Lymphoblastoid α-Interferon for Chronic Hepatitis C: A Randomized Controlled Study

Forty patients with chronic hepatitis C (CHC) were included in an open randomized controlled trial of lymphoblastoid α-interferon (L-IFN) versus no treatment. Twenty patients entered each group, and features of therapy and control cases were similar. L-IFN was given in low doses (1.5-4.5 megaunits) for 1 yr. In 16 of 20 patients treated with L-IFN (80%), but in only one of 20 nontreated cases (0.5%; p < 0.001), aminotransferase activities became normal. In four patients there was a reactivation of the disease during treatment after 4, 5, 6, and 8 months with normal aminotransferase levels. A posttherapy reactivation of hepatitis was observed in four additional cases after 1, 1, 1, and 3 months of follow-up. The other eight patients (40%) continued with normal aminotransferase levels for 1.52 ± 0.74 (range, 1-2.1) yr after IFN doses were discontinued. In all treated patients except two nonresponders, but in only one of 20 nontreated cases ( p < 0.001), Knodell's histological activity index decreased. Procollagen type III aminoterminal peptide levels did not change significantly in nontreated and nonresponder patients, diminished slightly in patients with a transient response, and normalized in cases with a long-standing response, suggesting that this serum test may be a reliable marker for monitoring response to IFIN therapy in patients with CHC. Finally, L-IFN treatment induced significant increments in CD4/CD8 index, phytohemagglutinin-induced blastogenesis, and natural killer activity. This study shows that L-IFN diminish inflammatory and fibrogenic activity in most patients with CHC. In 40% of patients treated in this trial, a long-standing remission of the disease was observed.     

Distribution and function of cholinergic receptors in the sheep detrusor muscle

The distribution of cholinergic nerve fibres, as well as the characterization of the muscarinic receptors responsible for the contraction, were determined in the detrusor smooth muscle of the sheep. The results obtained demonstrated a rich presence of acetylcholinesterase (AChE)-positive fibres distributed throughout the bladder body forming dense neuromuscular, subepithelial and perivascular plexuses. Furthermore, intramural ganglia containing AChE-positive cell bodies were identified. However, acetylcholine and carbachol induced a dose-dependent contraction of detrusor smooth muscle. The effect observed with carbachol was competitively antagonized by atropine (pA2: 8.94), pirenzepine (pA2: 7.38), AF-DX 116 (pA2: 7.35), 4-DAMP (pA2: 9.26) and hexahydroxiladifenidol (HHSiD) (pA2: 8.49). The pA2 value for pirenzepine is intermediate between M1- and M2-receptors which suggests that this antagonist does not act on M1- or M2-receptors, but that it does on M3-receptors. The pA2 value for AF-DX 116 is consistent with the presence of M2-receptors in this tissue. Moreover, the pA2 values obtained for both 4-DAMP and HHSiD are in agreement with the presence of M3-receptors, due to the lack of effect of pirenzepine on M1-muscarinic receptors. These results indicate the existence of a rich parasympathetic innervation in the sheep detrusor muscle and suggest that its contraction could be mediated by the stimulation of muscarinic receptors belonging to both M3- and M2-subtypes.     

Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity.

The anatomic response to intravitreal bevacizumab injection in three patients with aggressive, posterior retinopathy of prematurity is described. In all cases, the worse eye was treated with a single intravitreal injection of 0.75 mg of bevacizumab as monotherapy or complementary to laser therapy. In 24 hours, all injected eyes showed regression of the tunica vasculosa lentis and iris vessel engorgement and disappearance of iris rigidity. In addition, plus disease and retinal proliferation began to regress. None of the eyes required additional treatment. Follow-up of up to 10 months     

Renal dysfunction after myocardial revascularization.

