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Biomedical subjects

R Norberg

Publications and source records attributed to R Norberg.

At least 19 recordsLinked to original sources
PubMed2001

Tuberculosis mortality during a civil war in Guinea-Bissau.

CONTEXT: Tuberculosis (TB) is an increasing global problem, despite effective drug therapies. Access to TB therapy during conflict situations has not been studied. OBJECTIVE: To determine the effect of irregular TB treatment due to an armed conflict in Guinea-Bissau, West Africa. DESIGN, SETTING, AND PATIENTS: Ongoing retrospective cohort study conducted in the capital city of Bissau among 101 patients with TB who received irregular or no treatment during the civil war (war cohort; June 7-December 6, 1998) and 108 patients with TB who received treatment 12 months earlier (peace cohort; June 7-December 6, 1997) and comparison of an additional 42 patients who had completed treatment before June 6, 1998, and 69 patients who had completed treatment before June 6, 1997. MAIN OUTCOME MEASURE: Mortality rates, compared by irregular (war cohort) vs regular (peace cohort) access to treatment, by intensive vs continuation phase of treatment, and by those who had previously completed treatment for TB. RESULTS: Irregular treatment was associated with an increased mortality rate among patients with TB. The mortality rate ratio (MR) was 3.12 (95% confidence interval [CI], 1.20-8.12) in the war cohort, adjusting for age, sex, human immunodeficiency virus (HIV) infection, residence, and length of treatment. Each additional week of treatment before the war started increased probability of survival by 5% (95% CI, 0%-10%). In the intensive phase of treatment, the adjusted MR was 3.30 (95% CI, 1.04-10.50) and in the continuation phase it was 2.26 (95% CI, 0.33-15.34). Increased mortality among the war cohort was most marked in HIV-positive patients, who had an adjusted MR of 8.19 (95% CI, 1.62-41.25). Mortality was not increased in HIV-positive or HIV-negative patients who had completed TB treatment when the war started. CONCLUSIONS: Interruption of treatment had a profound impact on mortality among patients with TB during the war in Guinea-Bissau. Regular treatment for TB was associated with significantly improved survival for HIV-infected individuals. In emergencies, it is crucial to ensure availability of TB drugs.

Adult↗
PubMed2000

Three-year follow-up of patients with pulmonary tuberculosis in Guinea-Bissau, West Africa.

SETTING: Raoul Follereau Hospital, Bissau, Guinea-Bissau. OBJECTIVE: To study the long-term outcome of patients with bacteriologically verified tuberculosis (TB), with or without human immunodeficiency virus (HIV) co-infection. DESIGN: Sputum samples were collected from all patients referred to the hospital with clinical symptoms of pulmonary tuberculosis. Direct microscopy and culture was performed at the Health Laboratory. Patients with a culture positive for Mycobacterium tuberculosis were followed for 3 years, and underlying factors were analysed regarding the outcome of treatment. A group of sex and age-matched HIV-negative individuals was used as controls. RESULTS: Of 206 bacteriologically verified pulmonary TB patients, 168 were followed up. Antibodies to HIV-2 were found in 33 patients (19.6%); eight patients (4.8%) had antibodies to HIV-1 or showed dual reactivity. Of 149 patients discharged to follow ambulatory treatment, the survival rate of HIV-2-positive patients was 42.3% (11/26) and for HIV-negative patients it was 81.9% (95/116). The difference in survival between HIV-2-positive and HIV-negative patients was highly significant (P < 0.00001). HIV-negative TB patients had a significantly higher mortality than their controls (mortality ratio 3.75, 95% confidence interval 1.58-8.90). Most patients who survived, regardless of HIV status, also became free from symptoms compatible wtih pulmonary TB. CONCLUSION: Although the mortality rate among HIV-positive TB patients was very much higher than among HIV-negative patients, there are weighty arguments for active contact tracing and effective treatment of all TB patients.

AIDS-Related Opportunistic Infections↗
PubMed1999

Evolution and clonal traits of Mycobacterium tuberculosis complex in Guinea-Bissau.

