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J Genesca

Publications and source records attributed to J Genesca.

At least 19 recordsLinked to original sources

Role of Doppler echocardiography in the assessment of portopulmonary hypertension in liver transplantation candidates.

BACKGROUND: Portopulmonary hypertension is a severe complication of liver cirrhosis that carries a high risk for posttransplantation mortality. We aimed at evaluating the utility of Doppler echocardiography in screening for portopulmonary hypertension in liver transplantation candidates. METHODS: One hundred seven cirrhotic patients candidates for liver transplantation were studied by Doppler echocardiography and subsequently, by cardiac catheterization at transplantation. Two parameters were estimated by Doppler: systolic pulmonary arterial pressure (SPAP) derived from tricuspid regurgitation and the pulmonary acceleration time. Portpulmonary hypertension was suspected when SPAP was > or = 40 mm Hg and/or pulmonary acceleration time < 100 ms. RESULTS: Portpulmonary hypertension was suspected by Doppler study in 17 patients (15%). However, portopulmonary hypertension (mean pulmonary arterial pressure > or = 25 mm Hg and pulmonary vascular resistance > 120 dynes.s/cm5) was confirmed by the hemodynamic study in five patients (4.7%). Sensitivity and specificity of Doppler echocardiography for detecting portopulmonary hypertension was 100 and 88%, respectively, with a positive predictive value of 30%. The diagnostic accuracy of pulmonary acceleration time alone (96%) was better than pulmonary arterial pressure alone (90%). CONCLUSIONS: Doppler echocardiography, and especially the determination of pulmonary acceleration time, is a useful screening method for portopulmonary hypertension in patients with liver cirrhosis who are candidates for liver transplantation.

Adult↗

Nitric oxide may contribute to nocturnal hemodynamic changes in cirrhotic patients.

OBJECTIVE: Patients with liver cirrhosis have a nocturnal worsening of hemodynamic parameters that has been associated with an increased risk of variceal bleeding at nighttime. The aim of this study was to investigate whether nitric oxide and cytokines are implicated in these hemodynamic changes. METHODS: Ten cirrhotic patients and eight controls were studied. Mean blood pressure, heart rate, plasma norepinephrine, tumor necrosis factor alpha and interleukin-6 levels, and serum nitrite + nitrate levels were determined at 0800, 1600, and 2400 h. All determinations were performed in supine rest and at least 4 h after meals. In a second study, nitrite + nitrate levels were assessed in 10 cirrhotic patients before and after eating a standard meal. RESULTS: Mean arterial pressure levels that were always lower in the patient group showed a nocturnal decrease in both groups of subjects. Heart rate values that were always higher in cirrhotic patients showed a nocturnal fall in controls, whereas cirrhotics maintained elevated values at nighttime. Norepinephrine levels were higher in cirrhotics and maintained similar values during the study, whereas controls had a significant nocturnal decrease. Nitrite + nitrate levels that were higher in cirrhotic patients showed a significant mean increase of 40% from morning (0800 h) to night (2400 h) in the patient group, whereas in controls no change was observed (p < 0.05). Tumor necrosis factor alpha and interleukin-6 levels did not change either in patients or controls during the entire period. Cirrhotic patients with or without ascites maintained a pattern of hemodynamic and biochemical changes similar to the pattern observed in the entire group of patients. Finally, no changes in serum nitrite + nitrate levels were observed in patients before and after eating the standard meal. CONCLUSION: An increased nocturnal nitric oxide production might contribute to the hemodynamic changes observed in cirrhotic patients during nighttime.

Aged↗

Adrenomedullin, a vasodilator peptide implicated in hemodynamic alterations of liver cirrhosis: relationship to nitric oxide.

