Antioxidants and narrow band-UVB in the treatment of vitiligo: a double-blind placebo controlled trial.

BACKGROUND: Vitiligo is an acquired depigmenting disease with uncertain aetiopathogenesis, possibly associated with oxidative stress. Narrowband ultraviolet B phototherapy (NB-UVB) is the most widely used and effective treatment. AIM: To evaluate the clinical effectiveness of NB-UVB and the repairing of oxidative stress-induced damage, using oral supplementation with an antioxidant pool (AP). METHODS: Patients (n = 35) with nonsegmental vitiligo were enrolled in a randomized, double-blind, placebo-controlled multicentre trial. The treatment group received, for 2 months before and for 6 months during the NB-UVB treatment, a balanced AP containing alpha-lipoic acid, vitamins C and E, and polyunsaturated fatty acids. The area and number of lesions, as well as some parameters of the oxidation-reduction (redox) status of the peripheral blood mononuclear cells (PBMCs) were estimated at the beginning, after 2 months, and at the end of the trial. RESULTS: In total, 28 patients completed the study. After 2 months of AP supplementation, the catalase activity and the production of reactive oxygen species (ROS) were 121% and 57% of the basal values (P < 0.05 and P < 0.02 vs. placebo, respectively). The AP increased the therapeutic success of NB-UVB, with 47% of the patients obtaining > 75% repigmentation vs. 18% in the placebo group (P < 0.05). An increase in catalase activity to 114% (P < 0.05 vs. placebo) and decrease in ROS level of up to 60% (P < 0.02 vs. placebo) of the basal value was observed in PBMCs. Finally, the AP intake maintained the membrane lipid ratio (saturated : unsaturated fatty acids 1.8 : 3.1; P < 0.05), counteracting phototherapy-induced saturation. CONCLUSIONS: Oral supplementation with AP containing alpha-lipoic acid before and during NB-UVB significantly improves the clinical effectiveness of NB-UVB, reducing vitiligo-associated oxidative stress.

[Comparative clinical study between standard hemodialysis, PHF (HDF on-line) and PHF AF (HDF on-line acetate free)]. / Studio clinico comparativo fra HD standard, PHF (HDF on-line) e PHF AF (HDF on-line acetate free).

PURPOSE AND METHODS: In this study, three different techniques were compared in eight uremic patients on regular dialysis treatment: standard hemodialysis (HD), paired hemodiafiltration (PHF) and PHF acetate free (AF). We evaluated the Kt/V, the percentage reduction in Beta 2-microglobulin, the acid-base balance (blood samples were drawn pre-treatment and after 30, 60, 120 and 180 min, post-treatment and pre-treatment of the following session) and the acetate plasma concentration pre- and post-treatment. RESULTS: Between these treatments there were no significant differences in Kt/V and in urea reduction rate (URR). The percentage reduction in plasma Beta 2-microglobulin levels was significantly higher in PHF and in PHF AF than in standard HD. CONCLUSIONS: The correction of acidosis was not significantly different between standard HD and PHF, while it was significantly less effective in PHF AF. The post-dialysis plasma acetate concentration was significantly lower in PHF AF than in standard HD and in PHF with an improvement in cardiovascular (CV) stability and a reduction in oxidative stress.

Model-based dialysis adequacy prediction by continuous dialysate urea monitoring.

A modeling approach for on-line estimation of urea kinetics from continuous measurement of urea concentration in the effluent dialysate stream (DUN) is presented. On-line identification of urea kinetics response parameters is used to predict and update dialysis adequacy during the treatment. Dialysis adequacy can be quantified in several ways, but its strict dependence on final urea concentration is a major fact. For this reason, a good predictive skill on the time course of DUN may enable better performances in the control of dialysis outcome by treatment parameters adjustment. A post-filter enzymatic sensor performs continuous measurement of DUN on patients undergoing standard haemodialysis. To get an early prediction of the end dialysis urea level, the solution of a variable volume double-pool (VVDP) model is used, whose parameters are identified at each time on the basis of the past DUN history Unlike the variable volume single-pool (VVSP) model, this enables a prompt and accurate estimation of the final DUN. In fact, after 75 min the estimates always differ by less than 10% from the values measured by the sensor at the end of the treatment. Moreover, values predicted by the model in the last hour always lie within 1% of measured final values. Real-time knowledge of an analytic expression for whole DUN time course also enables the accurate prediction of total removed urea, with no need of cumbersome dialysate collection techniques.

A new biosensor for continuous monitoring of the spent dialysate urea level in standard hemodialysis.

