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Biomedical subjects

G Porta

Publications and source records attributed to G Porta.

At least 19 recordsLinked to original sources
PubMed2002

Establishment of standardised SLA/LP immunoassays: specificity for autoimmune hepatitis, worldwide occurrence, and clinical characteristics.

BACKGROUND: Antibodies to soluble liver antigen/liver pancreas (SLA/LP) are specific markers of autoimmune hepatitis. Their target antigen has recently been cloned. AIMS: To establish standardised immunoassays using the recombinant antigen, and to assess the frequency and significance of seropositivity in patients from different countries. METHODS: An enzyme linked immunoassay was developed using purified recombinant antigen and validated by testing sera from 200 healthy blood donors and 1026 patients with various liver and non-liver diseases. The assay was then applied to 454 sera from 419 patients with autoimmune hepatitis from different countries. All sera were also tested by inhibition immunoassay and western blot. RESULTS: Antibodies were reliably detected by the recombinant immunoassay and occurred exclusively in patients with autoimmune liver disease. Twenty three of 149 patients from the USA (15%), 23/132 from Brazil (17%), 21/108 from Germany (19%), and 2/30 from Japan (7%) were seropositive. Clinical features at presentation were similar between seropositive and seronegative patients. However, relapse after corticosteroid withdrawal or during maintenance therapy occurred more commonly in seropositive patients. CONCLUSIONS: Antibodies to SLA/LP can be reliably detected by these standardised immunoassays based on recombinant antigen. Antibodies to SLA/LP occur with similar frequencies in different geographical regions, races, and age groups, and are of exquisite diagnostic specificity. Whether SLA/LP positive patients represent a clinically distinct subgroup remains to be determined; relapse during treatment reduction appeared to be more common in the SLA/LP group.

Adolescent↗
PubMed2001

Autoimmune hepatitis in Brazilian patients is not linked to tumor necrosis factor alpha polymorphisms at position -308.

BACKGROUND/AIMS: Susceptibility to autoimmune hepatitis (AIH) has been linked to different HLA-DR antigens. Recently, AIH type 1 was associated with polymorphisms in the tumor necrosis factor alpha gene promoter (TNFA) at position -308. In this respect, the frequency of the TNFA*2 allele, in linkage disequilibrium with HLA-DRB1*0301, was shown to be significantly increased in whites with AIH type 1. The aim of this study was to assess the role of TNFA alleles in conferring susceptibility to AIH, studying a population where the disease is not primarily associated with HLA-DRB1*03. METHODS: The determination of HLA-DRB1 and TNFA alleles was performed in 92 patients with AIH type 1, 29 subjects with AIH type 2 and 83 healthy controls by polymerase chain reaction-based techniques. RESULTS: The distribution of TNFA alleles was similar in patients with AIH types 1 and 2, when compared with controls. In addition, the TNFA*2 allele was identified in patients carrying HLA-DR antigens other than HLA-DRB1*03. Interestingly, higher gammaglobulin levels were observed in TNFA*2 positive patients. CONCLUSIONS: Our data indicate that susceptibility to AIH remains primarily linked to the HLA-DRB1 locus, and suggest that the association of AIH with TNFA*2 previously observed in whites might be secondary to a linkage disequilibrium with HLA-DRB1*0301.

Adolescent↗
PubMed2001

Analysis of HLA haplotypes in autoimmune hepatitis type 1: identifying the major susceptibility locus.

Susceptibility to autoimmune hepatitis type I (AIH-1) has been associated with HLA-DR3, DR52, and DR4 antigens in Caucasian and Oriental patients. However, in Brazil, disease susceptibility is primarily linked to DR13 and DR52. In this highly admixed population, we find different DR13-associated haplotypes, presenting a unique opportunity to discriminate relevant genes within a tightly linked genomic region. To identify the primary susceptibility locus, we sequenced DR13 alleles of 39 patients with AIH-1 and 22 controls. Patients were almost exclusively DRB1*1301, but half of controls typed DRB1*1302. HLA-DQ haplotypes were varied. Oligotyping of DRB3 locus of all patients and also within the HLA-DR13 positive group showed an allele distribution comparable to controls, confirming that the stronger association lies in the DRB1 locus. On the other hand, if DRB1*1301 is the major susceptibility factor in our sample, the only amino acid different from DRB1*1302 in position 86, corresponding to pocket 1 in the peptide-presenting groove, may be important. We propose that peptide presentation leading to pathogenesis of AIH-1 may be quite stringent, but will also be affected by other strong genetic or environmental susceptibility factors, which would explain the various HLA molecules associated to the disease in the different populations.

