Zbigniew Gonciarz

Effects of alendronate on bone mass in patients with primary biliary cirrhosis and osteoporosis: preliminary results after one year.

We report on an evaluation of the efficacy of alendronate in the treatment of osteoporosis coexisting with PBC. Twenty women with primary biliary cirrhosis (PBC) (AMA /) and no abnormalities of the upper gastrointestinal tract took part in the study. At the time of the study, all patients were receiving UDCA (15 mg/kg body-weight/day), calcium supplements (1000 mg/day) and vitamin D orally (0.25 mg/day). The patients were divided into two groups according to bone mineral density (BMD): group A consisted of 10 patients with osteoporosis treated with alendronate (10 mg/day) (Fosamax; MSD & Co., Whitehouse Station, N.J., USA) and group B consisted of 10 patients with osteopenia. BMD of the lumbar spine (L2-L4) was measured at entry and again after 12 months of therapy by dual X-ray absorptiometry (DXA). BMD values were expressed as grams hydroxyapatite per centimetre squared and T scores. Osteoporosis was defined according to WHO recommendations as a bone mineral density of the lumbar spine that was at least 2.5 SD below the mean value. Group A patients underwent a second endoscopy after the treatment was completed. Results are presented in the Table (mean, SD). It was found that alendronate had a positive effect on bone density after a 12-month period of therapy. A 5% increase in BMD from baseline was found in 9 out of 10 patients in Group A (no change in one), whereas in group B patients the mean value of BMD decreased (2.5% from baseline). These results obtained in Group A patients were similar to those found in postmenopausal women [1]. Guanabens et al. [2] reported that 2 years of therapy with etidronate in PBC patients resulted in only a 0.5% improvement in lumbar BMD. Some reports describe oesophagitis, oesophageal erosions and ulcerations in the upper gastrointestinal tract [3,4] during alendronate therapy. In our patients no symptoms or endoscopic signs were observed during treatment. Our study revealed that: 1) bisphosphonate therapy for patients with PBC without upper gastrointestinal symptoms is safe and 2) the potential of the beneficial effect on bone mass is large. However, careful selection of patients and close monitoring by the physician are needed.

Effect of single-dose administration of recombinant interferon-alpha2b on gastric myoelectrical activity in patients with chronic hepatitis C.

BackgroundUpper abdominal complaints during interferon therapy may result from impaired gastric motility and/or evacuatory function. We examined the effect of acute administration of interferon on gastric myoelectrical activity (GMA) with the use of surface electrogastrography.MethodsThe study population comprised 25 patients with chronic hepatitis C. All of them were naïve to interferon. On 2 days, after a 25-min basal GMA registration, in group A (5 men, 7 women, aged 44.3 ± 2.8 years) placebo or 5 million i.u. recombinant interferon alpha-2b (IFNA) was administered s.c. and the GMA was recorded in the interdigestive state for two periods (2 h and 4 h), separated by a 15-min break. In group B (7 men, 6 women, aged 44.7 ± 3.9 years) placebo or 5 million i.u. IFNA was injected s.c. after the ingestion of a semiliquid test meal of 364 kcal. Subsequently, the postprandial GMA was recorded for two periods (2 h and 4 h), separated by a 15-min break.ResultsA typical flu-like syndrome was observed in 91.7% of patients in group A, and in 92.3% of patients in group B, thus providing evidence of the pharmacodynamic efficiency of the IFNA administration. In the fasted state, IFNA brought about a negligible increase in the rhythmicity and power of the gastric slow waves. IFNA did not elicit any statistically significant effect on gastric slow-wave activity postprandially.ConclusionsAcute administration of interferon does not involve any deterioration of GMA that could be linked to the previously reported upper abdominal symptoms in patients undergoing treatment with this drug.

Reduction of CD45RA isoform expression and decrease in CD4 and CD8 receptor density in lymphocytes of patients with primary biliary cirrhosis

Background: The immunological background of primary biliary cirrhosis (PBC) remains largely obscure. Methods: Using double colour flow cytometry, we estimated the distribution of functionally different lymphocyte subpopulations in the peripheral blood of 25 PBC patients and 18 controls. We examined: 1) the expression of CD3, CD4, CD8, CD 19 and CD56 surface receptors, 2) the distribution of lymphocyte subsets bearing ‘naive’ (CD45RA+) and ‘memory’ (CD45RO+) phenotypes in both CD4+ and CD8+ cell populations, 3) the expression of an early activation marker (CD69), 4) the distribution of C1.7 mAb binding cytotoxic effectors in CD3+, CD8+ and CD56+ cells. The surface marker expression was evaluated in terms of percentage of positive cells and receptor density. Results: We found: 1) a decrease in the percentage of total CD3+ and CD4+ cells, an unchanged proportion of CD8+ cells but elevated proportion of CD 19+ cells and NK lymphocytes; 2) a reduction in the percentage of ‘naive’ CD4+ but normal proportion of ‘naive’ CD8+ as well as CD4+ and CD8+ ‘memory’ cell subsets; 3) a decrease in the density of CD4 and CD8 receptors in the subsets of ‘naive’ and ‘memory’ T cells, 4) an increase in the percentage of CD69 receptor bearing T cells but unchanged proportion of C1.7 mAb. Conclusions: It is concluded that the reduction in number of suppressor-inducer-like ‘naive’ CD4+ T-cell subsets in association with the decrease in fluorescence intensity for CD4 and CD8 may significantly contribute to the mechanisms that could account for a development of PBC.