Effects of manual therapy on treatment duration and motor development in infants with severe nonsynostotic plagiocephaly: a randomised controlled pilot study.

PURPOSE: Despite growing evidence regarding nonsynostotic plagiocephaly and their repercussions on motor development, there is little evidence to support the use of manual therapy as an adjuvant option. The aim of this study was to evaluate the effects of a therapeutic approach based on manual therapy as an adjuvant option on treatment duration and motor development in infants with severe nonsynostotic plagiocephaly. METHODS: This is a randomised controlled pilot study. The study was conducted at a university hospital. Forty-six infants with severe nonsynostotic plagiocephaly (types 4-5 of the Argenta scale) referred to the Early Care and Monitoring Unit were randomly allocated to a control group receiving standard treatment (repositioning and an orthotic helmet) or to an experimental group treated with manual therapy added to standard treatment. Infants were discharged when the correction of the asymmetry was optimal taken into account the previous clinical characteristics. The outcome measures were treatment duration and motor development assessed with the Alberta Infant Motor Scale (AIMS) at baseline and at discharge. RESULTS: Asymmetry after the treatment was minimal (type 0 or 1 according to the Argenta scale) in both groups. A comparative analysis showed that treatment duration was significantly shorter (p < 0.001) in the experimental group (109.84 ± 14.45 days) compared to the control group (148.65 ± 11.53 days). The motor behaviour was normal (scores above the 16th percentile of the AIMS) in all the infants after the treatment. CONCLUSIONS: Manual therapy added to standard treatment reduces the treatment duration in infants with severe nonsynostotic plagiocephaly.

Drug utilization pattern in children and off-label use of medicines in a pediatric intensive care unit.

OBJECTIVE: This study aims to assess the prescription profile and license status of drugs used in a neonatal and pediatric intensive care unit (NPICU). METHODS: A prospective observational study was conducted on a dynamic cohort of children admitted to an NPICU (N=81) in a tertiary hospital (Granada, Spain). All prescriptions were classified as off-label or unlicensed based on the summary of product characteristics (SPC). RESULTS: Of a total of 601 prescriptions, the patients received a mean of 7.4 ± 6 drugs each. The most commonly prescribed drugs corresponded to classes J (anti-infectious, systemic use) N (nervous system) and C (cardiovascular). A little over one-half of the prescriptions were off-label (52%), usually due to dosages differing from the SPC recommendations (79%), followed by different indications (13.5%), age (5%) and administration route (2.5%). In this NPICU, unlicensed usage represented only 5% of all prescriptions. CONCLUSIONS: This study contributes data on prescription of this kind in a Spanish NPICU, revealing at least one off-label prescription in 89% of the children and at least one unlicensed use in 22.3%. These are high figures, but are to be expected given the inclusion of newborn infants and the critical care setting. Even though such usage follows clinical protocols, we underscore the dual need to base treatment on the best available evidence, and to upgrade the SPC accordingly.

Clinical profile and evolution of infants with deformational plagiocephaly included in a conservative treatment program.

PURPOSE: The aim of this study was to evaluate the results of a conservative intervention in infants with plagiocephaly according to their specific clinical profile. METHODS: Prospective clinical trial in which 104 infants with plagiocephaly accompanied or not by congenital or positional torticollis were referred to Early Care and Monitoring Unit (USAT) of San Cecilio Hospital in Granada, between 2009 and 2012. All the infants, grouped into three categories of severity, were included in the physiotherapy protocol until adequate craniofacial morphology and motor development were achieved. The study included an assessment of parents and infants. Parents were assessed with a questionnaire about the mother's medical history and birth-related issues. The assessment of infants included anthropometric measures, a positional assessment, the observation of the head, the assessment of severity, and motor development. RESULTS: Birth characteristics were similar in the total sample but showed different clinical profiles according to treatment aspects. More specifically, infants with severe plagiocephaly were referred to treatment later and spent more time in treatment; use of an orthotic helmet was also more prevalent in this category. There were also significant differences (P < 0.05) in the acquisition of specific gross motor skills depending on the severity of plagiocephaly. CONCLUSION: The findings suggest that the physiotherapy protocol presented is effective to correct plagiocephaly. Severity of plagiocephaly is a marker that should be taken into account when designing actions aimed at improving gross motor skill development.

Mutations in E2-PePHD, NS5A-PKRBD, NS5A-ISDR, and NS5A-V3 of hepatitis C virus genotype 1 and their relationships to pegylated interferon-ribavirin treatment responses.

