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The aim of this study was to examine the impact of features of dysmetabolism on liver disease severity, evolution, and clinical outcomes in a real-life cohort of patients treated with direct acting antivirals for chronic hepatitis C virus (HCV) infection. To this end, we considered 7,007 patients treated between 2014 and 2018, 65.3% with advanced fibrosis, of whom 97.7% achieved viral eradication (NAVIGATORE-Lombardia registry). In a subset (n = 748), liver stiffness measurement (LSM) was available at baseline and follow-up. Higher body mass index (BMI; odds ratio [OR] 1.06 per kg/m 2 , 1.03-1.09) and diabetes (OR 2.01 [1.65-2.46]) were independently associated with advanced fibrosis at baseline, whereas statin use was protective (OR 0.46 [0.35-0.60]; P < 0.0001 for all). The impact of BMI was greater in those without diabetes (P = 0.003). Diabetes was independently associated with less pronounced LSM improvement after viral eradication (P = 0.001) and in patients with advanced fibrosis was an independent predictor of the most frequent clinical events, namely de novo hepatocellular carcinoma (HCC; hazard ratio [HR] 2.09 [1.20-3.63]; P = 0.009) and cardiovascular events (HR 2.73 [1.16-6.43]; P = 0.021). Metformin showed a protective association against HCC (HR 0.32 [0.11-0.96]; P = 0.043), which was confirmed after adjustment for propensity score (P = 0.038). Diabetes diagnosis further refined HCC prediction in patients with compensated advanced chronic liver disease at high baseline risk (P = 0.024). Conclusion: Metabolic comorbidities were associated with advanced liver fibrosis at baseline, whereas statins were protective. In patients with advanced fibrosis, diabetes increased the risk of de novo HCC and of cardiovascular events. Optimization of metabolic comorbidities treatment by a multi-disciplinary management approach may improve cardiovascular and possibly liver-related outcomes., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background & Aims: In the direct-acting antiviral era, treatment of genotype-3 HCV (HCV-GT3) is still challenging. Real-life comparisons between recommended regimens, sofosbuvir (SOF)+daclatasvir (DAC), SOF/velpatasvir (VEL), glecaprevir/pibrentasvir (GLE/PIB), are scarce. We aimed at filling this data gap., Methods: Sustained virological response 12 weeks after treatment completion (SVR12) was assessed for all HCV-GT3 patients consecutively treated within the Lombardia web-based Navigatore HCV-Network; differences in SVR12 across regimens were evaluated by logistic regression., Results: Of the 2082 subjects with HCV-GT3, 1544 were evaluable for comparisons between regimens: SOF + DAC (1023, 66.2%), SOF/VEL (369, 23.9%), GLE/PIB (152, 9.8%). Patients treated with former regimens were more frequently male, cirrhotic, HIV-positive, pretreated, used ribavirin in their regimen, and had lower baseline HCV-RNA. SVR12 was similar across groups: 94.8% in SOF + DAC, 97.6% in SOF/VEL, 96.7% in GLE/PIB (P = .065). At univariate analysis, SVR12 was associated with female gender (97.9% vs 94.8%, P = .007) and lower median pretreatment Log 10 HCV-RNA (5.87 vs 6.20, P = .001). At multivariate logistic regression analysis, treatment with SOF/VEL was associated with a higher likelihood of SVR12 than SOF + DAC, but only in the absence of ribavirin (98% vs 90.3%). Female gender and lower pretreatment HCV-RNA were independently associated with SVR12., Conclusions: In a large real-life setting of HCV-GT3-infected patients with a high proportion of cirrhosis, the success rate was remarkable. The slight advantage of SOF/VEL on SOF + DAC was significant only without ribavirin. The current prescription shift towards novel regimens (ie SOF/VEL and GLE/PIB) in easier-to-treat patients allows ribavirin-free and shorter schedules without mining SVR12 in this <> genotype., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The addition of the direct renin inhibitor aliskiren is demonstrated to improve blood pressure (BP) control rate and reduce progression of organ damage in treated hypertensive patients in clinical trials with a relatively short follow-up period., Aim: The objective of this study was to assess the effectiveness, safety and tolerability of aliskiren as an add-on antihypertensive therapy in high-risk, treated, hypertensive patients, who were not controlled with concomitant treatment with at least two antihypertensive drugs under 'real-life' conditions, during a planned observation and treatment period of at least 12 months in Italy., Methods: Clinical data were derived from medical databases of treated, uncontrolled, hypertensive patients followed by specialized physicians operating in different clinical settings (hospital divisions or outpatient clinics) in Italy. Aliskiren was added to stable antihypertensive treatment, including at least two drug classes (independently of class or dosage) and unable to achieve BP control. Follow-up visits for measuring clinic BP levels and collecting data on drug safety and tolerability were planned at time intervals of 1, 6 and 12 months. At each predefined follow-up visit, aliskiren could be up-titrated from 150 to 300 mg daily if BP control was not achieved., Results: From May 2009 to June 2011, a total of 1186 treated, uncontrolled, hypertensive patients (46.3% female, aged 65.2 ± 11.7 years, mean duration of hypertension 13.2 ± 9.3 years, mean clinic BP levels 156.5 ± 15.9/90.3 ± 9.5 mmHg) were enrolled. Systolic and diastolic BP levels were 141.1/82.4, 134.9/79.8 and 133.6/78.9 mmHg at 1-, 6- and 12-month follow-up visits, respectively (p < 0.0001 vs baseline for all comparisons). These effects were consistent in all predefined subgroups, including those with left ventricular hypertrophy, renal disease, diabetes mellitus, coronary artery disease or cerebrovascular disease. Reduced levels of microalbuminuria were also reported, without affecting other renal and electrolyte parameters. Overall, compliance to study medication was high (93.0%), with a very low proportion of patients experiencing adverse events leading to drug discontinuation (3.6%)., Conclusions: In this observational, prospective, open-label, multicentre study, we reported the 12-month clinical effectiveness, safety and tolerability of adding aliskiren to treated, uncontrolled, hypertensive patients in a 'real-life' setting in Italy. This strategy leads to a significantly improved BP control rate and low incidence of drug-related side effects or discontinuations.

