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Biomedical subjects

I Castillo

Publications and source records attributed to I Castillo.

At least 55 records · Page 3Linked to original sources
PubMed1994

Virological and biochemical long-term follow-up of patients with chronic hepatitis C treated with interferon.

We studied the long-term outcomes of 43 patients with chronic hepatitis C treated with one or two interferon cycles, in relation to hepatitis C virus RNA in serum and peripheral-blood mononuclear cells. After the first interferon cycle, 15 (35%) patients had normal transaminase levels, although only five of them had normal levels throughout follow-up (complete responders). After treatment, hepatitis C virus RNA was detected in serum and peripheral-blood mononuclear cells with a similar frequency among the five complete responders (60% and 40%, respectively) and the 10 responders with relapse (50% and 20%, respectively). During the follow-up of the complete responders (up to 27 mo), fluctuating viremia levels were found, as demonstrated by the intermittent serum hepatitis C virus RNA positivity. In responders with relapse serum hepatitis C virus RNA reappeared concurrent with the relapse, without changes in peripheral-blood mononuclear cells. A second interferon cycle was performed in 23 nonresponders. Six of them had normalized transaminase levels but four had relapses. After retreatment, hepatitis C virus RNA was detected in peripheral-blood mononuclear cells with the same frequency (50%) in complete responders and in responders with relapse. Loss of serum hepatitis C virus RNA was only achieved in responders with relapse. During the follow-up, half of the complete responders lost serum hepatitis C virus RNA. This marker reappeared in responders with relapse, and hepatitis C virus RNA was found de novo in PBMCs of one responder with relapse. None of the 17 nonresponders to retreatment lost hepatitis C virus RNA in serum or PBMCs during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Treatment with recombinant alpha-interferon of chronic hepatitis C in anti-HIV-positive patients.

A pilot study of chronic hepatitis C treatment was conducted in 14 patients (13 had chronic active hepatitis and 1 had liver cirrhosis). All patients were asymptomatic for the human immunodeficiency virus (HIV) type 1 (mean CD4 count of 584 +/- 283 cells/mm3). Patients received 9 MU rIFN-alpha 2A per day for three months. After this, patients received 9 MU three times weekly for three months, 6 MU for another three months on the same protocol, and finally 3 MU again three times weekly for the last three months. After the first month of ALT treatment in 9 patients (64%) returned to normal; a significant decrease in ALT levels was observed with respect to the pretreatment values (mean of 42 IU/l, range 15-75 vs 152 IU/l, range 69-355; P < 0.01). Of the 9 patients who completed the treatment period, 5 had a complete response, and 4 of these 5 continued with normal ALT values during follow-up (sustained response) while the other patient relapsed within one month after cessation of therapy. The remaining 4 patients were non-responders (including one case with a break-through of the response). HCV-RNA was not detectable in 3 of the 5 responders at the end of therapy while during follow-up viral RNA became undetectable in the other 2 patients. 2/4 non-responder patients had detectable HCV-RNA during follow-up. Liver histology improved in all the patients. No changes were observed in the immunological status or HIV infection.

Adult↗
PubMed1993

Effects of enhancer mutations on the expression of human immunodeficiency virus 1-regulated luciferase and diphtheria toxin A chain genes in transfected cells.

This study explores human immunodeficiency virus 1 (HIV-1)-regulated diphtheria toxin A (DT-A) gene expression as a means of eradicating HIV-infected cells. Previously, we constructed luciferase and DT-A plasmids, containing cis-acting Tat and Rev responsive elements, which showed low basal expression and required both Tat and Rev for maximal expression. Cell lines which had stably integrated the DT-A constructs were resistant to HIV production. To reduce toxicity due to basal expression, this study investigates the effect of mutations in the HIV enhancer on expression of luciferase and DT-A plasmids. Some mutations were found to substantially reduce basal expression while still allowing for trans-activation. Such mutations, in combination with attenuated versions of DT-A, may make regulated toxin gene expression feasible as a therapy for AIDS.

Diphtheria Toxin↗
PubMed1993

Detection of hepatitis C virus RNA in serum and peripheral blood mononuclear cells.

