German Cohort Of Patients Research Articles

Viral genomes in the pericardial fluid and in peri- and epicardial biopsies from a German cohort of patients with large to moderate pericardial effusions

The aetiology of pericardial effusion has been generally assessed by clinical work-up only, which leaves a large cohort of patients with "idiopathic" effusions virtually undiagnosed. In accordance with the ESC guidelines, this contribution intends to change this attitude. After therapeutic or diagnostic pericardiocentesis of 259 patients with large to moderate pericardial effusions, pericardial fluid, epicardial and pericardial biopsies, and blood samples were analysed by PCR for cardiotropic microbial agents. Cytology, histology, immunohistology of tissue and fluids and laboratory tests were performed. Of the 259 patients, 35% suffered from an autoreactive aetiology, 28% suffered from a malignant and 14% from an infectious cause. Investigating all samples by PCR, we identified viral genomes in 51 (19.7%) patients, parvovirus B19 (B19V) being identified in 25 and Epstein-Barr virus (EBV) in 19 cases. In patients with a sole infectious aetiology (n=36), B19V was detected in 21 and EBV in 10 cases. When differentiating with regard to the material investigated for the presence of cardiotropic viruses, parvovirus B19 was most often detected in the epicardium and EBV was most frequently detected in the pericardial fluid independent from the final diagnostic categorisation. Bacterial cultures including tests for tuberculosis were all negative. Molecular techniques improve sensitivity, specificity and diagnostic accuracy for the underlying aetiology in pericarditis patients with effusion. The identification of specific viral signatures will help to understand pathogenetic mechanisms in pericarditis and allow to tailor an adequate therapy beyond antiphlogistic treatment.

Keratin 8 variants are associated with cryptogenic hepatitis

Keratins 8 and 18 (K8 and K18) are the cytoskeletal intermediate filament proteins of adult hepatocytes. Murine models indicate that mutations in the K8- and K18-encoding genes predispose to liver injury. Moreover, studies showed an association of K8/K18 variants with human acute and chronic liver diseases. However, only little is known about a putative association of K8/K18 variants with cryptogenic hepatitis, a frequent liver disease of enigmatic etiology, often necessitating liver transplantation. Therefore, we analyzed whether K8 variants associate with cryptogenic hepatitis in a German cohort of patients in comparison to control blood bank donors. Genomic DNA isolated from liver biopsies of cryptogenic hepatitis patients or peripheral blood of healthy donors was analyzed for K8 variants by PCR amplification and direct DNA sequencing. We identified 8 novel heterozygous or homozygous amino acid-altering K8 variants in 5 of 62 cryptogenic hepatitis patients (8.1%) and in none of 67 controls (P = 0.02). Previously described K8 variants p.G62C and p.R341H were found at similar incidence in cryptogenic hepatitis patients and controls. Hence, they were considered as polymorphisms not associated with liver disease progression. In conclusion, previously undescribed K8 variants associate with cryptogenic hepatitis in a German cohort of patients, possibly predisposing carriers to the development of liver disease.

Economic Burden in a German Cohort of Patients with Multiple Sclerosis

Aims: To estimate costs of multiple sclerosis (MS) in a German cohort according to severity of the disease and clinical symptoms. Methods: 144 patients were recruited from an MS outpatient clinic. Costs were calculated according to current German health-economic guidelines from the perspective of the social health insurance system. Patients were either interviewed or completed a questionnaire. Cost assessment covered a 3-month period. Health outcomes were: Expanded Disability Status Scale, MS Functional Composite, Functional Assessment of MS, fatigue, depression (Beck Depression Inventory II) and patients’ socioeconomic status. Multivariate linear regression identified independent cost predictors. Results: Total quarterly costs per patient were EUR 10,329 (95% CI 9,357–11,390). Direct costs were EUR 5,344 for the social health insurance system and EUR 140 for the patient. Drugs represented the major share of direct costs (and 35% of total costs); indirect costs accounted for 47% of total costs. Univariate and multivariate analyses identified age, disability, fatigue and depression as independent predictors for total, indirect or drug costs. Conclusion: MS represents a high economic burden, with direct costs exceeding indirect costs. To reduce costs, research should focus on prevention that slows down progression of MS. Rehabilitation and symptomatic treatment may have merits in decreasing indirect costs.

Circulating Angiogenic Precursors in Idiopathic Pulmonary Arterial Hypertension

Vascular remodeling in idiopathic pulmonary arterial hypertension (IPAH) involves hyperproliferative and apoptosis-resistant pulmonary artery endothelial cells. In this study, we evaluated the relative contribution of bone marrow-derived proangiogenic precursors and tissue-resident endothelial progenitors to vascular remodeling in IPAH. Levels of circulating CD34+ CD133+ bone marrow-derived proangiogenic precursors were higher in peripheral blood from IPAH patients than in healthy controls and correlated with pulmonary artery pressure, whereas levels of resident endothelial progenitors in IPAH pulmonary arteries were comparable to those of healthy controls. Colony-forming units of endothelial-like cells (CFU-ECs) derived from CD34+ CD133+ bone marrow precursors of IPAH patients secreted high levels of matrix metalloproteinase-2, had greater affinity for angiogenic tubes, and spontaneously formed disorganized cell clusters that increased in size in the presence of transforming growth factor-beta or bone morphogenetic protein-2. Subcutaneous injection of NOD SCID mice with IPAH CFU-ECs within Matrigel plugs, but not with control CFU-ECs, produced cell clusters in the Matrigel and proliferative lesions in surrounding murine tissues. Thus, mobilization of high levels of proliferative bone marrow-derived proangiogenic precursors is a characteristic of IPAH and may participate in the pulmonary vascular remodeling process.

Frequency of the Amsterdam criteria in a regional German cohort of patients with colorectal cancer.

Estimates of the colon cancer burden associated with hereditary nonpolyposis colorectal cancer (HNPCC) vary from less than 1 % to more than 5 %. Amsterdam criteria fulfilled within a kindred (classic Amsterdam and Amsterdam II criteria) are widely used to identify patients prone to HNPCC. The present study was initiated to assess the frequency of the Amsterdam criteria within a regional German cohort of 207 patients with a history of colorectal cancer (CRC). Data on individual and family cancer histories were available in 154 patients (73 women, 81 men; mean age at diagnosis 62.4 +/- 13.3 years). A total of 843 first degree relatives have been identified within the kindreds of whom 121 had verified cancers. In 28 of 154 families (18 %), at least one first degree relative of the index patient had CRC. With respect to a typical family history, five kindreds (3.2 %) were likely to suffer from HNPCC on a clinical basis (4 kindreds met the classic Amsterdam criteria and one kindred the Amsterdam II criteria). Testing for microsatellite instability could additionally be performed in 4 of 5 patients who met the Amsterdam criteria and revealed DNA instability in 3 cases. Moreover, a missense mutation of MSH2 (Gly965Asp) was detected in one patient with microsatellite instability. Based on the classic Amsterdam and Amsterdam II criteria approximately 3 % of a regional German cohort of patients with CRC are likely to suffer from HNPCC. However, the final diagnosis of HNPCC can only be established by detection of pathogenic germline mutations within the DNA mismatch repair genes.