Frequency and clinicopathological features of fibroelastotic changes in the gastrointestinal tract

Fibroelastotic changes (FEC) and especially elastotic polyps of the gastrointestinal (GI) tract are considered rare benign lesions. They consist of accumulations of elastic fibers within the mucosal, submucosal, or muscular layer, occurring in all parts of the GI tract and often appearing as polyps, but also as diffuse non-polyp-forming deposits. They have been the subject of only a few studies. To explore the clinical and histopathological features of FEC in the GI tract, a series of 162 elastotic lesions was collected within a 2-year period. The clinical data and endoscopic findings were correlated. FEC appeared as polyp-forming lesions of the large intestine in 23 samples (14 %), all other samples concerning histological findings without an identifiable gross mass. Frequently related findings were postinterventional status (9 %), previous irradiation (7 %), and history of GI lymphoma (4 %). Eight samples (5 %) presented endoscopically with lesions justifying surgical intervention. We identified three different histological patterns of FEC, which we have called fibroelastosis, angioelastosis, and elastofibroma. Consistent with previous studies, CD34 immunohistochemical staining (performed on 38 polypoid FEC specimens) showed an increase of CD34-positive mesenchymal cells in 95 % of immunostained samples, suggesting a potential role for CD34-positive mesenchymal cells in the accumulation of elastic fibers. In conclusion, FEC are more common in the GI tract than previously recognized. They often present as a benign polyp. Many accompany other diseases like ulcers and atrophic gastritis or represent a residual finding after an intervention.     

Antibodies to ribosomal P proteins of Trypanosoma cruzi in Chagas disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in lupus

Anti-P antibodies present in sera from patients with chronic Chagas heart disease (cChHD) recognize peptide R13, EEEDDDMGFGLFD, which encompasses the C-terminal region of the Trypanosoma cruzi ribosomal P1 and P2 proteins. This peptide shares homology with the C-terminal region (peptide H13 EESDDDMGFGLFD) of the human ribosomal P proteins, which is in turn the target of anti-P autoantibodies in systemic lupus erythematosus (SLE), and with the acidic epitope, AESDE, of the second extracellular loop of the β₁-adrenergic receptor. Anti-P antibodies from chagasic patients showed a marked preference for recombinant parasite ribosomal P proteins and peptides, whereas anti-P autoantibodies from SLE reacted with human and parasite ribosomal P proteins and peptides to the same extent. A semi-quantitative estimation of the binding of cChHD anti-P antibodies to R13 and H13 using biosensor technology indicated that the average affinity constant was about 5 times higher for R13 than for H13. Competitive enzyme immunoassays demonstrated that cChHD anti-P antibodies bind to the acidic portions of peptide H13, as well as to peptide H26R, encompassing the second extracellular loop of the β₁ adrenoreceptor. Anti-P antibodies isolated from cChHD patients exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats, which resembles closely that of anti-β₁ receptor antibodies isolated from the same patient. In contrast, SLE anti-P autoantibodies have no functional effect. Our results suggest that the adrenergic-stimulating activity of anti-P antibodies may be implicated in the induction of functional myocardial impairments observed in cChHD.     

Alkylphosphocholine-induced production of nitric oxide and tumor necrosis factor α by U 937 cells

The human histiocytic cell line U937, which expresses a number of monocyte markers and properties, was investigated with regard to its ability to be activated for NO and tumor necrosis factor (TNF) release after treatment with alkylphosphocholines (APC) and APC liposomes. Using APC multilamellar vesicles (MLV) a clear dose-dependent increase of NO production could be demonstrated for U 937 cells, whereas the corresponding soluble substances had no effect. The time course of NO release was characterised by a peak between 2 h and 12 h and a strong decrease after 24 h. LPS caused no NO release nor the production of TNF in U 937 cells. The simultaneous incubation of the cells with lipopolysaccharide and APC or APC-MLV, led to a strong increase in TNF production. Closer investigation of the time sequence of this synergistic effect demonstrated that cells, that had first been treated with hexadecylphosphocholine (HPC)-MLV and 4 h later with lipopolysaccharride secreted significantly more TNF into the supernatants than in the experiment where both substances were added simultaneously. From these results it was concluded that APC-MLV are possibly able to act as a primer in the process of lipopolysaccharide mediated TNF induction. Furthermore, a positive influence of phorbol 12-myristate 13-acetate (PMA) on the ability of U 937 cells to produce TNF following a treatment with HPC or HPC-MLV could be observed. PMA-pretreated cells were shown to release much more TNF compared to control cells, which led to the supposition that the immunomodifying activity of APC becomes effective only in more highly differentiated cell types.Abbreviations APC alkylphosphocholines - DPC dodecylphosphocholine - HPC hexadecylphosphocholine - TPC tetradecylphosphocholine - MLV multilamellar vesicles - PMA phorbol 12-myristate 13-acetate - TNF tumour necrosis factor Partly supported by the Bundesministerium für Forschung und Technologie (9319564A)     