This study gives the results in terms of precision and repeatability of a new on-line urea monitoring system (Ureascan P2 Hospal) capable of measuring the urea concentrations in the spent dialysate. The Ureascan P2 Hospal (UP2H), fitted on single-pass dialysis machines (Integra-Hospal), functions by the presence of a disposable mini-reactor containing urease. The passage through the reactor of a minimum quantity of spent dialysate from the filter diluted with a pH 7 buffer solution (1 ml/min) increases its ionic strength, which is detected by a differential measurement of conductivity in proportion to the urea concentration in the dialysis liquid. We studied 13 dialysis sessions, with bicarbonate buffer, in 8 anuric patients. From 4 to 7 dialysate samples were taken during each treatment to determine the urea and 65 samples were analysed overall. Urea values from the UP2H were compared with those measured on the Dimension Du Pont analyser. Simple linear regression analysis showed an excellent correlation between the 2 measuring methods (r=0.987; p<0.001). The Bland-Altman test gave an average difference between the urea values measured with the UP2H and in the laboratory of 1.3+/-1.2 mg/dl. The agreement limits between 2 SD were -1.2 mg/dl and +3.8 mg/dl respectively. In conclusion, the UP2H we have developed has proved to be a reliable and very useful instrument for adapting, through the urea kinetic mathematical models, the dialysis dose for individual patients.

Low sodium concentration solution in normohydrated CAPD patients.

The aim of this study was to examine the possibility of increasing sodium and water removal with peritoneal dialysis. Ten patients aged 67.3 +/- 6.2 years, on continuous ambulatory peritoneal dialysis (CAPD) for 28.1 +/- 13.9 months, with no episodes of peritonitis for at least 2 months and clinically normohydrated, gave their informed consent to undergo two consecutive peritoneal equilibration tests (PETs) with dialysis solution at a sodium concentration of 126 mEq/L (low sodium) and 132 mEq/L (normal sodium), both with 2.5% glucose. Net ultrafiltration and sodium mass transfer were 319.4 +/- 178.5 and 443.2 +/- 234.4 mL (p = 0.0346) and 27.7 +/- 24.5 and 28.2 +/- 27.1 mEq (p = NS), respectively. There were no variations in natremia or the transport indices of the studied solutes or in the arterial pressure or heart rate. All patients showed drowsiness or torpor during the low sodium PET and one had cramps. The 126 mEq/L sodium dialysis solution showed no advantages compared to the more common solution, 132 mEq/L. However, further study is necessary to check the potentiality of solutions with different sodium and glucose compositions for both acute and chronic use.

Correction of glucose concentration interference on Jaffé kinetic creatinine assay in peritoneal dialysis.

Overestimation of creatinine measurement using the Jaffé kinetic method in peritoneal dialysis solutions, due to glucose interference, has been quantified and corrected through the elaboration of linear formulas obtained from 110 recovery and 301 biological tests. The added pure powdered creatinine and enzymatic method were considered as references after proven accuracy. Considering creatinine as well as glucose concentration interference, we obtained correction formulas from multiple regression application. All the computed formulas gave satisfactory corrections but different accuracy levels. The best model in biological samples was: Corrected CR = K1JafféCr + K2Glucose (all values in mg/dl) where K1 = 0.973 and K2 = -0.00035 (Rsq = 0.987, F ratio = 10,945, p = 0.00001). Applying formulas to biological samples there was a drop in accuracy, possibly explained by the presence of numerous unidentified substances in peritoneal dialysis biological samples that can amplify scatter. Every laboratory can reduce the error of the Jaffé kinetic assay by calculating their own correction formula in relation to the method and instrument used, because Jaffé kinetic assay gives different results with different kinetic windows. So, especially when applied to peritoneal dialysis fluid measurements, if a creatinine assay reference method is not available, the correction formula can be applied directly as given. Otherwise the method we have described can be followed with a well-structured creatinine recovery fest to identify and quantify assay interferences.

Persistence of human T cell lymphotropic virus type 1 (HTLV-1) sequences in peripheral blood mononuclear cells from patients with mycosis fungoides.

Mycosis fungoides (MF) is a rare form of cutaneous T cell lymphoma suspected of having a viral etiology. As in adult T cell leukemia, the virus involved may be human T lymphotropic virus type 1 (HTLV-1). We cultured the peripheral blood mononuclear cells (PBMC) of 29 patients with MF HTLV-1 seronegative by enzyme-linked immunosorbent assay and Western blot. The presence of reverse transcriptase (RT) and p24 antigen was investigated in the concentrate supernatant of the culture. The DNA of all studied patients was submitted to polymerase chain reaction and Southern blot analysis using primers and probes recognizing the tax region of HTLV-1/2 and the pol region of HTLV-1. 10 of 29 patients were found positive to HTLV-1, whereas they were always negative to RT and p24. The same results were confirmed in double blind after 6 mo. Our findings suggest HTLV-1 may be involved in the etiology of MF, at least in certain cases.

Alterations in erythrocyte morphology induced by blood pumps.