The objective of this study was to evaluate the analytical performance of the Abbott ARCHITECT Cyclosporine (CsA) immunoassay in 7 clinical laboratories in comparison to liquid chromatography/tandem mass spectrometry (LC/MS/MS), Abbott TDx, Cobas Integra 800, and the Dade Dimension Xpand immunoassay. The ARCHITECT assay uses a whole blood specimen, a pretreatment step with organic reagents to precipitate proteins and extract the drug, followed by a 2-step automated immunoassay with magnetic microparticles coated with anti-CsA antibody and an acridinium-CsA tracer. Imprecision testing at the 7 evaluation sites gave a range of total % coefficient of variations of 7.5%-12.2% at 87.5 ng/mL, 6.6%-14.3% at 411 ng/mL, and 5.2%-10.7% at 916 ng/mL. The lower limit of quantification ranged from 12 to 20 ng/mL. Purified CsA metabolites AM1, AM1c, AM4N, AM9, and AM19 were tested in whole blood by the ARCHITECT assay and showed minimal cross-reactivity at all 7 sites. In particular, AM1 and AM9 cross-reactivity in the ARCHITECT assay, ranged from -2.5% to 0.2% and -0.8% to 2.2%, respectively, and was significantly lower than for the TDx assay, in which the values were 3.2% and 16.1%, respectively. Comparable testing of metabolites in the Dade Dimension Xpand assay at 2 evaluation sites showed cross-reactivity to AM4N (6.4% and 6.8%) and AM9 (2.6% and 3.6%) and testing on the Roche Integra 800 showed cross-reactivity to AM1c (2.4%), AM9 (10.7%), and AM19 (2.8%). Cyclosporine International Proficiency Testing Scheme samples, consisting of both pooled specimens from patients receiving CsA therapy as well as whole-blood specimens supplemented with CsA, were tested by the ARCHITECT assay at 6 sites and showed an average bias of -24 to -58 ng/mL versus LC/MSMS CsA and -2 to -37 ng/mL versus AxSYM CsA. Studies were performed with the ARCHITECT CsA assay on patient specimens with the following results: ARCHITECT CsA assay versus LC/MSMS, average bias of 31 ng/mL; ARCHITECT versus the Dade Dimension assay (4 sites), average biases of -7 to -228 ng/mL; ARCHITECT versus AxSYM and TDx, average biases of -4 and -53 ng/mL, respectively. Spearman correlation coefficients were >or=0.89. The ARCHITECT CsA assay has significantly reduced CsA metabolite interference relative to other immunoassays and is a convenient and sensitive semiautomated method to measure CsA in whole blood.

Different types of stem cells have a role in liver regeneration or fibrous repair during and after several liver diseases. Otherwise, the origin of hepatic and/or extra-hepatic stem cells in reactive liver repopulation is under controversy. The ability of the human body to self-repair and replace the cells and tissues of some organs is often evident. It has been estimated that complete renewal of liver tissue takes place in about a year. Replacement of lost liver tissues is accomplished by proliferation of mature hepatocytes, hepatic oval stem cells differentiation, and sinusoidal cells as support. Hepatic oval cells display a distinct phenotype and have been shown to be a bipotential progenitor of two types of epithelial cells found in the liver, hepatocytes, and bile ductular cells. In gastroenterology and hepatology, the first attempts to translate stem cell basic research into novel therapeutic strategies have been made for the treatment of several disorders, such as inflammatory bowel diseases, diabetes mellitus, celiachy, and acute or chronic hepatopaties. In the future, pluripotent plasticity of stem cells will open a variety of clinical application strategies for the treatment of tissue injuries, degenerated organs. The promise of liver stem cells lie in their potential to provide a continuous and readily available source of liver cells that can be used for gene therapy, cell transplant, bio-artificial liver-assisted devices, drug toxicology testing, and use as an in vitro model to understand the developmental biology of the liver., (Copyright (c) 2010 John Wiley & Sons, Ltd.)

Objective: This study evaluated a new chemiluminescent magnetic microparticle immunoassay (CMIA) for sirolimus on the ARCHITECT analyzer., Design and Methods: Patient and laboratory proficiency samples were tested at three European sites and one site in the United States., Results: The CMIA total %CV's were all <8% and the Limit of Quantification (LOQ) was <1.52 ng/mL across the four sites. It cross-reacts to sirolimus metabolites F4 and F5 and showed no hematocrit interference over a range of 25% to 55%. Patient specimen correlations to three LC/MS/MS methods gave R>or=0.91 at three sites and mean biases of 14%, 25% and 39%. CMIA patient specimen correlations to the Abbott IMx gave R>or=0.94 at 2 sites and mean biases of 5.4% and 6.9%., Conclusions: CMIA is a precise and sensitive immunoassay method without hematocrit interference. It correlates well to both LC/MS/MS and immunoassay results, but shows an expected positive bias to LC/MS/MS.

The objective of this study was to evaluate the analytical performance of the Abbott ARCHITECT Tacrolimus immunoassay. Proficiency panels and specimens from a population of organ transplant recipients were analyzed in 6 clinical laboratories in Europe and the United States, and the results were compared with other methods. The ARCHITECT assay requires a whole blood specimen pretreatment step with methanol/zinc sulfate to precipitate protein and extract the drug, followed by a 30-minute immunoassay using anti-tacrolimus antibody-coated paramagnetic microparticles and an acridinium-tacrolimus tracer. The assay was free from hematocrit interference in the range 25%-55% and from interference by extremes of cholesterol, triglycerides, bilirubin, total protein, and uric acid. The total percent of coefficient of variations of the assay were 4.9%-7.6% at 3 ng/mL, 2.9%-4.6% at 8.6 ng/mL, and 3.1%-8.2% at 15.5 ng/mL. Limit of detection was < or =0.5 ng/mL and limit of quantification (LOQ) ranged from 0.69 to 1.07 ng/mL across the 6 sites (based on the upper 95% confidence interval concentrations). The 2007 European Consensus Conference on Tacrolimus Optimization recommended the use of assay methods with an LOQ around 1 ng/mL, based upon the need to measure trough tacrolimus blood concentrations precisely down to 3 ng/mL during low-dose tacrolimus regimens. Tacrolimus International Proficiency Testing Scheme samples were measured by the ARCHITECT immunoassay at 5 sites and showed an average bias of -0.28 to +0.85 ng/mL versus IMx Tacrolimus II immunoassay historical values and -0.21 to +0.68 ng/mL versus liquid chromatography/tandem mass spectrometry (LC-MSMS) Tacrolimus historical values. Method comparison studies were performed with the ARCHITECT Tacrolimus immunoassay on patient specimens with the following results: ARCHITECT Tacrolimus assay versus the Abbott IMx Tacrolimus II immunoassay (4 sites) yielded average biases between -0.94 and +0.26 ng/mL; ARCHITECT assay versus the Dade Dimension Tacrolimus immunoassay (2 sites) yielded average biases of -0.46 and +0.11 ng/mL; and ARCHITECT assay versus LC-MSMS methods at 2 sites yielded average biases of +0.51 and +1.63 ng/mL. Spearman correlation coefficients were >/=0.90 on all method comparisons. The ARCHITECT Tacrolimus assay is a semiautomated, robust, and highly sensitive immunoassay, representing an alternative approach for laboratories not equipped with LC-MSMS, and meets the 1 ng/mL recommendation of LOQ by the European Consensus Conference on Tacrolimus Optimization.