Mutations in several subgenomic regions of hepatitis C virus (HCV) have been implicated in influencing the response to interferon (IFN) therapy. Sequences within HCV NS5A (PKR binding domain [PKRBD], IFN sensitivity-determining region [ISDR], and variable region 3 [V3]) were analyzed for the pretreatment serum samples of 60 HCV genotype 1-infected patients treated with pegylated IFN plus ribavirin (1b, n = 47; 1a, n = 13) but with different treatment outcomes, those with sustained virologic responses (SVR; n = 36) or nonresponders (NR; n = 24). Additionally, the sequence of the PKR/eIF-2alpha phosphorylation homology domain (E2-PePHD) region was determined for 23 patients (11 SVR and 12 NR). The presence of > 4 mutations in the PKRBD region was associated with SVR (P = 0.001) and early virologic responses (EVR; 12 weeks) (P = 0.037) but not rapid virologic responses (4 weeks). In the ISDR, the difference was almost statistically significant (68% of SVR patients with mutations versus 45% without mutations; P = 0.07). The V3 region had a very high genetic variability, but this was not related to SVR. Finally, the E2-PePHD (n = 23) region was well conserved. The presence of > 4 mutations in the PKRBD region (odds ratio [OR] = 9.9; P = 0.006) and an age of < or = 40 years (OR = 3.2; P = 0.056) were selected in a multivariate analysis as predictive factors of SVR. NS5A sequences from serum samples taken after 1 month of treatment and posttreatment were examined for 3 SVR and 15 NR patients to select treatment-resistant viral subpopulations, and it was found that in the V3 and flanking regions, the mutations increased significantly in posttreatment sera (P = 0.05). The genetic variability in the PKRBD (> 4 mutations) is a predictive factor of SVR and EVR in HCV genotype 1 patients treated with pegylated IFN and ribavirin.

Modulation of transcription by PARP-1: consequences in carcinogenesis and inflammation.

Post-translational modification of proteins by poly(ADP-ribosyl)ation is involved in the regulation of a number of biological functions. While an 18 member superfamily of poly(ADP-ribose) polymerases (PARP)s has been described PARP-1 accounts for more than 90% of the poly(ADP-ribosyl)ating capacity of the cells. PARP-1 act as a DNA nick sensor and is activated by DNA breaks to cleave NAD(+) into nicotinamide and ADP-ribose to synthesize long branching poly(ADP-ribose) polymers (PAR) covalently attached to nuclear acceptor proteins. Whereas activation of PARP-1 by mild genotoxic stimuli facilitate DNA repair and cell survival, severe DNA damage triggers different pathways of cell death including PARP-mediated cell death through the translocation of apoptosis inducing factor (AIF) from the mitochondria to the nucleus. PAR and PARP-1 have also been described as having a function in transcriptional regulation through their ability to modify chromatin-associated proteins and as a cofactor of different transcription factors, most notably NF-kappaB and AP-1. Pharmacological inhibition or genetic ablation of PARP-1 not only provided remarkable protection from tissue injury in various oxidative stress-related disease models but it result in a clear benefit in the treatment of cancer by different mechanisms including selective killing of homologous recombination-deficient tumor cells, down regulation of tumor-related gene expression and decrease in the apoptotic threshold in the co-treatment with chemo and radiotherapy. We will summarize in this review the current findings and concepts for the role of PARP-1 and poly(ADP-ribosyl)ation in the regulation of transcription, oxidative stress and carcinogenesis.

The antigenic variability of HCV in viral HLA-Ag binding is related to the activation of the host immune response.

Our previous data show that hepatitis C virus (HCV) genotype 1 patients expressing the HLA-DQB1 * 0301 allele have a combined response probability of 69%, while the remaining 31% do not respond, probably because the HCV immunodominant epitope (IE) against the DQB1 * 0301 allele is mutated. HCV IE (region sequenced in NS3 is a region encoding aa 1253-1272) from 37 patients (21 Sustained Virological Response, SVR; 16 non-SVR) HLA-DQB1 * 0301+, were analysed by pyrosequencing. In vitro cultures were also determined by CD4+ proliferation, using non-mutated IE (wild-type synthetic peptide) and synthetic mutated peptide. The pyrosequencing study revealed 34 different haplotypes. The SVR patients had fewer haplotypes (P = 0.07), mutations/haplotypes (P = 0.01) and polymorphic sites (P = 0.02) than non-SVR. Three polymorphic sites were associated with the non-SVR patients: haplotype 7 (L5P); haplotype 11 (L7P); and haplotype 15, (L15S) (P = 0.02). The in vitro study (n = 7) showed that in 4/7 patients (Group 1) the CD4+ proliferation obtained with wild-type synthetic peptide was higher than that obtained with the negative control and with the synthetic mutated peptide (P = 0.039). However, in the remaining 3/7 patients (Group 2) this pattern was not observed (P = 0.7). Our findings suggest that HLA-DQB1 * 0301+ patients with high antigenic variability in HCV IE (NS31253-1272) have a lower SVR rate, due to reduced CD4+ proliferation as a result of incorrect viral HLA-Ag binding.

