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Biomedical subjects

G Norkrans

Publications and source records attributed to G Norkrans.

At least 91 records · Page 5Linked to original sources
PubMed1992

One-year follow-up on the safety and efficacy of isoprinosine for human immunodeficiency virus infection. Scandinavian Isoprinosine Study Group.

The safety and clinical impact 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. Of 866 HIV-seropositive patients randomized, 832 subjects 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 and/or death. Within 48 weeks, 10/412 (2.4%) patients assigned isoprinosine and 27/420 (6.4%) patients assigned placebo progressed to AIDS (P = 0.005). Intention-to-treat analysis showed identical results. Viewing the open treatment phase in isolation revealed no difference in progression rates between those treated and those not receiving the drug, perhaps reflecting the higher proportion of patients receiving zidovudine or PCP prophylaxis in the latter group. No severe adverse reactions or toxicities were observed. We conclude that HIV-seropositive patients without AIDS may be safely and effectively treated with isoprinosine.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Peripheral blood lymphocyte subsets in patients with chronic hepatitis C--effects of interferon treatment.

Thirty-three patients with chronic hepatitis non-A, non-B/C were included in a randomized controlled study of recombinant alpha-2b interferon treatment 3 MU three times weekly for 36 weeks. In lysed whole blood, lymphocyte subpopulations were enumerated by flow cytometry detecting fluorescein or phycoerytrin conjugated monoclonal antibodies directed against seven different epitopes. Patients with chronic active hepatitis were significantly older than patients with chronic persistent hepatitis (p less than 0.05). Before treatment, the proportions of different subsets of lymphocytes were within the normal reference values and the CD4/CD8 ratio was also normal. No increased activation of T-cells was noticed. Patients over 50 years of age, however, had a significantly increased (p less than 0.01) proportion of HLA-DR+ lymphocytes, mainly B-cells. Treatment decreased the absolute number of peripheral blood leukocytes and lymphocytes. There was also a significant decline in the proportion of CD8+ lymphocytes and NK-cells, and a significant increase in the proportion HLA-DR+ cells and of the CD4/CD8 ratio. The increased proportion of HLA-DR+ cells, however, did not reflect peripheral T-cell activation; instead, it was due to increasing B lymphocyte numbers.

Alanine Transaminase↗
PubMed1992

Human immunodeficiency virus type 1 is present in the cerebrospinal fluid of a majority of infected individuals.

Cerebrospinal fluid (CSF) specimens from 63 patients with different severities of human immunodeficiency virus (HIV-1) infection, including asymptomatic virus carriers, were examined for the presence of HIV-1 by using polymerase chain reaction (PCR) and virus isolation. Polyadenylated RNA, presumably associated with virus particles, was extracted and reverse transcribed, and the pol region was amplified in a nested PCR. Virus could be detected in 90% of the CSF specimens examined by PCR, and data on isolation of virus from CSF were in agreement with these figures. In fact, when several CSF specimens from the same individual were studied, HIV-1 could be isolated from 80% of the patients. The presence of the viral RNA in CSF was independent of the clinical stage of infection and of neurological symptoms. These results show that the spread of HIV-1 to the brain represents an early event during infection and occurs in the majority of asymptomatic individuals.

Blood↗
PubMed1991

Cerebrospinal fluid catecholamine metabolites in HIV-infected patients.

Twenty-eight HIV-seropositive individuals--11 asymptomatic cases, 8 with lymphadenopathy syndrome (LAS), and 9 with AIDS--were investigated. Clinical staging of the AIDS dementia complex was done in the 9 AIDS patients. The catecholamine metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) in CSF were determined in all the HIV patients and in 20 healthy volunteers. The CSF MHPG levels did not differ significantly between healthy subjects and HIV-infected patients at any stage of the infection. The CSF concentrations of HVA differed between the groups only during the AIDS stage. The mean CSF HVA value in the AIDS patients was 42% lower than in the healthy subjects and significantly lower than in any other stage of HIV infection (P less than .01). Patients with signs of the AIDS dementia complex had reduced CSF HVA levels, but there was no clear relationship between HVA concentration and stage of the AIDS dementia complex.

