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Biomedical subjects

S Mangano

Publications and source records attributed to S Mangano.

At least 19 recordsLinked to original sources

Reduction in urea distribution volume over time in clinically stable dialysis patients.

We have previously shown that, assuming urea distribution volume (V) remains constant for 1 month, ionic dialysance (ID) allows the dialysis dose to be calculated without the need for blood sampling. The aim of this multicenter study was to verify whether the assumption of a constant V can be extended to 1 year. In clinically stable patients receiving thrice-weekly hemodialysis at 13 dialysis centers, V and Kt/V were assessed during three dialysis sessions at baseline and 1 year later using ID as dialyzer urea clearance and the single-pool urea kinetic model. Baseline albumin, hemoglobin, and C reactive protein were prespecified covariates for predicting the change in V over time. Of the 52 enrolled patients, 40 (25 males; age 63.0+/-13.5 years) completed the study. Baseline end-dialysis body weight (62.4+/-13.7 kg) showed a non-significant 1% reduction during follow-up (-0.6+/-2.8 kg; P=0.175), whereas V significantly decreased from 29.0+/-6.8 to 27.4+/-6.0 l (-1.6+/-3.0 l or 4.5%; P=0.002). The reduction in V was greater when baseline albumin was lower (P=0.001) and baseline V was higher (P=0.005). The single-pool K(t)/V calculated using baseline V underestimated the actual value by 0.07+/-0.16 (P=0.008). The slight underestimate of Kt/V during follow-up suggests that annual V evaluations may be sufficient for dialysis dose quantification as the only risk is underestimating the actually delivered dialysis dose. However, the relationship between baseline albumin and the reduction in V over time may have nutritional value, and suggests more frequent V evaluations.

Adolescent↗

Hepatitis C virus infection and diabetes mellitus in end-stage renal disease: evidence of a negative association.

Epidemiological studies have implicated hepatitis C virus (HCV) infection in the pathogenesis of diabetes mellitus (DM) both in the population as a whole and after solid organ transplantation. Whether this association exists in patients with end-stage renal disease (ESRD) undergoing dialysis is unclear. The aim of this study is to investigate the relationship between HCV and DM in a large group (n=742) of patients with ESRD from Europe and North America. The presence of diabetes was ascertained by using American Diabetes Association guidelines based on fasting glucose measurement and medication history. Presence of HCV infection was assessed by serum testing for anti-HCV antibodies. The prevalence of anti-HCV antibody positive patients was 15% (112/742); the frequency of DM was higher among anti-HCV positive than -HCV negative patients but the difference did not approach statistical significance, 32% (36/112) vs 29.5% (186/630). The frequency of patients with diabetic nephropathy was not higher in anti-HCV positive than -negative patients; 21.4% (24/112) vs 23.3% (147/630), NS. Logistic regression model showed an independent and significant link between anti-HCV seropositive status and raised GPT (P=0.032), male gender (P = 0.0462), positive history of prior renal transplant (P=0.0006), and longer time on dialysis (P=0.00001). In summary, no link between anti-HCV antibody and DM occurred in this ESRD population; there was no association between rate of anti-HCV antibody and diabetic nephropathy.

Adult↗

Occult hepatitis B virus infection in dialysis patients: a multicentre survey.

BACKGROUND: The epidemiology and clinical significance of occult hepatitis B virus infection (serum hepatitis B surface antigen-negative patients with detectable hepatitis B virus viraemia in serum) remains controversial with only limited information about its prevalence in patients on long-term dialysis. AIM: To address the epidemiology of occult HBV infection in a large cohort of dialysis patients. METHODS: We screened a large cohort (n = 585) of Italian chronic dialysis patients; from this population, a group of hepatitis B virus surface antigen seronegative patients (n = 213) was tested by Amplicor hepatitis B virus Monitor Test to detect hepatitis B virus viraemia (hepatitis B virus-DNA) in serum. RESULTS: Occult hepatitis B virus infection was absent (zero of 213 = 0%). Persistent hepatitis B virus surface antigen carriage was less frequent than anti-hepatitis B virus core antibody (anti-hepatitis B core antigen) seropositive status in this study group [1.88% (11 of 585) vs. 36% (216 of 585), P = 0.0001]. No dialysis patients seropositive for anti-hepatitis B core antibody in serum (zero of 123 = 0%) had detectable hepatitis B virus-DNA by polymerase chain reaction technology. No significant association between abnormal biochemical liver tests and serum anti-hepatitis B core antibody was noted in our population. Nominal logistic regression analysis demonstrated an independent and significant relationship between anti-HCV antibody and anti-hepatitis B virus core antibody in serum (Wald chi-square 16.06, P = 0.0001). The rate of seropositive patients for anti-hepatitis B virus core antibody was higher among study patients than controls with normal renal function [36.9% (216 of 585) vs. 21.4% (59 of 275), P = 0.0001]; this difference partially persisted after correction for demographic parameters, and viral markers. CONCLUSION: In conclusion, occult hepatitis B virus was absent in our study group. Anti-hepatitis B core antibody was significantly related to presence of anti-HCV antibody supporting shared modes of transmission. Clinical studies based on molecular biology techniques provided with higher sensitivity are planned.