Background: Chromogranin A (CgA) is the neuroendocrine (NE) marker most frequently employed in detecting NE differentiation in prostate cancer patients, either at the tissue level or in the general circulation., Methods: We compared the two commercially CgA assay kits in detecting NE differentiation, in benign hyperplasia (BPH) or prostate cancer (PC) patients (pts). 170 pts with BPH, 107 with BPH+inflammation, and 136 PC pts entered the study. CgA was measured in each patient with the immunoradiometric assay (IRMA) and with the enzyme-linked immunoabsorbent assay (ELISA)., Results: A moderate relationship was found between CgA measured with IRMA and ELISA in the whole population (Spearman's R=0.65, p<0.05), in BPH pts (R=0.76, p<0.05), in BPH+inflammation pts (R=0.53, p<0.05) and in PC pts (R=0.60, p<0.05). Twenty-two out of 62 pts (35.4%) with elevated ELISA CgA did not have increased IRMA CgA; by contrast, 21/61 pts (34.4%) with elevated IRMA CgA were not recognized as abnormal by the ELISA kit., Conclusions: CgA measured by the two assays provided a significant discordance rate, suggesting that the two kits might elicit different information.

It is well known that change in apoptosis may modulate the natural story of illness, and that many drugs may act through modulation of apoptosis, but the role of steroids in acting through apoptosis in different settings, including renal diseases, has still to be elucidated. We studied the in vivo effects of steroids by oral assumption (10 to 25 mg/deltacortene) or by intravenous pulses (300 to 1000 mg/dose) on apoptosis and cellular subsets of peripheral lymphocytes, by evaluating DNA-fragmentation and lymphocyte subsets in 79 subjects: 22 controls and 57 patients with various renal diseases (25 Lupus-GN, 19 membranous-GN (MGN), 6 rapidly progressive-GN (RPGN), 2 acute interstitial nephritis (AIN), 5 on chronic dialysis. Baseline apoptosis was present in 1/22 (4.5%) of controls, 3/25 (12%) SLE, 2/6 (33.3%) RPGN and 10/19 (52.6%) MGN. A significant decrease in CD3+CD8+ cell count and a significant increase of the CD3+CD4/CD3+CD8+ ratio were found in apoptosis-positive subjects. DNA fragmentation did not change after oral steroids, paralleling a 22 to 32% decrease in total lymphocytes. Following intravenous methylprednisolone pulses, a deeper drop of all lymphocyte subsets was observed, while DNA fragmentation turned from present to absent in 2 MGN, but not in 2 RPGN, and from absent to present in 1 ARF and 1 SLE, independently of the dosage. We demonstrated that the presence of apoptosis in renal diseases is associated with decreased CD3+CD8+ cell count. Furthermore, steroid intravenous pulses, besides inducing a profound decrease in lymphocyte subsets, do exert a dual effect on baseline leukocyte apoptosis, eventually leading to a reversal of baseline patterns, either turning from negative to positive or from positive to negative. Oral steroid therapy did not influence baseline apoptosis.

Background: Parathyroid hormone (PTH) has important applications in the nephrological clinical practice. Because assays of Intact PTH (I-PTH) are liable to interferences by N-truncated fragments, a novel method for whole-(1-84) PTH has been proposed. This study is aimed at comparing the latter with some of the previous I-PTH assays. For each method the results are referred to pertinent markers of mineral metabolism., Methods: We enrolled 171 subjects, including 56 healthy controls (C), 65 calcium stone- formers (CaSF), 40 haemodialysis patients (HD), 10 with primary hyperparathyroidism (PHP). On blood samples we measured: I-PTH by four methods (N-Tact, Advantage, Elecsys, Scantibodies), whole-(1-84) PTH, defined as CAP (Cyclase Activating PTH), total and ionised calcium, phosphate, vitamin D, osteocalcin and Crosslaps. The difference between I-PTH and CAP Scantibodies is defined as CIP (Cyclase Inhibiting PTH)., Results: Despite relating to each other (r>0.97) PTH values varied remarkably among methods. For all methods, the reference intervals differed from those provided by the producer. Assuming these new ranges, 10 CaSF had over-range values not always associated with abnormalities of mineral metabolism. One of the PHP patients was normal for I-PTH with 2/4 methods. In HD the differences among methods were even greater, there were inverse (p<0.05) and direct (p<0.001) relationships with ionised calcium and osteocalcin-crosslaps, respectively. The CAP/CIP ratio was lower in low bone turnover patients, but the two subgroups widely overlapped., Conclusions: This study indicates that the reliability of I-PTH assays is still unsatisfactory, and none of the four methods emerged as the best. Assay for CAP only improves diagnostic efficiency, whereas the CAP/CIP ratio does not exhibit powerful discriminating capacity. Our suggestion is that each Centre should establish its own reference ranges. PTH assay should always be coupled with measurements of other markers of mineral metabolism as well as renal function.

Background and Aims: Duration of gluten exposure seems to predispose adolescents with coeliac disease to autoimmune diseases. In a retrospective cohort study, we assessed the relationship between autoimmune disorders and actual gluten exposure in patients in whom coeliac disease was diagnosed in adult life (> or = 16 years)., Methods: We screened for the presence of autoimmunity in 605 controls (16-84 years) and 422 patients (16-84 years), all of whom had been on gluten withdrawal for at least one year (median follow up 9.5 years). A logistic regression analysis, setting the prevalence of autoimmunity as the dependent variable, was employed to control for independent covariates as predictors of the risk of autoimmunity., Results: The prevalence of autoimmunity was threefold higher (p < 0.00001) in patients than in controls. Mean duration of gluten exposure was 31.2 and 32.6 years for patients with or without autoimmunity. Logistic regression showed that increased age at diagnosis of coeliac disease was related to the prevalence of autoimmune disease while "actual gluten exposure" which takes into account diet compliance, follow up, and age at diagnosis of autoimmune disorders were not predictive for the risk of developing autoimmune diseases (odds ratio 0.82 per year)., Conclusion: The prevalence of autoimmune diseases in patients with a late coeliac disease diagnosis does not correlate with duration of gluten intake. Early exposure to gluten may modify the immunological response. Gluten withdrawal does not protect patients with a late diagnosis from autoimmune diseases.

Background: The study was aimed at comparing the diagnostic accuracy of the quantitative bladder tumor antigen (BTA) TRAK immunoassay with exfoliative urine cytology in the detection of primary and recurrent bladder cancer., Methods: The analysis was carried out on 194 high risk patients undergoing a diagnostic cystoscopy, 279 patients with previous history of transitional cell carcinoma awaiting a follow-up cystoscopy, and 45 healthy controls. Urine cytology was performed by a skilled cytopathologist on three consecutive samples., Results: BTA TRAK values resulted significantly higher in tumor positive cases than in absence of bladder tumor for both groups of patients. Non neoplastic urothelial diseases as well as the absence of mucosal abnormalities were associated with a marked increase in BTA TRAK levels with respect to the control group. Overall sensitivity and specificity was 63 and 63% for BTA TRAK (cut-off 34 U/ml), and 68.3 and 73.4% for urine cytology, respectively. The diagnostic advantage of urine cytology was maintained when patients were stratified by tumor grade., Conclusions: The clinical performance of the BTA TRAK in the detection of primary or recurrent bladder cancer is acceptable and reproducible as shown by similar results with previous reports, although urine cytology performed on three samples showed the highest sensitivity and specificity.

