PubMed Health⌕ Search

Biomedical subjects

S M Norris

Publications and source records attributed to S M Norris.

13 recordsLinked to original sources
PubMed2005

Apolipoprotein epsilon3 allele is associated with persistent hepatitis C virus infection.

BACKGROUND: Host genetic factors may significantly influence the ability to clear hepatitis C virus (HCV) following infection. HCV is associated with very low density lipoproteins (VLDL) and low density lipoproteins (LDL) in the host's circulation. Apolipoprotein E (APOE) is found in VLDL and binds to potential receptors involved in HCV entry into cells, the LDL receptor, and the scavenger receptor protein SR-B1. The APOE gene is polymorphic with three alleles coding for three isoforms: Apo-epsilon2, Apo-epsilon3, and Apo-epsilon4. The aim of this study was to assess if these functional polymorphisms determine disease outcome in HCV infected individuals. METHODS: The APOE genotype was determined in 420 Northern European patients with evidence of exposure to HCV. Genotype and allele distribution were compared with those of 288 healthy controls and progression of liver disease and viral clearance were analysed according to APOE allele status. RESULTS: The APOE*E2 and APOE*E4 alleles were both associated with a reduced likelihood of chronic infection (odds ratio (OR) 0.39 (95% confidence interval (CI) 0.211-0.728), p = 0.003; and OR 0.6 (95% CI 0.38-0.96), p = 0.032) and there was a notable absence of the E2E2 genotype in the HCV antibody positive group compared with the control population (p = 0.0067). Overall the genotypes carrying the E2 allele (E2,E3 and E2,E4) were associated with the equivalent of a 3-5-fold reduction in the risk of chronic HCV infection (genotype relative risk 0.36 and 0.20, respectively). CONCLUSION: This study indicates that functional APOE gene polymorphisms may be a determinant of outcome in HCV infection. We hypothesise that the E2 allele may protect against viral persistence via defective binding of HCV lipoviral particles to the cellular receptors involved in entry of these infectious particles.

Alleles↗
PubMed2001

Graft dysfunction mimicking autoimmune hepatitis following liver transplantation in adults.

In children, a type of graft dysfunction associated with autoimmune features has been described. We have identified 7 adult liver-transplant (LT) recipients from a series of over 1,000 consecutive transplant recipients who presented between 0.3 years and 7.2 years following transplantation with characteristic symptoms, autoantibody profiles, and histologic findings of autoimmune disease. The indications for transplantation were Ecstasy overdose, alcohol-related cirrhosis, primary sclerosing cholangitis (PSC) (2), primary biliary cirrhosis (PBC), hepatitis C cirrhosis, and cryptogenic cirrhosis. Two patterns of de novo autoantibody development were noted; anti-liver-kidney-microsome (LKM) antibody development at high titer in association with an aspartate transaminase (AST) > 500 and antinuclear (ANA) and antismooth muscle (AMA) antibody development at titers >1/80 with lower AST levels. All cases had elevated IgG. Liver biopsies showed changes of an autoimmune-type hepatitis with portal and periportal hepatitis in association with a marked infiltrate of plasma cells, lymphocytes, and bridging collapse. Two patients lost their grafts because of the disease. Patients were treated with reintroduction of steroids and azathioprine in cases in which it had been withdrawn. Major histocompatibility class I and II mismatching did not incur risk. Eight of 12 liver allografts were acquired from either DRB*0301- or DRB*0401-positive donors, and 4 recipients were DRB*0301-positive. This series illustrates that both symptoms and histologic findings of graft dysfunction compatible with autoimmune hepatitis (AIH) exist in adult LT recipients. Graft loss may be a consequence. This entity may represent a specific type of rejection that should currently be classified as "graft dysfunction mimicking autoimmune hepatitis."

Adult↗
PubMed2001

Management and outcome of pregnancy in autoimmune hepatitis.