Influence of HLA class I, HLA class II and KIRs on vertical transmission and chronicity of hepatitis C virus in children.

BACKGROUND & AIM: There is evidence that maternal viral load of HCV during delivery influences the risk for Mother-to-child transmission (MTCT), but this does not explain all cases. We study the role of the immunogenetic profile (HLA, KIRs and KIR-ligand binding) of mothers and children in HCV-MTCT and in chronicity in the children. METHODOLOGY: 79 HCV-RNA (+) mothers and their 98 children were included. 24 children were infected, becoming chronic in 8 cases and clearing in 16. HLA-class-I and II and KIRs were determined by Luminex. RESULTS: MTCT study: The presence of HLA-C1-ligand in mothers and/or their children reduces the risk of transmission (mothers: Pc = 0.011, children: P = 0.033), whereas the presence of HLA-C2C2-ligand in mothers increases it (Pc = 0.011). In children KIR2DL3-HLA-C1 is a protector factor (Pc = 0.011). Chronicity in children study: Maternal DQA1*01 allele (Pc = 0.027), KIR2DS1 (Pc = 0.011) or KIR3DS1 (Pc = 0.011) favours chronicity in the child. The presence of the DQB1*03 allele (Pc = 0.027) and KIR2DS3 (P = 0.056) in the child and homozygosity for KIR3DL1/3DL1 (Pc = 0.011) and for the HLA-Bw4/Bw4 ligand (P = 0.027) is associated with viral clearance, whereas the presence of HLA-Bw6 ligand (P = 0.027), the binding of KIR3DS1-HLA-Bw4 (P = 0.037) and heterozygosity for KIR3DL1/3DS1 (Pc = 0.011) favour viral chronicity. Mother/child allele matching: In the joint HLA analysis, matching was greater between mothers and children with chronic infection vs those who had cleared the virus (67%±4.1 vs 57%±1.2, P = 0.003). CONCLUSIONS: The HLA-C1 ligand in the mother is related to MTCT, while several genetic factors of the mother or child are involved in the chronification or clearance of infection in the child. Matching allelic data is considered to be an indicator of HCV chronicity in the child and can be used as a potential prognostic test. This implies that NK cells may play a previously undocumented role in protecting against MTCT and that both NK cell immunity and adaptive T-cell responses may influence viral clearance in infected children.

Follow-up of transmission of hepatitis C to babies of human immunodeficiency virus-negative women: the role of breast-feeding in transmission.

BACKGROUND: The studies on hepatitis C virus (HCV) vertical transmission, the effect of potential risk factors and the role of breast-feeding have reported conflicting results. PATIENTS AND METHODS: Seventy-three infants of 63 anti-HCV-positive and anti-HIV-negative mothers were studied from 1993 to 1999 in the south of Spain. The mean period of follow-up in children was 29.2 +/- 19 months (range, 8 to 76 months); 6 (8%) children were lost to follow-up. Breast milk was studied for HCV-RNA in 68 samples of 35 mothers. RESULTS: Alanine aminotransferase was high in 19 (26%) and HCV-RNA was positive in 46 (63%) pregnant woman. Breast milk HCV-RNA was negative in nonviremic mothers and positive in 20% of the viremic mothers. The overall rate of vertical HCV transmission was 11.9% (n = 8) (95% confidence interval, 6 to 23%) if HCV-RNA was positive one or more times, but only 1.5% (n = 1) (95% confidence interval, 0.1 to 9%) if HCV-RNA was permanently positive. Seven HCV-infected children did not develop antibodies to HCV, and they had a spontaneous clearance of the virus. A 10-month-old baby was HCV-RNA-positive from birth to the end of the follow-up. The genotype in each of the infants was consistent with that of their mother. The rate of HCV transmission was higher for infants of mothers with higher HCV viremia (P < 0.01) and also for infants whose mothers were HCV-RNA-positive in breast milk (P < 0.05). There were no statistically significant differences between other risk factors. CONCLUSION: The presence of transitory viremia without seroconversion indicates that the vertical transmission of HCV is not important. This could be related to the viral charge and ingestion of milk of HCV-RNA-positive mothers. However, to advise avoidance of maternal breast feeding, it would be necessary to conduct larger studies.