Hyperthyroidism is associated with enhanced osteoblastic and osteoclastic activity, and patients frequently have low bone mineral density and high bone turnover. The aim of this study was to examine the bone formation and resorption markers trend in 12 female patients, before and after normalization of thyroid activity. The following measurements were made at baseline and 1 and 6 months after hormone normalization induced by methimazole treatment: total alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), collagen type C-terminal propeptide (PICP), osteocalcin (BGP), telopeptide (ICTP), urinary-hydroxyproline/urinary creatinine (uOHP/uCreat), urinary calcium/urinary creatinine (uCa/uCreat) and deoxypyridinoline crosslinks (D-Pyr). Compared with controls, all of these parameters were significantly increased (ALP p = 0.014; BALP p = 0.0001; PICP p = 0.013; BGP p = 0.009; ICTP p = 0.0001; uOHP/uCreat p = 0.002; uCa/uCreat p = 0.044; crosslinks p = 0.0001). After treatment the values of ALP, BALP and PICP in hyperthyroid patients showed an initial slight increase and then a significant downwards trend (ALP p = 0.008, BAP p = 0.001, PICP p = 0.026). Furthermore, resorption markers showed a significant decrease (uOHP/ uCreat p < 0.005 and D-Pyr p < 0.008). As regards lumbar BMD patients, measurements were significantly reduced in comparison with the control group (p = 0.005). Six months after serum thyroid hormones level normalization, we observed a significant increase (p=0.014 vs baseline). Both neoformation and resorption markers are useful to assess pathological bone turnover and bone involvement in hyperthyroidism. They could also be employed to monitor the effect of antithyroid treatment on bone and to indicate if bone antiresorption therapy should be considered.

Objective: Percent free prostate-specific antigen (PSA) is a promising tool for prostate cancer (CaP) diagnosis. However, its diagnostic performances have not yet been established. The present study was carried out with the aim of evaluating percent free PSA in the most favourable analytical conditions., Materials and Methods: Eighty-eight patients affected by newly diagnosed, untreated, primary CaP, and 169 cases with biopsy-confirmed, untreated, benign prostatic hypertrophy (BPH) were prospectively enrolled. Abbott AxSYM total and free PSA were measured by the same technician using the same instrument and the same reagent batch., Results: Percent free PSA was more effective than total PSA in differential diagnosis between CaP and BPH in every evaluated dose range of total PSA. In cases with total PSA >4 microg/l, percent free PSA could have reduced by about 50% the rate of unnecessary biopsies with a probably still acceptable 93% cancer detection rate. The likelihood of CaP after the determination of percent free PSA was in fact higher than 50% using cut-off points which provide low sensitivity values (i.e. 58% in men aged 50-59 years)., Conclusions: Percent free PSA is superior to total PSA in distinguishing primary CaP from BPH in patients with total PSA between 2 and 30 microg/l and in reducing the rate of unnecessary biopsies in men with total PSA higher than 4 microg/l. However, percent free PSA should be cautiously interpreted in decision making in individual patients since post-test probability is relatively low in men aged 50-70 years.

The usefulness of intraoperative parathyroid hormone (PTH) monitoring has been extensively documented in primary hyperparathyroidism (HPT), whereas few data have been published on its use in reoperations or in secondary and tertiary HPT. We report our initial experience with a rapid (12 min response) PTH immunochemiluminometric assay performed in the operating room during surgery in 12 patients with primary HPT, 16 end-stage renal disease patients with secondary HPT and five kidney transplanted subjects with tertiary HPT. Blood samples were taken at baseline, within 10 min after resection and subsequently at various intervals whenever needed. The mean PTH levels before and after parathyroidectomy were 230.5 pg/mL (range 69-842) and 47.3 pg/mL (range 5-184), respectively, in primary HPT, 855.0 pg/mL (416-1655) and 202.2 pg/mL (53-440) in secondary HPT, and 205.6 pg/mL (116-301) and 45.4 pg/mL (18-97) in tertiary HPT. All patients but one had a significant percentage decline from pre-excision values (mean 76.9%, 76.0%, and 76.1% in primary, secondary and tertiary HPT, respectively). While a reduction of more than 50% was observed in 30 out of 33 patients after the first intraoperative sampling, additional measurements were performed in 10 cases. On-site PTH monitoring with this user-friendly and reliable system has proved helpful in targeting PTH tests to give the surgeon a rapid and accurate assessment of the intervention. The development of optimal PTH sequence strategies with decision-focused analytical and clinical limits will improve the efficacy of "point-of-care" PTH assay and resource utilization.

Purpose: Both BTA TRAK and NMP22 urine concentrations have shown a sensitivity superior to urine cytology in the detection of bladder cancer. We compared these tumor markers with urine cytology performed on 3 consecutive samples and evaluated by an expert cytopathologist., Patients and Methods: The investigations were conducted on 94 patients undergoing a diagnostic cystoscopy for a high suspicion of bladder cancer (group 1) and on 102 patients with previous history of transitional cell carcinoma awaiting a follow-up cystoscopy (group 2). Biopsy specimens were obtained also from tumor negative patients. Immunoassays for BTA TRAK and NMP22 were carried out according to standard methods. The choice of the cut-off was based on the ground of sensitivity and specificity curves intersection. Urine cytology results were expressed as positive, negative and 'dubious'., Results: Overall sensitivity was 56% for NMP22 (cut-off 11 U/ml) and 57% for BTA TRAK (cut-off 60 U/ml). When dubious results were considered as positive cases, urine cytology achieved a sensitivity of 73.3%. Assuming dubious cases as negative results, urine cytology sensitivity resulted 59.3%. When the 2 groups of patients were evaluated separately with different cut-off, there was no significant gain in sensitivity for BTA TRAK and NMP22 over urine cytology., Conclusions: Urine cytology performed on 3 samples showed the highest sensitivity and specificity. The diagnostic advantage of urine cytology over BTA TRAK and NMP22 was maintained when patients were stratified by tumor grade., (Copyright 2000 S. Karger AG, Basel)

Objectives: To evaluate the impact of a 1-year gluten-free diet on bone metabolism and nutritional status in coeliac disease., Methods: Bone mineral density, serum indices of bone remodelling, clinical and biochemical nutritional assessment were evaluated in 86 consecutive newly-diagnosed, biopsy proven, coeliac disease patients (untreated). A complete reevaluation, including intestinal biopsy, was repeated within 1 year of dietary treatment (treated)., Results: Untreated: according to WHO criteria, 34% of patients had a normal bone mineral density, 40% had osteopenia and 26% osteoporosis. Between males and females there were no statistical differences in bone metabolism or in most of the nutritional indices, while, between fertile and postmenopausal women, bone mineral density and several bone metabolism markers were significantly different. Compared to subjects with a normal bone mineral density, osteopenics had higher bone specific alkaline phosphatase (BAP) and Bone-Gla-protein (BGP) values. In patients with a concomitant BAP increase and 25OH vitamin D serum level reduction, bone mineral density and several bone turnover markers were statistically different compared to patients without such a serological pattern. Treated: notwithstanding intestinal biopsy which showed a mucosal recovery in only 57%, gluten-free diet led, even in postmenopausal women, to a significant improvement in bone mineral density, bone metabolism and nutrition, except for folic acid, albumin and pre-albumin serum levels which persisted as abnormal in patients with obdurate mucosal impairment., Conclusions: Coeliac disease patients are at high risk for developing a low bone mineral density and bone turnover impairment. A gluten-free diet can improve this situation even in postmenopausal women and in patients with incomplete mucosal recovery.