Case-Control Studies↗

Review article: hepatitis C virus infection and type-2 diabetes mellitus in renal diseases and transplantation.

A link between hepatitis C virus infection and development of diabetes mellitus has been suggested by many investigators; however, this remains controversial. The mechanisms underlying the association between hepatitis C virus and diabetes mellitus are unclear but a great majority of clinical surveys have found a significant and independent relationship between hepatitis C virus and diabetes mellitus after renal transplantation and orthotopic liver transplantation. We have systematically reviewed the scientific literature to explore the association between hepatitis C virus and diabetes mellitus in end-stage renal disease; in addition, data on patients undergoing orthotopic liver transplantation were also analysed. The unadjusted odds ratio for developing post-transplant diabetes mellitus in hepatitis C virus-infected renal transplant recipients ranged between 1.58 and 16.5 across the published studies. The rate of anti-hepatitis C virus antibody in serum was higher among dialysis patients having diabetes mellitus (odds ratio 9.9; 95% confidence interval 2.663-32.924). Patients with type-2 diabetes-related glomerulonephritis had the highest anti-hepatitis C virus prevalence [19.5% (24/123) vs. 3.2% (73/2247); P < 0.001] in a large cohort of Japanese patients who underwent renal biopsy. The link between hepatitis C virus and diabetes mellitus may explain, in part, the detrimental role of hepatitis C virus on patient and graft survival after orthotopic liver transplantation and/or renal transplantation. Preliminary evidence suggests that anti-viral therapies prior to renal transplantation and novel immunosuppressive regimens may lower the occurrence of diabetes mellitus in hepatitis C virus-infected patients after renal transplantation. Clinical trials are under way to assess if the hepatitis C virus-linked predisposition to new onset diabetes mellitus after renal transplantation may be reduced by newer immunosuppressive medications.

Antiviral Agents↗

Influence of hepatitis B virus virema upon serum aminotransferase activity in dialysis population.

BACKGROUND: The control of the spread of hepatitis B virus (HBV) infection within dialysis units has been one of the major advances in the management of patients with end-stage renal disease (ESRD). However, clinical and biochemical expression of HBV in dialysis patients have not been adequately addressed. Elevated values of serum aminotransferase activity are a sensitive measure of hepatocellular injury, but the role of HBV infection in the development of liver disease among dialysis patients has not been adequately analysed. Also, the clinical impact related to the virological characteristics of HBV in dialysis has not been evaluated. METHODS: Demographic, biochemical and virological data from 727 patients undergoing chronic dialysis in seven dialysis units in northern Italy were collected in order to assess the biochemical consequences related to the presence of HBV infection in this population. We have measured by RT-PCR technology the titers of HBV viremia in HBsAg positive patients receiving dialysis. RESULTS: Univariate analysis showed that AST and ALT values were significantly higher in HBsAg positive/HBV DNA positive than HBsAg negative patients on dialysis; AST, 22.86+/-31.34 vs. 14.19+/-9.7 IU/L (P=0.00001); and ALT, 25.07+/-41.59 vs. 13.9+/-41.59 IU/L (P=0.00001). In the subgroup of HBsAg positive patients, the frequency of detectable HBeAg in serum was 14.9% (7/47). The median value of HBV DNA in patients with detectable HBV DNA in serum was 2.160 x 10(3) copies/mL (range, 2.5 x 10(2)-4 x 10(6) copies/mL). HBsAg positive/HCV positive patients had higher aminotransferase activity than other subgroups (P=0.0001). Multivariate analysis showed a significant and independent association between detectable HBsAg/HBV DNA in serum and AST (P=0.00001) and ALT (P=0.0001) activity AST and ALT levels were lower in dialysis than healthy individuals--this finding persisted in age- and gender-matched comparisons. CONCLUSIONS: The HBV viral load in HBsAg positive patients receiving maintenance dialysis is not high. HBsAg positivity with detectable HBV DNA in serum is a strong and independent predictor of raised aminotransferase activity among dialysis patients. HBsAg positive patients had greater aminotransferase activity than HBsAg negative individuals even if both the groups had mean aminotransferase levels within the normal range considered for healthy population. Clinical trials aimed at identifying the best cut-off value to enhance the diagnostic yield of AST/ALT for detecting HBV in dialysis population are under way.