OBJECTIVES: In this study, we evaluate the incidence of and analyse the pre and intraoperative risk factors for the development of postoperative renal dysfunction (PRD), and the impact of such an event on perioperative mortality and on hospital length of stay. In addition, we sought to investigate the influence of a mildly increased serum creatinine (1.3-2.0 mg/dl) on perioperative mortality and morbidity. METHODS: The study included 2445 consecutive patients who had no pre-existing renal disease (creatinine or=2.1 mg/dl with a preoperative-to-postoperative increase >or=0.9 mg/dl. Univariate and multivariate analyses were performed where appropriate. RESULTS: Global 30-day mortality was 0.7%. The incidence of PRD was 5.6% (136 patients). Mortality for patients who experienced PRD was 8.8 vs. 0.1% for patients who did not (P<0.001). PRD increased the length of hospital stay by 3.4 days (7.6 vs. 11.0 days; P<0.001), and patients who needed haemodialysis (11%) had a perioperative mortality of 33.3% and a mean hospital length of stay of 16 days. Multivariable logistic regression identified the following variables as independent predictors of PRD: age (P=0.017; odds ratio (OR) 1.3 per 10 years), angina class III/IV (P=0.003; OR 1.7); cardiopulmonary bypass time (P=0.007; OR 1.01 per minute); preoperative serum creatinine levels: group 1 (1.3-1.6 mg/dl (P<0.001; OR 5.5)) and group 2 (1.7-2.0 mg/dl (P<0.001; OR 14.2)). Finally, a mild elevation of the preoperative creatinine level (1.3-2.0 mg/dl) increased significantly the probability of perioperative mortality, low cardiac output, haemodialysis and prolonged hospital stay. CONCLUSIONS: Although the likelihood of PRD in patients without pre-existing renal dysfunction is relatively low, it dramatically increases mortality, morbidity and length of stay after CABG. Mildly elevated (>1.2 mg/dl) preoperative serum creatinine level significantly increases the perioperative mortality and morbidity.     

Success determining factors in percutaneous transluminal balloon valvuloplasty of pulmonary valve stenosis

Twenty-two percutaneous transluminal balloon valvuloplasty procedures were performed on 21 patients with congenital pulmonary valve stenosis. The peak systolic pressure gradient was immediately reduced from 79.1 +/- 7.4 to 22.2 +/- 1.8 mmHg, (P less than 0.0001) and follow-up cardiac catheterization at 5.3 +/- 0.4 months in 19 patients revealed no further significant change in gradient (23.5 +/- 3.2 mmHg). The best results were obtained when balloons larger than the pulmonary annulus were used, i.e. an immediate residual transvalvular gradient of 22.0 +/- 2.2 mmHg with a balloon/annulus ratio greater than 1, as opposed to 44.2 +/- 5.4 with a balloon/annulus ratio = 1 (P less than 0.001). The angiographically determined cusp thickness of the stenotic pulmonary valves was significantly greater than that of the control group of 24 patients without pulmonary valve stenosis (1.21 +/- 0.09 vs 0.59 +/- 0.02 mmHg, P less than 0.00001). The relationship between this parameter and the residual transvalvular gradient at follow-up was found to be significant (r = 0.77, P less than 0.001). It is concluded that balloon size is a determinant factor in achieving good results with percutaneous balloon valvuloplasty although cusp thickness, a factor to which scant regard has hitherto been paid, also plays a significant role in the residual transvalvular gradient measured at follow-up.     

Improved Scoring System to Assess Adult Donors For Cadaver Renal Transplantation

We previously proposed a quantitative approach to assess donor organs for cadaver renal transplantation. To improve on our original scoring system, we studied 34 324 patients who received cadaver renal transplants from adult donors between 1994 and 1999 and were reported to the UNOS Scientific Renal Transplant Registry. A scoring system was developed from five donor variables (age, 0-25 points; history of hypertension, 0-4; creatinine clearance before procurement, 0-4; cause of death, 0-3; HLA mismatch, 0-3) that showed a significant correlation with renal function and long-term graft survival. Cadaver kidneys were stratified by cumulative donor score: grade A, 0-9 points; grade B, 10-19; grade C, 20-29; and grade D, 30-39. The influence of donor score on renal function and graft survival was most severe above 20 points, designated 'marginal' kidneys. In summary, a donor scoring system developed from a large population database was useful in predicting outcome after cadaver renal transplantation. The improved system provides a quantitative approach to evaluation of marginal kidneys and may improve allocation of these organs in cadaver renal transplantation.