Background: No studies about correlation between post-operative half-life of tumor markers and prognosis in lung cancer exist in literature. The aim of our study was to determine the half-life of CEA, TPA, NSE and CYFRA 21-1 in postoperative period after surgery of bronchogenic carcinoma, and to correlate it with the prognosis and survival of the patients., Methods: From March 1997 to March 1998, 35 patients with bronchogenic carcinoma were studied (29 males and 6 females, mean age 64.9 years, range 51-77 and 61.0 years, range 52-77 respectively). The mean follow-up for males was 125.70 days (from 30 to 198) after surgery and for females 125.79 days (from 30 to 180). CEA and NSE were tested by immunoenzymatic automated method, whereas TPA and CYFRA 21-1 were assayed by immunoradiometric techniques. For each patient both the dismission curve and the half-life of considered markers were calculated during follow-up., Results: A statistically significant difference was found for preoperative values of TPA (p = 0.027) and CYFRA 21-1 (p = 0.025) between SqCLC and adenocarcinoma. The preoperative levels of markers were higher in patients who would develop a relapse, even if statistical significance was not reached. CEA half-life was of 1.4 days, while in patients with a history of relapse or metastatic spreading was 4.5 days. No differences were revealed concerning CYFRA 21-1 between the two groups., Conclusions: Seriate determination of some markers (CEA and TPA in particular) during postoperative follow-up after surgery for bronchogenic carcinomas can be a useful prognostic tool. Longer follow-up would provide additional informations in order to determine individual predictive threshold between poor and good prognosis.

Autoimmune events, although rarely reported during interferon beta-1b (IFNB) treatment of relapsing-remitting (RR) multiple sclerosis (MS), may be more frequent than expected due to the many immunologic abnormalities associated with this disease. We report the prospective two-year follow-up of autoimmune events in 40 RR MS patients treated with IFNB and in 21 untreated MS controls. Thyroid and liver function and serum level of 12 autoantibodies (autoAbs) against organ- (thyroid, gastric, pancreatic) and non-organ-specific antigens were serially monitored. In contrast to control patients, autoAbs (anti-nuclear, -smooth muscle or -thyroid antigens) were detected in 13 IFNB-treated patients, and these were associated with thyroid or liver function alteration in many cases. Persistent autoimmune thyroid dysfunction occurred in three IFNB-treated patients, all of whom were women with a familial history of thyroid disease or baseline anti-thyroid autoAb positivity. For improvement of the MS relapse rate, thyroid dysfunction was adequately treated without stopping IFNB. Liver function alteration (17 IFNB-treated patients, associated with non-organ-specific autoAbs in four) was transient and did not require IFNB treatment to be stopped, with the exception of one patient who was already suffering from a drug-induced hepatopathy at baseline. During the IFNB treatment of MS, several autoimmune events may occur, indicating that thyroid and liver function and autoAbs must be carefully monitored.

Although general consensus exists that percent free prostate-specific antigen (PSA) is superior to total immunoreactive PSA for prostate cancer (CaP) detection, its diagnostic performance is not yet well established. Analytical problems may account for difficulties in evaluating percent free PSA because the free PSA concentration is substantially lower than that of total PSA. The aim of the present study was to establish the diagnostic performances of the IMMULITE percent free PSA assay from Diagnostics Products Corp. under experimental conditions optimized to minimize analytical variability. Eighty-five patients with untreated primary CaP and 261 with untreated benign prostate hypertrophy (BPH) were prospectively enrolled. The Diagnostics Products IMMULITE total (Third Generation) and free PSA were measured by the same technician, using the same instrument and the same reagent batch. We calculated the post-test probability to express how the likelihood of the diagnosis of CaP changed after the percent free PSA was determined. Areas under the ROC curves of percent free PSA were better than those of total PSA in every evaluated range of total PSA. The percent free PSA could have reduced the rate of unnecessary biopsies by 47% in patients with total PSA >/=4 microg/L with only 3.8% false-negative results. The post-test probability of percent free PSA was, however, <50% in men 50-70 years of age, using cutoff points providing sensitivity from 99% to 80%. Percent free PSA is superior to total PSA in distinguishing primary CaP from BPH in patients with total PSA between 2 and 30 microg/L. In men with low total PSA, the diagnostic performance of the percent free PSA assay may be optimized by controlling methodological variability. The percent free PSA assay is effective in reducing the rate of unnecessary biopsies in men with total PSA >4 microg/L. However, the post-test probability provided by percent free PSA is relatively low in asymptomatic patients 50-70 years of age.

We have used cyclosporin to treat patients with acute steroid-resistant ulcerative colitis since the beginning of 1991. Of the 55 patients so far elected for treatment, 40 received the drug intravenously at 2 mg/kg/day for 14 days, with the responders being maintained on traditional soft-gelatin-capsule cyclosporin at a dose of 6-8 mg/kg/day for 6 months; the remaining 15 received oral microemulsion cyclosporin, 5 mg/kg/day, for 3 months. The doses were titrated to ensure whole-blood drug concentrations of 60-240 ng/ml, with levels of approximately 200 ng/ml being attained by both regimens. One-hundred percent of the patients receiving oral microemulsion cyclosporin and 65% of those receiving the intravenous regimen achieved a short-term response (p = 0.011). Both the responder subsets received additional azathioprine and relapsed on treatment with the same frequency of 40%. However, 17% of the patients who received intravenous cyclosporin developed major toxicity (including one fatality), whereas no major toxicity was observed in the oral microemulsion cyclosporin group. The microemulsion formulation was therefore more effective than intravenous cyclosporin in achieving the short-term remission of steroid-unresponsive ulcerative colitis. As the maintenance drug, it led to the same frequency of disease relapse as traditional oral cyclosporin. However, because it did not involve invasive in-hospital procedures or cause major toxicity, it was more efficient than the combination of the intravenous and traditional oral drug.

