Effects of beta 1-selective and nonselective beta-adrenoceptor blockade during exercise conditioning in healthy adults

The interaction of beta 1-selective (cardioselective) and nonselective beta-adrenoceptor blockade with exercise conditioning was investigated in 30 healthy adult persons. A double-blind protocol was used and the effects of atenolol (100 mg/day), propranolol (80 mg twice daily), and placebo were studied by treadmill testing (Bruce protocol) before and after a 2-month supervised program of dynamic exercise. Exercise tolerance was assessed by time and work performed to exhaustion. Subjects who received propranolol, but not those who received atenolol or placebo, showed an acutely impaired exercise tolerance after drug administration but before training (-8 +/- 4%, p less than 0.05). All 3 groups showed significantly improved exercise capacity following training after drug treatment had been discontinued (atenolol, 22 +/- 6% improvement; propranolol, 13 +/- 6%; placebo, 10 +/- 3%). However, when tested while still receiving medication, subjects who received propranolol failed to show significant improvement in exercise capacity. In contrast, patients who received atenolol and placebo improved significantly. The data indicate that enhancement of maximal work capacity by exercise conditioning can occur despite administration of either beta 1-selective or nonselective beta-adrenoceptor antagonists. However, the fatiguing effects of propranolol that were evident when work performance during propranolol therapy was compared with work performance while not receiving propranolol before the training program persists after training and may limit the net improvement in work capacity induced by exercise conditioning compared with the pretraining state.     

Consensus-recommendations for sirolimus in liver transplantation

Sirolimus is an m-TOR inhibitor without renal side effects and potentially protects against the development of malignancy. Due to a higher incidence of complications in two trials and an official warning in the drug information, the use of Sirolimus in liver transplantation is limited. The participants of this consensus meeting had to analyse and evaluate the literature with respect to the potential role of Sirolimus in liver transplantation. This consensus statement follows the scheme normally employed for the presentation of guidelines including the grading of evidence (1a-5) and the extent of recommendation (A-C). Moreover, the consensus included the experience of the authors with respect to the handling of Sirolimus after liver transplantation.     

Decreased frequency of HLA-B35 in patients with gastric MALT lymphoma

Persistent infection with Helicobacter pylori has been shown to be strongly associated with the development of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, the prevalence of H. pylori infection exceeds the incidence of MALT lymphoma by far. This discrepancy might at least partially be explained on a genomic basis of the host. To evaluate the association between HLA type and MALT lymphoma, we investigated 46 patients with MALT lymphoma recruited in a prospective multicenter study from October 1998 to March 2001. Over 13,000 voluntary stem cell donors from over 40 German blood banks represented the control group. Exploratory statistical analysis using Fishers exact test showed significantly decreased frequency of HLA-B35 in the MALT lymphoma group compared to the control group. Our data suggest a negative association between HLA-B35 and MALT lymphoma; however, larger studies are necessary to confirm a protective role of this HLA antigen.     

Chronic upper abdominal pain without improvement after using proton pump inhibitors

HISTORY AND CLINICAL FINDINGS: A 57-year-old woman was admitted to our hospital because of relapsing, therapy-resistant pain, predominantly in the upper abdomen. The symptoms began 6 years previously, after a resection of parts of the small intestine for an ileus of unclear cause. Subsequently 11 (!) gastroscopies showed repeatedly gastritis and Helicobacter pylori- negative gastric and/or small intestinal ulcers which were treated with proton pump inhibitors. This led to no significant improvement of the complaints and produced no healing. DIAGNOSTIC FINDINGS AND THERAPY: Gastroscopy showed, at the transition of the gastric fundus to the corpus, an area with multiple, fibrin coated ulcers. Histologically an active, chronic gastric ulcer was seen, with perifocally dense inflammatory infiltration by predominantly eosinophils. In the colon these histological findings, although clearly less pronouncedly, were also seen i.e. an eosinophilic gastroenteropathy. This was initially treated with 60 mg/day prednisone. Under this treatment she became completely symptom-free. After a dose reduction to 5 mg prednisone daily the symptoms occurred again. Thereupon long-term immunosuppressive therapy with 100 mg azathioprine daily was introduced. Regular clinical and endoscopic monitoring showed a complete remission of the ulcers and no complaints after 1.5 years. CONCLUSION: Our case report shows that in patients with uncharacteristic abdominal pain and gastric ulcers, which improve inadequately under the usual medication such as proton pump inhibitors, less common illnesses must be considered. Despite the rarity of eosinophilic gastroenteropathy the exact (histological) diagnosis plays an important role, because a specific therapy with corticosteroids and/or azathioprine can induce improvement of the symptoms.     

