Biomedical subjects

G Norkrans

Publications and source records attributed to G Norkrans.

At least 55 records · Page 3Linked to original sources

PubMed1996

Hepatitis B virus carriers without precore mutations in hepatitis B e antigen-negative stage show more severe liver damage.

Hepatitis B e antigen (HBeAg) is considered to be a major target for the immune response in chronic hepatitis B. The G-->A mutation at nucleotide 1896 may mediate viral escape by creating a TAG stop codon in the precore region, thus preventing HBeAg production. This mutation frequently evolves during HBe seroconversion if thymine, but rarely if cytosine, is present in position 1858. Applying a combination of polymerase chain reaction (PCR) and restriction enzyme action, we have studied the relation of the TAG mutation and the nucleotide (nt) 1858 variants to liver damage assessed by histology activity index (HAI) scoring in 175 chronic hepatitis B virus (HBV) carriers. A TAG mutation was found in 68 of 71 (96%) of HBeAg-negative carriers infected with a T-1858 strain, but not in any of 33 carriers infected exclusively with a C-1858 strain. Four patients showed a mutation of the precore start codon, and 2 had a TAA stop mutation at codon 2. HBeAg-positive infection with a mixture of wild-type and TAG mutant virus indicated active liver damage, because 8 of 9 (89%) of such patients had a Knodell HAI greater than or equal to 8. In HBeAg-negative stage, both inflammation and fibrosis were more pronounced in carriers infected with wild-type HBV compared with precore mutants. C-1858 strains were associated with more inflammation and fibrosis compared with T-1858 strains. C-1858 strains were found in 71% of northern European, 17% of southern European, 31% of African, 2% of Middle Eastern, and 10% of Far Eastern carriers. Analysis of these variants and mutants may prove useful for clinical evaluation and choice of therapy, and may be facilitated by the methods described.

Adolescent↗

PubMed1996

Increase of tryptophan in serum and in cerebrospinal fluid of patients with HIV infection during zidovudine therapy.

A high percentage of patients with human immunodeficiency virus infection presents with decreased tryptophan concentrations in serum and cerebrospinal fluid. In parallel degradation products of tryptophan like kynurenine and quinolinic acid are increased. We investigated the behavior of tryptophan concentrations in 14 patients with HIV infection before and during treatment with zidovudine, and we found a significant increase of tryptophan in serum and cerebrospinal fluid after 4-14 months of therapy. In parallel, neopterin concentrations decreased significantly. Moreover, an association existed in cerebrospinal fluid between the degree of tryptophan increase and neopterin decrease. Thus, treatment with zidovudine contributes to a gradual normalization of tryptophan metabolism in patients with HIV-1 infection. The data imply that zidovudine therapy is associated not only with a reduction of virus replication but also immune activation is reduced.

Anti-HIV Agents↗

PubMed1996

Ribavirin treatment for patients with chronic hepatitis C: results of a placebo-controlled study.

BACKGROUND/AIMS: Small, uncontrolled studies of ribavirin for patients with chronic hepatitis C have reported efficacy in chronic hepatitis C. We have evaluated the efficacy and safety of a 24-week course of oral ribavirin in patients with chronic hepatitis C, compared to placebo. METHODS: A total of 114 patients were randomised to ribavirin or placebo. Ribavirin was administered in doses of 1000 or 1200 mg/day for 24 weeks. Efficacy was determined in the intention-to-treat population: 76 received ribavirin and 38 placebo. RESULTS: Ribavirin was significantly more effective than placebo in reducing and normalising serum ALT levels: 42/76 (55%) of ribavirin-treated patients vs 2/38 (5%) placebo recipients had either normalisation of the ALT levels or a reduction from baseline of at least 50% (p < 0.001). ALT levels were normal in 22/76 (29%) of ribavirin-treated patients vs 0/38 placebo recipients (p < 0.001). Twenty-four weeks after stopping ribavirin, the majority of patients had abnormal ALT levels. There was no difference between the treatment groups in reduction or disappearance of HCV-RNA levels. HCV RNA disappeared during treatment in 3% of ribavirin-treated patients and 3% of placebo recipients. More ribavirin than placebo patients showed improvement in total Knodell score (45% vs 31%), but these differences were not statistically significant. Analysis of each component of a histology activity index revealed no statistically significant differences between treatment groups. Ribavirin patients had fewer lymphoid aggregates than did placebo recipients at the post-treatment assessment (p = 0.05). Ribavirin was associated with reversible haemolytic anaemia: a fall in haemoglobin occurred in 3% of placebo- and 32% (25/78) of ribavirin-treated patients, respectively (p < 0.001). CONCLUSIONS: These data indicate that ribavirin was no more effective than placebo in reducing or eliminating HCV-RNA levels, and was not significantly more effective than placebo in improving hepatic histology after 6 months of treatment. The role of a 6-month treatment of chronic hepatitis C with ribavirin alone, without a significant effect on HCV RNA, is therefore limited.