AIDS Dementia Complex↗
PubMed1991

Histological outcome in interferon alpha-2b treated patients with chronic posttransfusion non-A, non-B hepatitis.

The histological outcome in liver biopsies following 9 months of interferon alpha-2b treatment was assessed in detail in 19 patients with chronic posttransfusion non-A, non-B hepatitis (PTH-NANB) and compared with 12 untreated PTH-NANB patients. Fourteen (74%) treated and 7 (58%) control patients were reactive for antibodies against hepatitis C virus (anti-HCV). Liver biopsies taken before and after the 9-month period were scored numerically for portal inflammation, piecemeal necrosis (PMN) and fibrosis, without knowledge of whether the specimens came from control or treated patients. There were no score differences in the initial biopsies between the treated and control group. In the follow-up biopsies the treated group showed significantly less portal inflammation, PMN and fibrosis than the control group (p less than 0.05-0.01). When paired samples from the treated group were compared, significantly regressed portal inflammation, PMN and fibrosis were noted in the follow-up biopsies (p less than 0.05-0.001). The presence or not of anti-HCV antibodies in serum had no impact on the histological response to interferon treatment. We conclude that a 9-month course of interferon alpha-2b treatment significantly diminishes not only inflammation but also fibrosis in the liver of patients with PTH-NANB whether they are anti-HCV reactive or not.

Biopsy↗
PubMed1991

Long-term follow-up of chronic hepatitis non-A, non-B--with special reference to hepatitis C.

One hundred and twenty-seven patients with histologically verified chronic non-A, non-B hepatitis were followed for up to 23 years (mean 6.3 years). Thirty-nine were infected by blood transfusion, 58 were drug-addicts and 30 had no obvious source of infection. Chronic persistent hepatitis (CPH) was diagnosed in 84 (66%), while 43 patients (34%) had chronic active hepatitis (CAH) with or without cirrhosis. Patients with CPH were significantly younger (29.7 years vs 46.8 years; p less than 0.01), irrespective of the type of virus exposure. Antibodies to hepatitis C virus (anti-HCV) were detectable in 91 patients (72%) and 36 (28%) were anti-HCV negative. Fifteen patients with acute onset, and negative for anti-HCV at the start, became positive during follow-up; 12 of them within 4.5 months. We found no differences among anti-HCV positive and anti-HCV negative patients in liver function tests, resolving rate, morphological progression in serial biopsies or mortality rate. Five previously anti-HCV positive patients became negative during follow-up and in two of them this was accompanied by decreasing hepatic inflammation.

Adult↗
PubMed1991

Effect of zidovudine on cerebrospinal fluid in patients with HIV infection and acute neurological disease.

Two cases of HIV infection associated with neurological complications are described. The patients had been followed with repeated cerebrospinal fluid (CSF) analyses 1-3 years before the neurological disease and 5 months after zidovudine treatment. CSF mononuclear cell count and the AIDS predictors beta 2-microglobulin and neopterin decreased in CSF after treatment and were lower or at the level seen 1-3 years before treatment. The results suggest that zidovudine has a suppressive effect on the HIV infection in CNS at least for 5 months, even when low zidovudine doses (500 mg daily) were used.

AIDS Dementia Complex↗
PubMed1991

The lack of transmission of NANB/C hepatitis between acute and chronically infected patients and their heterosexual partners.

In order to study the risk of heterosexual transmission of non-A, non-B/C (NANB/C) hepatitis, 34 spouses and/or sexual partners to 34 index patients (13 women, 21 men; median age 39 years) with acute NANB/C hepatitis (anti-HCV positive 13/34) were repeatedly tested for antibodies to hepatitis C virus (anti-HCV) and serum alanine aminotransferase (S-ALAT) values. Spouses and/or sexual partners to 13 patients with chronic NANB/C hepatitis (11/13 anti-HCV positive) were also studied by determining anti-HCV and S-ALAT levels. No conclusive evidence of heterosexual transmission of NANB/C hepatitis was found.

