Cholesterol metabolism in patients with chronic renal failure on hemodialysis

Premature atherosclerosis is a major concern in patients on chronic dialysis and the identification of risk factors is important for preventive and interventional strategies. Other than the recognized atherogenic lipoprotein levels, little is known about overall cholesterol metabolism in patients on chronic hemodialysis (HD) and the best therapeutic intervention is still being debated. Therefore, we investigated intestinal cholesterol absorption, cholesterol and bile acid synthesis, and non-cholesterol plasma sterols in eight patients on dialysis and compared the results to those of 16 healthy male controls matched for body mass index and dietary cholesterol intake. Total, low-density lipoprotein (LDL) cholesterol, and triglycerides did not differ between the groups, but dialysis patients had a significantly lower high-density lipoprotein (HDL) cholesterol level (39 +/- 11 mg/dL vs. 48 +/- 10 mg/dL, p < 0.045). However, fractional cholesterol absorption, was significantly lower in dialysis patients (42.8 +/- 10.9% vs. 53.4 +/- 11%, p < 0.035), whereas plasma plant sterol concentrations and their ratios to cholesterol did not differ. Bile acid and total cholesterol synthesis were lower in dialysis patients (40% and -25%, respectively), although the differences were not significant. In contrast, lathosterol and its ratio to cholesterol in plasma was significantly lower in dialysis patients (0.176 +/- 0.084 mg/dL vs. 0.251 +/- 0.102 mg/dL, p < 0.024 and 0.733 +/- 0.353 microg/mg vs. 1.172 +/- 0.407 microg/mg, p < 0.017, respectively), indicating reduced hepatic de novo cholesterol synthesis. It is concluded that reduced HDL cholesterol and reduced bile acid synthesis contributes to atherosclerosis pathogenesis in dialysis patients, whereas intestinal cholesterol absorption and hepatic cholesterol synthesis did not seem dominant in this process at this stage of disease. Consequently, treatment with bile acid binding resins could be preferable to treatment with cholesterol absorption and synthesis inhibitors.     

The epidemiology of major depressive episodes: results from the International Consortium of Psychiatric Epidemiology (ICPE) Surveys

Absence of a common diagnostic interview has hampered cross-national syntheses of epidemiological evidence on major depressive episodes (MDE). Community epidemiological surveys using the World Health Organization Composite International Diagnostic Interview administered face-to-face were carried out in 10 countries in North America (Canada and the US), Latin America (Brazil, Chile, and Mexico), Europe (Czech Republic, Germany, the Netherlands, and Turkey), and Asia (Japan). The total sample size was more than 37,000. Lifetime prevalence estimates of hierarchy-free DSM-III-R/DSM-IV MDE varied widely, from 3% in Japan to 16.9% in the US, with the majority in the range of 8% to 12%. The 12-month/lifetime prevalence ratio was in the range 40% to 55%, the 30-day/12-month prevalence ratio in the range 45% to 65%, and median age of onset in the range 20 to 25 in most countries. Consistent socio-demographic correlates included being female and unmarried. Respondents in recent cohorts reported higher lifetime prevalence, but lower persistence than those in earlier cohorts. Major depressive episodes were found to be strongly co-morbid with, and temporally secondary to, anxiety disorders in all countries, with primary panic and generalized anxiety disorders the most powerful predictors of the first onset of secondary MDE. Major depressive episodes are a commonly occurring disorder that usually has a chronic-intermittent course. Effectiveness trials are needed to evaluate the impact of early detection and treatment on the course of MDE as well as to evaluate whether timely treatment of primary anxiety disorders would reduce the subsequent onset, persistence, and severity of secondary MDE.     

Comorbidity and mixed anxiety-depressive disorder: clinical curiosity or pathophysiological need?

The paper reviews available epidemiological evidence for the existence of and the implications of comorbidity of anxiety and depressive disorders and mixed anxiety-depressive (MAD) disorders. Using epidemiolological evidence of prevalence and incidence and data relating to time-course of illness, risk factor and outcome, it is concluded: (1) that anxiety-depression comorbidity is quite frequent in epidemiological and clinical settings throughout the world; (2) this comorbidity is diagnosis-specific and is associated with increased vulnerabilities and risks as well as poorer outcome and marked disabilities; and (3) no such evidence was found for MAD disorders. Contrary to what was predicted, the prevalence of MAD disorders was quite low even when using the more recent criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. (4) Furthermore, there was quite a heterogeneous pattern in terms of risk, severity and outcome making it questionable whether this disorder, as currently defined, is a clinical entity. These findings are discussed in terms of two perspectives, the 'lumpers' with their dimensional view and the 'splitters' with their categorical view. It is concluded that although comorbidity of threshold anxiety and depressive disorders seems to be an important phenomenon, no such evidence is provided for MAD disorders. Copyright 2001 John Wiley & Sons, Ltd.     

