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Biomedical subjects

J Prieto

Publications and source records attributed to J Prieto.

At least 253 records · Page 14Linked to original sources
PubMed1993

Randomised trial of lymphoblastoid alpha-interferon in chronic hepatitis C. Effects on inflammation, fibrogenesis and viremia.

Seventy-two patients with chronic hepatitis C were included in a randomised trial of lymphoblastoid interferon versus no treatment. Thirty-six patients entered each group. Interferon was given in a step-down schedule for 12 months. Aminotransferase activities became normal during treatment in 30 of 36 (83.3%) treated patients, but in only 1 out of 36 (2.7%) non-treated cases (p < 0.001). However, a reactivation of the disease during the interferon course was observed in 12 patients after a mean of 5.58 +/- 1.55 months of therapy, and a post-treatment relapse was observed in 5 additional cases. The remaining 13 patients (36%) had sustained normalization of the aminotransferase levels for 15.27 +/- 10.34 months (range 3-30) after discontinuation of interferon, thus representing a long-term sustained remission of the disease. Knodell's histological activity index decreased in all treatment patients, except for 3 non-responders (91.5%), but in only 9 of 36 non-treated cases (25%) (p < 0.001). Procollagen type III peptide levels normalized in most cases (83%) with a sustained response. A significant decrease in the detection of hepatitis C virus RNA was observed in patients with a sustained response (p < 0.05). Anti-interferon antibodies were only detected in one non-responder. Thus, interferon diminishes inflammatory and fibrogenic activity in the majority of patients with chronic hepatitis C and abolishes viremia in most of the patients with a sustained response.

Adult↗
PubMed1993

Ribavirin in the treatment of chronic hepatitis C unresponsive to alfa interferon.

For the 30-50% of patients with chronic hepatitis C who do not respond to alpha-interferon therapy there is no alternative treatment. Some previously untreated patients have shown a biochemical response to ribavirin, but the antiviral effects of this substance on alpha-interferon-resistant cases is largely unknown. Twelve patients with chronic hepatitis C who had not responded to a 6-12 month course of alpha-interferon were included in this study. Oral ribavirin was administered at a dose of 16 mg/kg per day for 6 or 9 months. Aminotransferase levels had not significantly changed during interferon therapy but decreased significantly during ribavirin treatment (mean alanine aminotransferase at baseline, 102 +/- 18 IU/l vs. 55 +/- 14 IU/l at 6 months; P = 0.0001). Aminotransferase levels became normal in 6 cases (50%), significantly decreased in 3 patients (25%), and did not significantly change in the remaining 3 cases (25%). All patients with normalized aminotransferase values relapsed after ribavirin was discontinued and aminotransferase activity returned to pretreatment levels. Before therapy serum hepatitis C virus RNA was detected by polymerase chain reaction in 10 cases. None of them had cleared viral RNA when tested following 3, 6 and 9 months of ribavirin therapy. Side-effects were mild and reversible. In conclusion, about half of the patients with chronic hepatitis C who are unresponsive to alpha-interferon show a clear-cut biochemical response after 6-9 months of ribavirin administration. However, ribavirin does not clear circulating hepatitis C virus RNA and relapses occur after withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

N-acetyl cysteine enhances the response to interferon-alpha in chronic hepatitis C: a pilot study.

Hepatitis C virus (HCV) is an RNA virus that replicates in both the liver and lymphoid cells. Interferon-alpha (IFN-alpha) is a useful treatment of chronic hepatitis C (CHC) although resistance to this drug occurs frequently. The mechanisms underlying resistance to IFN remain unknown. In this work, we have measured the levels of glutathione in plasma and peripheral lymphoid cells from 15 healthy controls and 24 CHC patients, 10 of whom were without treatment and 14 showed high serum alanine aminotransferase (ALT) values despite therapy with lymphoblastoid IFN for more than 4 months. In all patients, glutathione levels in plasma and in mononuclear cells were depressed in comparison to controls. In IFN-unresponsive patients, the addition of 600 mg tid of oral N-acetyl cysteine (NAC), a glutathione precursor, resulted in a steady decrease of ALT values in all patients, with complete normalization in 41% of cases after 5-6 months of combined therapy. Administration of NAC alone for 1 month was without effect in the 10 patients that were not receiving IFN. Supplementation of IFN with NAC induced a near normalization of intralymphocytic glutathione, but plasma levels were only moderately increased. HCV replication was markedly inhibited in lymphocytes and viremia was cleared in one of the 8 patients tested. In conclusion, NAC enhances the response to IFN in CHC. Controlled studies are needed to ascertain whether antioxidant therapy might act in synergy with IFN in chronic viral hepatitis.