Detection of hepatitis B virus in the liver by in situ hybridization (ISH) in HBsAg seropositive and seronegative patients.

The presence of hepatitis B virus (HBV) DNA in the liver of 119 patients was studied to assess the diagnostic value of in situ hybridization (ISH) and its relationship with viral replication and histological liver damage. Liver biopsies of 119 patients (55 hepatitis B surface antigen -HBsAg- seropositive and 64 HBsAg seronegative) were studied retrospectively. Among the HBsAg seropositive patients, the ISH was positive in 26 cases (47%) and negative in 29 (53%) and the former group had higher levels of serum transaminases. The hepatocyte number with positivity for HBsAg and hepatitis B core antigen (HBcAg) in the liver were similar in both ISH-positive and -negative patients. The histological activity index (Knodell) was higher in ISH-positive patients (11 vs 7, p < 0.001). Six patients out of 12 were positive by PCR. In the HBsAg seronegative patients, the ISH was negative in 57 cases and positive in 7. These 7 were positive for anti-HBs (5 cases) and/or anti-HBc (6 cases); 4 were confirmed by PCR. Thus, our data suggest that the ISH technique is useful for detecting viral nucleic acid in the liver, but that the HBV-DNA cannot always be considered as a replication marker, because we also show that some HBsAg seronegative patients with chronic liver disease do have HBV-DNA in their liver cells.

Determination of HCV RNA concentration by direct quantitation of the products from a single RT-PCR.

A novel method for the estimation of HCV RNA levels in vivo was developed, based on competitive RT-PCR. The use of the Tth DNA polymerase and 5' 32P-labeled antisense primer respectively reduced cross-contamination and permitted the direct quantification of viral loads by the analysis of the radioactivity of PCR products derived from a clinical sample and a competitive deleted template, separated previously on a polyacrilamide gel. A HCV fragment (H) and a competitive (deltaH) RNA templates were synthesized for optimizing the method. The minimal starting RNA detectable by RT-PCR was 40 copies. RT-PCR performed with ratios deltaH/H ranging from 1/1 to 1/20 revealed different relative percentages of both H and deltaH products, changing from 90% of deltaH product when the ratio was 1/1 to 5%, when it was 1/20. Regression analysis was adjusted to a linear model and served to further estimate HCV RNA loads from clinical samples. HCV RNA quantitation was carried out in 19 patients. Higher viral loads were related to type 1b infection and persistence of HCV RNA after interferon therapy. This method is simple, reproducible and useful for rapid estimation of HCV RNA load in vivo.

Low-dosage prophylactic vancomycin in central-venous catheters for neonates.

Neonatal infectious pathology remains one of the main causes of morbidity and mortality in this age group. The introduction of plasticized catheters for the administration of medication, fluidotherapy and parenteral nutrition was a significant advance in treatment of patients at risk, but also led to the appearance of infectious complications. Negative coagulase staphylococcus is the principal pathogen in most neonatal intensive care units. Recent studies have examined the prophylactic use of vancomycin in preterm babies receiving parenteral nutrition. We have evaluated the efficacy of this procedure, applied via the central venous catheters employed for all neonates, within the intensive care unit over a period of one year. Prophylactic vancomycin administered via the catheters significantly reduced the incidence of Gram-positive infections, despite the presence within this group of a greater number of septic risk factors than in the control group.

Neurodevelopment of neonates in neonatal intensive care units and growth of surviving infants at age 2 years.