Two hundred twenty-nine consecutive isolates of Mycobacterium tuberculosis complex from patients with pulmonary tuberculosis in Guinea-Bissau, which is located in West Africa, were analyzed for clonal origin by biochemical typing and DNA fingerprinting. By using four biochemical tests (resistance to thiophene-2-carboxylic acid hydrazide, niacin production, nitrate reductase test, and pyrazinamidase test), the isolates could be assigned to five different biovars. The characteristics of four strains conformed fully with the biochemical criteria for M. bovis, while those of 85 isolates agreed with the biochemical criteria for M. tuberculosis. The remaining 140 isolates could be allocated into one of three biovars (biovars 2 to 4) representing a spectrum between the classical bovine (biovar 1) and human (biovar 5) tubercle bacilli. By using two genotyping methods, restriction fragment length polymorphism analysis with IS6110 (IS6110 RFLP analysis) and spoligotyping, the isolates could be separated into three groups (groups A to C) of the M. tuberculosis complex. Group A (n = 95), which contained the majority of classical human M. tuberculosis isolates, had large numbers of copies of IS6110 elements (mean number of copies, 9) and a distinctive spoligotyping pattern that lacked spacers 33 to 36. Isolates of the major group, group B (n = 119), had fewer IS6110 copies (mean copy number, 5) and a spoligotyping pattern that lacked spacers 7 to 9 and 39 and mainly comprised isolates of biovars 1 to 4. Group C isolates (n = 15) had one to three IS6110 copies, had a spoligotyping pattern that lacked spacers 29 to 34, and represented biovar 3 to 5 isolates. Four isolates whose biochemical characteristics conformed with those of M. bovis clustered with the group B isolates and had spoligotype patterns that differed from those previously reported for M. bovis, in that they possessed spacers 40 to 43. Interestingly, isolates of group B and, to a certain extent, also isolates of group C showed a high degree of variability in biochemical traits, despite genotypic identity in terms of IS6110 RFLP and spoligotype patterns. We hypothesize that isolates of groups B and C have their evolutionary origin in West Africa, while group A isolates are of European descent.

Adult↗
PubMed1996

Pulmonary tuberculosis in Guinea-Bissau: clinical and bacteriological findings, human immunodeficiency virus status and short term survival of hospitalized patients.

OBJECTIVE: To study tuberculosis patients in Guinea-Bissau with regard to clinical findings, bacteriologically verified diagnosis, human immunodeficiency virus (HIV) status and short term survival. DESIGN: 763 consecutive patients referred to the tuberculosis clinic with pulmonary symptoms underwent clinical examination and Ziehl-Neelsen sputum microscopy. Sputum for culture of mycobacteria on Löwenstein-Jensen medium was collected from all hospitalized patients, who were also screened by enzyme linked immunosorbent assay for the presence of HIV-1 and HIV-2 antibodies. HIV-positivity was confirmed by Western blot. RESULTS: 350 patients were diagnosed with tuberculosis and hospitalized. Adequate sputum samples were obtained from 301 patients, of whom 184 (61%) were positive on direct microscopy and the remaining 116 patients were diagnosed from clinical findings. Mycobacterium tuberculosis was cultured from 184 patients and M. avium in 16 patients, whereas in 101 patients the culture was negative. HIV-1 antibodies were found in 3.0%, HIV-2 antibodies in 16.4%, and dual infections in 2.0%. These figures, however, did not differ significantly from those of randomly selected age and sex matched controls. The prevalence of HIV-antibodies was statistically as common in patients with culture verified tuberculosis as in patients with clinically defined tuberculosis. Clinical acquired immunodeficiency syndrome was commonly diagnosed (80/301 patients) but significantly more often in HIV-positive, culture-positive tuberculosis patients, as were weight loss and lymphadenopathy. There was no statistical difference in short-time survival rate between the various patient groups. CONCLUSION: The diagnostic criteria applied, which are generally used in developing countries, identified most patients with pulmonary tuberculosis; however, a substantial number of patients are treated for tuberculosis without definite diagnostic criteria. The prevalence of HIV-infection was high but statistically no significant difference was demonstrated between the patient groups, controls and patients hospitalized for diseases other than tuberculosis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Direct detection of Mycobacterium tuberculosis in sputum samples from Guinea Bissau by an rRNA target-amplified test system.