Administration, Oral↗

PubMed1996

Intrathecal immunoactivation in patients with HIV-1 infection is reduced by zidovudine but not by didanosine.

The effect of zidovudine and didanosine on the cerebrospinal fluid (CSF) concentrations of neopterin was studied in 12 patients with human immunodeficiency virus type-1 (HIV-1) infection 3-12 months after initiation of antiretroviral therapy. Ten treatment periods on zidovudine and 7 on didanosine were analysed. The CSF concentrations of neopterin decreased by 63% (from 29.6 to 12.9 nmol/l, p < 0.01) during zidovudine but increased by 15% (from 22.6 to 25.9 nmol/l, not significant during didanosine treatment. The CSF monocytic cell count decreased during zidovudine but increased during didanosine treatment. The results suggest that zidovudine but not didanosine reduces intrathecal immunoactivation during HIV-1 infection.

Adult↗

PubMed1995

[A secondary case of hepatitis E. Since 1990 only one of the 17 imported cases was transmitted].

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Adult↗

PubMed1995

[Half of the patients respond to interferon treatment. Combination therapy is an alternative in chronic hepatitis C].

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Chronic Disease↗

PubMed1995

Hepatitis C: natural history of a unique infection.

In 1988 investigators defined the agent causing most cases of non-A, non-B hepatitis and named this agent hepatitis C virus (HCV). Assays for antibody to HCV and more specific diagnostic tests (immunoblot and polymerase chain reactions) were subsequently developed. Exposure to HCV seems to result in chronic infection in a majority of cases, with progressive chronic liver disease sometimes leading to hepatocellular carcinoma. This virus is spread mainly by parenteral routes; intravenous drug users are at high risk. Sexual and intrafamilial spread has also been documented but seems to occur to a limited extent. Perinatal transmission, which is prominent in infection with hepatitis B virus, does not play an important role in the spread of HCV. Antiviral therapy with interferon alpha is usually tried in chronic hepatitis C but permanently normalizes liver function in only one-fourth of patients. The failure to demonstrate protective immunity after single or multiple episodes of infection raises doubts about the existence of neutralizing antibodies and concerns about the potential for the development of a vaccine against HCV.

Autoimmune Diseases↗

PubMed1995

Detection of hepatitis B virus precore TAG mutant by an amplification-created restriction site method.

A new method for detecting the hepatitis B virus (HBV) precore 1896 G-->A mutation is described. This mutation prevents hepatitis B e antigen production by introducing a TAG stop codon and has been associated with severe chronic and fulminant hepatitis. The method is based on a polymerase chain reaction (PCR) that creates a restriction enzyme (Bsu36I) cleavage site if the mutation is present. After incubation of the PCR product with Bsu36I and a subsequent agarose gel electrophoresis, the presence of the TAG mutant is revealed by an altered position of the DNA band. The method was compared with direct sequencing on 36 serum samples and correctly identified all samples containing mutant HBV. The TAG mutant was present in 17 cases (as mixed wild type and mutant virus in 4). Twelve of 18 patients with advanced liver disease confirmed by biopsy carried mutant HBV. This method of detecting HBV precore 1896 G-->A should be useful for evaluation and follow-up of patients and for prevalence studies.

