Long-term outcomes of thymosin-alpha 1 and interferon alpha-2b combination therapy in patients with hepatitis B e antigen (HBeAg) negative chronic hepatitis B.

Hepatitis B e antibody (HbeAb) and hepatitis B virus (HBV) DNA positive chronic hepatitis is a clinical entity, distinct from classical hepatitis B e antigen (HbeAg) positive chronic hepatitis B. Our aim was to evaluate the long-term therapeutic efficacy of the combination of interferon alpha-2b and thymosin-alpha1 compared with lamivudine plus interferon alpha-2b and interferon alpha-2b alone. Fifty-two patients with HbeAg-negative chronic hepatitis B were assigned to three different groups in a nonrandomized manner. Group 1 (n = 27) received thymosin-alpha1 [1.6 mg subcutaneously (sc), twice a week] and interferon alpha-2b (10 MIU sc, three times per week) for 26 weeks, subsequently followed by interferon alpha-2b monotherapy at the same dosage for an additional 26 weeks. Group 2 (n = 10) received interferon alpha-2b (10 MIU sc, three times per week) for 52 weeks. Group 3 (n = 15) received interferon alpha-2b (10 MIU sc, three times per week) and lamivudine [100 mg orally (po), q.d.] for 52 weeks, followed by continuous lamivudine (100 mg po, q.d.) therapy. By the end of 78 weeks, a sustained response (SR-6 mo) was seen in 74% (20/27) of the patients within Group 1. On the contrary, Groups 2 and 3 had sustained response rates of 40 (4/10) and 53.3% (8/15), respectively (p = 0.13). At the end of 12 months post-treatment in Group 1, a virological and biochemical response rate was seen in 70.3% of patients (19/27); in contrast, Groups 2 and 3 had response rates of 20 (2/10) and 26.6% (4/15), respectively (p = 0036). At the end of the 18-month post-treatment follow-up period, 71.4% (19/27) of patients in Group 1, 10% of patients in Group 2 (1/10), and 20% of patients in Group 3(3/15) preserved their sustained response (p = 0.0003). Interferon alpha-2b and thymosin-alpha1 combination therapy results in significant virological and biochemical response rates compared with standard therapeutic regimens and is well tolerated.

The role of heme in hemolysis-induced acute pancreatitis.

BACKGROUND: The aim was to reveal the mechanism of hemolysis-induced acute pancreatitis and to evaluate the role of heme and heme oxygenase activity in inducing pancreatic inflammation in an experimental hemolysis model. MATERIAL/METHODS: Hemolytic anemia was induced in rats by intraperitoneal injection of 60 mg/kg acetylphenylhydrazine (APH). To evaluate the toxic effect of free heme after hemolysis, heme oxygenase inhibitor (HOI) was used to inhibit the enzyme which decreases the free heme concentration after hemolysis. One hundred and fifty rats were divided into two treatment and three control groups. Rats in the hemolysis group were given APH intraperitoneally. Rats in the HOI+hemolysis group were given Cr(III)mesoporphyrin IX chloride as HOI and then APH intraperitoneally. Serum amylase and lipase levels as well as pancreatic tissue cytokine content were determined and histological examination performed. RESULTS: No hemolysis or pancreatitis was seen in the control groups. Massive hemolysis was seen in 22 of the 30 rats of the hemolysis group and 20 of the 30 rats of the HOI+hemolysis group. The total pancreatitis rates were 60% and 76.6% in the hemolysis and HOI+hemolysis groups, respectively (p<0.05). Pancreatic cytokine levels were significantly higher in the HOI+hemolysis and hemolysis groups than in all control groups. The highest ICAM-1 and MCP-1 levels were in the HOI+hemolysis group. Histological signs of acute pancreatitis were also more severe in this group. CONCLUSIONS: Acute massive hemolysis can induce acute pancreatitis. Excess of free vascular heme seems to be an inducer of inflammation by modulating ICAM-1 and MCP-1.

The effect of perendoscopic sclerosing agent injection in Forrest's II ulcers -- a pilot study from Turkey.