SETTING: There is a need for more sensitive and rapid methods for laboratory confirmation in the diagnosis of tuberculosis. OBJECTIVE: To investigate the applicability of a target rRNA amplified test system (AMTDT, Gen-Probe, CA) for rapid detection of Mycobacterium tuberculosis. DESIGN: The rRNA amplified test system was compared to standard methods for acid fast microscopy and mycobacterial culture for the demonstration of M. tuberculosis in sputum samples from 247 patients in Guinea Bissau with suspected tuberculosis. RESULTS: The highest incidence of positive samples was obtained with the AMTDT test. Out of 274 sputum samples 96 (35%) were positive by the AMTDT test, 82 (30%) were positive by culture and 38 (14%) by direct microscopy. Using culture as reference method the sensitivity of the test was 85% (after discrepancy analysis 87%), and the specificity was 86% (after discrepancy analysis 93%). CONCLUSION: The sensitivity and specificity of the AMTDT test used in this setting indicates that it may be a valuable complement for improving the laboratory diagnosis of tuberculosis.

Bacteriological Techniques↗
PubMed1996

Mycobacterium avium complex sputum isolates from patients with respiratory symptoms in Guinea-Bissau.

In total, 814 patients with clinically suspected tuberculosis were examined at the Raoul Follerau Hospital in Bissau, Guinea-Bissau. Sputum samples were collected, and cultures were grown on Löwenstein-Jensen medium. Isolates were further characterized by standard biochemical methods and nucleic acid probes for Mycobacterium tuberculosis and Mycobacterium avium complex (MAC). Serum samples were collected and analyzed for antibodies against human immunodeficiency virus (HIV) types 1 and 2. Of 17 patients who had MAC organisms in sputum, 2 were HIV-2-positive and none was HIV-1-positive. Of the total 814 patients, 189 had culture-verified tuberculosis; 36 (19%) of them were HIV-2-positive. Thus, of 206 patients with sputum culture positive for M. tuberculosis or MAC, 17 (8%) had MAC organisms in sputum. MAC infection may be the cause of some treatment failures in areas where MAC pulmonary infection is common.

Adult↗
PubMed1993

Drug susceptibility in Mycobacterium tuberculosis of a sample of patients in Guinea Bissau.

Sputum samples from patients with known or suspected tuberculosis were collected in Bissau, Guinea Bissau, and isolates belonging to the Mycobacterium tuberculosis complex (M. tuberculosis, M. bovis or M. africanum) were examined for their susceptibility to the 4 drugs streptomycin, isoniazid, ethambutol and rifampicin. Of 59 M. tuberculosis complex isolates only 2 were resistant to any of the drugs (isoniazid). Thus there is little resistance to these first line drugs among M. tuberculosis isolates from patients in Guinea Bissau.

Drug Resistance, Microbial↗
PubMed1993

Biochemical heterogeneity of Mycobacterium tuberculosis complex isolates in Guinea-Bissau.

Fifty-six strains of the Mycobacterium tuberculosis complex from patients in Guinea-Bissau were examined by using four biochemical tests (niacin production, nitrate reductase, pyrazinamidase, and resistance to thiophen-2-carboxylic acid hydrazide). The isolates were divided into five different biovars within a spectrum ranging from classical human M. tuberculosis to classical M. bovis.

Culture Media↗
PubMed1992

Multilocus markers for mouse genome analysis: PCR amplification based on single primers of arbitrary nucleotide sequence.