Alleles↗
PubMed2001

Laparoscopic cholecystectomy and unsuspected gallbladder cancer.

Gallbladder cancer is a relatively uncommon malignancy. Its presentation is similar to that of gallstone disease and sometimes with non-specific symptoms. Laparoscopic cholecystectomy has become the method of choice for removing the gallbladder in most benign conditions. Occasionally, unsuspected gallbladder carcinoma is encountered in association with laparoscopic cholecystectomy. Overall gallbladder cancers have a poor prognosis, despite surgery or adjuvant therapies. However, in selected cases, a favourable outcome can be expected and the less favourable predicted outcome can be improved. Management of patients with gallbladder cancer in different situations is discussed: gallbladder cancer noted post-operatively on final pathology, gallbladder cancer noted after removal of the gallbladder and opening of the specimen at the time of surgery, difficulty encountered at the time of dissection and resultant suspicion of gallbladder cancer, and diagnosis of extensive disease at initial placement of the laparoscope.

Cholecystectomy, Laparoscopic↗
PubMed2000

Long-term outcome after partial external biliary diversion for intractable pruritus in patients with intrahepatic cholestasis.

BACKGROUND: Chronic intrahepatic cholestasis is associated with severe pruritus that is often refractory to maximal medical management and leads to significantly impaired quality of life. The hypothesis in this study was that partial external biliary diversion (PEBD) can substantially improve intractable pruritus secondary to intrahepatic cholestasis with subsequent improvement of functional quality of life. METHODS: Parents' and/or patients' clinical rating of pruritus, growth percentiles, biochemical parameters, and liver biopsies performed before and after surgery were compared in a retrospective medical record review. RESULTS: Eight children underwent PEBD from 1990 through 1997. Complete follow-up data were available for seven patients. Before surgery, all patients had intense pruritus, which was not responsive to maximal medical therapy. Specimens obtained in preoperative liver biopsies showed moderate (n = 1), minimal (n = 6), or no (n = 1) portal fibrosis. After PEBD, all patients received ursodeoxycholic acid (10-15 mg/kg/dose two to three times daily) until resolution of pruritus. Of the seven patients with complete follow-up data, six had complete resolution of pruritus and sustained resolution up to 8 years after surgery. The patient with mild to moderate residual pruritus was the youngest to undergo PEBD. Growth improved from below the 5th percentile before surgery to the 5th through the 25th percentiles for five of six patients with more than 6 years' follow-up. All families reported improved quality of life, defined by school attendance and ability to resume normal activity with peers. There has been no clinical evidence of progression of liver disease. CONCLUSION: Partial external biliary diversion is effective in the long-term treatment of pruritus refractory to medical therapy and provides a favorable outcome in a select group of patients with chronic intrahepatic cholestasis without cirrhosis.

Bile Acids and Salts↗
PubMed2000

Laparoscopic versus open splenectomy: a comparative study.

Laparoscopic splenectomy (LS) is gaining wide acceptance as a safe, effective alternative to open splenectomy (OS) in the treatment of hematologic disorders in adult and pediatric patients, with low conversion rates and complications. The aim of this retrospective case-control study was to compare two cohorts of patients, with similar characteristics, who underwent OS or LS in a single institution. The medical records of the initial 20 consecutive patients who underwent LS were reviewed and compared with a control group of 28 patients undergoing OS, matched for age, gender, diagnosis, splenic size and weight, and American Society of Anesthesiologists score. Data were collected regarding operative time, blood loss, blood transfusions, pathologic findings, accessory spleen detection, complications, ileus duration, and postoperative hospital stay. Nineteen patients underwent attempted LS. One procedure (5%) was converted to OS for uncontrolled hilar bleeding. Accessory spleens were detected in two cases in the LS group compared with four cases in the OS group (14%). Mean operative time was 165 minutes (range: 100-240 minutes) for LS and 114 minutes (75-180 minutes) for OS (P < 0.001). In the LS group a regular diet was tolerated 36 hours (range: 24-48 hours) after surgery compared with 72 hours (range: 48-96 hours) for the OS group (P < 0.001), and mean postoperative hospital stay was 4.1 days (range: 3-8 days) for LS, compared with 8.1 days (range: 5-12 days) for OS (P < 0.001). No differences were observed in blood loss, complication rates, or transfusion requirements. Compared with OS, LS requires more operative time (showing a learning curve), is comparable in blood loss, transfusion requirements, complication rates, and detection of accessory spleens and appears to be superior in terms of return of bowel function and hospital stay.