Adolescent↗

PubMed1995

Emergence of precore TAG mutation during hepatitis B e seroconversion and its dependence on pregenomic base pairing between nucleotides 1858 of 1896.

The G-->A mutation of nucleotide (nt) 1896 in the precore region of hepatitis B virus (HBV) prevents production of hepatitis B e antigen (HBeAg) by creating a TAG stop codon. This mutation is often found in anti-HBe-positive patients with productive HBV infection and has been associated with severe chronic and fulminant hepatitis in some geographic areas. Emergence of the TAG mutation during HBe seroconversion was studied as was its relationship with nt 1858, which forms a base pair with nt 1896 in the pregenomic RNA loop. A TAG mutant evolved in 18 (72%) of 25 patients with a T-1858 strain but in only 1 (8%) of 13 with a C-1858 strain. Viremia with C-1858 strains was, despite their limited ability to develop the TAG mutation, as persistent as with T-1858 strains. Generally, T-1858-infected patients in whom a TAG mutant did not emerge were HBV DNA-negative by polymerase chain reaction on follow-up, whereas patients who developed the TAG mutation had prolonged viremia.

Adolescent↗

PubMed1995

Virus-specific antibody production and polyclonal B-cell activation in the intestinal mucosa of HIV-infected individuals.

OBJECTIVE: To examine possible changes in mucosal B-cell activation status. DESIGN: To examine the frequency and isotype distribution of total and HIV-specific antibody-secreting cells (ASC) in the intestinal mucosa of HIV-infected individuals. METHODS: Mucosal lymphocytes were obtained by enzymatic treatment of duodenal pinch biopsies and the numbers of ASC were assayed with the enzyme-linked immunospot technique. RESULTS: High numbers of HIV-specific ASC were found in the intestine of all HIV-infected individuals despite low levels of HIV-specific blood ASC. All HIV-infected individuals had large numbers of intestinal immunoglobulin (Ig) A-ASC against the HIV envelope glycoprotein gp160. Eight out of nine patients also had HIV gp160-specific intestinal IgG-ASC. These HIV-specific ASC were detected irrespective of disease stage, route of infection, or levels of circulating CD4+ T cells. HIV-specific ASC were found in peripheral blood from patients with CD4+ T cells > or = 100 x 10(6)/l blood, but in none of three patients with low CD4+ T-cell counts. The frequencies of virus-specific ASC in the blood were on average 100-fold lower than that observed within the intestinal mucosa. Mucosal polyclonal B-cell activation was evident in HIV-infected individuals, as documented by significantly elevated numbers of Ig-secreting cells (ISC) in all three major Ig classes; on average, seven-, five- and 20-fold numbers of IgA, IgG and IgM-ISC compared with healthy controls. Furthermore, substantial numbers of ASC reacting with unrelated antigens such as dog albumin and keyhole limpet haemocyanin were detected in HIV-infected patients. Interestingly, patients with CD4+ T cells < 100 x 10(6)/l blood displayed large numbers of HIV-specific intestinal ASC even though total numbers of ISC, including ASC reactive to unrelated antigens, were decreased. CONCLUSIONS: The large numbers of virus-specific ASC found in the intestine of HIV-infected individuals may be a consequence of local replication of HIV-1 resulting in a continuous antigen stimulation. The persistence of strong intestinal anti-HIV responses even at late stages of disease suggest that the mucosal B-cell responses are functionally intact throughout the disease. Furthermore, these results suggest that there is no correlation between HIV-specific ASC numbers and polyclonal B-cell activation. These observations indicate that intestinal B-cell activation is profoundly disregulated in HIV-infected individuals.

Antibodies, Viral↗

PubMed1995

Reverse transcriptase sequence of paired isolates of cerebrospinal fluid and blood from patients infected with human immunodeficiency virus type 1 during zidovudine treatment.