Adult↗

Effect of on-line conductivity plasma ultrafiltrate kinetic modeling on cardiovascular stability of hemodialysis patients.

The aim of this multicenter, prospective, randomized cross-over study was to clarify whether on-line conductivity ultrafiltrate kinetic modeling (treatment B), as a substitute for sodium kinetic modeling, is capable of reducing intradialytic cardiovascular instability in comparison with standard treatment (treatment A), by reducing the sodium balance variability. Both treatments were performed by means of a modified hemodiafiltration technique. Treatment A was performed using fixed dialysate conductivity; treatment B made use of the dialysate conductivity derived from a conductivity kinetic model, in order to obtain an end-dialysis ultrafiltrate conductivity at each dialysis session that was equal to the mean value determined in the same patient during the four-week run-in period. Thus, during treatment B, the expected end-dialysis ultrafiltrate conductivity value of each patient should have been constant. The study was carried out according to a multicenter cross-over design of 16 weeks with two treatments (A or B), two sequences (1 = ABB and 2 = BAA), a run-in period of four weeks (period 1, treatment A), and three consecutive experimental periods of four weeks each. Analysis of variance for a cross-over design was used for the statistical analysis. Forty-nine hemodialysis patients prone to intradialytic hypotension (> 25% of sessions) were enrolled from 16 participating centers, and randomly assigned to either sequence 1 (26 patients) or sequence 2 (23 patients). Six patients dropped out and four were protocol violators, which left 39 patients selected for statistical analysis. There was no difference in the average dialysate conductivity, predialysis and end-dialysis plasma water ultrafiltrate conductivity or body weight between treatment A and treatment B. Thus, the observed mean sodium balance was not different and, as expected, only the intra-patient variability of end-dialysis ultrafiltrate conductivity (index of sodium balance variability) was reduced (21%). During treatment A, systolic blood pressure decreased by 23 mm Hg (95% confidence intervals 21 to 24 mm Hg) at the end of dialysis with respect to the pre-dialysis values. Treatment B reduced this intradialytic decrease (P = 0.001) with a maximum effect at the third hour of dialysis (4.4 mm Hg, 95% confidence intervals 1.9 to 6.9 mm Hg, 23% less than during treatment A, P 0.0005) without any period or carry-over effect (P = 0.53 and 0.08, respectively). There was no treatment effect on intradialytic diastolic blood pressure (P = 0.291). In conclusion, intradialytic cardiovascular stability was significantly improved by matching the interdialytic sodium load with intradialytic sodium removal using on-line conductivity ultrafiltrate kinetic modeling as an alternative to sodium kinetic modeling. Although highly significant, this effect was clinically not very large. By applying this conductivity kinetic model to patients with a more variable sodium intake from one session to another, a greater benefit can be expected.

Aged↗

Influence of hepatitis C virus (HCV) viraemia upon serum aminotransferase activity in chronic dialysis patients.

BACKGROUND: There are many reports concerning HCV in dialysis patients and most of them conclude that the clinical and biochemical features of hepatitis C are often silent in chronic dialysis patients. Elevated levels of serum alanine aminotransferase activity are a sensitive measure of hepatocellular injury, but so far the relationship between anti-HCV and ALT among chronic dialysis patients has been considered imperfect. To our knowledge, however, such an issue has not been adequately addressed. METHODS: Demographic, biochemical, and virological data from 506 patients undergoing chronic dialysis treatment in four dialysis units in Lombardy, northern Italy were collected in order to assess the influence of virological and host factors on serum aminotransferase values. RESULTS: Analysis of covariance showed that positivity for anti-HCV antibody was significantly associated with raised serum AST (P = 0.0001) and ALT (P = 0.0001) levels in the dialysis patients of the whole study group. Logistic regression analysis performed in the subset of patients tested for HCV viraemia and genotype showed that detectable HCV RNA in serum is a strong predictor of raised AST (P = 0.0001) and ALT (P = 0.000001) values. Gender showed an independent weak influence on AST levels (P = 0.055), serum levels of ferritin were significantly (P = 0.042) associated with AST values, the coexistence of HBsAg infection and positivity for anti-HCV antibody was independently associated with raised ALT levels (P = 0.016). The other factors (including positivity for anti-HCV) showed no independent effect on serum aminotransferase levels when they were matched with HCV viraemia in our multivariate analysis. HCV RNA positive patients showed serum AST (P < 0.008) and ALT levels (P < 0.0001) higher than HCV RNA negative patients. There was no relationship between HCV genotypes and liver enzymes. CONCLUSIONS: Our data show that detectable HCV RNA in serum is a strong independent predictor of raised aminotransferase values in chronic dialysis patients; the relationship between serum aminotransferase values and anti-HCV antibody was exclusively related to the association between raised aminotransferase values and HCV viraemia; HCV RNA positive patients show higher hepatic enzyme levels than dialysis patients with no detectable HCV RNA; no association between HCV genotype and serum aminotransferase activity was apparent.