This prospective cohort study was aimed at investigating the role of adrenomedullin, a potent vasodilator peptide, in liver cirrhosis and its relationship with nitric oxide and cytokines. Overall, 66 consecutive patients with liver cirrhosis and 15 controls matched for age and sex distribution were included. Adrenomedullin levels in patients with cirrhosis were higher than in controls [28.1 (23.5-34.8) vs 21.9 (21.1-26.4) pmol/liter, P = 0.002]. Child class A patients had adrenomedullin levels similar to those of controls, but lower than patients in class B and C, respectively (P = 0.01). Patients with ascites showed more elevated adrenomedullin levels than patients without (P = 0.001). Adrenomedullin levels had significant correlations with aldosterone (r = 0.55; P < 0.001), plasma renin activity (r = 0.49; P < 0.001) and nitrates-nitrites levels (r = 0.52; P < 0.001). Weak correlations were found with tumor necrosis factor-alpha and interleukin-6. This study shows that high levels of adrenomedullin in liver cirrhosis correlate with features associated with plasma volume expansion, and suggests that, in late stages of cirrhosis, adrenomedullin might contribute to vasodilatation by increasing the generation of nitric oxide.

Adrenomedullin↗

Interleukin-6, nitric oxide, and the clinical and hemodynamic alterations of patients with liver cirrhosis.

OBJECTIVE: Nitric oxide has been proposed as a mediator of hyperdynamic circulation in cirrhosis. Endotoxin and cytokines induce the synthesis of nitric oxide. The aim of this study was to investigate the relationship between endotoxemia, cytokines, and nitric oxide in patients with cirrhosis, and to correlate these findings with clinical, biochemical, and hemodynamic parameters. METHODS: Clinical, biochemical, and hemodynamic parameters were assessed in 66 patients with cirrhosis and 15 controls. Levels of antidiuretic hormone, plasma renin activity, aldosterone, interferon gamma, interleukin-1, interleukin-6, tumor necrosis factor alpha, endotoxin, and nitrates-nitrites were determined. RESULTS: Mean arterial pressure was lower and interleukin-6, tumor necrosis factor alpha, nitrites-nitrates levels, and endotoxin positivity rates were higher in cirrhotics than in controls (p < 0.005). Mean arterial pressure decreased and interleukin-6 levels increased with worsening of Child score (p < 0.005). Patients with ascites had higher levels of interleukin-6, tumor necrosis factor alpha, and nitrates-nitrites than patients without ascites (p < 0.01). Elevated levels of interleukin-6 were found in patients with encephalopathy grade I, compared with patients without (p < 0.001); this association was independent of the severity of liver disease. In patients with low mean arterial pressure, interleukin-6 levels were higher than in patients with high mean arterial pressure (p = 0.001), whereas tumor necrosis factor alpha and nitrates-nitrites levels were not different. By multivariate analysis, high interleukin-6 levels showed independent associations with the presence of ascites, encephalopathy, and low mean arterial pressure. Only interleukin-6 levels had significant correlations with Child score, plasma renin activity, serum and urinary sodium, and mean arterial pressure (r > or = 0.4, p < 0.005). CONCLUSIONS: Although the activity of the nitric oxide pathway is increased in patients with cirrhosis and might contribute to the hemodynamic alteration, other factors are involved. Interleukin-6, possibly through nitric oxide-independent mechanisms, also might play a role in the vasodilatation of cirrhosis and the pathogenesis of hepatic encephalopathy.

Aged↗

Efficacy of screening donors for antibodies to the hepatitis C virus to prevent transfusion-associated hepatitis: final report of a prospective trial.