Human immunodeficiency virus type 1 (HIV-1) isolates obtained from the blood of patients undergoing treatment with 3'-azido-3'-deoxythymidine (zidovudine [AZT]) show a decreased sensitivity to the drug in vitro. The aim of the present study was to determine if HIV-1 variants resistant to AZT are present also in the brain compartment. We selected sequential HIV-1 isolates from the blood and the cerebrospinal fluid (CSF) of six patients with HIV-1 infection undergoing AZT therapy for a time varying between 1 and 3 years. The isolates were used to infect peripheral blood mononuclear cell cultures which were used to prepare viral DNA. The viral DNA was amplified by PCR and then directly sequenced. Analysis of the reverse transcriptase (RT) sequence of the isolates from the CSF during therapy demonstrated that CSF-resistant isolates are characterized by the same mutations documented in resistant isolates from the blood compartment. Isolates obtained from one patient (patient 3) showed the same two mutations (codons 70 and 215) in blood and CSF, whereas isolates obtained from an additional four patients presented a different pattern of mutations in the two compartments. We also analyzed the degree of amino acid homology between RT sequences from blood and CSF isolates in patients before and during AZT treatment. The percentages of amino acid variations were approximately equal when isolates from the same or different compartments were considered. Excluding the codons involved in AZT resistance, the time point of sampling did not affect RT variations during therapy significantly. In conclusion, our studies show that AZT-resistant HIV-1 can be found in the CSF of patients undergoing treatment. The mutations linked to AZT resistance in the CSF isolates are the same as those identified in AZT-resistant isolates from blood.

AIDS Dementia Complex↗

PubMed1995

Risk factor exposure among hepatitis C virus RNA positive Swedish blood donors--the role of parenteral and sexual transmission.

The potential modes of transmission for hepatitis C virus (HCV) infections were studied using a multivariate analysis of risk factor exposure among 51 2nd generation anti-HCV and HCV-RNA positive and matched anti-HCV negative blood donors. The following variables were found to be independently associated with anti-HCV and HCV-RNA positivity: intravenous drug use (IVDU) (p < 0.001), blood transfusion (p < 0.01), tattoos (p < 0.001), previous hospitalization (p < 0.05), history of sexually transmitted disease (STD) (p < 0.001) and lack of travels outside of Europe (p < 0.05). Among the 23 HCV-RNA positive donors without a history of IVDU or blood transfusion, an increased frequency of hospitalization (p = 0.017) and history of STD (p = 0.023) were found. Five of 22 sexual partners of the 51 index blood donors were HCV-RNA positive and in one of these couples sexual transmission was suspected. Anti-HCV and HCV-RNA positive donors were more often seropositive for herpes simplex virus type 2 (HSV-2) antibodies than were HCV-negative controls (p = 0.015). Sexual transmission of HCV may occur, but the possible role of HSV-2 requires further investigation.

Adult↗

PubMed1995

Hepatitis E virus infections in patients with acute hepatitis non-A-D in Sweden.

A total of 12 patients previously treated for acute hepatitis of unknown aetiology were retrospectively found to be anti-hepatitis E virus (HEV) IgG-positive. Four patients were anti-HEV IgM- and IgG-positive consistent with an acute HEV infection. All 4 had travelled to or were immigrants from HEV-endemic countries. One anti-HEV IgM-negative patient seroconverted from anti-HEV IgG-negative to positive and 3 from anti-HEV IgG-positive to negative in 2 consecutive serum samples. Of the remaining 4 patients without anti-HEV IgM, 3 had a history of recent travel to an HEV-endemic country. Most patients were young adults and all but 1 recovered from the hepatitis. One patient with a fulminant hepatitis was anti-HEV IgG-positive when tested 4 months after a journey to Turkey. She died from her fulminant hepatitis shortly after admission. All the other patients but 1 normalized their serum liver enzymes within 1-2 months after the onset of disease.

Acute Disease↗

PubMed1995

Intestinal immune responsiveness in HIV-infected individuals.

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Administration, Oral↗

PubMed1995

Two-year biochemical, virological, and histological follow-up in patients with chronic hepatitis C responding in a sustained fashion to interferon alfa-2b treatment.