Polymerase chain reaction (PCR) based on single primers of arbitrary nucleotide sequence provides a powerful marker system for genome analysis because each primer amplifies multiple products, and cloning, sequencing, and hybridization are not required. We have evaluated this typing system for the mouse by identifying optimal PCR conditions; characterizing effects of GC content, primer length, and multiplexed primers; demonstrating considerable variation among a panel of inbred strains; and establishing linkage for several products. Mg2+, primer, template, and annealing conditions were identified that optimized the number and resolution of amplified products. Primers with 40% GC content failed to amplify products readily, primers with 50% GC content resulted in reasonable amplification, and primers with 60% GC content gave the largest number of well-resolved products. Longer primers did not necessarily amplify more products than shorter primers of the same proportional GC content. Multiplexed primers yielded more products than either primer alone and usually revealed novel variants. A strain survey showed that most strains could be readily distinguished with a modest number of primers. Finally, linkage for seven products was established on five chromosomes. These characteristics establish single primer PCR as a powerful method for mouse genome analysis.

Animals↗
PubMed1991

Opinions on treatment of women with habitual abortion based on investigations for blocking antibody and autoantibodies.

Three hundred and thirty-seven women with habitual abortion of unknown etiology were studied for cellular reactivity and blocking antibody in one-way mixed lymphocyte culture. Their sera were investigated for anti-cardiolipin antibodies, antinuclear antibodies, and antibodies against DNA, and the activated partial thromboplastin time (APTT) and complement levels of their plasma were determined. Increased anti-cardiolipin antibody levels were demonstrated in 77 (22%) of the 337 women, all of whom were considered healthy and had no signs of autoimmune disease. Most patients with high anti-cardiolipin antibody levels displayed lowered values of complement factor C4. According to our experiences, the mere occurrence of anti-cardiolipin antibody in women with habitual abortion is no absolute cause for treatment with prednisolone, not even in cases with greatly elevated anti-cardiolipin values. Therapy with prednisolone and acethylsalicylic acid (ASA) during pregnancy should be given to those women who have high levels of anti-cardiolipin antibodies concomitant with high APTT values, low values of complement C4, and strong blocking antibody. Anti-cardiolipin antibody has been investigated during pregnancy in 136 normal pregnant women, 11 of whom (8%) were positive at any sampling occasion, but only one of whom (1%) had high levels. Evidently the development of anti-cardiolipin antibody is no normal feature of pregnancy among Swedish women and thus the high frequency found among healthy Swedish women with habitual abortion remains unexplained. We have introduced an immunization program of leukocyte transfusions in habitual abortion. The development of previously absent blocking antibody seems to be a valuable prognostic sign of possible success for immunization therapy against habitual abortion.

Abortion, Habitual↗
PubMed1991

Platelet aggregating activity in serum from patients with HLA-B27 associated rheumatic and cardiac disorders: a possible link to the proliferative vascular changes.

OBJECTIVE: To search for possible serum factors (immunochemical abnormalities) that reflect HLA-B27 associated inflammatory process with the proliferative endarteritis, which is an important cause of severe bradycardia and aortic valve regurgitation. PATIENTS AND METHODS: Seventy four men with pacemakers were studied: 24 were HLA-B27 positive and had associated rheumatic and cardiac disorders, 13 were B27 positive but had no clinical or radiographic signs of a related rheumatic condition, and 37 were B27 negative controls. Randomly obtained serum samples were examined for a series of serum factors. RESULTS: Thirteen (57%) of the 23 patients with HLA-B27 and associated rheumatic and cardiac conditions had platelet aggregating activity in their serum. No such activity was found in sera from patients in the other groups. None the less, immunochemical abnormalities were common among patients of all groups; 30 (41%) had antinuclear antibodies or rheumatoid factor or both. CONCLUSION: The platelet aggregating activity found in patients with HLA-B27 and associated rheumatic and cardiac conditions may reflect serum factors that increase the stickiness of platelets and increase their adhesion to the vessel wall. This suggests a link via release of platelet derived growth factor(s) with the characteristic histopathological feature of proliferative endarteritis. Immunochemical abnormalities were common in serum from all men with pacemakers.

Adult↗
PubMed1989

Autoantibody formation after bone marrow transplantation. Comparison between acetylcholine receptor antibodies and other autoantibodies and analysis of HLA and Gm markers.