Unlabelled: The percent free PSA value is a promising diagnostic tool for prostate cancer. However, its actual role has not yet been established because of the widely diverging sensitivity and specificity values. This could depend at least in part on analytical difficulties, since the free PSA concentration is much lower than that of total PSA. The present investigation was designed to evaluate the diagnostic performance of the percent free PSA in the most favorable analytical conditions., Materials and Methods: 81 patients affected by newly diagnosed, untreated primary prostate cancer (CaP) and 239 patients with untreated benign prostatic hyperplasia (BPH) were prospectively enrolled. Hybritech total and free PSA were measured by the same technician using the same reagent batch., Results: The percent free PSA was not significantly associated with age, tumor stage, gland volume, Gleason score, and total PSA, nor was it significantly affected by concomitant prostatic complications either in CaP or BPH. Percent free PSA was more effective than total PSA in the differential diagnosis between CaP and BPH in every evaluated dose range of total PSA. Percent free PSA determination could have reduced the rate of unnecessary biopsies in cases with total PSA > or = 4 ng/mL and > or = 10 ng/mL (avoided biopsies 61% and 63%, respectively). The post-test probability of the disease, which represents the proportion of patients with a positive percent free PSA value who have the disease, was, however, relatively low in younger patients with total PSA within the normal range., Conclusions: The diagnostic performance of the percent free PSA value is enhanced when the methodological variability is reduced, particularly in men with low total PSA. Percent free PSA is superior to total PSA in distinguishing primary CaP from BPH in patients with total PSA between 2 and 30 ng/mL. The percent free PSA value is effective in reducing the rate of unnecessary biopsies in men with total PSA higher than 4 or 10 ng/mL. However, due to its relatively low post-test probability, the percent free PSA value should be interpreted with caution in the decision-making related to individual patients and should be used in association with clinical and instrumental evaluation of the patient.

Background: Few data exist on the prevalence of genetic hemochromatosis among diabetic patients., Objective: To compare the prevalence of genetic hemochromatosis in diabetic patients and a matched control group and to evaluate the accuracy of iron-related indexes in detecting hemochromatosis., Design: Cross-sectional study., Setting: Diabetes clinics of four hospitals in northern Italy., Patients: 894 diabetic patients (117 with type 1 diabetes and 777 with type 2 diabetes) and 467 matched controls., Measurements: Transferrin saturation and serum ferritin levels were measured in all study participants. After secondary iron overload was excluded as the cause of persistently elevated transferrin saturation and serum ferritin levels, liver biopsy was performed and siderosis was estimated semiquantitatively and quantitatively. A hepatic iron index greater than 1.9 was considered diagnostic for hemochromatosis., Results: Hemochromatosis was diagnosed in 12 patients with type 2 diabetes (prevalence, 1.34% [95% CI, 0.7% to 2.3%]) and 1 control (prevalence, 0.2% [CI, 0.1% to 1.4%]; P = 0.032). The odds ratio of hemochromatosis in association with diabetes was 6.3 (CI, 1.1 to 37.7). Measurement of transferrin saturation was the most sensitive test for hemochromatosis., Conclusions: Genetic hemochromatosis is frequently not diagnosed in patients with diabetes, although it is a hallmark of the disease. Screening for hemochromatosis could be beneficial for patients with diabetes.

We developed a modified anti-acetylcholine receptor (AChR) antibody (Ab) assay based on a radioreceptor assay and a calibration curve. We compared the analytical and clinical performances of this modified assay with those of the conventional anti-AChR Ab radioreceptor assay. Serum specimens were from patients with myasthenia gravis (MG) (n = 156) and from control subjects (n = 106). The modified assay demonstrated lower within-assay (4.0-6.6%) and between-assay (5.3-7.8%) CVs, greater linearity, lower cost, and shorter assay time than the conventional method. ROC curve analysis indicated almost identical specificity and sensitivity (> 0.92) for these two anti-AChR Ab assays. The modified and conventional assays were also equivalent for blocking anti-AChR Ab assay. Moreover, the modified anti-AChR Ab assay, differently from the conventional assay, allowed us to reveal anti-AChR Ab concentration differences among different clinical grades of MG.

Aims and Background: The free/total (F/T) prostate-specific antigen (PSA) ratio is probably the most promising tool proposed to increase the specificity of PSA in the diagnosis of prostate cancer. The aim of the present study was to evaluate the clinical value of the F/T ratio in 138 patients with benign hyperplasia, 101 with untreated prostate cancer, and 176 apparently healthy men., Methods: We used a new immunometric assay of free PSA (FPSA-RIACT, CIS Diagnostici, Italy) which has shown good analytical performance; sample handling and storage under routine conditions did not affect the antigen stability., Results: The diagnostic efficiency of the F/T ratio was significantly better than that of total PSA. In patients with total PSA ranging from 4 to 10 ng/ml, at a specificity level of 95% total PSA showed a sensitivity of 7%, whereas the sensitivity of F/T increased to 70%. Using the F/T ratio as a decision tool in association with total PSA and considering all cases candidate to biopsy (total PSA greater than 3.79 ng/ml corresponding to the 95% level), we demonstrated a 35% reduction of total biopsies that would have been required on the basis of total PSA alone., Conclusions: The determination of the percentage of F/T serum PSA significantly improves the specificity of the marker, particularly in the 4-10 ng/ml dose range where unnecessary prostate biopsies can be reduced.

Chronic systemic high-dose recombinant alpha 2a-interferon (rIFNA) therapy reduces exacerbation rate and MRI signs of disease activity in relapsing/remitting multiple sclerosis (RR MS) patients. In order to clarify the possible mechanisms underlying the clinical efficacy of rIFNA in MS, several immunologic studies were performed as a part of a pilot clinical trial. Twenty RR MS patients were treated with 9 x 10(6) IU of rIFNA (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Cytokine production by cultured lymphocytes, major histocompatibility complex class II (MHC-II) antigen expression on cultured macrophages, peripheral blood (PB) and cerebrospinal fluid (CSF) lymphocyte phenotype, and IgG and beta 2 microglobulin levels were studied before therapy, after 6 months of therapy, and 6 months after stopping therapy. rIFNA therapy was associated with reduction of interferon-gamma and tumor necrosis factor-alpha production by PB lymphocytes (p < 0.04), and with slight, not significant, increase of transforming growth factor-beta 2 or interleukin (IL)-10 production. IL-4 was undetectable in the culture supernatants both before and after therapy. rIFNA therapy had no effect on macrophage MHC-II molecule expression. An increased percentage of CD8+, CD8+ high CD11b+ low, and CD3- CD16+ CD56+ cells, and of CD4+ absolute cell number was observed in CSF after rIFNA therapy. After rIFNA administration, IgG level significantly increased both systemically (p < 0.02) and intrathecally (p < 0.001). Serum beta 2 microglobulin level increased (p < 0.01), as well. Only 1 out of the 12 rIFNA treated patients developed neutralizing antibodies against rIFNA during therapy. Six months after stopping therapy all the immunologic changes returned to baseline. These data suggest that the beneficial effect of rIFNA therapy on MS disease activity is probably mediated by a downregulation of proinflammatory cytokine synthesis by PB lymphocytes rather than by macrophage MHC-II antigen expression. The immunologic effects of high-dose systemic rIFNA therapy are temporary and restricted to the period of drug administration.

