Troponin T after endoscopic retrograde cholangiopancreatography: no evidence of harm

BACKGROUND AND STUDY AIMS: It is well recognized that myocardial ischemia can occur during endoscopic retrograde cholangiopancreatography (ERCP). Acute arrhythmias and ST segment changes have been reported by a number of authors, but the longer-term sequelae with regard to permanent myocardial damage are not known. The aim of this study was to determine the presence or absence of significant injury to the heart muscle. PATIENTS AND METHODS: Sixty-two patients undergoing therapeutic ERCP were assessed clinically and with electrocardiography (ECG) for the presence of ischemic heart disease before the procedure. Extensive intraprocedural monitoring was carried out, postprocedural ECGs were recorded, and serum troponin T levels were measured. The ECGs were evaluated blindly by a single cardiologist. RESULTS: In 61 of the 62 patients, no changes were observed between the ECGs before and after the procedure. One patient had postprocedural T wave inversion but a normal troponin T level, excluding myocardial damage. One patient with mild renal insufficiency and treated heart failure had borderline troponin T elevation (0.05 microg/l) but no ECG changes. No complications of ERCP occurred. CONCLUSIONS: Whilst ECG and rhythm changes indicating transient myocardial ischemia do occur during ERCP, there is no evidence that myocardial damage takes place as a consequence of this.     

RNA-based mutation analysis identifies an unusual MSH6 splicing defect and circumvents PMS2 pseudogene interference

Heterozygous germline mutations in one of the mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 cause hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome, a dominantly inherited cancer susceptibility syndrome. Recent reports provide evidence for a novel recessively inherited cancer syndrome with constitutive MMR deficiency due to biallelic germline mutations in one of the MMR genes. MMR-deficiency (MMR-D) syndrome is characterized by childhood brain tumors, hematological and/or gastrointestinal malignancies, and signs of neurofibromatosis type 1 (NF1). We established an RNA-based mutation detection assay for the four MMR genes, since 1) a number of splicing defects may escape detection by the analysis of genomic DNA, and 2) DNA-based mutation detection in the PMS2 gene is severely hampered by the presence of multiple highly similar pseudogenes, including PMS2CL. Using this assay, which is based on direct cDNA sequencing of RT-PCR products, we investigated two families with children suspected to suffer from MMR-D syndrome. We identified a homozygous complex MSH6 splicing alteration in the index patients of the first family and a novel homozygous PMS2 mutation (c.182delA) in the index patient of the second family. Furthermore, we demonstrate, by the analysis of a PMS2/PMS2CL "hybrid" allele carrier, that RNA-based PMS2 testing effectively avoids the caveats of genomic DNA amplification approaches; i.e., pseudogene coamplification as well as allelic dropout, and will, thus, allow more sensitive mutation analysis in MMR deficiency and in HNPCC patients with PMS2 defects.     

Nonalcoholic steatohepatitis. Predictor and consequence of diabetes

Nonalcoholic fatty liver (NAFL) and particularly nonalcoholic steatohepatitis (NASH) are not only risc factors for liver fibrosis, liver zirrhosis and hepatocellular carcinoma, but are also strongly associated with insulin resistance and type 2 diabetes. This is probably due to the fact that the same mechanisms are operative in the pathogenesis of these diseases. In addition fatty liver predicts incident type 2 diabetes, but also atherosclerosis, indicating a causal role of fatty liver in the pathogenesis of these diseases. This hypothesis is supported by novel findings deriving from translational research involving precise genotyping and phenotyping strategies in humans. The precise investigation of mechanisms involved will deliver new knowledge which may be important for the prevention and therapy of these diseases.     

Comparison of tamsulosin efficacy in subgroups of patients with lower urinary tract symptoms

We have compared the results of treatment with tamsulosin (0.4 mg once daily) in subgroups of patients with lower urinary tract symptoms suggestive of benign prostatic obstruction, based on two large-scale, open-label, observational studies. Improvements of IPSS or Q(max) were largely unaffected by patient age. Patients with severe symptoms benefited at least as much from treatment as those with mild or moderate symptoms, and the majority of patients with severe symptoms were shifted to the moderate or even mild symptoms group. We conclude that tamsulosin is effective in patients of all age groups, and should be considered as an alternative to surgery even in patients with severe symptoms.     