Hepatitis C virus (HCV) RNA is the most reliable marker of HCV infection. However, because of HCV genome heterogeneity and the procedures used to isolate the viral genome and to perform the amplification steps, results do not accurately reflect the actual rate of HCV infection. In this study, several isolation procedures and sets of primers to perform PCR were compared for the detection of HCV-RNA in serum and peripheral blood mononuclear cells (PBMC) of patients with HCV infection. It was found that the extraction with guanidinium isothiocyanate prior to cDNA synthesis followed by PCR amplification of the 5'-UTR region gave the best results in serum and PBMC. The presence of the viral genome in PBMC is a frequent event during HCV infection and this has important consequences for the understanding of the viral pathogenesis.

Base Sequence↗
PubMed1993

Significance of low HDV replication levels during the natural history of HDV infection. Long-term follow-up.

The use of genetic amplification of the hepatitis delta virus (HDV) genome reveals the existence of different HDV replicative behaviours during the natural history of chronic HDV infection. While some of the patients (8/19, 42%) presented high and long-term maintained levels of HDV replication, as detected by slot-blot hybridization, others showed fluctuations from positive to negative, and in 5/7 (71%) polymerase chain reaction (PCR) demonstrated the presence of the HDV genome. Finally, 4 patients were persistently slot-blot-negative and in 3 of them HDV-RNA was detected by PCR in all samples tested. The correlation observed between the low levels of HDV replication and the ALT values, as well as the reactivation observed in one of the patients, suggests that PCR is useful in the virological surveillance of HDV infection, and indicates its usefulness in evaluating the effectiveness of antiviral therapy for chronic hepatitis D.

Follow-Up Studies↗
PubMed1993

Treatment of chronic hepatitis B with recombinant interferon alpha versus recombinant interferon alpha plus levamisole.

To compare the efficacy and tolerance of the simultaneous administration of levamisole plus IFN versus treatment with IFN alone in chronic hepatitis B, 39 patients were randomly assigned into two groups. Nineteen patients received 15 million units of recombinant alpha interferon 2b (rIFN-alpha 2b) 3 times a week for 4 months. The other 20 patients were treated with the same dose and schedule of rIFN-alpha 2b and 150 mg of levamisole simultaneously given during the first 6 weeks of treatment. At the end of the study (thirteenth month), serum HBV-DNA was negative in 59% of patients treated with interferon alone and in 37% of those treated with interferon and levamisole. HBeAg was negative in a similar percentage in the two groups (41% vs. 37%). Serum alanine aminotransferase levels decreased in patients who lost viral DNA. These data demonstrate that the combination of alpha interferon and levamisole, at the doses and under the schedule used in this study, does not achieve better results than the treatment with alpha interferon alone. Although tolerance to the simultaneous administration of alpha interferon and levamisole is good, secondary effects may be hazardous.

Adolescent↗
PubMed1993

Levamisole and interferon in children with chronic hepatitis B.

To evaluate the possible usefulness of simultaneous administration of levamisole and interferon, we randomly allocated 38 children with chronic hepatitis B to receive either 10 MU/m2 interferon-alpha-2a, three times a week for 6 mo (group 1, n = 20) or 90 mg/m2 of levamisole for 45 days, together with 10 MU/m2 of interferon-alpha-2a, three times a week for 6 mo (group 2, n = 18). At the end of the follow-up period (15 mo), no significant differences were observed between the groups with respect to loss of hepatitis B virus DNA and HBeAg from serum and normalization of serum ALT levels. During therapy, a significant increase in the serum levels of ALT and soluble interleukin-2 receptor was observed in both groups but was higher in patients from group 2. The combination of levamisole with interferon was associated with severe side effects. In summary, the combination of levamisole with interferon in children with chronic hepatitis B does not improve the results obtained with interferon alone.

Adolescent↗
PubMed1993

Vaginal birth after cesarean section: the patient's point of view.

