Suppressor cell activity in a randomized trial of patients receiving active specific immunotherapy with melanoma cell vaccine and low dosages of cyclophosphamide

Previous studies have shown that melanoma patients develop an immune response to cell surface melanoma-associated antigens. The presence of this antibody response to cell surface antigens has been correlated with a better clinical outcome when melanoma patients are treated with an allogeneic melanoma cell vaccine (MCV) as an active immunotherapy protocol. It was hypothesized that the inability to consistently induce or enhance existing immune responses to melanoma-associated antigens was related to the downregulation by suppressor cells. Patients received treatments of MCV 3 times in a 4-week interval and then every fourth week. The biological response modifier cyclophosphamide (CYP) is an immunomodulator of suppressor T-cell function. In this study we set out to determine whether CYP given prior to MCV could reduce suppressor cell activity during vaccination. In a randomized trial stage II and III melanoma patients (n = 41) were given MCV alone or in conjunction with CYP at dosages of 300, 150, or 75 mg/m2. CYP was given 3 days prior to each MCV treatment. Suppressor cell activity in patients was monitored by a concanavalin A suppressor assay using peripheral blood lymphocytes from serial phlebotomies during a 12-week period of treatment. In each trial group there were patients who had major reduction in suppressor cell activity (greater than 50%). Overall, the greatest reduction in suppressor cell activity occurred in patients receiving 300 mg/m2 CYP compared to the other CYP dosages or MCV alone. For the first two treatments at all CYP dosages there was a greater number of patients showing reduced suppressor cell activity compared to later treatments. In a comparison of patients receiving MCV alone to MCV + CYP 300 mg/m2 phenotypic analysis of lymphocyte subsets showed significant (P = 0.03) reduction in the CD8+CD11B+ (suppressor) cells of the latter group. These studies suggest that CYP can be used at low dosages in conjunction with MCV to reduce suppressor cell activity.     

Clinical predictors of steroid-induced exacerbation in myasthenia gravis

Although oral corticosteroids are effective for the treatment of myasthenia gravis (MG), the possibility of steroid-induced exacerbation of symptoms, especially during the initial course of steroid therapy, has limited their use patients with severe MG. However, the factors influencing or predicting in exacerbation are not well understood. The purpose of this study was to identify the clinical factors that predict the initial paradoxical exacerbation of MG in response to steroid therapy. Fifty-five consecutive patients who were administered for the first time high doses of prednisone (40-80 mg) in a tertiary medical centre in Seoul, were included. Prednisone-induced exacerbation was defined as a significant reduction in a patient's Myasthenia Gravis Severity Scale (MSS) score within 4 weeks of prednisone administration. We divided the patients into two groups on the basis of whether or not they experienced prednisone-induced exacerbation, and investigated the differences between the two groups with respect to clinical, laboratory and electrophysiological features. Twenty-three patients (42%) experienced definite exacerbation after prednisone therapy. Older age, predominantly severe bulbar symptoms, and low MSS score were found to be significant clinical predictors of exacerbation by multivariate logistic regression analysis. A high daily dosage of prednisone relative to body weight was found to be neither a predictor of exacerbation nor a predictor of early improvement in bivariate correlation analysis. Steroid-induced exacerbation in MG is a frequently encountered and challenging problem. Clinicians should be aware of the possibility of exacerbation of MG when prescribing prednisone, especially when treating elderly, bulbar dominant, or severely myasthenic patients.     

Endovascular stent placement for interposed middle hepatic vein graft occlusion after living-donor liver transplantation using right-lobe graft.

Middle hepatic vein (MHV) reconstruction is performed to drain the right paramedian sector to prevent hepatic venous congestion (HVC). The aim of the present study was to evaluate endovascular stent placement in patients with stenosed and/or occluded interposition vein graft (IVG) to segment V hepatic vein (V5) and segment VIII hepatic vein (V8) after living-donor liver transplantation (LDLT). The procedure was performed in 11 recipients; 7 underwent it within 24 hours of LDLT. The following parameters, including technical success, clinical success, complications, patient survival data, and serial computed tomography (CT) findings during follow-up, were documented retrospectively. Technical success was defined as both successful stent placement and resolution of stenosis or occlusion with copious flow of contrast medium through the stent, while clinical success was defined as both improvement of liver function tests (LFTs) and reduction or disappearance of hepatic low-attenuation areas on follow-up CT scans taken within 1 week of stent placement. Technical success was achieved in 10 of 11 patients (91%), and clinical success was achieved in 9 of 11 patients (82%). Acute thrombotic occlusion of the stent-inserted hepatic vein occurred in 1 patient 1 day following stent placement. During the mean follow-up period of 468 days (range, 13-891 days), 9 patients survived and 2 patients died. No death was directly related to stent placement or its related complications. The low-attenuation area in the involved hepatic segment V (S5) and/or VIII (S8) area prior to stent placement disappeared completely on follow-up CT scans performed at 3-12 days (mean, 5.4 days) after stent placement in all 9 patients with clinical success. No attenuation change occurred even in cases with chronic occlusion of the stent-inserted hepatic veins. In conclusion, though IVG to V5 and V8 remains controversial, the treatment of their stenosis or occlusion is safe and effective, even during their immediate postoperative period.     

Outcome of mid-urethral sling procedures in Korean women with stress urinary incontinence according to body mass index

BACKGROUND: The objective of this study was to determine whether the outcome of mid-urethral sling procedures is influenced by the body mass index of Korean women suffering from stress urinary incontinence (SUI). METHODS: A total of 285 women, ranging in age from 28 to 80 years (mean 55.4), all of whom were followed up for at least 6 months, were ultimately included in this study. The patients were classified as follows: normal weight, 18.5-23 kg/m2; overweight, 23-27.5 kg/m2; obesity, 27.5 kg/m2 or higher. RESULTS: We noted bladder perforations in 11 cases (4.9%, 3.8% and 2.2% in the normal weight, overweight, and obesity groups, respectively; P = 0.449). We determined there to be no significant differences among the three groups with regard to cure rate (P = 0.173). The rates of postoperative urinary retention were 9.9% in the normal weight group, 10.1% in the overweight group, and 15.6% in the obesity group (P = 0.396). We determined there to be no significant differences among the three groups with regard to the persistence of urgency (P = 0.312). Seventy-nine patients (27.7%) exhibited symptoms indicative of voiding disorder (hesitancy, poor flow, or sensations of incomplete emptying). The postoperative development of these voiding symptoms was not significantly different among the three groups (P = 0.106). CONCLUSION: Our results demonstrate both the feasibility and the safety of mid-urethral sling procedures for obese Korean women who suffer from SUI. Additional studies, including prospective randomized trials with longer follow-up periods, will be required in order to confirm these findings.