BACKGROUND: There is a paucity of data in the literature on the risks associated with, and optimal management of, pregnancy in patients with autoimmune hepatitis (AIH). AIMS: To assess maternal and fetal outcomes in relation to clinical management of pregnancy in a large cohort of patients with well defined AIH. METHODS: A review of all known pregnancies in 162 females with definite AIH attending our clinics between 1983 and 1998, with respect to treatment, natural history, and outcome. RESULTS: Thirty one live births (one twin) resulted from 35 pregnancies in 18 women (seven with cirrhosis). Median age at conception was 28 years (range 18-36). Two patients presented with AIH de novo during pregnancy. At conception, in 15 pregnancies patients had been receiving azathioprine alone or (in nine) with prednisolone, in seven prednisolone alone, and in one cyclosporin. Fetal loss at > or =20 weeks' gestation occurred in two instances. Flares in disease activity occurred during four pregnancies and within three months of delivery in a further four. Among the 31 children born (median follow up 10 years) only two abnormalities have been identified: Perthes' disease in one and severe mental and physical handicap in a second who was born prematurely following decompensation of the mother's liver disease. Neither mother was receiving azathioprine. CONCLUSIONS: Successful completion of pregnancy is a realistic expectation for patients with well controlled AIH. Treatment options vary, but azathioprine appears to be generally safe and without adverse outcomes for mother or baby. Vigilance is required, however, and patients need to be monitored carefully during pregnancy and for several months post partum.

Adolescent↗
PubMed1985

The efficacy of antibiotic prophylaxis in the prevention of post-cesarean section endometritis.

Endometritis is an infectious complication in 9% to 65% of patients delivered by cesarean section. The risk of developing endometritis is greater in the high-risk emergent patient as compared to routine repeat abdominal deliveries. This study describes the incidence of endometritis following cesarean section delivery in different patient groups at the University of Virginia Hospital during a 1-year period and reviews the literature on the efficacy and risks of prophylactic antibiotics in this setting. Of patients not receiving antibiotic prophylaxis, 11 (less than 1%) of 1,461 normal spontaneous vaginal delivery patients, 7 (16.7%) of 42 repeat and 39 (29.8%) of 131 emergent cesarean section patients developed endometritis. This contrasts to none of the 24 emergent patients who received antibiotic prophylaxis. The literature review shows multiple prospective well-designed and executed studies that demonstrate reliable decreases in the incidence of endometritis with short course antibiotic prophylaxis. Our conclusion is that short course antibiotic prophylaxis is a safe, reproducible, cost-effective and indicated method of reducing the incidence of this costly and serious postoperative infection.

Anti-Bacterial Agents↗
PubMed1985

Comparative activity of seven extended-spectrum cephalosporins against gram-negative bacilli from blood cultures.

One hundred sequential Gram-negative rod isolates from patients with hospital-acquired bloodstream infections were tested against seven new cephalosporins. Duplicate broth microdilution tests indicated superior activity for ceftazidime with 97% of strains susceptible to 16 mg/l. Less in-vitro activity was demonstrated cefotaxime (91% susceptible to 16 mg/l, P = 0.07), latamoxef (moxalactam) (90%, P = 0.04), cefoperazone (90%, P = 0.04), ceftriaxone (87%, P = 0.008), cefmenoxime (80%, P = 0.0001), and ceftizoxime (79%, P less than 0.0001). With the exception of cefoperazone, the newer drugs had mean MICs of less than or equal to 0.6 mg/l against Enterobacteriaceae. Ceftazidime and cefoperazone had highest activities against Pseudomonas aeruginosa with MIC90S of 4 and 16 mg/l, respectively. A comparison of recently published data shows important geographic differences in MIC90 data for the new cephalosporins against specific species.

Cefmenoxime↗
PubMed1984

Pharmacokinetics of antimicrobial agents.

The use of formulas or nomograms is not a substitute for or in conflict with measurement of drug levels. We are always obligated to use the best available strategy in choosing a loading and maintenance dose. We must likewise measure and use serum levels for drugs with a narrow therapeutic margin, drugs administered for a long duration of time, and when there is uncertainty about a drug's kinetics. (The classic example is a patient on an aminoglycoside for more than three days, elderly or in renal failure).

Aged↗