Adolescent↗
PubMed1999

Emotion-induced myoclonic absence-like seizures in a patient with inv-dup(15) syndrome: a clinical, EEG, and molecular genetic study.

We have described a clinical EEG and molecular genetic study of a 9-year-old boy with inv-dup(15) syndrome in whom seizures were induced by emotionally gratifying stimuli. The reflex seizures began 5-20 s after the onset of repeated cheek-kissing from his mother or after viewing of pleasant or funny events. They were characterized by bilateral discharges involving mainly the temporal regions and evolving into myoclonic absence-like seizures. Nonemotional stimuli, such as a pinch, sucking or rubbing his cheeks, or the sound of the kiss alone, failed to provoke seizures. The seizures were resistant to antiepileptic (AED) treatments. Molecular genetic investigations revealed a correct methylation pattern of the chromosomes 15, and three copies (two maternal and one paternal) of the segment 15q11-q13, including the GABRb3 gene. We hypothesize that an overexpression of cerebral gamma-aminobutyric acid (GABA)-mediated inhibition accounts for the severe epilepsy that we observed in this patient.

Child↗
PubMed1999

Genetic heterogeneity in susceptibility to autoimmune hepatitis types 1 and 2.

OBJECTIVE: Susceptibility to autoimmune hepatitis (AIH) type 1 has been associated with DRB1*03, DRB1*04, and DRB3 alleles in European and North-American whites, with DRB1*04 in Japan, and with DRB1*04 and DRB1*13 in Latin America. Very few studies have been performed on AIH type 2. The aim of the present study was to evaluate the association of AIH types 1 and 2 with HLA-DR and DQ loci. METHODS: We performed HLA-DRB and -DQB1 typing by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP) in 139 AIH patients. Most had AIH type 1 associated with circulating anti-smooth muscle antibody with F-actin specificity or antinuclear antibody. Twenty-eight patients presented AIH type 2 with anti-liver/kidney microsome type 1 or anti-liver cytosol type 1 antibodies. RESULTS: We observed a significant increase of DRB1*13 (70% vs 26% of controls, p < 0.00001) and DRB3 (93% vs 69% of controls, p < 0.00001) in AIH type 1 patients. Analysis of patients without DRB1*13 disclosed a secondary association with DRB1*03 (70% vs 30% of controls, p = 0.0001) and either the DRB1*13 or the DRB1*03 alleles were present in the majority of these patients (91% vs 48% of controls, p = 0.001). Comparison of DRB1*13- and DRB1*03-positive subjects revealed that the former alleles conferred susceptibility to younger patients with AIH type 1. DQB1 typing showed a significant increase in DQB1*06 (68% vs 41% of controls, p = 0.00007) in strong linkage disequilibrium with DRB1*13, and a decrease in DQB1*0301 (8% vs 47% of controls, p(c) = 0.0003). On the other hand, HLA typing of patients with AIH type 2 disclosed a significant increase in the DRB1*07 (68% vs 20% of controls, p(c) < 0.00014), DRB4 (79% vs 43% of controls, p(c) = 0.004), and DQB1*02 (86% vs 42%, p = 0.00002) alleles. After exclusion of DRB1*07, a secondary association with HLA-DRB1*03 was further observed in these patients (78% vs 30%, p = 0.007) and most of them had either DRB1*07 or DRB1*03 (93% vs 44% of controls, p(c) < 0.0001). CONCLUSIONS: Our data indicate that predisposition to AIH types 1 and 2 is associated, respectively, with the DRB1*13 or DRB1*03 and DRB1*07 or DRB1*03 alleles, and suggest that protection against type 1 disease may be conferred by DQB1*0301. In addition, the cluster of DRB1*13 in children with AIH type 1 also supports the concept that different HLA alleles might influence the onset of the disease.

