Inhaled prostacyclin (PGI(2)) aerosol induces selective pulmonary vasodilation. Further, it improves right ventricular ( RV) function, which may largely rely on pulmonary vasodilation, but also on enhanced myocardial contractility. We investigated the effects of the inhaled PGI(2) analogs epoprostenol (EPO) and iloprost (ILO) on RV function and myocardial contractility in 9 anesthetized pigs receiving aerosolized EPO (25 and 50 ng center dot kg(-1) center dot min(-1)) and, consecutively, ILO (60 ng center dot kg(-1) center dot min(-1)) for 20 min each. We measured pulmonary artery pressure ( PAP), RV ejection fraction (RVEF) and RV end-diastolic-volume (RV-EDV), and left ventricular end-systolic pressure-volume-relation (end-systolic elastance, E-es). EPO and ILO reduced PAP, increased RVEF and reduced RVEDV. E-es was enhanced during all doses tested, which reached statistical significance during EPO25ng and ILO, but not during EPO50ng. PGI(2) aerosol enhances myocardial contractility in healthy pigs, contributing to improve RV function. Copyright (C) 2005 S. Karger AG, Basel.

Background/Aims: Degradation of adenine nucleotides to adenosine has been suggested to play a critical role in ischemic preconditioning (IPC). Thus, we questioned in patients undergoing partial hepatectomy whether (i) IPC will increase plasma purine catabolites and whether (ii) formation of purines in response to vascular clamping (Pringle maneuver) can be attenuated by prior IPC. Methods: 75 patients were randomly assigned to three groups: group I underwent hepatectomy without vascular clamping; group II was subjected to the Pringle maneuver during resection, and group III was preconditioned (10 min ischemia and 10 min reperfusion) prior to the Pringle maneuver for resection. Central, portal venous and arterial plasma concentrations of adenosine, inosine, hypoxanthine and xanthine were determined by high-performance liquid chromatography. Results: Duration of the Pringle maneuver did not differ between patients with or without IPC. Surgery without vascular clamping had only a minor effect on plasma purine transiently increased. After the Pringle maneuver alone, purine plasma concentrations were most increased. This strong rise in plasma purines caused by the Pringle maneuver, however, was significantly attenuated by IPC. When portal venous minus arterial concentration difference was calculated for inosine or hypoxanthine, the respective differences became positive in patients subjected to the Pringle maneuver and were completely prevented by preconditioning. Conclusion: These data demonstrate that (i) IPC increases formation of adenosine, and that (ii) the unwanted degradation of adenine nucleotides to purines caused by the Pringle maneuver can be attenuated by IPC. Because IPC also induces a decrease of portal venous minus arterial purine plasma concentration differences, IPC might possibly decrease disturbances in the energy metabolism in the intestine as well. Copyright (C) 2005 S. Karger AG, Basel.

Previous studies showed that mitoxantrone can reduce disability progression in patients with multiple sclerosis (MS). There is, however, concern that it may cause irreversible cardiomyopathy with reduced left ventricular (LV) ejection fraction (EF) and congestive heart failure. The aim of this prospective study was to investigate cardiac side effects of mitoxantrone by repetitive cardiac monitoring in MS patients. The treatment protocol called for ten courses of a combined mitoxantrone (10 mg/m(2) body surface) and methylprednisolone therapy. Before each course, a transthoracic echocardiogram was performed to determine the LV end-diastolic diameter, the end-systolic diameter and the fractional shortening; the LV-EF was calculated. Seventy-three patients participated (32 males; age 48 +/- 12 years, range 20-75 years; 25 with primary progressive, 47 with secondary progressive and 1 with relapsing-remitting MS) who received at least four courses of mitoxantrone. Three of the 73 patients were excluded during the study (2 patients discontinued therapy; 1 patient with a previous history of ischemic heart disease developed atrial fibrillation after the second course of mitoxantrone). The mean cumulative dose of mitoxantrone was 114.0 +/- 33.8 mg. The mean follow-up time was 23.4 months (range 10-57 months). So far, there has been no significant change in any of the determined parameters (end-diastolic diameter, end-systolic diameter, fractional shortening, EF) over time during all follow-up investigations. Mitoxantrone did not cause signs of congestive heart failure in any of the patients. Further cardiac monitoring is, however, needed to determine the safety of mitoxantrone after longer follow-up times and at higher cumulative doses. Copyright (C) 2005 S. Karger AG, Basel.