Hyperthyroidism is a well documented cause of impaired bone turnover characterized by increased osteoblastic and osteoclastic activity, resulting in predominance of bone resorption and in decreased bone mass. Thyroid hormones can carry out a direct effect on osteoblasts which express specific receptors on their surface membrane; differently effect on osteoclast seems to be mediated by local factors, cytokynes released by activated osteoblasts or by bone monocytes cells. Interleukin 1 beta is the first purified cytokyne shown to have bone resorbing activity. In ten thyrotoxic female patients IL 1 beta in the cellular medium of the monocytes blood cells culture has been measured, compared to PYD/cr urinary excretion, and FT3, BGP serum levels, before and after thyrostatic treatment. Ten normal females were studied as control group. The results before treatment showed osteopenia in 20% (DEXA densitometry), increased values of FT3, BGP, IL 1 beta and PYD/cr in patients versus controls (p < 0.001). The thyrostatic therapy obtained normalization of IL 1 beta, PYD/cr, BGP, and FT3 levels. Our data demonstrate that increased thyroid hormone levels in vivo are associated to increased secretion of monocytes cytokynes in vitro and suggest that alterations in local production of bone acting cytokyne may underlie to thyrotoxic osteodistrophy.

The aim of this study was to assess the value of the monoethylglicinexylidide assay, a dynamic liver function test based on the determination of the serum concentration of lidocaine major metabolite, as a predictor of survival in cirrhosis. For this purpose, the predictive value of monoethylglicinexylidide was evaluated in comparison with the Pugh score, ascites, encephalopathy and a number of different biochemical parameters as collected from the prospective follow-up of 118 patients with cirrhosis. A stepwise regression analysis was performed on the variables of prognostic value according to the Cox model and with respect to 1-yr survival; because Pugh score and monoethylglicinexylidide were the sole variables selected, they were proved to supply independent prognostic information. The most reliable cutoff values for discrimination between death and survival were 25 ng/ml or less for monoethylglicinexylidide and less than 9 for the Pugh score. In 74 patients without overt signs of liver failure (i.e., Pugh < or = 9), monoethylglicinexylidide provided a wide range of results (i.e., 4 to 77 ng/ml), namely values ranging from very low to elevated. Of the 38 patients with satisfactory Pugh scores (< or = 9) but poor monoethylglicinexylidide values (< or = 25), 11 died during follow-up and 3 underwent liver transplantation, despite having shown no clinical signs of liver failure at entry. On the bases of discriminant levels, the monoethylglicinexylidide test is suitable for adoption as a reliable and sensitive indicator of survival in patients with cirrhosis because it supplies more accurate prognostic information compared with the Pugh score.(ABSTRACT TRUNCATED AT 250 WORDS)

It's known that some psychologic factors could be implicated in dyspepsia. Therefore, the psychologic aspects of 38 dyspeptic patients (17 males, 21 females, aged 18-65 years), who underwent digestive endoscopy, were evaluated by means of Rorschach and MMPI test. Patients with previous peptic ulcer history, with chronic ethanol or NSAID intake, operated on digestive tract and patients with behavioural problems were excluded. The results of psychological tests enhanced two main groups: anxiety patterns (17 patients--49%) and normal patterns (21 patients--55%). Endoscopic and histological findings moreover showed: "anxious" group--12 patients with chronic gastritis (HP+ 50%), 5 patients with normal endoscopy; "normal" group--16 patients with chronic gastritis (HP+ 87.5%), 5 patients with normal endoscopy. This study suggests that in about 50% of dyspeptic patients anxious pattern is present. Moreover chronic gastritis is more frequently associated to Helicobacter pylori in non-anxious patients.

Biocompatibility in hemodialysis is now regarded as a multifactorial problem and dialysate represents a main risk. Pyrogenic fractions mostly coming from gram-negative bacteria easily pass through dialysis membrane, either by backdiffusion or by backfiltration, and induce blood cell activation. To demonstrate the long-term efficiency of a 2 m2 polyamide ultrafilter in producing a pyrogen free solution, we used an experimental circuit ultrafiltering for 240 hours (500 ml/min) a bicarbonate dialysate contaminated (5 to 48 EU/ml) by a Pseudomonas aeruginosa filtrate. The efficiency was monitored by LAL-test and IL-1 PBMC so to detect not only lipid A containing endotoxins but also other cytokines inducing bacterial fractions. At the post-ultrafilter sampling port the LAL-test was < 0.005 to 0.034 EU/ml; IL-1 PBMC was below the detection limit (20 pg/ml) being 27 to 63 pg/ml at the pre-ultrafilter level. Polyamide ultrafiltration represents an efficient system to obtain an endotoxin-free dialysate and a single filter works up to 240 hours.

We have investigated which of the cytokines that are relevant in the in vitro growth of multiple myeloma (MM) malignant plasma cells are actually produced in vivo by MM patients. To this end, we have measured the levels of IL-1 beta, IL-3, IL-4, IL-6, IL-7, IL-8 and tumour necrosis factor-alpha (TNF-alpha) both in sera and in the supernatant of bone marrow (BM) stromal cell cultures from patients with MM and monoclonal gammopathy of undetermined significance (MGUS). The significance of our findings is three-fold. First, IL-6 and IL-8 are produced by MM BM stromal cells, while IL-1 beta, TNF-alpha, IL-4 and IL-7 are not. Second, IL-3 is the only cytokine consistently raised in serum samples: we have also detected low levels of serum IL-6 in a minority of cases, usually in advanced stage of the disease. Third, MM BM stromal cells are active IL-6 and IL-8 producers, while both normal and MGUS BM stromal cells are low producers, thus suggesting that in the BM of MM a number of environmental cells, that would normally be quiescent, are instead activated and that, in MM, activated BM stromal cells play an active role in supporting the progressive expansion of the B cell clone.

Although the aetiopathogenetic role of Helicobacter Pylori (HP) in duodenal ulcer and in chronic gastritis seems now well defined, we have not yet standardized therapeutic schedules to achieve disappearance of HP. This study was aimed at evaluating the efficacy of two different therapeutic schedules, colloidal bismuth alone [CB(1200 mg/day)], vs. association with amoxicillin [CB+A(3 g/day)] for six weeks, to clear HP from antral specimens in a cohort of dyspeptic patients. 49 consecutive patients (23 females, 26 males, mean age 47 years, range 22-69) with HP in gastric specimens, 30 suffering from chronic antral gastritis (CG) and 19 affected by duodenal ulcer (DU) were treated with CB (37 pts) or with CB+A (12 pts). DU patients were given also H2-blockers. These latter patients were all healed at the endoscopic control performed after therapy. 4 out of 13 DU patients (31%) treated with CB were found HP free. In 4 out of 6 DU patients (66%) treated with CB+A, HP was no more detectable. As for CG patients, 12 out of 24 (50%) were free from HP at control when treated with CB, while only 2 out of 6 (33%) when CB+A was administered. This study suggests that colloidal bismuth is more effective when administered associated with amoxicillin, but this concerns only DU patients. No relation between endoscopic healing of UD and HP presence was found.

Serum levels of soluble interleukin-2 receptors (IL2R) and of beta 2-microglobulin (beta 2M) were studied with the immunoenzymatic technique in 38 patients with primary glomerulonephritis (GN), in 10 patients with essential hypertension (EH) and in 30 healthy subjects. IL2R correlated with beta 2M (p < 0.05). IL2R and beta 2M were higher in patients with GN (p < 0.003, p < 0.001, respectively) and in patients with EH (p < 0.003, p < 0.01, respectively) than in healthy subjects. IL2R and beta 2M correlated with serum creatinine, but not with proteinuria. Our data would suggest the existence of lymphocyte activation in patients with GN. Only speculations can be advanced with regard to the observed increase in these parameters in EH patients.