Advocacy of vaginal birth after cesarean section (VBAC) is the current standard of care. We interviewed patients in our program about their attitudes toward VBAC and cesarean section. The success rate in our VBAC program is similar to rates reported in the literature (65 percent). However, interviews with our patients revealed that 40 percent had no desire to participate in the VBAC program, although they fulfilled the criteria for eligibility. The main reasons given for declining a trial of VBAC were the convenience of an elective cesarean section and fear of another prolonged, painful and potentially dangerous labor. Thirty-two percent of patients in whom VBAC was successful were dissatisfied with the experience and would have preferred an elective cesarean section. The reasons patients gave for attempting VBAC were different from the medical reasons proposed to them. The main reasons given were a desire to deliver "naturally," a fear of surgery and the concern that cesarean section might harm them or their baby.

Apgar Score↗
PubMed1992

Treatment of children with chronic hepatitis C with recombinant interferon-alpha: a pilot study.

Twelve children with chronic non-A, non-B hepatitis were entered in a pilot trial of recombinant interferon-alpha. Although all the children had hepatitis C virus RNA in serum, only five had antibodies against this virus. Children received 3 MU/m2 body surface area interferon-alpha 3 times/wk for 6 mo; they were followed for 24 mo, including the therapy period. One child was dropped from the study, so the results are from the 11 children who completed the study. At the end of the therapy period, 36% of the children had normal ALT levels; this percentage increased to 90% at mo 15 of follow-up. Thereafter, relapse occurred in five children; thus ALT normalization was observed in 5 of 11 children at the 24th month. Moreover, two different ALT patterns were found: HCV antibody-negative children had significant peaks of ALT levels with respect to the basal samples (p less than 0.05) until the third month of the therapy; these levels later decreased. In contrast, HCV antibody-positive children had slight fluctuations of ALT until normal levels were reached. At the end of treatment, three children had HCV RNA; one demonstrated a rebound in ALT levels. Finally, histological activity had decreased significantly in the second liver biopsy specimen in all children. In summary, interferon treatment in children with chronic hepatitis C may be helpful, although these results should be confirmed in controlled trials.

Adolescent↗
PubMed1992

Treatment of chronic hepatitis C by continuous subcutaneous infusion of interferon-alpha.

The effectiveness of a daily continuous infusion of interferon-alpha was evaluated in 12 patients (10 males, 2 females; mean age of 33 years, range 19-62) with biopsy-proven chronic active hepatitis C. Nine million units (MU) of recombinant interferon-alpha 2A (rIFN-alpha 2A) were administered by continuous subcutaneous infusion with a portable syringe pump, Graseby model MS 16A, for 24 h over 28 days. A significant decrease (P less than 0.01) in median serum alanine aminotransferase (ALT) levels was observed after the first week of treatment (96 IU/L, range 58-263) with respect to the pre-treatment values (188 IU/L, range 119-670). ALT became normal in four patients only by the fourth week. When IFN was interrupted, an increase in ALT was observed in all patients (1.5 to 5 times the pre-treatment values). The maximum decrease in ALT coincided with a significant increase in serum levels of the enzyme 2',5'-oligoadenylate (2-5A) synthetase (two to fourteen times the pretreatment values) and these parameters were inverse-correlated (r = -0.598, P less than 0.05). 2-5A synthetase levels returned to pre-treatment values after discontinuing IFN administration. Hepatitis C virus (HCV) RNA (as detected by the polymerase chain reaction using oligonucleotide primers of the NS5 region) was positive in all cases, remaining so during the treatment period. IgM antibody to HCV (as tested by ELISA) was present in 10/12 cases at baseline without changes throughout the study. No irreversible side effects were noted during therapy, which needed to modify the schedule.(ABSTRACT TRUNCATED AT 250 WORDS)

2',5'-Oligoadenylate Synthetase↗
PubMed1992

Immunoglobulin M antibody to hepatitis C virus during interferon therapy for chronic hepatitis C.