Fourteen patients with chronic hepatitis C who had a sustained response to a 60-week interferon alfa-2b treatment course were followed, biochemically and virologically, 2 years after treatment cessation. Biopsies were repeated in 12 of 14 for histological and virological evaluation at 2-year follow-up. All 14 patients had normal serum alanine transaminase (s-ALT) levels and were negative for hepatitis C virus (HCV) RNA in serum during treatment and at short-term follow-up 6 months post-treatment. At 2-year follow-up, 13 patients still had normal ALT levels (< 0.6 mukat/L for women; < 0.8 mukat/L for men), 1 a near normal level (0.76 mukat/L); all were HCV RNA negative in serum, and 11 of 12 also in the liver. Liver histology improved during treatment and remained stable during the 2-year follow-up. The authors conclude that most sustained responders, who have normal ALT levels and are nonviremic at short-term follow-up 6 months after interferon treatment, will continue to have a durable long-term response without relapse of the viremia.

Adult↗

PubMed1995

Efficacy of human leucocyte alpha-interferon treatment for chronic hepatitis C virus infection.

A total of 42 Swedish patients with biopsy-proven chronic hepatitis C virus (HCV) infection were treated with a natural human leucocyte alpha-interferon (HuIFN-alpha-Le), Alfanative (BioNative AB, Umeå, Sweden) in an open uncontrolled study. Two patients were withdrawn from treatment within 2 weeks due to non-compliance and were omitted from further analysis, and 40 patients (17 females), mean age 39 years (range 24-71) completed the study. All patients were HCV RNA-positive in serum prior to treatment, with raised alanine aminotransferase (ALT) levels > 1.5 times the upper normal limit known for more than 6 months. Interferon was given at a dose of 3 MU t.i.w. for an intended 24 weeks and follow-up was a further 24 weeks after treatment. Biochemical non-responders were withdrawn from treatment within 12-16 weeks but continued follow-up. Overall 21/40 (52.5%) patients had a complete biochemical response with normal ALT levels at the end of treatment. Sustained response during follow-up was seen in 8 (20%) whereas 13 (32.5%) had a non-sustained response. At the end of treatment 23 (58%) patients had undetectable serum HCV RNA and 9 (23%) at follow-up. Patients with sustained, non-sustained and non-response had a mean pretreatment HCV RNA level of 3.2 x 10(5), 2.5 x 10(6) and 3.2 x 10(6) genomes/ml, respectively, differences that did not reach statistical significance. Of the patients 3, 9, 10 and 14 had genotype 1b, 3a, 1a, and 2b, respectively, and 4 had mixed genotypes. Of the 23 patients with genotype 2b or 3a, 7 had a sustained response vs. none of the 13 patients with genotype 1a or 1b (p = 0.03). No patients with cirrhosis had a sustained response whereas 4/18 with chronic persistent and 4/18 with chronic active hepatitis had such a response. It is concluded that some 50% of patients treated with HuIFN-alpha-Le responded with normalisation of ALT levels but that only 20% had a durable response 24 weeks post-treatment, and that patients with genotypes 3a or 2b seem to respond better than patients with other genotypes.

Adult↗

PubMed1995

Efficacy of human leucocyte alpha-interferon treatment for chronic hepatitis C virus infection.

Adult↗

PubMed1994

[Controlled, clinical trial of isoprinosine administration to HIV-infected patients. Results of a Danish/Swedish multicenter study. The Scandinavian Isoprinosine Study Group].

The safety and efficacy of isoprinosine in HIV-infected individuals were assessed in a multicentre, randomized, double-blind, 24-week study phase, followed by an optional 24-week open treatment phase. The results of the double-blind phase have been reported separately. Of 866 HIV-seropositive individuals randomized, 832 were eligible for efficacy analysis. On completion of the double-blind phase, 596 patients started open treatment. All patients were evaluated with regard to progression to AIDS. Within 48 weeks, 10/412 patients (2.4%) assigned isoprinosine and 27/420 (6.4%) assigned placebo progressed to AIDS (p = 0.005; odds ratio: 2.8, 95% CI: 1.3-6.2). Intention-to-treat analysis showed identical results. No severe adverse reactions or toxicities were observed. We conclude that HIV-infected individuals without AIDS may be safely and effectively treated with isoprinosine.

Acquired Immunodeficiency Syndrome↗