Adult↗

Molecular epidemiology of hepatitis C virus infection in dialysis patients.

There are very few data on the molecular biology of hepatitis C virus (HCV) infection in dialysis patients. 101 patients undergoing dialysis treatment in 4 units in the Lombardy, northern Italy, were analyzed by RT-PCR for HCV viremia, by line probe assay technology for HCV genotyping and by a serological analysis for detecting type-specific antibodies. 61 of 101 (60%) patients showed detectable HCV RNA in serum; HCV genotype 2a was dominant (30/53 = 57%), followed by HCV genotype 1b (20/53 = 37%). There was no relationship between HCV genotyping and the clinical or demographic features of the patients. The antibody response toward the c33-c, c100-3, and 5-1-1 antigens was more frequent in HCV genotype 1b compared with genotype 2a (p = 0.046, p = 0.001 and p = 0.0001, respectively). The antibody levels to NS-3 and NS-4 HCV proteins were significantly higher in patients with-HCV genotype 1b in comparison with HCV 2a-infected individuals (p = 0.0001). There was a high level (82%) of agreement between HCV genotyping by RT-PCR and the assessment of type-specific antibodies by serological analysis; further, it was possible to detect type-specific antibodies in 6 of 22 (27%) patients in whom PCR amplification was unsuccessful. In conclusion, HCV subtype 2a was dominant in our population of HCV-infected dialysis patients, dialysis patients infected by different genotypes showed similar demographic and clinical characteristics, the antibody response toward the NS-3- and NS-4-related antigen of HCV was genotype dependent. There was a high level of agreement between HCV genotyping by RT-PCR and the detection of type-specific antibodies by serological analysis. As significant biological differences may exist among HCV strains, the assessment of HCV types may be very useful in the routine clinical activity of nephrologists in dialysis units.

Adult↗

[The allorhythmic distribution of ectopic ventricular beats. Observations on the electrogenesis and dynamics of concealed ventricular extrasystole].

BACKGROUND: A regular distribution of ventricular ectopic beats is thought to be a relatively uncommon phenomenon, known as "concealed extrasystole". Several experimental studies suggest that the phenomenon originates from a "protected" ventricular focus. The aim of the present study was to evaluate the 24-hour ECG monitoring incidence of ventricular concealed extrasystole in patients with highly frequent ventricular ectopic beats, looking for signs useful in postulating the electrogenesis of the arrhythmia. METHODS: The 24-hour ECGs of 10 patients (pts) with highly frequent ventricular extrasystoles were analysed, searching for significant sequences in the distribution of ectopic beats (i.e., ectopic beats separated by a number of interectopic sinus beats fulfilling one of the formulas of concealed extrasystole). RESULTS: Five cases (50%) showed an allorhythmic distribution resulting in a prevalent pattern of concealed bigeminy (2n-1) in 3 cases, and concealed trigeminy (3n-1) in 2 cases. The phenomenon, however, showed a dynamic behaviour, alternating the distributions from patterns of concealed bigeminy to concealed trigeminy or less common patterns, and vice versa. The evidence of the pure ectopic cycle and mathematically related interectopic intervals in 2 cases, the variability of coupling intervals, and the presence of fusion beats in the remaining 3 cases, strongly suggests a parasystolic origin of the phenomenon. CONCLUSIONS: The results suggest the following: Concealed extrasystole is a relatively common phenomenon, at least in patients with highly frequent ventricular extrasystoles; the phenomenon, however, is somewhat underestimated due to prevalent quantitative, instead of qualitative, Holter monitoring analyses. Among patients with allorhythmically distributed ventricular extrasystoles, none showed only one pattern of distribution. In fact, each single patient showed two or more patterns throughout the 24-hour recordings. Changes from one pattern to another is governed by several factors, such as sinus heart rate and/or the influence of electrotonic "modulation" upon the ectopic focus. Ventricular extrasystoles with regular allorhythmic distribution show a significantly higher variability of coupling intervals than the others (p = 0.005).

