The metabolism of 4-trifluoromethoxyaniline and [13C]-4-trifluoromethoxyacetanilide in the rat: detection and identification of metabolites excreted in the urine by NMR and HPLC-NMR

A combination of 19F, 1H NMR and HPLC-NMR spectroscopic approaches have been used to quantify and identify the urinary-excreted metabolites of 4-trifluoromethoxyaniline (4-TFMeA) and its [13C]-labelled acetanilide following i.p. administration at 50 mg/kg to rats. The major metabolite excreted in the urine for both compounds was a sulphated ring-hydroxylated metabolite (either 2- or 3-trifluoromethyl-5-aminosulphate) which accounted for approximately 32.3% of the dose following the administration of 4-TFMeA and approximately 29.9% following dosing of the acetanilide. The trifluoromethoxy-substituent appeared to be metabolically stable, with no evidence of O-detrifluoromethylation. There was no evidence of the excretion of N-oxanilic acids in urine, of the type seen with 4-trifluoromethylaniline.     

Myelodysplastische Syndrome

Background

Myelodysplastic syndromes (MDS) are an enormous challenge with respect to diagnostics and therapy.

Methods

Cytomorphological bone marrow diagnostics in combination with chromosomal analyses and diagnostics from peripheral blood are the gold standard of MDS diagnostics. Risk scores, such as the international prognostic scoring system (IPSS), the revised international prognostic scoring system (IPSS-R) and the World Health Organization classification-based prognostic scoring system (WPSS) which allow an estimation of the prognosis concerning overall survival and the risk of progression to acute myeloid leukemia (AML) are well established.

Results

Allogeneic stem cell transplantation is a curative option but only for the minority of patients. The basis of therapy is therefore supportive care especially with the transfusion of packed red blood cells and if necessary, iron chelation. For patients with advanced MDS who are not candidates for stem cell transplantation, 5-azacitidine is an effective and well-tolerated therapy that is also feasible in an outpatient setting.

Conclusion

Advanced age and patient co-morbidities on the one hand and toxicity of therapy in combination with an often unsatisfactory response to conventional therapy approaches on the other hand result in an extremely complex management of patients with MDS. The treatment options should always be adjusted individually for each patient with the goal to improve the quality of life.     

Serial surveillance of carcinoid heart disease: factors associated with echocardiographic progression and mortality

Background:

Carcinoid heart disease is a complication of metastatic neuroendocrine tumours (NETs). We sought to identify factors associated with echocardiographic progression of carcinoid heart disease and death in patients with metastatic NETs.

Methods:

Patients with advanced non-pancreatic NETs and documented liver metastases and/or carcinoid syndrome underwent prospective serial clinical, biochemical, echocardiographic and radiological assessment. Patients were categorised as carcinoid heart disease progressors, non-progressors or deceased. Multinomial regression was used to assess the univariate association between variables and carcinoid heart disease progression.

Results:

One hundred and thirty-seven patients were included. Thirteen patients (9%) were progressors, 95 (69%) non-progressors and 29 (21%) patients deceased. Baseline median levels of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and plasma 5-hydroxyindoleacetic acid (5-HIAA) were significantly higher in the progressors. Every 100 nmol l⁻¹ increase in 5-HIAA yielded a 5% greater odds of disease progression (OR 1.05, 95% CI: 1.01, 1.09; P=0.012) and a 7% greater odds of death (OR 1.07, 95% CI: 1.03, 1.10; P=0.001). A 100 ng l⁻¹ increase in NT-proBNP did not increase the risk of progression, but did increase the risk of death by 11%.

Conclusions:

The biochemical burden of disease, in particular baseline plasma 5-HIAA concentration, is independently associated with carcinoid heart disease progression and death. Clinical and radiological factors are less useful prognostic indicators of carcinoid heart disease progression and/or death.     

The variable spectrum of cutaneous Lyme borreliosis. Diagnosis and therapy

Lyme borreliosis can affect almost all human organs. Erythema migrans is the first and most frequent manifestation in 80-90% of patients in the early stage of localized skin infection. Besides the typical clinical appearance, many atypical variants can be observed. The solitary borrelial lymphocytoma is much less common and occurs mostly in children. Due to improvement in the early recognition of Lyme borreliosis, the diagnosis is made in the disseminated and late stage in only 10-20% of patients. Multiple erythemata migrantia indicating the hematogenous dissemination of B. burgdorferi remain frequently unrecognized. Late stages of infection feature chronic plasma-cell rich cutaneous inflammation and acrodermatitis chronica atrophicans in its edematous to atrophic forms. Cultivation or DNA detection of B. burgdorferi in skin biopsies are options to prove unusual skin manifestations. Serological detection of Borrelia-specific IgG- and IgM antibodies should be performed according to the two step protocol with ELISA and immunoassay according to the criteria of the MIQ 12. Serological tests have limited utility for follow-up. Antibiotic therapy is very effective if performed according to evidence-based protocols, such as the AWMF guidelines.     

Virtuelle Dermatohistopathologie bei http://www.pathowiki.org

PATHOWIKI ( http://www.pathowiki.org ) is a new specialized information system in the form of a web‐based wiki with content from all sub‐disciplines of human pathology. Essential components are articles and specimens which are located thematically in dermatopathology. The project is presented on the basis of impressive examples and possibilities. The ability to link all kinds of content and integrate pattern analysis theories creates an effective tool for teaching and training in dermatopathology. Collaborative work ensures the effective usage of available resources and a continually growing amount of content, the quality of which depends on the number of users and should be as high as possible. Therefore, all interested colleagues are invited to support the project.     

Virtual dermatohistopathology at http://www.pathowiki.org

PATHOWIKI (http://www.pathowiki.org) is a new specialized information system in the form of a web-based wiki with content from all sub-disciplines of human pathology. Essential components are articles and specimens which are located thematically in dermatopathology. The project is presented on the basis of impressive examples and possibilities. The ability to link all kinds of content and integrate pattern analysis theories creates an effective tool for teaching and training in dermatopathology. Collaborative work ensures the effective usage of available resources and a continually growing amount of content, the quality of which depends on the number of users and should be as high as possible. Therefore, all interested colleagues are invited to support the project.