Blood pressure and vascular effects of leptin in humans

Background: Leptin may play a role in mediating obesity-related hypertension. However, its effects on the vasculature and blood pressure (BP) remain poorly defined in humans. Methods: In the first study, we performed a short-term, placebo-controlled, randomized, double-blind, cross-over experiment investigating the actions of recombinant human leptin (r-metHuLeptin) in 15 nonobese adults. To compliment the acute study, we retrospectively analyzed available BP results from a previously performed 85-day, placebo-controlled, randomized, double-blind, parallel weight-loss study using r-metHuLeptin in 284 obese adults. Results: In the acute study, conduit artery endothelial function determined by brachial flow-mediated dilatation (FMD) increased 2 hours following 0.2 mg . Kg(1) subcutaneously (SC) of r-metHuLeptin versus placebo (+3.3% versus -2.8%, P = .02). BP remained unchanged 4 hours after injections. In the retrospective analysis of the weight loss study data, 10 mg every day before noon (QAM), 10 mg every day after noon (QPM), or 10 mg twice a day (BID) SC of r-metHuLeptin was found to not alter the degree of weight loss (-3.2 +/- 3.7 versus -2.9 +/- 3.2 Kg, P = .54), change in systolic (-1.6 + 12.9 versus -2.0 +/- 13.9 mmHg, P = .85) and diastolic BP (-0.2 +/- 8.7 versus -1.5 +/- 8.6, P = .30), as well as heart rate (-1.4 +/- 10.7 versus -1.4 +/- 10.4 beats/min, P = .98) compared to placebo. Conclusions: In our acute study, marked hyperleptinemia rapidly enhanced endothelial function and did not alter BP. The available data from a longer-term study in healthy obese adults did not demonstrate a significant effect of hyperleptinemia upon BP. These combined findings do not support a direct role for leptin in linking obesity to hypertension, however more studies are required to corroborate these observations.     

Quality of life among bipolar disorder patients misdiagnosed with major depressive disorder

Objective: Bipolar disorder is frequently misdiagnosed as major depressive disorder (MDD). We aim to quantify the prevalence of misdiagnosed bipolar disorder among the depression population and evaluate the quality-of-life (QOL) impact of misdiagnoses.Method: Data were collected from 2 self-administered, cross-sectional studies in 2003. Patients participating in The Bipolar Disorder Misdiagnosis Study (N = 1156) were previously diagnosed with depression, experienced a depressive episode within the past year, and had no previous diagnosis of bipolar disorder or schizophrenia. Patients who experienced a manic episode in the past year, based on DSM-IV criteria, were classified as misdiagnosed. Patients participating in The Bipolar Disorder Project (N = 1214) self-reported a diagnosis of bipolar disorder and were recruited through community mental health centers and support groups. Quality of life was assessed via the Psychological General Well-Being (PGWB) Index and Medical Outcomes Study 8-Item Short-Form Health Survey (SF-8). Demographic differences between groups were controlled using linear regression models.Results: Of the diagnosed MDD sample, 14.3% met criteria for misdiagnosed bipolar disorder. When controlling for demographic differences, the PGWB overall score for the misdiag-nosed averaged 12.77 (p < .001) points lower than that of MDD patients and 9.55 (p < .001) points lower than that of diagnosed bipolar disorder patients. The average SF-8 mental component summary score for the misdiagnosed was 5.85 (p < .001) points lower than that of MDD patients and 3.18 (p = .002) points lower than that of diagnosed bipolar disorder patients.Conclusion: Misdiagnosis is associated with poorer QOL than MDD or diagnosed bipolar disorder, which are recognized as having a considerable impact on QOL.     

Medication use, service utilization, and medical costs associated with new episodes of bipolar disorder: evidence from a retrospective claims database

Objective: To identify resource use patterns and costs incurred during new episodes of bipolar disorder.Method: Researchers examined Medstat MarketScan databases covering the interval of January 1, 1998, to December 31, 2002, to identify 6148 patients with new episodes of bipolar disorder as defined by the International Classification of Diseases, Ninth Revision. Resource utilization patterns and costs for the 6 months prior to the index date and for the 30 days and 1 year after the index date were examined. Differences among subcategories of bipolar patients in terms of the resources used before and after the index date were also examined.Results: The majority of the individuals in the study were female (61.3%) and the mean age was 41.9 years. Patients diagnosed as manic had higher bipolar treatment costs (p < .01) and were more likely to be hospitalized for mental health diagnoses 30 days (p < .01) and 1 year after the index diagnosis (p = .02) compared with individuals diagnosed as depressive, mixed, or other/ unknown. Median total medical costs in the 1 year after the index date were highest for those diagnosed as depressed (p = .02), while patients diagnosed as mixed bipolar had significantly more psychiatrist visits after the index date (p < .01). Approximately 15% of patients were not treated with any central nervous system medication, and over 50% of patients were treated with antidepressants.Conclusion: The subcategory of bipolar disorder that an individual is diagnosed as having significantly affects resource use and costs after such diagnosis. Patients diagnosed as manic generally used more resources than other individuals. In addition, results suggest that a large proportion of individuals are not being treated in accordance with recommended treatment guidelines.     