Adolescent↗

Modification of the characteristics of regurgitant jets when impinging upon a surface: an in-vitro investigation using Doppler colour flow mapping.

Free jets were compared in vitro by colour Doppler flow mapping with jets striking a flat and a hemispherical surface, located 3 and 6 cm from a circular orifice (5 mm in diameter). The angles of the impinging jets were 45 degrees and 90 degrees. Flow rates from 6-52 ml.s-1 were tested (pulsatile jets, 0.5 s duration). Free jet areas (21.7 +/- 9.6 cm2) were larger (P less than 0.01) than that of impinging jets (14.3 +/- 5.6 cm2). The distance of the target was a significant factor for reducing areas of striking jets (P less than 0.001). The angle of incidence of the striking jet and the shape of the target surface were not independent factors, but they were important when interacting with flow rate (P less than 0.001). The percentage of total jet area of impinging jets occupied by swirling flow was larger for targets located at 3 cm (P less than 0.01), for a 90 degrees angle of incidence (P less than 0.01), for a flat target surface (P less than 0.05). We conclude that jets visualized in vitro by colour Doppler flow mapping are significantly modified when impinging a surface, with the interplay of several factors. This can be of importance in clinical settings.

Blood Flow Velocity↗

Prevalence of antibodies against hepatitis C virus in a dialysis unit.

Anti-HCV was tested in 77 uremic patients, 48 on hemodialysis (HD), 29 on CAPD, by immunoenzymatic 1st and 2nd generation assays (ELISA I, II) and 4-antigen (4-RIBA) immublotting. The investigation was extended to the staff (n = 29) and to HCV-positive patients' families (n = 30). The prevalence using 2nd generation tests was double (21%) that in 1st generation tests (11%). A greater incidence in the HD than in the CAPD group (23 vs. 17%) and a highly significative correlation to dialytic age were observed. No one among the sanitary personnel and only 2 family members were found HCV positive, suggesting a low infectivity via the parenteral inevident route. Extracorporeal circulation and particularly the exposure time to the treatment seem to be the main risk factors.

Family↗

Hemimegalencephaly and neurofibromatosis.

Hemimegalencephaly, which previously has been associated with a poor clinical course characterized by intractable seizures and severe encephalopathy, was found without these conditions in two children with neurofibromatosis. These children showed relatively similar and favourable prognostic features: no presence of seizures before one month, seizures controlled or absent, no focal neurological signs and peculiar EEG findings. In our opinion the absence of heterotopias and hamartomas can be related with less severe outcome.

Brain↗

[Color Doppler identification of early diastolic turbulence in the left atrium in patients with mitral valve insufficiency: persistence of regurgitation or inertia phenomenon?].

Color Doppler flow mapping represents the most recent non invasive diagnostic tool for the visualization of intracardiac blood flow. By using the color Doppler flow mapping technique, two independent observers identified the persistence of turbulence in early diastole inside the left atrium in a selected group of 8 patients (3 F and 5 M) with mitral insufficiency. All the patients had moderate or severe mitral insufficiency, due to dilated cardiomyopathy and/or ischemic cardiomyopathy and/or valvular disease. The persistence of early diastolic turbulence inside the left atrium was documented and confirmed by using 30 degrees color sector images, which show the highest possible frame rate. The frame by frame analysis facilitated the identification of two simultaneous flow velocities during early diastole, after the mitral valve was open. The first flow was anterograde and was coded as a red signal; it flowed from the mitral valve into the left ventricle and represented early diastolic left ventricular filling. The second flow was retrograde, and was coded as a blue mosaic signal, due to turbulent aliased jet, extending from the mitral valve into the left atrium, away from the transducer. The interpretation of these two dimensional color Doppler findings is uncertain. We believe, however, that these turbulent velocity signals which persist in early diastole and flow from the mitral valve into the left atrium are probably caused by inertial blood flow due to the impact of regurgitant mitral jets during the previous systole.

Adult↗

[Usefulness of the Doppler color technic in the diagnosis of thrombosis in a mitral valve mechanical prosthesis and in the monitoring of the results of thrombolytic therapy].

We report the usefulness of Doppler color echocardiography in diagnosis and follow-up in a case of thrombosis of a prosthetic mitral valve. The patient received thrombolytic therapy for this disorder and a favorable clinical outcome was observed. Integrated echocardiographic techniques (M-Mode, cross-sectional, continuous-wave, pulsed-Doppler and color Doppler) could increase the amount of diagnostic information in these situations.

Aged↗