Glatiramer acetate attenuates the pro‐migratory profile of adhesion molecules on various immune cell subsets in multiple sclerosis

An altered expression pattern of adhesion molecules (AM) on the surface of immune cells is a premise for their extravasation into the central nervous system (CNS) and the formation of acute brain lesions in multiple sclerosis (MS). We evaluated the impact of glatiramer acetate (GA) on cell‐bound and soluble AM in the peripheral blood of patients with relapsing–remitting MS (RRMS). Fifteen patients treated de novo with GA were studied on four occasions over a period of 12 months. Surface levels of intracellular cell adhesion molecule (ICAM)‐1, ICAM‐3, lymphocyte function‐associated antigen (LFA)‐1 and very late activation antigen (VLA)‐4 were assessed in T cells (CD3⁺CD8⁺, CD3⁺CD4⁺), B cells, natural killer (NK) cells, natural killer T cells (NK T) and monocytes by five‐colour flow cytometry. Soluble E‐selectin, ICAM‐1, ICAM‐3, platelet endothelial cell adhesion molecule (PECAM)‐1, P‐selectin and vascular cell adhesion molecule (VCAM)‐1 were determined with a fluorescent bead‐based immunoassay. The pro‐migratory pattern in RRMS was verified by comparison with healthy controls and was characterized by up‐regulation of LFA‐1 (CD3⁺CD4⁺ T cells, B cells), VLA‐4 (CD3⁺CD8⁺ T cells, NK cells), ICAM‐1 (B cells) and ICAM‐3 (NK cells). Effects of GA treatment were most pronounced after 6 months and included attenuated levels of LFA‐1 (CD3⁺CD4⁺) and VLA‐4 (CD3⁺CD4⁺, CD3⁺CD8⁺, NK, NK T, monocytes). Further effects included lowering of ICAM‐1 and ICAM‐3 levels in almost all immune cell subsets. Soluble AM levels in RRMS did not differ from healthy controls and remained unaltered after GA treatment. The deregulated pro‐migratory expression profile of cell‐bound AM is altered by GA treatment. While this alteration may contribute to the beneficial action of the drug, the protracted development and unselective changes indicate more secondary immune regulatory phenomena related to these effects.     

Examining Relations Between Obsessive-Compulsive Features,Substance-Use Disorders,and Antisocial Personality Disorder in the Vietnam Era Twin Cohort

Classes of obsessive-compulsive features differing both quantitatively and qualitatively have been linked to gambling disorder. This secondary data analysis sought to extend this line of investigation to examine the extent to which previously reported latent obsessive-compulsive classes may relate to externalizing conditions in a sample of 1675 twin male veterans recruited and surveyed for studies of gambling behaviors/disorder. Using latent class analysis and multivariate regression, we found that participants who reported the highest levels of obsessive-compulsive features were more likely to meet criteria for cannabis abuse and dependence and antisocial personality disorder. When adjusting for co-occurring disorders, the relationship with antisocial personality disorder remained significant whereas those for cannabis use disorders did not. These results highlight the potential utility of considering obsessive-compulsive features within a transdiagnostic framework and suggest that specific externalizing disorders have important links to obsessive-compulsive features. Future research is needed to extend these findings to other samples.