Acetylcysteine↗
PubMed1993

Prediction of the response of chronic hepatitis C to interferon alfa: a statistical analysis of pretreatment variables.

Pretreatment variables that could predict the response of chronic hepatitis C to interferon alfa treatment have not been fully assessed. Eighteen baseline variables were evaluated in a series of 100 consecutive patients treated with a 12 month course of interferon alfa. For the purposes of this study, response was defined as the return to normal of aminotransferase activities before the third month of treatment. Seventy per cent of the patients responded to treatment. Six variables were associated with an increased likelihood of response assessed by univariate analysis. With stepwise multiple regression analysis assessment, however, only three variables remained independently predictive of response: low gamma glutamyltransferase (gamma GT) activities (p < 0.001), absence of obesity (p = 0.005), and absence of cirrhosis (p = 0.01). The response rate in patients with gamma GT activities < 0.66 mu kat/l (n = 55) was 78% and 60% in patients with values > 0.66 mu kat/l (n = 45) (p = 0.048). Response was attained in 75% of non-obese patients (n = 80), compared with only 50% of obese patients (n = 20) (p = 0.03). Finally, 80% of patients without cirrhosis (n = 76) responded, while among those with cirrhosis (n = 24) the response rate was only 37% (p < 0.001). All 23 patients without cirrhosis, <40 years old, and with gamma GT activities <0.66 mu kat/l responded to treatment, while only 28.5% of 14 patients with cirrhosis, >40 years old, and with gamma GT activities >0.66 mu kat/l responded to interferon alfa (p<0.001). Those findings may be useful when evaluating interferon alfa trials and it is suggested that this treatment should be applied early in the course of chronic hepatitis C.

Adult↗
PubMed1993

Transjugular intrahepatic portosystemic shunt: evaluation with Doppler sonography.

To assess the potential role of ultrasound (US) in evaluating transjugularly inserted intrahepatic portosystemic shunts, the authors performed sonographic, including duplex and color Doppler, studies in 23 patients. Imaging was performed before, during the first week after, and 2-3 months after shunt placement. The prostheses were readily visualized and shunt patency was easily determined with Doppler US in all patients. The mean of the maximum blood flow velocity in the main portal vein increased from 7 (range, 3-16) cm/sec before shunting to 24 (range, 18-47) cm/sec 2-3 months after shunting. Flow reversal was detected in the intrahepatic portal branches in 16 (69%) of the 23 patients. US allowed prompt detection and management of two cases of incomplete stent expansion and one case of shunt stenosis due to pseudo-intimal hyperplasia. Sonography is a valuable tool for evaluation of changes in hepatic hemodynamics after transjugular intrahepatic shunt placement.

Adult↗
PubMed1993

Hepatic and extrahepatic HCV RNA strands in chronic hepatitis C: different patterns of response to interferon treatment.

We investigated the presence of positive (genomic) and negative (replicative intermediate) hepatitis C virus RNA strands in liver, peripheral mononuclear cells and serum from patients with chronic hepatitis C using a selective and semiquantitative polymerase chain reaction procedure. Negative and positive hepatitis C virus RNA strands were present in liver, serum and lymphoid cells in all untreated patients and in all those who did not respond to interferon therapy. In the latter group of patients, the titers of RNA strands in the liver and peripheral mononuclear cells at the end of the treatment were similar to those encountered in untreated patients, but the serum titers were about 100 times lower than pretreatment values. In patients who responded to interferon with normalization of serum aminotransferase levels (n = 10), the rate of detection and the titer of the two viral strands in liver, serum and mononuclear cells were markedly decreased at the end of the therapy. In the six responders who did not relapse after interferon withdrawal, both hepatitis C virus RNA strands were absent from the liver, serum and lymphoid cells. By contrast, the positive RNA strand was present in liver cells, mononuclear cells or both at the end of therapy in all patients who experienced posttherapy relapse. In conclusion, our results indicate that interferon can clear hepatitis C virus from hepatic and extrahepatic sites only in responder patients. Disappearance of genomic hepatitis C virus RNA from the liver and from mononuclear cells may predict complete response without posttherapy relapse.