SUMMARY: The presence of development disorders in neonates attended in a Neonatal Intensive Care Unit (NICU) is highly variable; the aim of this study, therefore, was to determine the evolution of somatic and neurosensory development in a group of neonates requiring treatment in the NICU and to analyse the perinatal and developmental aspects of children presenting abnormalities. PATIENTS AND METHODS: A total of 492 neonates (275 premature, 106 with birthweight < or =1500 g), who were treated in the NICU between January 1994 and December 1997, were followed-up until the age of 2 years. Data were obtained concerning birthweight, body length, head circumference, gestational age, normality of weight for gestational age, single/multiple birth, duration of stay in the NICU and the hospital, duration of mechanically assisted respiration and evolutive somatometry, neurological examination and the Brunet-Lezine development test, adjusted for the gestational age of the neonates, at 6, 12, 18 and 24 months. When abnormal results were detected, Early Attention (EA) programmes were applied. RESULTS: Somatometry at birth in relation to gestational age revealed a weekly weight gain of 8.6%, an increase in body length of 1% and in head circumference of 1% (p<0.001). The evolution of somatic development to the age of 2 years showed that neonates with a birthweight < or =1500 g did not reach the values of neonates with a greater birthweight. The prevalence of cerebral palsy among all neonates was 6.8%, 14.6% among those weighing < or =1500 g, 4% among those weighing 1501-2500 g and 5% among those weighing >2500 g. The overall rate of neurosensory injury was 10.5%. These neonates presented less somatic development than those did with no neurologic disorder. To sum up, most of the neonates attended in the NICU during the 1990s presented a normal pattern of development. Nevertheless, they should be the object of special attention during the first years of life, particularly those neonates with a birthweight < or =1500 g and those presenting neurosensory risk.

[Retrospective study of the incidence of hepatitis G virus infection in transfused patients]. / Estudio retrospectivo de la incidencia de infección por el virus de la hepatitis G en los pacientes transfundidos.

BACKGROUND: Recently the parenteral transmission of hepatitis G virus (HGV) has been shown. The aim of the study was to investigate the incidence of post-transfusion HGV. PATIENTS AND METHODS: HGV (RNA-HGV and anti-HGVE2) were retrospectively studied in 140 transfused patients. RESULTS: 12 (8.6%) were infected after transfusion: 9 of 12 (75%) the RNA-HGV remained detectable after 6 months and 3 (25%) seroconverted to anti-HGVE2. No patient had post-transfusional hepatitis criteria. In 5 (42%) the transaminases levels were slightly increased. The clinical evolution was favourable. No significant differences were found between patients with or without HGV infection. CONCLUSIONS: HGV is an agent associated with transfusion but it carries a low pathogenic capability.

[Coinfection with hepatitis G virus in chronic hepatitis C. Response to treatment with interferon alpha]. / Estudio de la coinfección por el virus de la hepatitis G en la hepatitis crónica C. Respuesta al tratamiento con interferón alfa.

BACKGROUND: It is thought that the cytopathic effect of HGV is not important. Nevertheless, the cytopathic effect on liver is less known in the cases of co-infection with HCV. The aim was to study the prevalence of co-infection in patients with chronic hepatitis C (CHC) and to analyse the clinical-epidemiological and histological data and the interferon (IFN) response. PATIENTS AND METHODS: We included 180 patients with CHC and the HGV-RNA was determined. RESULTS: The prevalence of co-infection was 12.2% (n = 22). No statistical differences were observed between the non co-infected and co-infected groups with regard to the age, sex, mechanism of transmission and alcohol abuse. Also, there were no differences in the hepatic biochemical, no organ-specific antibodies, histological lesions and Knodell index. The HCV biochemical response (BR) and virological response (VR) after 6 months post-IFN were the same in both groups (HGV negative: BR = 29%, VR = 12%; HGV positive: BR = 22%, VR = 18%). HGV was determined after 6 months posttreatment in the co-infected group (first cycle of IFN, n = 22; second cycle of IFN, n = 9): 12 (55%) were HGV-RNA negative and 5 (23%) HCV-RNA negative, (p = 0.021). When we compared the BR vs VR in this group, there were 12 HGV-RNA negative but only two had BR (NS). On the contrary, the BR was related to HCV-RNA negative (p = 0.023). CONCLUSION: The prevalence of HGV co-infection is important in our area (12.8%). The HGV does not increase the pathogenicity of HCV and does not change the IFN response, although the HGV is more IFN sensible than HCV. The determination of HGV is not necessary in patients with HCV.

[Intrafamilial contagion with the hepatitis B virus]. / Contagio intrafamiliar del virus de la hepatitis B.