Pseudotumoral pulmonary cryptococcosis in association with Cushing's syndrome

Opportunistic infections in endogenous Cushing's syndrome are associated with severe cortisol excess and carry a high mortality. Pulmonary cryptococcosis is one of these opportunistic infections and can mimic a lung neoplasm, therefore making its diagnosis difficult. We report a case of a young male with ACTH-dependent Cushing's syndrome and severe hypercortisolism. The patient achieved cure after the transfenoidal surgery, but developed a febrile state. A chest computed tomography showed a pulmonary nodule that did not change in serial chest radiographs. Diagnosis of tuberculosis, fungal and bacterial infections were inconclusive, so the hypothesis of lung neoplasm became more probable. The necropsy, however, disclosed a pseudotumoral cryptococcosis. Opportunistic infections, like Cryptococcus neoformans, should be considered in patients with Cushing's syndrome and a pulmonary infiltrate.     

Use of medications for secondary prevention in stroke patients at hospital discharge in Australia

Background Stroke is one of the leading causes of death and disability. Significant proportions (33 %) of stroke presentations are by patients with a previous stroke or transient ischaemic attack. Consequently, the stroke management guidelines recommend that all ischaemic stroke patients should receive three key evidence-based preventive drug therapies: antihypertensive drug therapy, a statin and an antithrombotic drug therapy (anticoagulant and/or antiplatelet). Objective To determine the rates of utilization of the three key evidence-based drug therapies for the secondary prevention of stroke and to identify factors associated with use of treatment at discharge. Setting Five metropolitan hospitals in New South Wales, comprising two tertiary referral centres and three district hospitals. Method A retrospective clinical audit was conducted in the study hospitals. Patients discharged with a principal diagnosis of ischaemic stroke during a 12-month time period (July 2009–2010) were identified for review. Main outcome measure The rate of utilization of each of the three key evidence-based drug therapies and the factors associated with use of treatment at discharge. Results A total of 521 medical records were reviewed. Of these, 469 patients were discharged alive with a mean age of 73.6 ± 14.4 years. Overall, 75.4 % were prescribed an antihypertensive agent at discharge versus only 65.7 % on admission (P < 0.05). Three hundred-sixty patients (77.6 % of the eligible patients) were prescribed a statin at discharge (compared to only 43.9 % on admission, P < 0.05), of whom 74.0 % received monotherapy. Almost all (97.6 %) eligible patients were prescribed an antithrombotic drug therapy at discharge, of whom 68.5 % were prescribed monotherapy and 28.2 % were prescribed dual therapy. Only 60.0 % of eligible patients were discharged on all three key guideline recommended secondary preventive drug therapies. Multivariate logistic regression analyses showed that hypertension (OR 6.67; 95 % CI 4.35–11.11), hypercholesterolemia (OR 2.04; 95 % CI 1.32–3.23), and discharge destination (OR 0.22; 95 % CI 0.10–0.48) were associated with the utilization of all three guideline recommended therapies. Conclusion There is a scope for improvement in implementing the stroke management guidelines when it comes to prescribing secondary preventive drug therapies using antihypertensives, antithrombotics and statins. Appropriate risk/benefit assessment is indispensable for optimal prescribing and maximizing patient outcomes, particularly in older people.     

Risk in elderly patients after stentless versus stented aortic valve surgery

Recent studies suggest that the hemodynamic advantage of stentless bioprostheses over the stented type improves long-term survival after aortic valve replacement, but the more complex and time-consuming implantation technique may increase the risks of operative death and postoperative complications. Between April 1996 and June 2001, 519 patients with a mean age of 76 +/- 5 years underwent aortic valve replacement using a stentless (Medtronic Freestyle, n = 277) or stented bioprosthesis (Medtronic Mosaic, n = 242). Multiple logistic regression analysis considering different patient populations revealed no increased risk of operative death, postoperative complications, or neurological impairment after implantation of a stentless bioprosthesis. Survival curves in respect of 367 patients who underwent aortic valve replacement up to September 2000 and were followed up for 3 years were not different (p = 0.98). As the patients were elderly, improved survival due to implantation of a stentless valve could not be demonstrated within this time span.