Adolescent↗
PubMed1993

[Effect of ciprofloxacin on the phagocytosis of Escherichia coli by human polymorphonuclear leukocytes].

BACKGROUND: Brief exposure of bacteria to high concentrations of some antimicrobials enhanced their susceptibility to phagocytic killing by human polymorphonuclear leucocytes. This effect was defined as Post Antibiotic Leukocyte Enhancement or PALE. In this study we have investigated the effect of prior exposure of E. coli for ten minutes to 0.99 mg/l of ciprofloxacin and 0.40 mg/l of meropenem. METHODS AND RESULTS: The pretreated bacteria were incubated for three hours in a mixture containing leukocytes and leukocytes plus serum (10% v/v). Leukocytes were prepared from blood of healthful volunteers and were extracting with ammonium chloride and differential centrifugation. At one hour intervals, aliquots were taken and added to basic water to dispute leukocytes and spread onto agar plates. Viable bacteria were counted. PALE of ciprofloxacin was higher than meropenem. CONCLUSION: Whether PALE is confirmed, it must be taken into consideration in dosage schedules.

Ciprofloxacin↗
PubMed1993

Partial splenic embolization for the treatment of hypersplenism in cirrhosis.

Hypersplenism is of great relevance in the management of cirrhosis because of the widespread use of myelodepressant drugs such as interferon or antineoplastic agents. Because no standard therapy exists for this complication, we have evaluated the efficacy and risks of splenic embolization in the treatment of hypersplenism in cirrhosis. Partial splenic embolization was performed in 40 consecutive patients with the following indications: 25 patients with active viral cirrhosis before interferon therapy, 8 patients with unresectable hepatocellular carcinoma before anti-neoplastic chemotherapy and 7 patients with thrombocytopenia associated with spontaneous bleeding events, with high risk of central nervous system hemorrhage or facing major surgery. After selective catheterization of the splenic artery, partial splenic embolization was performed by means of repeated injections of gelatin sponge until a 40% to 60% reduction in the splenic blood flow was achieved. After partial splenic embolization a significant and sustained increase in platelet and white blood cell count was observed during the follow-up period (mean = 13.9 +/- 2.2 mo; range = 1 to 36 mo). The goal of partial splenic embolization was achieved in all but two patients in whom a dose reduction of interferon was needed. Hypersplenism relapsed in only seven patients, and all of them exhibited an embolization of less than 50% of the splenic mass. Postembolization syndrome was the main side effect, but no life-threatening complications were detected. In conclusion, partial splenic embolization is a safe and effective therapy of hypersplenism in cirrhosis.

Adult↗
PubMed1993

Lymphoblastoid alpha-interferon for chronic hepatitis C: a randomized controlled study.

Forty patients with chronic hepatitis C (CHC) were included in an open randomized controlled trial of lymphoblastoid alpha-interferon (L-IFN) versus no treatment. Twenty patients entered each group, and features of therapy and control cases were similar. L-IFN was given in low doses (1.5-4.5 megaunits) for 1 yr. In 16 of 20 patients treated with L-IFN (80%), but in only one of 20 nontreated cases (0.5%; p < 0.001), amino-transferase activities became normal. In four patients there was a reactivation of the disease during treatment after 4, 5, 6, and 8 months with normal aminotransferase levels. A posttherapy reactivation of hepatitis was observed in four additional cases after 1, 1, 1, and 3 months of follow-up. The other eight patients (40%) continued with normal aminotransferase levels for 1.52 +/- 0.74 (range, 1-2.1) yr after IFN doses were discontinued. In all treated patients except two nonresponders, but in only one of 20 nontreated cases (p < 0.001), Knodell's histological activity index decreased. Procollagen type III aminoterminal peptide levels did not change significantly in nontreated and nonresponder patients, diminished slightly in patients with a transient response, and normalized in cases with a long-standing response, suggesting that this serum test may be a reliable marker for monitoring response to IFN therapy in patients with CHC. Finally, L-IFN treatment induced significant increments in CD4/CD8 index, phytohemagglutinin-induced blastogenesis, and natural killer activity. This study shows that L-IFN diminish inflammatory and fibrogenic activity in most patients with CHC. In 40% of patients treated in this trial, a long-standing remission of the disease was observed.