BACKGROUND: A study of the intrafamilial transmission of the hepatitis B virus (HBV) and its relationship with the viral replication and epidemiological factors. METHODS: The intrafamilial transmission of 106 chronic carriers of HBV was evaluated: 79 were asymptomatic carriers (AC) and 27 had chronic liver disease (CLD). Overall 347 relatives of the first group individuals and 112 of the second group were investigated. In the index cases, all HBV markers were investigated, and also DNA-HBV in those with CLD. In the relatives, HBsAg, HBsAc and HBcAc were investigated. Also, a survey to evaluate the influence of socioeconomic and cultural factors was also carried out. RESULTS: The prevalence of markers was significantly higher in the relatives of patients with CLD (HBcAg, HBcAc and evidence of contact) followed by AC and controls. The most infective relation in AC was that of other contacts with significant differences from the mother-child relationship (HBsAc p less than 0.003, HBcAc p less than 0.01, and evidence of contact p less than 0.001). By contrast, in CLD the most infective relation was mother-child. The mother-child relation was more infective than the father-child one (HBsAg p less than 0.05, HBcAc p less than 0.03, and evidence of contact p less than 0.02). Regarding viral replication, it was found that the HBeAg and DNA positive patients were more infective. The prevalence of HBcAc and the evidence of contact increased with the time of living together of spouses. Finally, it can be stated in a general sense that, according to the results of the survey, the socioeconomic factors have a small influence on the familial transmission. CONCLUSIONS: The relatives of HBV carriers, particularly in the case of HC with high replication, have a high risk of transmission. Thus, their investigation and subsequent vaccination is mandatory.

[Prospective study of the incidence of post-transfusion hepatitis after the exclusion of donors positive for anti-HCV ELISA 2]. / Estudio prospectivo de la incidencia de hepatitis postransfusional después de la exclusión de los donantes anti-VHC ELISA 2 positivos.

BACKGROUND: The incidence of post transfusional hepatitis (PTH) after the exclusion of anti-HCV ELISA 2 positive donors is not well known. The aim of this study was to determine the incidence and type of PTH in 113 post transfused patients. METHODS: A post transfusional follow up was performed for at least one year with periodic controls of transaminase levels. When an increase in GPT level compatible with PTH was demonstrated investigation of all the virus related with the transfusion was carried out in both the donor and the transfused subject: HAV, HCV, HEV, HBV and CMV. RESULTS: Four cases (3.5%) were detected which fulfilled the PTH criteria with the following characteristics: short period of time between transfusion and the increase in GPT level, moderate GPT increase, moderate clinical expression and good evolution. In all the cases the viral study was negative and other non viral possibilities were eliminated. CONCLUSIONS: Transfusions are currently relatively safe and the increase in transaminases may not be related with transfusion.

[Retrospective multicenter study of the efficacy of interferon alpha in chronic hepatitis C]. / Estudio multicéntrico retrospectivo de la eficacia del interfeón alfa en la hepatitis crónica C.

BACKGROUND: Until very recently, interferon (INF) in Spain was authorized in chronic hepatitis C (C-HCV) at a dosis of 3 megaunits (mu) for 6 months. Nonetheless, the rate of maintained complete response is lower than that obtained with more prolonged treatments. The first aim of this study was to retrospectively know the effectiveness of alpha INF in patients treated for 6 or 12 months with a dosis of 3 or 5-6 MU. The second was to analyze the characteristics of the patients who achieved a maintained complete response. PATIENTS AND METHODS: Patients with C-HCV treated in 9 hospitals in Andalucía, Spain who fulfilled the following conditions were retrospectively analyzed: liver biopsy prior to treatment, positive test for anti HCV and a follow up of at least 6 months after alpha INF treatment. A total of 344 patients were studied: 267 treated with alpha INF-2b, 51 with alpha INF-2a and 26 with lymphoblastoid INF. One hundred ninety-five patients were treated for 6 months and 149 for 12 months. RESULTS: Seventy-seven (22%) of the patients presented maintained complete response, 170 (50%) did not respond and 97 (28%) relapsed. On comparing the three types of interferon used over 6 months, no significant differences were observed. Neither were differences found on comparing the dosis of 3 mu versus 5 or 6 mu. On analyzing the treatments of 6 and 12 months, the following was observed, respectively: maintained complete response 15% vs 32%, relapse 29% vs 30% and non responders 57% vs 38% (p < 0.001). Multivariate analysis demonstrated that the patients who responded the best to INF were those who presented the following characteristics: female sex, age under 40 years last, history of transfusion or IVDA, basal GPT level higher than 145 IU/I, GGT less than 55 IU/I, less evolved histologic lesions and duration of treatment over 12 months. CONCLUSIONS: Of the different treatments analyzed with alpha interferon in chronic hepatitis C, the best was found to be that with 3 mu during 12 months.