Clinical and immunological effects of low-dose IFN-alpha treatment in patients with corticosteroid-resistant asthma

BACKGROUND: Interferon (IFN)-alpha is a cytokine that possesses potent anti-viral and immunoregulatory activities. We aimed to assess clinical and immunological effects of low-dose IFN-alpha in patients with severe corticosteroid-resistant asthma with and without Churg-Strauss syndrome. There is currently no efficient pharmacological treatment available for this group of patients. METHODS: We studied 10 patients with corticosteroid-resistant asthma, in which 3x10(6) IU/day IFN-alpha were administrated in addition to the prednisone dose given already before introduction of the cytokine therapy. The prednisone dose was gradually reduced dependent on the clinical situation and used as a clinical readout to evaluate the efficacy of the cytokine therapy. To distinguish between IFN-alpha- and prednisone-mediated immunological changes, the corticosteroid dose was kept constant for at least 2 weeks upon introduction of the cytokine therapy in seven patients. The effects of treatment on clinical and immunological parameters were measured at 2-4 weeks and 5-10 months depending on the availability of the patient. RESULTS: Interferon-alpha treatment rapidly improved the clinical situation as assessed by lung function parameters and required prednisone dose. Important immunological changes included: decreased leukocyte numbers, increased relative numbers of CD4+ T cells, increased differentiation of T helper (Th)1 cells, and increased expression of interleukin (IL)-10 in peripheral blood mononuclear cells. CONCLUSION: Interferon-alpha treatment was associated with dramatic improvements in the condition of patients with corticosteroid-resistant asthma with and without Churg-Strauss syndrome. Potential mechanisms of action include the establishment of a correct Th1/Th2 balance and the induction of the anti-inflammatory IL-10 gene.     

MRI in mucoviscidosis (cystic fibrosis)

Cystic fibrosis (CF) is a multi-systemic disease with major impact on the lungs. Pulmonary manifestation is crucial for the prognosis and life expectancy of patients. Imaging modalities and lung function tests reflect the pulmonary status in these patients.The standard imaging modality for diagnosis and follow-up of pulmonary changes is chest x-ray. The gold standard for the detection of parenchymal lung changes remains high resolution computed tomography (HRCT), but this is not used routinely for CF-patients due to radiation exposure.Magnetic resonance imaging (MRI) used to be of no importance in monitoring cystic fibrosis lung disease, as shown in studies from the 1980s and early 1990 s. The continuing improvement of MRI techniques, however, has allowed for an adequate application of this non-radiation method in diagnosing the major pulmonary findings in CF, in addition to the assessment of lung function.     

Multiple myeloma is affected by multiple and heterogeneous somatic mutations in adhesion- and receptor tyrosine kinase signaling molecules

Multiple myeloma (MM) is a largely incurable plasma cell malignancy with a poorly understood and heterogeneous clinical course. To identify potential, functionally relevant somatic mutations in MM, we performed whole-exome sequencing of five primary MM, corresponding germline DNA and six MM cell lines, and developed a bioinformatics strategy that also integrated published mutational data of 38 MM patients. Our analysis confirms that identical, recurrent mutations of single genes are infrequent in MM, but highlights that mutations cluster in important cellular pathways. Specifically, we show enrichment of mutations in adhesion molecules of MM cells, emphasizing the important role for the interaction of the MM cells with their microenvironment. We describe an increased rate of mutations in receptor tyrosine kinases (RTKs) and associated signaling effectors, for example, in EGFR, ERBB3, KRAS and MAP2K2, pointing to a role of aberrant RTK signaling in the development or progression of MM. The diversity of mutations affecting different nodes of a particular signaling network appears to be an intrinsic feature of individual MM samples, and the elucidation of intra- as well as interindividual redundancy in mutations that affect survival pathways will help to better tailor targeted therapeutic strategies to the specific needs of the MM patient.     