BACKGROUND: We aimed to clarify the outcome of perendoscopic prophylactic injection of sclerosing agent in Forrest's II ulcers. MATERIAL/METHODS: Patients with upper gastrointestinal bleeding in last 6 hours were performed emergency endoscopy and were enrolled. The patients in group-1 were performed prophylactic injection therapy with 1% aethoxysclerol and then given medical treatment with intravenous 40 mg omeprazole twice a day and somatostatin infusion at the dose of 6 mg/day during 3 days. Group-2 patients were only given medical treatment with same agents and at same doses without having any perendoscopic therapy. RESULTS: There were 32 patients in group-1 and 20 in group-2. In emergency endoscopy, 20 (62.5%) patients had IIa ulcers and 12 (37.5%) patients had IIb ulcers in group-1. These patients underwent prophylactic perendoscopic hemostasis by 1% aethoxysclerol in addition to medical treatment. Early rebleeding occurred in 9 (28.1%) patients of group-1 and 3 (15%) in group-2 (p<0.001). At the endoscopic control after 48 hours 13 (40.6%) patients in the group-1 and 15 (75%) patients in group-2 showed improved local ulcer stigmata (p<0.001). The numbers of blood units transfused were lower in the group-2 (p=0.002). The hospital stay was longer in group-1 (p=0.01). In the group-1, more endoscopic intervention was needed. Any death and the need for surgical intervention did not occurred in any groups. CONCLUSIONS: According to our results; the indication of perendoscopic prophylactic injection of sclerosing agent in non-bleeding ulcers with high risk of rebleeding must be reviewed by large population based, prospective, randomized trials.

Somatostatin infusion and hemodynamic changes in patients with non-variceal upper gastrointestinal bleeding: a pilot study.

BACKGROUND: Intravenous somatostatin decreases acid secretion, splanchnic blood flow, and portal pressure, but the evidence for its efficacy in the treatment of non-variceal upper gastrointestinal bleeding has been mixed. We aimed to evaluate the vasoactive effect and possible mechanisms of somatostatin infusion in the cessation of non-variceal upper gastrointestinal bleeding. MATERIAL/METHODS: Patients with non-variceal upper gastrointestinal bleeding without portal hypertension were enrolled in the study. They were given somatostatin infusion in a dose of 250 microgr/hour for 72 hours. Superior mesenteric arterial average flow velocity (SMA-V), SMA pulsatility index (SMA-PI), portal venous volume flow (PV-F), and renal artery resistance index (RA-RI) were measured two times for each patient by Doppler ultrasound; once on the first day of infusion therapy and again 6 hours or more after stopping the infusion. RESULTS: 21 patients (12 male, mean age 44.1 +/- 9.9) with bleeding peptic ulcer were enrolled. During somatostatin infusion, PV-F was 33.7 +/- 12.7 cm3/sec. After stopping infusion, it increased to 56.3 +/- 16.0 cm3/sec (p=0.001). SMA-V was 39.7 +/- 13.1 cm/sec and 64.4 +/- 15.1 cm/sec during somatostatin infusion and after cessation of somatostatin respectively (p=0.01). SMA-PI was 2.0 +/- 0.8 during somatostatin infusion but 2.8 +/- 0.8 without somatostatin infusion (p=0.02). However, RA-RI showed no difference between states with or without somatostatin infusion (p>0.05). CONCLUSIONS: Somatostatin infusion causes a decrease in arterial blood flow to the stomach and duodenum in patients with non-variceal upper gastrointestinal bleeding without portal hypertension. Somatostatin therapy also decreases portal blood flow while not altering renal blood.

Midazolam-induced sedation for upper gastrointestinal endoscopy: assessment of endoscopist and patient satisfaction.

Upper gastrointestinal endoscopy can be performed without intravenous sedation but the evidence suggests most patients and endoscopists prefer some form of premedication. Intravenous diazepam or midazolam are used by the majority of endoscopists in the United States, though it is not common practice in Turkey where this study was conducted. This study aimed to evaluate the efficacy and safety of midazolam in performing upper gastrointestinal endoscopy. A total of 352 patients undergoing upper gastrointestinal endoscopy were sedated with midazolam given as a bolus injection over 5 seconds. Ages of the patients ranged between 16 and 79 years (average: 41.6 +/- 12.7 years). The course of endoscopy, anterograde memory, degree of cooperation, degree of sedation, side effects, and acceptability of further intervention were evaluated by a questionnaire given to the patients and endoscopists.