Acute Disease↗
PubMed1991

Interferon alpha-2b treatment of chronic posttransfusion non-A, non-B/C hepatitis: long-term outcome and effect of increased interferon doses in non-responders.

The biochemical and histological long-term outcome of interferon alpha-2b treatment for chronic posttransfusion non-A, non-B/C hepatitis was evaluated in a randomized study. 4/19 treated patients had a sustained response with normal serum alanine aminotransferases (s-ALAT) levels during follow-up, at present for 18-20 months after the end of interferon treatment. None of 11 responders with biochemical relapse normalized their s-ALAT levels during 1 year follow-up after treatment. Histological changes were assessed by a scoring system. The scores for portal inflammation, piecemeal necrosis and fibrosis were essentially unchanged in all treated patients between biopsies taken at the end of treatment and 1 year later. Six non-responders to 3 million units (MU) alpha-2b interferon thrice weekly (t.i.w.) were given 6 MU t.i.w. for at least 8 weeks. None normalized the s-ALAT levels during treatment with the higher dose, instead the side effects were much more pronounced, an obstacle to the usefulness of higher interferon doses. The biochemical non-responders had higher pretreatment histologic inflammation scores indicating a more severe infection. They also had a higher body weight and seemed to have prominent macrovesicular steatosis more often than responders, a finding that could contribute to raised aminotransferases, thereby in some of the non-responders, masking a positive biochemical effect of interferon treatment.

Adult↗
PubMed1991

Lack of correlation between hepatitis B virus infection and the increasing incidence of primary liver cancer in Sweden.

The incidence of primary carcinoma of the liver in Sweden has been reported to increase. In order to study the role of chronic hepatitis B virus (HBV) infection for liver cancer development 40 cases with hepatocellular carcinoma (HCC) were examined for the presence of HBV surface antigen and HBV core antigen in the cancer and in the surrounding non-neoplastic liver tissue. It was not possible to demonstrate a single case with tissue HBV antigen, indicating that HBV plays a minor role in the etiology of HCC in Sweden and thus does not seem to be responsible for the increasing incidence of this cancer.

Aged↗
PubMed1990

The efficacy of inosine pranobex in preventing the acquired immunodeficiency syndrome in patients with human immunodeficiency virus infection. The Scandinavian Isoprinosine Study Group.

We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of inosine pranobex (Isoprinosine) [corrected] in the treatment of patients with human immunodeficiency virus (HIV) infection but without manifest acquired immunodeficiency syndrome (AIDS). A total of 866 patients were enrolled in 21 centers in Denmark and Sweden. The patients were stratified in three groups according to their CD4+ cell count and randomly assigned to receive either inosine pranobex (1 g three times a day) (n = 429) or matching placebo (n = 437) for 24 weeks. Of the 831 patients who could be evaluated, AIDS developed in 17 in the placebo group as compared with 2 in the inosine pranobex group (P less than 0.001; odds ratio, 8.6 [95 percent confidence limits, 2.2 and 52.6]). There were no significant differences between the groups with respect to changes in CD4+ cell count or the development of other HIV-related conditions, with the exception of thrush, which developed in fewer patients in the inosine pranobex group (P = 0.05). No serious side effects were observed. We conclude that treatment with inosine pranobex delays progression to AIDS in patients with HIV infection. The duration of this beneficial effect, the optimal dose, and the mode of action of inosine pranobex remain to be clarified.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Mother to infant transmission of hepatitis C virus infection.