Routine screening of blood donors for anti-hepatitis C virus (HCV) has been implemented in most developed countries. However, the independent efficacy of such screening has not been established in a controlled, prospective study. We tracked 478 patients transfused with anti-HCV-negative blood by first-generation enzyme-linked immunoassay (EIA) between July 1989 and May 1990 and compared the incidence of transfusion-associated hepatitis and HCV infections with that found among 280 patients transfused with blood unscreened for anti-HCV during the immediately preceding year. Of the 280 patients who had received transfusions before donors were screened for anti-HCV, 27 (9.6%) developed posttransfusion hepatitis and 1 additional patient seroconverted to anti-HCV without evidence of hepatitis, for a risk of posttransfusion HCV infection of 10.7% (28 of 262 recipients seronegative for anti-HCV before transfusion). Of the 478 patients transfused after July 1989 with blood screened for anti-HCV, only 9 (1.9%) developed posttransfusion hepatitis for a risk reduction of 80%. Seven of the 9 residual cases of hepatitis were caused by HCV (7 of 456 recipients seronegative before transfusion or 1.5%) for a risk reduction of transfusion-associated HCV infection of 86%. In retrospect, an anti-HCV positive donor was detected by second-generation immunoassay in 4 (57%) of the 7 HCV cases from the study cohort and in 19 of the 23 (83%) cases from whom all donor samples were available for testing in the historical cohort. No additional infectious donors were detected by third-generation immunoassay or serum HCV-RNA by polymerase chain reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Disappearance of serum hepatitis B virus DNA by polymerase chain reaction after adenine arabinoside 5'-monophosphate therapy in chronic hepatitis B.

The aim of antiviral therapy in chronic hepatitis B is the cessation of viral replication, which may be demonstrated by the loss of hepatitis B "e" antigen (HBeAg) and serum hepatitis B virus DNA (HBV-DNA) detected by dot-blot hybridization. With the development of the sensitive polymerase chain reaction (PCR) technique for detecting HBV-DNA, it has become apparent that many HBeAg negative patients may still have small amounts of circulating viral DNA. We assessed 19 of 25 patients with chronic hepatitis B who seroconverted from HBeAg to anti-HBe after adenine arabinoside 5'-monophosphate therapy (5 mg.kg-1.day-1 for 7 weeks) to determine whether serum HBV-DNA became undetectable. Sixteen of the 19 HBeAg negative patients remained hepatitis B surface antigen (HBsAg) positive, and the other three lost HBsAg during follow-up. All of them were HBV-DNA negative by dot-blot hybridization. Using the PCR technique, HBV-DNA became negative in 13 (81.2%) of the 16 patients who seroconverted to anti-HBe without losing HBsAg, and in all the patients who lost HBsAg. These data suggest that the majority of patients who respond to adenine arabinoside 5'-monophosphate show a complete inhibition of hepatitis B virus replication, as demonstrated by the absence of viral DNA by PCR. This inhibition was present in all patients who, at the same time, lost HBsAg.

Adult↗

Hepatitis C virus markers in patients with acute post-transfusion hepatitis treated with interferon alfa-2b.

This trial was undertaken to establish the long term biochemical and serological outcome of patients with acute post-transfusion hepatitis C virus infection after treatment with interferon alfa-2b. After 12 months, 12 patients (eight treated, four controls) had self limited disease and 16 patients (seven treated, nine controls) had chronic disease. After a total mean 31 months of follow up in 23 patients, nine (six treated, three controls) had self limited disease while 14 (five treated, nine controls) developed chronic liver disease; all patients with spontaneous or self limited hepatitis C (HCV) infection maintained normal serum alanine amino-transferase activity and absence of HCV-RNA, and tended to lose anti-HCV antibodies.

Acute Disease↗

Clinical correlation and genetic polymorphism of the human immunodeficiency virus proviral DNA obtained after polymerase chain reaction amplification.

Polymerase chain reaction (PCR) was used to amplify a long sequence of human immunodeficiency virus (HIV) DNA, to assess the correlation between PCR signal and clinical stage of disease, and to demonstrate the genotypic variability of different HIV isolates. Twenty-four (96%) of 25 anti-HIV-reactive patients and none of 12 controls were positive for HIV proviral DNA by PCR. After quantification of the PCR signal, a significant difference in the relative amount of HIV proviral DNA per 10(5) peripheral blood mononuclear cells between symptomatic patients (Centers for Disease Control [CDC] class IV) (32,284 +/- 5225 cpm [mean +/- SE], equivalent to 802 HIV plasmid DNA copies) and patients without symptoms (CDC class II/III) (5484 +/- 1469 cpm [mean +/- SE], equivalent to 67 HIV plasmid DNA copies) was observed (P less than .01). Restriction analysis of PCR products in selected samples showed extensive genetic polymorphism between different isolates and more than one viral genotype per isolate. There was a clear correlation between the appearance of clinical symptoms in HIV infection and high levels of viral replication.

