Treatment of Raynaud's phenomenon with intravenous prostaglandin E1alpha-cyclodextrin improves endothelial cell injury in systemic sclerosis.

OBJECTIVE: To evaluate the efficacy and safety of prostaglandin (PG) E1alpha-cyclodextrin for Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc) and its effect on variables of immune activation and endothelial injury in SSc such as tumor necrosis factor-alpha (TNF-alpha), soluble interleukin 2 receptor (sIL-2R), circulating intercellular adhesion molecule-1 (cICAM-1), von Willebrand factor (vWF), and tissue-type plasminogen activator (t-PA). METHODS: We studied 36 women with SSc, 24 of them given three 60 microg intravenous PGE1alpha-cyclodextrin infusions on 5 consecutive days at 6 week intervals during the winter. RP symptoms and healing of digital lesions were evaluated. Twenty age matched healthy women were the controls. TNF-alpha, sIL-2R, cICAM-1, vWF, and t-PA were measured after the first and last infusion of PGEE1alpha-cyclodextrin and correlated with clinical features. RESULTS: RP symptoms improved in 87% of the patients. The benefit of each 5 day cycle lasted 4 or more weeks in 75%. PGE1alpha-cyclodextrin reduced the daily frequency of RP symptoms by 20% (p < 0.05), 41% (p < 0.005), and 53% (p < 0.0005) from baseline after the 1st, 2nd, and 3rd infusions, respectively. The severity of the attacks was reduced to a limited degree. In 12 of the 14 patients with digital lesions, these healed completely. Ten patients had mild side effects during treatment (headache, increased intestinal motility, flushing). TNF-alpha, sIL-2R, cICAM-1, vWF, and t-PA plasma concentrations were significantly higher in patients with SSc than controls (p < 0.05, p < 0.001). TNF-alpha, sIL-2R, and cICAM-1 were higher in diffuse SSc and patients with lung involvement. The plasma levels of cICAM-1 and t-PA were significantly reduced after the 1st infusion of PGE1alpha-cyclodextrin (both p < 0.005) and further reduced after the last (p < 0.0005 and p < 0.005). CONCLUSION: PGE1alpha-cyclodextrin reduces RP symptoms and plasma levels of the markers of endothelial injury in SSc, suggesting that an improvement of endothelial dysfunction contributes to its prolonged therapeutic effect.

Tauroursodeoxycholic acid for the treatment of HCV-related chronic hepatitis: a multicenter placebo-controlled study.

BACKGROUND/AIMS: Tauroursodeoxycholic acid is a promising drug for the treatment of chronic cholestatic liver diseases since it has more favourable physicochemical and metabolic properties than ursodeoxycholic acid. Tauroursodeoxycholic acid may be of benefit also for necroinflammatory liver disease, especially for HCV-related chronic hepatitis in which bile duct damage and some degree of cholestasis are frequently seen at histology. METHODOLOGY: One hundred and fifty patients with chronic hepatitis were randomly assigned to receive tauroursodeoxycholic acid at daily doses of 500 mg or 750 mg, or a placebo for 6 months. RESULTS: A consistent decrease in aminotransferase serum levels was observed in patients treated with tauroursodeoxycholic acid compared with placebo (p<0.001) and a progressive improvement with time was also found (p<0.05; linear time effect). CONCLUSIONS: Tauroursodeoxycholic acid improves the biochemical expression of chronic hepatitis. Long-term studies with clinically relevant end-points are warranted.

Evaluation of tests for heparin control during long-term extracorporeal circulation.

Two coagulation tests, Recalcified Activated Clotting Time (RACT) and Hemochron, were compared with the activated partial thromboplastin time (APTT) in in vitro heparinization experiments and in patients heparinized for long term extracorporeal circulation (ECC) to determine their suitability as guidelines for heparin administration. All tests had good precision, with a small variability between methods. There was satisfactory correlation with the heparin level in vivo (r = 0.77 for RACT; r = 0.80 for Hemochron and r = 0.82 for APTT) too, while the in vitro r was always greater than or equal to 0.94. Nevertheless, APTT values for plasma heparin levels higher than 1.5 U/ml were markedly prolonged, with a large standard deviation, and often "unclottable". The good correlation between the three tests, makes it possible to substitute RACT and Hemochron for APTT, during long-term ECC.

Serum myoglobin, total CK and MB CK isoenzyme after D.C. cardioversion and during the early phase of acute myocardial infarction.

Myoglobin, total CK and MB CK isoenzyme were determined in the sera of 6 patients admitted with arrhythmias and treated with D.C. countershock and also in 37 patients with acute myocardial infarction or anginal syndrome. All the three tests were increased in patients with myocardial infarction. Serum myoglobin seems sufficiently sensitive and specific but the time required for the assay is a limiting factor for practical use in emergencies. After electrical cardioversion, myoglobin and CPK remain normal, although MB isoenzyme was increased in two of six patients. These results suggest that electrical cardioversion in itself does not influence serum levels of myoglobin. The occasional increase of MB CK observed after cardioversion seems to be the consequence of an easier release of the enzyme due to a myocardial injury.

Hemoglobin oxygen affinty in patients with low-output heart failure and cardiogenic shock after acute myocardial infaraction.

The aim of this study was to determine the oxigen affinity actually present in vivo in blood from patients with acute myocardial infarction. Patients with uncomplicated acute myocardial infarction had normal value of P50 in vivo (partial pressure of oxygen at which 50 percent of the hemoglobin is saturated with oxygen at fixed levels of pHand PC02 present in vivo). Also the values of P50 in vivo of blood from patients with low cardiac output with mild or severe heart failured did not differ from the normal mean. This was the consequence of an increase of 2, 3-diphosphoglycerate levels (which reduces the oxygen affinity of hemoglobin) and of the immediate effect of alkalosis (Bohr effect). By contrast, the values of P50 in vivo were significantly increased in patients with cardiogenic shock. This could be ascribed to the state of acute acidiosis present in these patients. In these conditions the changes in the values of P50 in vivo play an important role in the oxygen delivery to the tissues. However, high values of P50 do not enhance oxygen delivery when a severe arterial hypoxemia (P02 smaller than 40-45 mm Hg) is also present.