Treatment of alcohol-dependent patients was primarily focused on inpatient settings in the past decades. The efficacy of these treatment programs has been evaluated in several studies and proven to be sufficient. However, with regard to the increasing costs in public healthcare systems, questions about alternative treatment strategies have been raised. Meanwhile, there is growing evidence that outpatient treatment might be comparably effective as inpatient treatment, at least for subgroups of alcohol dependents. On that background, the present study aimed to evaluate the efficacy of a high-structured outpatient treatment program in 103 alcohol-dependent patients. 74 patients (72%) terminated the outpatient treatment regularly. At 6 months' follow-up, 95% patients were successfully located and personally re-interviewed. Analyses revealed that 65 patients (64%) were abstinent at the 6-month follow-up evaluation and 37 patients ( 36%) were judged to be non-abstinent. Pretreatment variables which were found to have a negative impact (non-abstinence) on the 6-month outcome after treatment were a higher severity of alcohol dependence measured by a longer duration of alcohol dependence, a higher number of prior treatments and a stronger alcohol craving (measured by the Obsessive Compulsive Drinking Scale). Further patients with a higher degree of psychopathology measured by the Beck Depression Inventory (depression) and State-Trait Anxiety Inventory (anxiety) relapsed more often. In summary, results of this study indicate a favorable outcome of socially stable alcohol-dependent patients and patients with a lower degree of depression, anxiety and craving in an intensive outpatient rehabilitation program.

Introduction: Various disease-specific serum antibodies were described in patients with inflammatory bowel disease and their yet healthy first-degree relatives. In the latter, serum antibodies are commonly regarded as potential markers of disease susceptibility. The present long-term follow-up study evaluated the fate of antibody-positive first-degree relatives. Patients and Methods: 25 patients with Crohn's disease, 19 patients with ulcerative colitis and 102 first-degree relatives in whom presence of ASCA, pANCA, pancreatic- and goblet-cell antibodies had been assessed were enrolled. The number of incident cases with inflammatory bowel disease was compared between antibody-positive and antibody-negative first-degree relatives 7 years after storage of serum samples. Results: 34 of 102 (33%) first-degree relatives were positive for at least one of the studied serum antibodies. In the group of first-degree relatives, one case of Crohn's disease and one case of ulcerative colitis were diagnosed during the follow-up period. However, both relatives did not display any of the investigated serum antibodies (p = 1). Discussion: The findings of our pilot study argue against a role of serum antibodies as a marker of disease susceptibility in first-degree relatives of patients with inflammatory bowel disease. However, these data have to await confirmation in larger ideally prospective multicenter studies before definite conclusions can be drawn.

Background: Microvascular alterations contribute to the development of stroke and vascular

dementia. The goal of this study was to evaluate age and hypertension related changes of the basal

lamina in cerebral microvessels of individuals, who died from non-cerebral causes.

Results: We examined 27 human brains: 11 young and 16 old patients. Old patients were divided

into two subgroups, those with hypertension (n = 8) and those without hypertension (n = 8). Basal

lamina changes of the cerebral microvessels were determined in the putamen using antibodies

against collagen type IV and by quantitative analysis of vessel number, total stained area of collagen,

thickness of the vessel wall and lumen, and relative staining intensity using immunofluorescence.

The total number of collagen positive vessels per microscopic field was reduced in old compared

to young subjects (12.0+/-0.6 vs. 15.1+/-1.2, p = 0.02). The relative collagen content per vessel

(1.01+/-0.06 vs. 0.76+/-0.05, p = 0.01) and the relative collagen intensity (233.1+/-4.5 vs. 167.8+/-

10.6, p < 0.0001) shown by immunofluorescence were higher in the older compared to the younger

patients with a consecutive reduction of the lumen / wall ratio (1.29+/-0.05 vs. 3.29+/-0.15, p <

0.0001). No differences were observed for these parameters between old hypertensive and nonhypertensive

patients.

Conclusions: The present data show age-related changes of the cerebral microvessels in sections

of human putamen for the first time. Due to the accumulation of collagen, microvessels thicken and

show a reduction in their lumen. Besides this, the number of vessels decreases. These findings might

represent a precondition for the development of vascular cognitive impairment. However,

hypertension was not proven to modulate these changes.