Testing for immunoglobulin (Ig) M antibody to hepatitis C virus (anti-HCV) as a predictive factor of therapeutic response to recombinant interferon alfa (rIFN-alpha) in chronic hepatitis C was evaluated in 122 patients with IgG anti-HCV. IgM anti-HCV was present in the pretreatment sample of 88% of patients who responded to treatment, including 20 of 21 (95%) long-term responders and 24 of 29 (83%) responders who had relapses after cessation of therapy. In contrast, IgM anti-HCV was present in only 23 of 39 (59%) nonresponders and 22 of 33 (66%) untreated controls (P less than 0.05). The number of cases with detectable IgM anti-HCV tended to decrease in responder patients, which was more evident for complete responders (42%) than for responders who relapsed (72%). During follow-up, the antibody became undetectable in the majority of long-term responders (28% were still IgM anti-HCV positive) but remained detectable in 69% of responders who relapsed (P less than 0.05). No special changes were noted in nonresponder or control patients. Thus, testing for IgM anti-HCV may help to identify a subset of patients who will benefit from rIFN-alpha therapy in chronic hepatitis C.

Adult↗
PubMed1992

Comparison of several PCR procedures for detection of serum HCV-RNA using different regions of the HCV genome.

Different methods for the isolation of hepatitis C virus RNA and several sets of primers from the 5' untranslated, core, NS3, NS3/NS4 and NS5 regions of the hepatitis C virus genome were used for the detection of the viral genome by the polymerase chain reaction. Serum samples from 10 patients with chronic hepatitis C and 10 healthy controls were studied. The best method for the RNA extraction was with cold guanidinium isothiocyanate followed by a denaturation step prior to the polymerase chain reaction. Using this method, the percentage of positivity to hepatitis C virus sequences in serum depending on the region amplified were: 5' untranslated, 90%; Core, 20%; NS3, 80%; NS3/NS4, 60% and NS5, 60%.

Base Sequence↗
PubMed1992

Long-term follow-up of hepatitis B chronic carriers who responded to interferon therapy.

We studied the long-term outcome of patients with chronic hepatitis B virus (HBV) infection who responded to interferon (IFN) therapy. Between 1983 and 1988, 120 patients were included in 5 different protocols; 94 patients were treated with IFN and 26 were controls. Loss of serum HBV-DNA was considered a partial response and occurred in 34 of the treated patients and in 10 of the controls. Only the partial-response patients were followed up for 14-64 months (mean 46 months). HBeAg disappeared in 32/34 of the partial-response treated patients and in 9/10 of the controls. During the follow-up period, 6/34 (18%) treated patients and 1/10 controls suffered a reactivation of the disease with reappearance of HBV-DNA. Only 8/34 (23%) treated patients and 1/10 of the controls lost HBsAg; no statistical differences were observed in baseline characteristics between HBsAg-negative patients and patients who remained HBsAg-positive. Of eight HBsAg-negative treated patients, four were serum HBV-DNA-negative upon polymerase chain reaction and thus formed the HBsAg-negative control cases. Although the frequency of HBsAg loss in treated patients is relatively low, the improvement in liver disease obtained from IFN therapy is sustained over a long period.

Adolescent↗
PubMed1992

Protein composition of the hepatitis B virus e antigen in the natural course of disease and following interferon therapy.

The protein composition of hepatitis B virus (HBV) e antigen (HBeAg) in serum was analyzed for 63 viremic patients with chronic HBV and found to consist of polypeptides with molecular masses of 16, 18, and 20 kDa (P16e, P18e, and P20e, respectively). Several experiments demonstrated their viral nature and HBeAg specificity and that P16e occurs either in free soluble form or as aggregates or immunocomplexes, while P18e and P20e occur essentially as immunocomplexes. Of 63 patients, 45 (71%) had P16e, P18e, and P20e, and the remaining 18 (29%) had only P16e. During the natural history of the disease, spontaneous clearance of HBV DNA and HBeAg took place only in six of nine (67%) patients with the three HBe polypeptides but in none of the five patients having P16e alone (P less than 0.05). Similarly, 22 of 23 (96%) patients responding to interferon therapy had P16e, P18e, and P20e, but these polypeptides occurred in only 14 of 26 (54%) nonresponder patients (P less than 0.001). Following the loss of HBV DNA and HBeAg, before the development of anti-HBe, the only HBe species detected were P18e and P20e, but these became no longer detectable after complete normalization of liver function tests. Therefore, persistence of P16e represents a failure to recover from HBV, and the appearance of HBe polypeptides P18e and P20e is associated with virus clearance and a favorable outcome of the disease.