Bullous delayed pressure urticaria: pathogenic role for eosinophilic granulocytes?

Bullous delayed pressure urticaria (DPU) is a rare variant of DPU. Treatment of DPU is difficult and the underlying pathogenic mechanism of DPU remains elusive. We report a 72-year-old man with DPU and associated chronic urticaria as well as delayed urticarial dermographism. Pressure challenge gave rise to a deep weal covered by multiple vesicles and bullae after 24 h. Histological examination of a skin biopsy specimen obtained 24 h after pressure challenge demonstrated intraepidermal bullae filled with eosinophils accompanied by a dense, predominantly eosinophilic infiltrate in the dermis. Whereas the numbers and morphology of mast cells were unaltered, the extracellular deposition of eosinophil cationic protein revealed evidence for eosinophil activation. Concomitantly, both CD4+ and CD8+ T lymphocytes were present in the infiltrate and expressed interleukin 5. As bullous DPU may represent the maximal variant of DPU, the investigation of the cellular infiltrate and the chemokines/cytokines released may reveal potential pathogenic mechanisms. A possible effector role of eosinophilic granulocytes, T-cell subsets and mast cells is discussed.     

Long-term outcome after local recurrence of soft tissue sarcoma: a retrospective analysis of factors predictive of survival in 135 patients with locally recurrent soft tissue sarcoma

Background:

The aim of this study was to identify prognostic indicators of survival in patients with locally recurrent soft tissue sarcoma (STS) through a long-term follow-up.

Methods:

We retrospectively assessed the relationship between post-recurrence survival (PRS) and potential prognostic factors in 135 patients who had experienced local recurrence, which was suitable for further surgical treatment. The median follow-up time after initial recurrence was 12.3 years (95% confidence interval (CI): 10.4–14.2 years).

Results:

The 5-year estimate of the PRS rate was 53.1% (95% CI: 44.3–61.2%) for the entire series. Patients with negative margins after the final surgery experienced improved survival compared with patients with positive margins (5-year survival: 46.7% (35.2–57.5%) vs 35.5% (23.4–47.8%); P=0.01). In a multivariate analysis, the significant prognostic indicators for PRS were histologic grade, tumour site, time to initial recurrence, the number of recurrences and the surgical margin status attained at the last resection.

Conclusions:

Complete surgical resection with microscopically clear margins is desirable in patients with locally recurrent STS. However, when achieving clear surgical margins will require major functional impairment of the extremity, a radical surgical approach should be weighed for the patient in each case.     

The association between social phobia, social anxiety cognitions and paranoid symptoms

Schutters SIJ, Dominguez M‐d‐G, Knappe S, Lieb R, van Os J, Schruers KRJ, Wittchen H‐U. The association between social phobia, social anxiety cognitions and paranoid symptoms. Objective: Previous research suggests high levels of comorbidity between social phobia and paranoid symptoms, although the nature of this association remains unclear. Method: Data were derived from the Early Developmental Stages of Psychopathology study, a 10‐year longitudinal study in a representative German community sample of 3021 participants aged 14–24 years at baseline. The Munich‐Composite International Diagnostic Interview was used to assess social phobia and paranoid symptoms, along with data on social phobia features. Cross‐sectional and longitudinal analyses were conducted. Differential associations with environmental risk factors and temperamental traits were investigated. Results: Lifetime social phobia and paranoid symptoms were associated with each other cross‐sectionally (OR = 1.80, 95% CI = 1.31–2.47). Lifetime paranoid symptoms were associated specifically with social anxiety cognitions. Lifetime cognitions of negative evaluation predicted later onset of paranoid symptoms, whereas onset of social phobia was predicted by cognitions of loss of control and fear/avoidance of social situations. Lifetime social phobia and paranoid symptoms shared temperamental traits of behavioural inhibition, but differed in environmental risks. Conclusions: The present study showed that paranoid symptoms and social phobia share similarities in cognitive profile and inhibited temperament. Avoidance appears to be important in the development of social phobia, whereas cannabis use and traumatic experiences may drive paranoid thinking in vulnerable individuals.