Blotting, Southern↗

What do western blot indeterminate patterns for human immunodeficiency virus mean in EIA-negative blood donors?

To investigate the specificity of western blot indeterminate (WBi) patterns for antibodies to the human immunodeficiency virus type 1 (HIV-1), 100 enzyme immunoassay (EIA) negative donors from whom prospectively obtained recipient sera were available were tested by WB. 20 were WBi, with p24 being the predominant (70%) and generally the only band. Among recipients of WBi blood, 36% were WBi in their 6 month post-transfusion sample, but so were 42% of a control population that had received only WB-negative blood. When serial samples from recipients with a WBi pattern were tested on two occasions, only 35% of results were reproducible. No reciepient of WBi blood became EIA positive, true positive for WB, positive for HIV-1 antigen, or positive for EIA reactivity against recombinant p24 or gp41. The polymerase chain reaction was negative for gag and env HIV-1 sequences in all donors and recipients. Thus WBi patterns are exceedingly common in randomly selected donors and recipients and such patterns do not correlate with the presence of HIV-1 or the transmission of HIV-1 from donor to recipient.

Blood Donors↗

Comparison of four different antigen-capture assays for the detection of human immunodeficiency virus antigen (HIV-Ag).

Three enzyme immunoassays (EIA), two polyclonal and one monoclonal, and one polyclonal radioimmunoassay (RIA) for the detection of human immunodeficiency virus antigen (HIV-Ag) have been evaluated and compared. The three EIAs had similar sensitivity in detecting HIV viral lysate and were more sensitive than the RIA, which was the only assay with a one-step probing-detection format. However, the EIA that used a monoclonal anti-p24 as the capturing reagent was unable to detect any of the serial supernatant samples of a positive viral culture from an HIV-infected patient. Only the two polyclonal, non-p24-restricted assays were able to detect an unusual expression of HIV-Ag in the serum of an acute HIV-infected patient. Overall, the sensitivity of HIV-Ag capture assays was enhanced when (a) the capture antibody was polyclonal rather than monoclonal, (b) the polyclonal antibody was broad rather than p24-restricted, and (c) the probing-detecting procedure was in a two-step format rather than one-step format. In addition, the use of neutralizing assays to confirm the results was absolutely necessary.

Antibodies, Monoclonal↗

Clinical and serological outcome of acute delta infection.

To assess the clinical and serological outcome of hepatitis delta virus (HDV) infection, 59 patients with acute delta hepatitis were followed for 6-28 months. Forty-two patients had simultaneous HDV and HBV coinfection (anti-HBc IgM-positive, group I) and 17 were HBsAg carriers with HDV superinfection (anti-HBc IgM-negative, group II). Overall, serum HD-Ag and anti-HD IgM were the most sensitive markers for diagnosis of delta infection during the first 2 weeks after onset of symptoms. The clinical presentation was similar in both groups; 4 patients (1 in group I and 3 in group II) (7%) developed fulminant hepatitis, but none of them died. The majority of patients with HBV-HDV coinfection (group I) eventually recovered, whereas all HBsAg carriers with HDV superinfection (group II) developed chronic liver disease. Liver histology in these patients showed chronic active hepatitis and/or cirrhosis in 90%. The hepatic lesion was probably due to persistent HDV infection, as indicated by the presence of intrahepatic HD-Ag and/or persistence of serum anti-HD IgM in 90% of the patients.

Antibodies, Viral↗