Effects of fluvastatin on biliary lipids in subjects with an elevated cholesterol saturation index

OBJECTIVE: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have been suggested as agents to reduce the biliary cholesterol saturation index (CSI) in duodenal bile and therefore might be supportive in primary or secondary prevention of gallstones. However, the efficiency of the therapy seems to depend on both the HMG-CoA reductase inhibitor used and the study population selected. METHODS: We therefore investigated the effect of a high-dose application of fluvastatin on biliary lipid composition in 21 subjects exhibiting mild hypercholesterolaemia and a history of current gallstones or cholecystectomy due to gallstone disease. Subjects were treated either with 40 mg fluvastatin twice per day over a 3-month period (n = 14) or with placebo (n = 7). Bile samples were aspirated during endoscopy after intravenous ceruletid stimulation before and after therapy. RESULTS: Both groups were comparable in CSI (mean +/- SD) at baseline (1.78 +/- 0.2 placebo vs. 1.97 +/- 0.4 verum). CSI significantly decreased in the verum group to 1.45 +/- 0.4 (P = 0.003) mainly due to increased phospholipid levels, whereas no difference was observed in the placebo group (1.85 +/- 0.7, n.s.). In addition, the verum group exhibited a significant reduction of hydrophobic deoxycholic acid, which has been reported to induce cholesterol crystal precipitation, and an increase of hydrophilic cholic acid. CONCLUSION: Fluvastatin might decrease the risk of cholesterol gallstone formation in patients with elevated biliary CSI during long-term treatment by reduction of biliary cholesterol saturation and percentage change in deoxycholic acid content.     

Navigation in medical Internet image databases

The world wide web (WWW) changes common ideas of database access. Hypertext Markup Language allows the simultaneous presentation of information from different sources such as static pages, results of queries from) databases or dynamically generated pages. 'Therefore, the metaphor of the WWW itself as a database was proposed by Mendelzon and Nlilo in 1998. Against this background the techniques of navigation within WWW-databases and the semantic types of their queries has e been analysed. Forty eight image repositories of different types and content, but all concerning medical essence, have been found by search-engines. Many different techniques are offered to enable navigation ranging from simple HTML-link-lists to complex applets. The applets in particular promise an improvement for navigation. Within the meta-information for querying, only ACR- and UMLS-encoding were found, but not standardized vocabularies like ICD10 or Terminologia Anatomica. UMLS especially shows that a well defined thesaurus can improve navigation. However, of the analysed databases only the UMLS 'metathesaurus' is currently implemented without providing additional navigation support based on the UMLS 'semantic network'. Including the information about relationships between the concepts of the metathesaurus or using the UMLS semantic network could provide a much easier navigation within a network of concepts pointing to multimedia files stored somewhere in the WWW.     

Test-Retest Reliability of a standardized psychiatric interview (DIS/CIDI)

The reliability of DSM-III diagnoses using an expanded version of the Diagnostic Interview Schedule (DIS), called the Composite International Diagnostic Interview (CIDI), was evaluated by examining 60 psychiatric inpatients on a test-retest basis. Acceptable agreement coefficients of (kappa) 0.5 or above were found for all but two disorders: dysthymic disorder and generalized anxiety disorder. The sub-classification of DSM-III affective disorders also revealed some discrepancies between the test and the retest interviews. When compared with results from earlier versions of the DIS, diagnostic reliability was found to have improved for the DSM-III anxiety disorders in particular. These improvements can possibly be attributed to some changes in the wording of the respective items of this section. Several reasons for lowered test-retest reliability are discussed.This research was supported by the German Research Foundation (DFG). The study was done in close collaboration with members of the Task Force on Instrument Development, established within the framework of the joint WHO/ADAMHA Project on Diagnosis and Classification. Lee Robins, PhD, John Helzer, MD, John Wing, MD, Norman Sartorius, MD, and Jack Burke, MD, provided us with helpful comments. Parts of the reliability analysis were done under contract with the NIMH, Division of Biometry and Epidemiology.     

Acknowledgement to translators

Acknowledgement to referees     

A Comparison of microCT and microPET for Evaluating Lymph Node Metastasis in a Rat Model

Purpose

The demand to optimize multidisciplinary treatment strategies in patients with benign and malignant diseases of the lung and other organs has led to the increased need of mechanistic proof-of-concept studies in preclinical small animal models using new non-invasive imaging methods. Therefore, we evaluated the role of microPET and microCT for mediastinal lymph node staging in an orthotopic lung cancer model in rats.

Procedures

Human lung cancer cells (NCI-H460) were injected transthoracically in nude rats (NIH-RNU). After 2 weeks of tumour growth, animals underwent multiphase contrast-enhanced microCT using ExiTron nano 12000 as a contrast agent and dynamic microPET using the tracer 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG). Thereafter, animals were sacrificed for histological analysis.

Results

Late phase micro X-ray computed tomography (microCT) revealed the best delineation of lymph node metastases, as compared to earlier scans. In terms of an increased [¹⁸F]FDG uptake over time, dynamic micro positron emission tomography (microPET) delineated lymph node metastases and enabled metabolic examinations of the induced lung cancer metastases.

Conclusion

The combination of contrast-enhanced microCT and dynamic microPET is feasible in rats for the visualization of mediastinal lymph node metastases.