSP. The objective of this study was to determine the size of the H1E haplotype associated with PSP and CBD in different populations and to identify specific subhaplotypes in the background of H1E haplotype. Nineteen single nucleotide polymorphisms (SNPs) in the 17q21 region were genotyped in two case-control samples. The SNPs that were associated with higher risk for the disease in the homozygous state delimit a region of more that 1 Mb. Haplotype analyses in the Spanish sample showed that the most frequent haplotype found among the patients (H1E'), which extends 1.04 Mb and contains several genes such as MAPT, CRHR1, IMP5, Saitohin, WTN3, and NSF. A specific subhaplotype (H1E'A) was present in 16% of PSP patients but was not observed in the controls. Furthermore, the H2E'A haplotype, was rarely present in the disease group suggesting that it plays a protective role. The identification of these specific subhaplotypes that modify risk for PSP/CBD supports the hypothesis that a pathogenic allele exists in a subgroup of PSP patients.     

Symptoms of depression and anxiety (MHI) following acute medical/surgical hospitalization and post-discharge psychiatric diagnoses (DSM) in 839 geriatric US veterans

OBJECTIVE: We addressed the relatively unexplored use of screening scores measuring symptoms of depression and/or anxiety to aid in identifying patients at increased risk for post-discharge DSM-IV Axis I diagnoses. We were unable to find such studies in the literature. METHOD: Elderly veterans without recent psychiatric diagnoses were screened for depression and anxiety symptoms upon admission to acute medical/surgical units using the Mental Health Inventory (MHI). Following discharge, those who had exceeded cut-off scores and had been randomized to UPBEAT Care (Unified Psychogeriatric Biopsychosocial Evaluation and Treatment, a clinical demonstration project) were evaluated for DSM diagnoses. We report on 839 patients, mostly male (96.3%; mean age 69.6 +/- 6.7 years), comparing three groups, i.e. those meeting screening criteria for symptoms of (i) depression only; (ii) anxiety only; and (iii) both depression and anxiety. RESULTS: Despite absence of recent psychiatric history, 58.6% of the 839 patients received a DSM diagnosis post-discharge (21.8% adjustment; 15.4% anxiety; 7.5% mood; and 14.0% other disorders). Patients meeting screening criteria for both depression and anxiety symptoms received a DSM diagnosis more frequently than those meeting criteria for anxiety symptoms only (61.9% vs 49.0%, p = 0.017), but did not differ significantly from those meeting criteria for depressive symptoms only (61.9% vs 56.8%, p = 0.174). Although exceeding the MHI screening cut-off scores for depression, anxiety, or both helped to identify patients with a post-discharge DSM diagnosis, the actual MHI screening scores failed to do so. CONCLUSION: Screening hospitalized medical/surgical patients for symptoms of depression, anxiety, and particularly for the combination thereof, may help identify those with increased risk of subsequent DSM diagnoses, including adjustment disorder.