Adolescent↗
PubMed1998

Integrated YAC/STS physical and genetic map of 22.5 Mb of human Xq24-q26 at 56-kb inter-STS resolution.

A yeast artificial chromosome sequence-tagged site-based (YAC/STS) physical map of 22.5 Mb of the Xq24-q26 cytogenetic band region of the human X chromosome has been assembled. DNA coverage includes 857 large-insert clones formatted with 405 STSs to provide ninefold depth of DNA. At five points, no bridging clones have been recovered from 20 X-chromosome equivalents of human DNA in YACs or bacterial clones, but the placement of 25 ("CA")n polymorphic markers permits the ordering of contigs by comparison with the genetic linkage map and radiation hybrid data. The map localizes the X3000 translocation breakpoint and six genes (ANT2, NDUFA1, LAMP2, OCRL, IGSF1, and HDGF) at better than 100-kb resolution. The relatively gene-poor nature of the region is consistent with relatively low uniform 34-42% GC content in STSs across nearly all of the region.

Chromosome Breakage↗
PubMed1998

Management of biliary atresia in the liver transplantation era: a 15-year, single-center experience.

BACKGROUND/PURPOSE: The aim of this study was to address the perioperative aspects of hepatoportoenterostomy (HPE) for biliary atresia (BA), through the study of a 15-year, single-center experience of the management of this disease. METHODS: One hundred twenty-seven patients were divided into three groups, depending on the variant of HPE performed: group A (n = 53) underwent HPE with external diversion of the Roux-en-Y anastomosis; group B (n = 54) underwent HPE with a long (35 to 40 cm) Roux-en-Y anastomosis, without diversion; and group C (n = 20) underwent the same kind of HPE as group B, but with a modified, "super extensive" dissection of the porta hepatitis. Eleven children in group B had an intussusception type antireflux valve in the Roux-en-Y loop. The porta hepatitis of 105 children was histologically classified in types I to III and correlated with rate of postoperative bile flow and age at surgery. Liver transplantation was performed after HPE in 20 patients. RESULTS: Overall, biliary drainage was achieved in 72.5% of the children after HPE and 26.8% of all patients became jaundice free. Porta hepatitis type III was associated with a significantly higher rate of biliary drainage post-HPE then types I and II. There was no difference in the rate of bile drainage, relative number of jaundice-free patients, and mean number of episodes of cholangitis per year among surgical groups A, B, C. In group A, 43.7% of the patients had complications related to the stoma. The actuarial survival of children who underwent HPE followed by liver transplantation was 85%. CONCLUSIONS: (1) There is no correlation between type of porta hepatis and age at surgery for BA; (2) type III porta hepatis is associated with higher rates of bile drainage post-HPE; (3) children older than 16 weeks with BA should still be considered for HPE; (4) in these older patients, factors other than the type of porta hepatis, possibly the degree of liver damage, play a role in the lower rate of bile drainage observed; (5) external diversion of the Roux-en-Y in HPE is not beneficial and is detrimental because of stoma-related complications; (6) an antireflux valve in the Roux-en-Y loop does not reduce the incidence of cholangitis post-HPE; (7) Surgical reexploration does not restore biliary drainage; and (8) sequential therapy with HPE followed by liver transplantation remains the treatment of choice for BA.

Actuarial Analysis↗
PubMed1998

Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene.

X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.

Antigens, CD↗
PubMed1998

High-resolution mapping of the X-linked lymphoproliferative syndrome region by FISH on combed DNA.