Tumor Necrosis Factor (TNF) was determined in the serum of 72 lung carcinoma patients. Twenty-four healthy subjects younger than 50 years and 10 healthy subjects older than 70 years were considered as control group. TNF was also measured in 20 patients with stage I sarcoidosis and in 15 patients with pulmonary fibrosis. The marker was detected in 32% of cases in the neoplastic group, in 37.5% of disease confined to the chest and in 25% of advanced disease cases. A large proportion of TNF-positive samples was found in sarcoidosis (30%), and even larger in pulmonary fibrosis (66.6%). TNF was also present in healthy subjects older than 70 (40%). We conclude that TNF is not specific of malignancy, being demonstrable in other benign pulmonary diseases and even in the course of physiological aging.

Tumor necrosis factor (TNF) was detected, before and after dialysis, in sera from 69 patients and, at various times during dialysis, in 28 patients carefully selected for the absence of intercurrent illness. Blood samples were also sequentially collected for separation of monocytes, and cells were sonicated to detect intracellular TNF. Compared with serum levels obtained from 41 healthy subjects, basal TNF values of the unselected group of 69 patients were significantly higher (p < 0.01), independent of the dialyzer membrane. A significant increase in TNF levels by the end of dialysis was found only with Cuprophan (p < 0.01). In the selected group of 28 patients, no significant changes in TNF values were observed in sequential samples. However, a significant increase of intramonocyte TNF levels was found in Cuprophan patients (p < 0.025). Soluble interleukin-2 receptor (IL-2R) levels, measured in parallel in sera from unselected and selected patients, were found to be very much higher than healthy controls without significant changes during the dialysis procedure. While the diverse profiles of TNF obtained from differently selected patients suggest that mechanisms other than membrane biocompatibility play a role in the appearance of these low cytokine levels, the possible nature of uremic toxin for soluble IL-2R can be envisaged by detection in dialysis patients.

IgG and IgA immune complexes, mononuclear phagocytic system function, interleukin-2 (IL-2) production by peripheral blood lymphocytes (PBL), serum-soluble IL-2 receptors, tumor necrosis factor, beta 2-microglobulin and IL-1 beta, HLA-DNA polymorphisms, immuno-isoelectrofocusing, phenotype of PBL, lymphocyte cytotoxicity, activation of lymphokine-activated killer cells and natural killer cell activity were evaluated in 8 patients with tubular/fibrillary glomerulonephritis (GN). No common serologic, immunologic or immunogenetic features suggestive of plasma cell dyscrasias were found. No elements to state whether these GNs represent a new entity or just atypical forms of known GN were found.

The prevalence of cholelithiasis (gallstones or previous cholecystectomy) was evaluated in a series of 500 cirrhotic patients from Northern Italy (329 males and 171 females, mean age 58 +/- 11 (SD) yr and 61 +/- 10 yr, respectively). Cirrhosis was related to chronic alcohol abuse in 180 cases, non-A non-B (NANB) hepatitis in 160, hepatitis B virus (HBV) in 94 (including 38 with concomitant alcohol abuse), idiopathic hemochromatosis in 44, and miscellaneous causes in the remaining 22 (including 15 with primary biliary cirrhosis). One hundred and sixteen patients (23.2%) had gallstones, and 31 others (6.2%) had previously undergone cholecystectomy, with an overall prevalence of cholelithiasis of 29.4%. The frequency was similar in both sexes (91/329 males, 27.7% vs. 56/171 females, 32.7%; p = NS), showed a slight increase with age, and differed significantly according to etiology (p less than 0.05), with the highest prevalence in the miscellaneous group and the alcoholics (36.4% and 33.3%, respectively). No significant difference was found in the prevalence of cholelithiasis according to Child's A, B, or C class.

A delayed gastric emptying of solids but not of liquids has been recorded in diabetic patients with autonomic neuropathy by radionuclide labelled test meals. Acetaminophen test (rate of acetaminophen absorption after ingestion of 1500 mg of the drug) has been previously validated for quantitative indirect measurement of gastric emptying. In the present study we measured gastric emptying of liquid and solid meals by acetaminophen test in 14 insulin-requiring diabetic patients (7 with and 7 without autonomic neuropathy) and 14 healthy subjects, matched for age, sex, BMI and blood pressure. All values recorded after liquid meal were not significantly different in the three groups of subjects. After solid meal, the mean area under the plasma acetaminophen concentration-time curve was significantly lower in neuropathic diabetic patients vs control subjects (p less than 0.05), and the emptying index (peak time/peak plasma concentration ratio) was significantly higher in neuropathic diabetic patients vs non-neuropathic diabetic patients (p less than 0.01) and vs control subjects (p less than 0.05). These results confirm a delayed gastric emptying of solids but not of liquids in diabetic patients with autonomic neuropathy, and indicate that acetaminophen test may be proposed as simple, safe and noninvasive test for quantitative assessment of gastric emptying in diabetic patients.

In a series of 646 heroin addicts anti-HIV was detected in 428 (66.2%) and HBsAg in 53 (8.2%). Forty-eight (90.5%) of the latter had concomitant chronic HDV infection. Markers of past HBV infection were found in 481 (74.4%). The prevalence of anti-HIV was significantly higher in the 534 subjects with HBV markers than in the other 112 without markers (69.8% versus 49.1%, p less than 0.001). Of the 266 anti-HIV positive subjects followed for 3-48 months (median 12), nine progressed from no disease to persistent generalized lymphadenopathy (PGL), 52 from PGL to AIDS-related complex (ARC) or AIDS (30 and 22 cases respectively), and six from ARC to AIDS. Baseline T4 + cell count was significantly lower and reduction during follow-up significantly greater in heroin addicts with disease progression than in those without.

We enrolled 253 HIV-antibody positive heroin addicts without HIV-related disease (n = 81) or with persistent generalized lymphadenopathy (n = 172) in a prospective study to evaluate clinical progression to AIDS related complex (ARC) or AIDS and to identify factors of possible prognostic relevance. Follow-up lasted between 6 and 40 months (median 12 months). According to the non-parametric Cox's model the only significant (P less than 0.001) prognostic variable was T4+ cell count considered in three classes: greater than 800/microliters (no depletion), 400-800/microliters (moderate depletion) and less than 400/microliters (absolute depletion). Subjects with T4+ cell count of less than 400/microliters had a risk of developing ARC or AIDS that was 6.46 and 1.98 higher than those with values of greater than 800/microliters or between 400 and 800/microliters respectively. The estimated probability of progression to ARC or AIDS was 0.029, 0.056 and 0.172 at one year in subjects with T4+ cell count of greater than 800/microliters 400-800/microliters and less than 400/microliters, respectively, and 0.296, 0.501, and 0.896 at two years.