A scanning electron microscopy was used after in vitro and in vivo tests to investigate any alterations caused by the peristaltic roller pump in erythrocyte morphology. The electron micrographs of samples were examined as follows: 1) by image analyser; 2) by applying Bessis's classification for the qualitative study of crenated red blood cells (RBCs). The in vitro test was repeated four times using blood from healthy donors. Each basal blood sample was divided into 250 ml portions, each of which was recirculated for 12 minutes at different flow rates. In order to verify any persistent erythrocyte damage caused by the peristaltic pump, 15 minutes after recirculation at 450 ml/min, another sample was prepared using the blood remaining from the last test. A statistically significant direct correlation was found between blood flow (Qb) increase and the percentage of morphologically altered RBCs, when either using an image analyser (r = 0.97; p < 0.05) or Bessis's classification (r = 0.95; p < 0.05). However, neither method showed any statistically significant difference between the percentage of deformed RBCs, determined in the basal sample, or in the percentage found at the end of the 450 ml/min test after standing 15 minutes at room temperature. The in vivo test was carried out on 6 patients over 2 dialysis sessions, which differed only for the Qb: 250 versus 400 ml/min. The two dialysis sessions gave comparable results when using both study methods regarding the presence of deformed RBCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Generalized melanosis associated with malignant melanoma: unusual histologic appearance.

A case of generalized melanosis associated with malignant melanoma, characterized by up-to-date, previously undescribed histologic findings, is reported. Markedly dilated dermal lymphatics with features resembling secondary lymphangioma were found. We speculate that a further mechanism, as well as those previously reported in the literature, could be operative in the pathogenesis of this disorder of altered pigmentation.

The role of hypertension as a damaging factor for kidney grafts under cyclosporine therapy.

The relative importance of glomerular filtration rate (GFR) and hypertension (permanent need for antihypertensive drugs) for the prognosis of kidney grafts was studied in 135 cyclosporine-treated primary cadaver kidney transplant recipients whose grafts lasted more than 1 year. The start point of 1 year after transplantation was chosen because hypertension developed within the first year in all our hypertensive patients. Graft prognosis in hypertensive patients was not significantly worse than that of normotensive patients; moreover at multivariate analysis, age at transplantation and GFR at 1 year (P = 0.014), but not hypertension, were significant prognostic factors for the graft. At logistic regression, GFR was a significant variable for hypertension (P = 0.009), but hypertension was not a significant variable for renal failure at 1 year (GFR < or = 0.83 mL/sec [50 mL n]; P, NS). Accordingly, hypertension per se resulted much more as a consequence of reduced renal function than as a direct cause of graft damage. However, when hypertensive patients were divided into controlled and uncontrolled, uncontrolled hypertensive patients had the worst prognosis (P = 0.03), and blood pressure control proved a strong prognostic factor for the graft, even after GFR was considered (P = value of the model considering blood pressure control, GFR, and age at transplantation: 0.007). Our data suggest that, apart from being an expression of reduced renal function, hypertension is also a direct kidney graft damaging agent, a role that can be controlled by strict reduction of blood pressure levels.

Long-term survival on renal replacement therapy for primary hyperoxaluria type I.

We describe the case of a patient in end-stage renal failure due to primary hyperoxaluria type I (PH1) who started hemodialysis in 1977 and is still alive and active. The diagnosis of PH1 was first suspected after a bone biopsy performed in 1981 to investigate hyperparathyroidism. Oxalosis recurred as early as 3 months after transplantation in a cadaver kidney grafted in 1987; nevertheless, graft function remained good enough to make possible the discontinuation of dialysis treatment for 5 months and thereafter to have only 1 dialysis a week for 17 months. The diagnosis of PH1 has been recently confirmed despite the patient being already anuric by means of the determination of plasma oxalate and glycolate levels as well as by determining hepatic alanine:glyoxylate amino-transferase.

Hepatitis C virus in dialysis units: a multicenter study.

Three hundred and eighty-seven chronic hemodialysis patients were evaluated, in a multicenter study, to investigate the epidemiology of hepatitis C virus. In anti-HCV seropositive patients, serum ALT values and blood transfusions were retrospectively compared; blood donors were studied for serum transaminases. In seropositive patients without previous blood transfusions, analysis of dialysis schedule was done. Eventually, the intrafamilial transmission of hepatitis C virus was studied in 104 family members. The prevalence of HCV infection in hemodialysis patients was 15.7%. The incidence of acute hepatitis was frequent, while chronic hepatitis incidence was less than expected (17.5%). Intrafamilial diffusion was low (1.9%). Blood-transfusion-related infections seem to be negligible, while cross-contamination in dialysis units seems to be very important.

Comparison between first- and second-generation test for anti-hepatitis C virus antibodies in hemodialysis patients.

The serum of 387 hemodialysis patients from 9 dialysis units was checked for anti-hepatitis C virus antibodies with a 1st-generation ELISA (Ortho) test: 61 patients were repeatedly positive. In order to avoid false-positive results, these sera were tested with a 1st-generation confirmatory RIBA test, 2nd-generation screening ELISA test and 2nd-generation confirmatory RIBA test. The 2nd-generation ELISA test confirmed data obtained with 1st-generation ELISA, however, the 1st-generation confirmatory RIBA test underestimated the number of anti-HCV-positive patients.