X-linked lymphoproliferative syndrome is an inherited immunodeficiency for which the responsible gene is currently unknown. Several megabase-sized deleted regions mapping to Xq25 have been identified in XLP patients, and more recently a 130-kb deletion has been reported (Lamartine et al., 1996; Lanyi et al., 1996). To establish a physical map of this deleted region and to identify the XLP gene, two cosmid contigs were established (Lamartine et al., 1996). However, the physical map of this region is still uncompleted and controversial and three points remain unsolved: (1) the centromeric-telomeric orientation of the whole region, (2) the relative orientation of the two contigs, and (3) the size of the gap between the two contigs. To provide a definitive answer to these questions, high-resolution mapping by fluorescence in situ hybridization on combed DNA and molecular approaches were combined to establish the physical map of the XLP region over 600 kb. Our results identified a gap of 150 kb between the two contigs, established the relative orientation of one contig to the other, and determine the centromeric-telomeric orientation of the whole region. Our results show that the order of the marker over this region is: cen.1D10T7-DF83-DXS982.tel.

Chromosome Mapping↗
PubMed1998

Thoracic infection caused by Streptococcus milleri.

The objective of this study was to increase our understanding of the importance of members of the Streptococcus milleri (SM) group as respiratory pathogens, by studying the epidemiological and clinical features of thoracic infections caused by this group and comparing the epidemiology and prognosis of empyema caused by SM with cases of pneumococcal aetiology. The clinical histories and microbiology reports were reviewed in 27 cases of thoracic infection caused by SM over a period of 8 yrs. Cases of pneumococcal empyema that occurred during the same period were also analysed. Diagnoses were made of cases of empyema, including six with pneumonia and one with pulmonary abscess, three cases of pneumonia and two of mediastinitis. In 17 cases, SM was the only pathogen isolated. There was a history of instrument or surgical procedures on the digestive or respiratory tract in 59%. Secondary bacteraemia was documented in three cases. The treatment administered, a combination of antibiotics and surgery, was successful in 22 of 27 (81%) of cases. All strains were susceptible to penicillin. When the characteristics of the empyemas caused by monomicrobial SM infection were compared with those of pneumococcal aetiology from the same period of study, significant differences were found with respect to age, origin of the infection and the need for surgery. In conclusion, thoracic infections caused by Streptococcus milleri are largely pleural. They are polymicrobial in one-third of cases, commonly acquired in hospital and, in most patients, associated with major surgery and/or surgical procedures of the respiratory or digestive tract. The empyema frequently requires thoracotomy for complete resolution.

Anti-Bacterial Agents↗
PubMed1998

[3-Hydroxy-3-methyl-glutaryl-CoA-lyase deficiency as coma etiology in the neonatal period: case report].

We report a patient that presented two episodes of coma in the neonatal period, with severe metabolic acidosis and hypoglycemia, without ketosis. The urinary organic acid analysis showed increased amounts of 3-hydroxy-3-methyl-glutaric, 3-methylglutaconic, 3-methylglutaric and 3-hydroxyisovaleric acid. The deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase was diagnosed by the clinical and metabolic features. This disease shows autosomal recessive inheritance and the treatment is done by a diet with restriction of protein (mainly leucine) and lipids, high in carbohydrate content, and the avoidance of fasting and carnitine supplementation.

Coma↗
PubMed1997

4.5-Mb YAC STS contig at 50-kb resolution, spanning Xq25 deletions in two patients with lymphoproliferative syndrome.

Sequence-tagged site (STS) content mapping in yeast artificial chromosomes (YACs) was used to cover the region deleted in two patients affected with X-linked lymphoproliferative disorder. The order of markers includes, centromere to telomere, DXS8009-DXS1206-DXS8078-DXS8044-DXS982- DXS6811-DXS8093-AFM240xblO- DXS75-DXS737-DXS100-DXS6-DXS1046-DXS803 8. The order of six major markers is confirmed by fluorescent in situ hybridization, and all the markers assigned by linkage mapping fall within a 1.6-cM interval. The contig comprises 90 clones containing 89 STSs, yielding a resolution of 50 kb; DNA in a gap just telomeric to DXS8044 has not been found in > 20 equivalents of YACs or bacterial clones. The two deletions were found to have centromeric breakpoints that lie close to DXS1206 and may be identical; the telomeric breakpoints are -150 kb apart, one falling between DXS737 and DXS100, the other between DXS100 and DXS1046. Several STSs near the breakpoints show weak amplification from more than one site; one gives products from three groups of YACs, and lie, respectively, within 50 kb of the centromeric and the two telomeric deletion borders. Such partially duplicated segments of DNA are candidates for involvement in the formation of the deletions.

Chromosome Deletion↗