Adult↗
PubMed1992

The stilbene disulfonic acid DIDS stimulates the production of TNF-alpha in human lymphocytes.

Exposure of human peripheral blood mononuclear cells (PBMC) to the stilbene derivative DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) (60 microM and above) significantly increased the release of tumor necrosis factor-alpha (TNF-alpha), as determined by TNF-alpha activity in the incubation media. When the TNF-alpha message was analyzed in PBMC by a reverse transcription/polymerase chain reaction (RT/PCR)-based procedure, it was found that incubation with DIDS (60 microM) was followed by a time-dependent accumulation of TNF-alpha mRNA. Measurements of intracellular pH showed that the presence of increasing concentrations of DIDS resulted in a progressive intracellular alkalinization of PBMC. It is suggested that the known DIDS effect of inhibiting transmembrane anion exchange, i.e., chloride/bicarbonate exchange, might play a role in the stimulation of TNF-alpha production by PBMC exposed to DIDS.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

[Monocytic dysfunction by opioid peptides in patients with major depression].

BACKGROUND: Patients with depression present immunodepression and it has been proposed that, in these patients, endogenous opioid peptides may be mediators between the dysfunction of the central nervous system and immune alterations. METHODS: The function and the surface markers of monocytes were studied in 15 patients with major unipolar depression and in 24 healthy controls by biological trials of phagocytosis of Candida albicans and latex particles and immunofluorescence with monoclonal antibodies. RESULTS: Most of the patients studied (86%) presented monocytic dysfunction characterized by diminished phagocytic activity and a decrease in the expression of intermediate filaments of vimentin of the cytoskeleton and membrane molecules (CR1, receptor for the Fc fraction of the IgG and HLA DR antigens). Incubation of the patients monocytes with naloxone led to the disappearance of monocytic alterations in most of the patients. CONCLUSIONS: Patients with major unipolar depression present a high opioid tone which has consequences in the function of the immune system.

Adult↗
PubMed1992

Expression of integrins and other adhesion molecules in Epstein-Barr virus-transformed B lymphoblastoid cells and Burkitt's lymphoma cells.

Lymphocytes adhere to cells or extracellular matrices to perform functions relating to cytotoxicity, extravasation and tissue localization, as well as modulation of lymphocyte growth and maturation. This adherence is mainly mediated by 3 families of cell-surface adhesion molecules: integrins, immunoglobulin-related molecules and selectins. Since variations in the degree of adherence may affect the pathophysiology of lymphoproliferative disorders, the expression of a large number of adhesion molecules was analysed on Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs), and on EBV-positive or EBV-negative Burkitt's lymphoma (BL) lines, by immunofluorescence flow cytometry and immunoprecipitation with monoclonal antibodies. With regard to the beta 1, beta 2 and beta 3 integrin subfamilies, LCLs strongly expressed CD49d/CD29 (VLA-4), CD11a/CD18 (Leu-CAMa, LFA-1) and CD51/CD61 (vitronectin receptor). These cells also abundantly expressed CD54 (ICAM-1) and CD58 (LFA-3) as well as the "homing receptors" L-selectin (LECAM-1) and CD44. BL lines had considerably lower amounts of VLA-4 than LCLs, and ICAM-1 was expressed only by some of the tumor lines. All other adhesion molecules were absent or minimally expressed in the BL cells.

Antibodies, Monoclonal↗
PubMed1992

Induction of cytotoxic T lymphocytes in mice against the principal neutralizing domain of HIV-1 by immunization with an engineered T-cytotoxic-T-helper synthetic peptide construct.