[Treatment of chronic non-A, non-B-C hepatitis]. / Tratamiento de la hepatitis crónica NANB-C.

Preventive measures, and particularly screening for anti-HCV donors, have diminished the incidence of HCV infections, however, a vaccine against the disease is necessary for an effective prevention. The most active treatment at this time, seems to be alpha-interferon, at the dosage of 3 MU during 6 months. Possibly larger doses during longer periods of time might improve response and recurrence indexes, but not sufficiently as to give indiscriminate treatment to all patients at great cost and with many adverse reactions. While waiting for better predictive factors, the most convenient therapy remains the indicated dosage during 6 months, followed by periodic assessment during 2-3 months of transaminase levels: if they remain normal, the patient should be reassessed later on, if there is a recurrence, another course of treatment should be tried; non-responders should not be treated again with single interferon; other combinations or different treatments should be tried.

Genomic and antigenomic chains of hepatitis C virus and hepatitis G virus in serum, liver and peripheral blood mononuclear cells.

OBJECTIVE: To determine HCV and HGV replication sites in patients with chronic hepatitis C and to study interaction between these two viruses. PATIENTS: HGV RNA was studied in 272 patients with chronic hepatitis C. Of these, 35 were positive (group I). Twenty-three patients with chronic hepatitis C not co-infected with HGV were selected (group II). RESULTS: Genomic and antigenomic chains of HCV were studied in both groups and those of HGV in group I in serum samples, peripheral blood mononuclear cells and liver tissue. In group I genomic chains of HCV and HGV were observed in 86 and 100%, respectively (ns), in serum samples (n = 35), and antigenomic chains in 17 and 23%, respectively (ns). In mononuclear cell samples (n = 15) 100% presented the genomic chain of HCV and 60% presented that of HGV (p < 0.05). Antigenomic chains were detected in 13 and 33%, respectively (ns). In liver tissue (n = 25) genomic chains were observed in 100 and 12%, respectively (p < 0.001); the antigenomic chain of HCV was detected in 76% while that of HGV was not present (p < 0.001). In group II genomic chains of HCV were found to be present in a very high percentage in all samples, while antigenomic chains appeared in 13% of serum and mononuclear cell samples and 89% of liver samples. CONCLUSIONS: HCV and HGV have different sites of replication: whereas HCV replicates mainly in the liver, HGV is not hepatotropic. Mononuclear cells could represent a replication site for HGV but they are less important for HCV. Lastly, HGV does not modify the viral replication of HCV.

Post-transfusional hepatitis in neonates hospitalized in a Neonatal Intensive Care Unit.

OBJECTIVE: To assess the significance of increased serum transaminase levels in neonates admitted to a Neonatal Intensive Care Unit and its relationship with blood transfusion. METHODS: Follow-up prospective study of 209 patients; 177 completed follow-up, of whom 129 were transfused and 48 were not; 57 were born after full gestation and 120 were born prematurely. The activity of serum levels of ALT, AST, and GGT was measured monthly up to six months of age, and until six months after the last transfusion. At the end of follow-up, and whenever an increase in serum transaminase levels was detected, the viral agents of hepatitis A, B, C, G, TT, cytomegalovirus, Epstein-Barr, and herpes 1 and 2, and toxoplasma were studied. Viral serology was also carried out in mothers and in donors when children tested positive. RESULTS: One hundred twenty nine neonates (73%) received 461 U red blood cell transfusions (3.6 +/- 3 U/patient). ALT levels increased in 54 (30.5%) patients, of whom 46 (36%) were transfused and eight (17%) were not (p < 0.05). The independent variables were 'infection by G virus' and 'parenteral nutrition for more than 12 days'; the variable 'transfusion' was close to the limit for statistical significance. Twenty patients (11.3%) had increased serum ALT levels 2.5 times above the normal value: 18 (14%) were transfused and two (4%) were not (p = 0.106). Only the G and TT viruses were related with transfusion; patients remained asymptomatic, although most neonates were chronically infected. CONCLUSION: Follow-up showed that increased serum ALT levels are common among severely ill neonates. Blood transfusions are safe concerning most hepatotropic viruses, but transmission of viruses G and TT is possible.