Pulmonary arterial hypertension: noninvasive detection with phase-contrast MR imaging

PURPOSE: To retrospectively identify pulmonary arterial (PA) flow parameters measured with phase-contrast magnetic resonance (MR) imaging that allow noninvasive diagnosis of chronic PA hypertension (PAH). MATERIALS AND METHODS: The study was HIPAA compliant and was approved by the institutional review board; a waiver of informed consent was obtained. Fifty-nine patients (49 female patients; mean age, 46 years; range, 16-85 years) known to have or suspected of having PAH underwent breath-hold phase-contrast MR imaging and right-sided heart catheterization (RHC). The presence of PAH (mean pulmonary artery pressure [mPAP], >25 mm Hg) was confirmed in 42 patients. Parameters, including PA areas, PA strain, average velocity, peak velocity, acceleration time, and ejection time, were measured in each patient by investigators blinded to RHC results. These measurements were correlated with mPAP, systolic pulmonary artery pressure (sPAP), and pulmonary vascular resistance index (PVRI). The diagnostic ability of phase-contrast MR imaging to depict PAH was quantified. Statistical tests included Spearman rho coefficients, receiver operating characteristic curve analysis, and Bland-Altman plots. RESULTS: Results showed average velocity to have the best correlation with mPAP, sPAP, and PVRI (r = -0.73, -0.76, and -0.86, respectively; P < .001). Average velocity (cutoff value = 11.7 cm/sec) revealed PAH with a sensitivity of 92.9% (39 of 42) and a specificity of 82.4% (14 of 17). Sensitivity and specificity for the minimum PA area (cutoff value = 6.6 cm(2)) were 92.9% (39 of 42) and 88.2% (15 of 17), respectively. CONCLUSION: The average blood velocity throughout the cardiac cycle is strongly correlated with pulmonary pressures and resistance.     

Stringent regulation of complement lectin pathway C3/C5 convertase by C4b-binding protein (C4BP)

The complement lectin pathway, an essential component of the innate immune system, is geared for rapid recognition of infections as each C4b deposited via this pathway is capable of forming a C3/C5 convertase. In the present study, role of C4b-binding protein (C4BP) in regulating the lectin pathway C3/C5 convertase assembled on zymosan and sheep erythrocytes coated with mannan (E_Man) was examined. While the C4BP concentration for inhibiting 50% (IC₅₀) formation of surface-bound C3 convertase on the two surfaces was similar to that obtained for the soluble C3 convertase (1.05 nM), 3- and 41-fold more was required to inhibit assembly of the C5 convertase on zymosan (2.81 nM) and E_Man (42.66 nM). No difference in binding interactions between C4BP and surface-bound C4b alone or in complex with C3b was observed. Increasing the C4b density on zymosan (14,000–431,000 C4b/Zym) increased the number of C4b bound per C4BP from 2.87 to 8.23 indicating that at high C4b density all seven α-chains of C4BP are engaged in C4b-binding. In contrast, the number of C4b bound per C4BP remained constant (3.79 ± 0.60) when the C4b density on E_Man was increased. The data also show that C4BP regulates assembly and decay of the lectin pathway C3/C5 convertase more stringently than the classical pathway C3/C5 convertase because of a 7- to 13-fold greater affinity for C4b deposited via the lectin pathway than the classical pathway. C4BP thus regulates efficiently the four times greater potential of the lectin pathway than the classical pathway in generating the C3/C5 convertase and hence production of pro-inflammatory products, which are required to fight infections but occasionally cause pathological inflammatory reactions.     

Prevalence and correlates of septal delayed contrast enhancement in patients with pulmonary hypertension

Using cardiac magnetic resonance, the presence of myocardial delayed contrast enhancement (DCE) has been described in the ventricular septum at the level of the right ventricular insertion points in patients with pulmonary hypertension (PH). The aim of this study was to investigate the prevalence, extent, and correlates of this finding. Septal DCE was evaluated in 55 patients with known or suspected PH of various causes. The extent of DCE was estimated visually with an insertion enhancement score (range 0 to 4) and quantified as DCE mass. The results were correlated with cine magnetic resonance and right-sided cardiac catheterization. Predictors of DCE were investigated using multivariate analysis. PH at rest was present in 42 patients (group 1) and absent in 13 (group 2). DCE was noted in 41 patients (97%) in group 1 and 3 (23%) in group 2 (p <0.0001). The extent of DCE was higher in group 1 than group 2 (median insertion enhancement score 3 vs 0, median DCE mass 8.7 vs 0 g, respectively; p <0.0001 for both). The extent of DCE showed moderate to good univariate correlations (r = 0.5 to 0.73) with pulmonary pressures and with right ventricular volumes, mass, and ejection fractions. In multivariate analysis, systolic pulmonary pressure was the only predictor of DCE. In conclusion, the presence of septal DCE at the right ventricular insertion points is common in PH of different causes, and the level of systolic pulmonary pressure elevation appears to be the main determinant of this finding.     

Utility of B-type natriuretic peptide in predicting medium-term mortality in patients undergoing major non-cardiac surgery

This study was conducted to assess the ability of preoperative B-type natriuretic peptide levels to predict medium-term mortality in patients who undergo major noncardiac surgery. During a median of 654 days of follow-up, 33 patients from a total cohort of 204 patients (16%) died, 17 from cardiovascular causes. The optimal cutoff in this cohort, determined using a receiver-operating characteristic curve, was >35 pg . ml(-1). This was associated with a 3.5-fold increase in the hazard of death (p = 0.001) and a 6.9-fold increase in the hazard of cardiovascular mortality (p = 0.003). In conclusion, these findings extend recent work demonstrating that B-type natriuretic peptide levels obtained before major noncardiac surgery can be used to predict perioperative morbidity and indicate that they also forecast medium-term mortality, particularly cardiovascular death.     

Bilateral temporal bone xanthoma. Case report

Xanthoma formation is frequently seen over the subcutaneous tissue of extensor surfaces and tendons that have received minor trauma or friction in patients with hypercholesterolemia. However, temporal bone xanthomas with intracranial extension are uncommon. To the best of the authors' knowledge, this is the second report in the literature in which bilateral extension of a xanthoma is described. Xanthomas of the temporal bone are benign lesions, and complete or even partial removal is effective. The predisposing cause of the lesion should also be treated.