Adolescent↗
PubMed1991

High doses of recombinant alpha-interferon or gamma-interferon for chronic hepatitis C: a randomized, controlled trial.

Chronic hepatitis C is often a progressive liver disease for which there is no satisfactory treatment. We studied the efficacy of recombinant alpha-interferon or gamma-interferon in the treatment of this disease in comparison with a control group. Thirty patients were randomly assigned to three groups. Ten patients received 7.5 MU alpha-interferon/m2 body surface three times weekly for 3 mo, then 5 MU/m2 for 3 mo and 2.5 MU/m2 for 6 mo. Ten patients were treated with gamma-interferon at a dose of 2 MU/m2 for 6 mo and the other 10 served as controls without treatment. The mean serum ALT levels and liver histological findings improved significantly only in the patients treated with alpha-interferon. No changes were observed in patients treated with gamma-interferon or in controls. Five of 10 patients treated with alpha-interferon had complete responses (mean ALT normal during therapy). After treatment ALT returned to pretreatment levels in two of 5 patients. The long-term response rate after alpha-interferon therapy was 30% at 18 mo. We conclude that alpha-interferon is effective in controlling disease activity in a portion of patients with chronic hepatitis C. High doses of alpha-interferon do not appear to add further benefit in the response rate or relapse rate. gamma-Interferon therapy is ineffective.

Adult↗
PubMed1991

Detection of serum inhibitory factor for lymphocyte stimulation in chronic viral hepatitis: relationship with the replication level.

Sera from 111 patients with chronic viral hepatitis and from 55 cases with other liver disorders were assayed for serum inhibitory factor. The prevalence of this immunosuppressive factor was very similar between chronic hepatitis B (61%), chronic hepatitis delta (57%) and chronic hepatitis C (68%). At the same time, serum inhibitory factor was never detected in the other disorders studied. The presence of this inhibitory factor was detected in a significantly higher percentage (p less than 0.05) of HBeAg, HBV-DNA positive cases (75%) than in anti-HBe positive, HBV-DNA negative cases (44.4%). In chronic hepatitis delta, this immunosuppressive factor was also related to HDV-RNA positivity. The detection of this serum immunosuppressive factor in chronic viral hepatitis and its association with a high viral replication level implies a possible role of this factor in the immune pathogenic mechanism in infectious viral hepatitis.

Adult↗
PubMed1991

Analysis of hepatitis B virus DNA, liver disease and influence of antibody to hepatitis C virus in anti-HBe chronic carriers.

Hepatitis B virus DNA (HBV-DNA) in serum was studied in 67 anti-HBe patients using dot-blot hybridization, a modified technique and polymerase chain reaction (PCR). All patients had abnormal aminotransferase (ALT) levels. Serum HBV-DNA was detected in 14/67 cases by dot-blot and in 39/67 (DNA probe) and 45/67 (RNA probe) using the modified technique. The RNA probe was more sensitive than the DNA probe when they were compared, using serial dilutions of HBV-DNA of known concentration (0.1 pg vs 1 pg, respectively). HBV-DNA was found by PCR in 57/67 patients. Ten patients were negative to serum HBV-DNA. The ALT level was significantly higher in patients with serum HBV-DNA by dot-blot as compared to those who had serum HBV-DNA by the modified technique and PCR. With respect to the presence of anti-HCV, 6/67 had anti-HCV confirmed by RIBA test. These 6 patients had serum HBV-DNA. The route of acquisition of HBV infection in anti-HCV positive patients was by parenteral exposure in 67% of the cases and 15% in HCV negative (p less than 0.05). All patients were negative to nonorganic specific autoantibodies. In summary, most of the anti-HBe patients (85%) had viral replication. HCV superinfection plays a minor role in the activity of liver disease.

Adult↗