Eight women with chronic hepatitis C virus (HCV) infection during pregnancy gave birth to 11 children. Five of these children had elevated ALT, but only two had increased levels in more than one sample. All children tested before 6 months of age were positive for anti-HCV at most up to 7 months of age and then became negative. One child with a maximum ALT level of 8.4 mukat/l however, regained anti-HCV positivity at 12 months of age, and a liver biopsy at 21 months of age showed resolving hepatitis. Passively acquired HCV antibodies are obviously found in newborns of anti-HCV-positive mothers with chronic hepatitis. In 1 of 11 children, active anti-HCV production and concomitant liver disease suggested mother to infant transmission of hepatitis C virus infection.

Alanine Transaminase↗
PubMed1990

Cerebrospinal fluid interleukin-6 activity in HIV infection and inflammatory and noninflammatory diseases of the nervous system.

Interleukin-6 (IL-6) activity was measured in the cerebrospinal fluid (CSF) of patients at different stages of human immunodeficiency (HIV) virus infection and of patients with multiple sclerosis (MS) or other inflammatory (OID) and noninflammatory neurological diseases (OND). In the advanced stages of HIV infection and in OID, IL-6 was detected more frequently (80 and 75% of the cases) and at higher concentrations than in the early stages of HIV infection. MS and OND (44, 48, and 44% of cases). Analysis of CSF and paired sera indicated that IL-6 production can be compartmentalized to either of the fluids. Evidence that altered blood-brain barrier functions can, at least in part, influence the CSF IL-6 levels was found in OID patients. No association was evident between intrathecal immunoglobulin synthesis and CSF IL-6 levels. Interleukin-1 (IL-1) levels were detectable in a minority of the samples from neurological patients; one OID patient had high levels of both CSF IL-1 and IL-6.

Cerebral Infarction↗
PubMed1990

Therapy of chronic post-transfusion non-A, non-B hepatitis with interferon alfa-2b: Swedish experience.

Thirty-three Swedish patients with chronic post-transfusion non-A, non-B hepatitis entered a randomized trial of interferon alfa-2b treatment (INTRON A, Schering-Plough Corporation) (3 million units, three times weekly, subcutaneously for 36 weeks). Twenty-two patients (67%) were reactive for antibodies against hepatitis C virus. Nineteen patients completed the course of therapy; 11 (58%) had a complete response with normalization of serum alanine aminotransferase levels, compared to none of the 12 controls (p less than 0.001). Four treated patients with chronic active hepatitis were non-responders. Non-responders had a significantly higher mean body weight than responders (p less than 0.05) and tended to have a longer duration of prior disease. During the 10-month follow-up period post treatment, 4/11 (36%) complete responders had a sustained response and three (75%) of these four were reactive for antibodies against hepatitis C virus, whereas 7/11 (64%) relapsed, of whom four (57%) were reactive for antibodies against hepatitis C virus. All patients who were treated again responded but relapsed once more after retreatment was stopped. We conclude that the majority of patients with chronic post-transfusion non-A, non-B hepatitis will respond to 9 months' interferon alfa-2b treatment, but that only one of three responders will have a sustained response 10 months post treatment. Reactivity for antibodies against hepatitis C virus is not predictive of the outcome of therapy.

Adult↗
PubMed1990

Immune activation and decreased tryptophan in patients with HIV-1 infection.

We compared tryptophan, neopterin, and interferon-gamma (IFN-gamma) concentrations in serum and cerebrospinal fluid (CSF) of 22 patients with human immunodeficiency virus type 1 (HIV-1) infection. Tryptophan levels were found to be decreased in CSF and serum of patients whereas neopterin levels in CSF and serum and serum IFN-gamma concentrations were increased compared to healthy HIV-1 seronegatives. Tryptophan concentrations correlated negatively to neopterin concentrations, and serum neopterin concentrations correlated positively to IFN-gamma concentrations. Thus, decrease of tryptophan levels is associated with chronic immune stimulation in patients with HIV-1 infection. From the data it appears that reduced tryptophan in patients may result from induction of indoleamine (2,3)-dioxygenase by IFN-gamma.

Adult↗