Peptide constructs were engineered by colinear synthesis of two short synthetic peptide determinants; a determinant recognized by T helper cells (TDh) and a determinant recognized by T cytotoxic cells (TDc). Three types of constructs were synthesized: TDc-TDh, TDh-TDc, and TDh-KK-TDc, where KK are two lysine residues. In vivo immunization with free construct induced cytolytic lymphocytes (CTL) only in the case of TDc-TDh. However, immunization with spleen cells to which these constructs had been internalized by hypertonic shock, induced CTL activity in all three cases. No CTL could be induced after immunization with free TDc in either protocol. These results indicate that cell internalization of the construct might be essential for CTL induction, and also, that "help" from the TDh seems to be required.

Amino Acid Sequence↗
PubMed1992

[Detection of hepatitis B virus DNA in serum by gene amplification in patients with chronic hepatitis B and in patients chronic hepatitis C].

BACKGROUND: The polymerase chain reaction (PCR) constitutes important methodological progress for detecting the presence of viral nucleic acids when these are found in small quantities in serum or tissues. The aim of this study was the use of PCR to detect DNA of the hepatitis B virus (HBV) in patients with chronic HBsAg positive hepatitis (HC-B) and in patients with chronic non A non B hepatitis with antibodies against the virus of hepatitis C (anti-HCV) positive (HC-C). METHODS: The DNA of the HBV was determined with PCR in the serum of 40 patients with HC-B and in 15 with HC-C. Moreover, the presence of anti-HCV was studied in the patients with HC-B. RESULTS: The presence of DNA of the HBV was detected by PCR in 69% of the HC-B patients presenting HBeAg positive and DNA of the HBV negative by simple hybridization as well as in 50% of the patients with HBeAg negative, anti-HBe positive and DNA of HBV negative by simple hybridization. In addition, DNA of HBV was detected by PCR in 27% (4/15) of the subjects with HC-C, three of whom had anti-HBc antibodies. On the other hand, 20% of the patients with HC-B had anti-HCV. Anti-HCV positivity was associated to a greater hypertransaminasemia in patients with HC-B in a non replicative phase. CONCLUSIONS: PCR is a sensitive method for detecting viral replication. Its use permits the detection of low DNA concentrations of the HBV in a low but appreciable percentage of chronic negative HBsAg hepatitis. Coinfection by the B and C viruses of hepatitis is not exceptional and explains hypertransaminasemia in some HC-B in a non replicative phase.

DNA, Viral↗
PubMed1992

Hepatitis B and C viral infections in patients with hepatocellular carcinoma.

The prevalence of hepatitis B and C virus infections was studied in 70 patients diagnosed as having hepatocellular carcinoma. In addition to viral serological markers, serum hepatitis B virus DNA and hepatitis C virus RNA were determined with a nested polymerase chain reaction assay. Twelve patients (17%) were HBsAg positive, 26 (37%) had antibodies to HBs, HBc or both and 32 (46%) were negative for all hepatitis B virus serological markers. Prevalence of the antibody to hepatitis C virus was 63% (44 patients). Hepatitis B virus DNA was detected in 24 of the 66 tested patients (36%). Twelve of these hepatitis B virus DNA-positive patients were HBsAg negative (seven were positive for antibody to HBs, antibody to HBc or both and five were negative for all hepatitis B virus serological markers). Hepatitis C virus RNA was found in 42 of 68 patients (62%). A high correlation (95%) existed between hepatitis C virus RNA and hepatitis C virus antibodies. Nevertheless, two patients without antibody to hepatitis C virus had serum hepatitis C virus RNA sequences. Coinfection by the two viruses was detected in nine subjects (14%), but no clinical differences were found between these and the rest of the patients. We conclude that nearly 90% (62 of the 70 patients studied) of cases of hepatocellular carcinoma in our geographical area are related to hepatitis virus infections (detected by serological or molecular studies). Hepatitis C is more prevalent than hepatitis B virus in patients with hepatocellular carcinoma, and the infection is still active when the tumor is diagnosed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