Clinical myasthenia gravis has been reported in an increased frequency after bone marrow grafting. The number of bone marrow transplanted patients making IgG autoantibodies directed against the autoantigens cardiolipin, SS-B (La) and thyroglobulin was found to be significantly lower as compared to the autoantigen acetylcholine receptor protein. The occurrence of antibodies to single-stranded DNA was found in a lower frequency than acetylcholine receptor antibodies but the difference was not statistically significant. Antibodies to cardiolipin were frequently observed prior to grafting. The G1m1,2 and G3m5 phenotype frequency did not differ in individuals who developed receptor antibodies from that found in the normal population. Analysis of HLA antigens in this patient group revealed no association to HLA B8/DR3 or B35/DR1. This may indicate that the etiology of myasthenia gravis induced by bone marrow grafting differs as compared with the spontaneous form of myasthenia gravis and the penicillamine-induced disease.

Antibody Formation↗
PubMed1989

Immunoglobulin allotypes are normally distributed in Swedish AIDS patients.

Immunoglobulin allotypes G1m(a), G1m(x), G3m(b) and Km(1) were determined in 83 Swedish AIDS patients. Twenty of the patients had Kaposi's sarcoma and 29 had Pneumocystis carinii pneumonia. The distribution of the Gm and Km allotypes did not significantly differ between these different disease categories and the general Swedish population.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Mortality and morbidity from invasive bacterial infections during a clinical trial of acellular pertussis vaccines in Sweden.

A double blind placebo-controlled efficacy trial of two acellular pertussis vaccines was conducted in 3801 6- to 11-month-old children. Four vaccinated children died during 7 to 9 months follow-up as a result of Haemophilus influenzae type b meningitis, heroin intoxication with concomitant pneumonia, suspected septicemia, and Neisseria meningitidis Group B septicemia. From the actual death rate in children belonging to the same birth cohort in Sweden that could have been eligible for the trial, one death was expected among vaccinated children. Several investigations were carried out to examine the possibility that the deaths could be causally related to the vaccination. The relative risk for hospitalization due to systemic or respiratory infections was 1.07 (95% confidence interval, 0.95 to 1.20) and 0.83 (95% confidence interval, 0.64 to 1.08) in the vaccine groups as compared with the placebo group. Subsets of the population were studied for signs of immunosuppression. There was no indication of immunoglobulin deficiency or any sign of clinically significant leukopenia or lymphocytosis in vaccine recipients. The results of this analysis provide no evidence for a causal relation between vaccination with the studied acellular pertussis vaccines and altered resistance to invasive disease caused by encapsulated bacteria. The hypothesis that the two variables are related, however, cannot be refuted from these data.

Antibodies, Bacterial↗
PubMed1988

Primary biliary cirrhosis: indication for a single mitochondrial antigenic epitope detected by patient autoantibodies and a novel monoclonal antibody.

A monoclonal antibody specific for the major primary biliary cirrhosis (PBC)-associated mitochondrial antigen (subunit I of NADH-ubiquinone reductase) was produced and used to study the binding sites recognized by anti-mitochondrial autoantibodies (AMA) in PBC sera. Immunization of mice with purified beef heart mitochondrial inner membranes resulted in one monoclonal antibody which reacted with mitochondrial proteins. This antibody (PBC-MoAb), which was of the IgG2b subclass with kappa light chains, exhibited a pattern of immunofluorescence reactivity with rat kidney, human thyroid, and cultured human epithelial cells (Hep-2) similar to that obtained with sera from PBC patients. Similar binding patterns between PBC-MoAb and AMA were also found in western blot analysis using mitochondria as antigen. Both types of antibodies revealed a major antigen of 75 kDa, a minor antigen of 60 kDa, and a third antigen (70 kDa), which was detected only in samples that had not been boiled prior to electrophoresis. Furthermore, optimal binding of the PBC-MoAb and AMA to the 75 and 70 kDa antigens required reduction of the antigen with mercaptoethanol prior to electrophoresis. Competition ELISA experiments were conducted to compare the epitopes recognized by PBC-MoAb and AMA. Of 28 PBC sera tested, 27 inhibited the binding of PBC-MoAb to mitochondrial inner membranes by almost 100% and one serum inhibited binding by 50%, indicating that most PBC sera contain autoantibodies reactive with the same or a closely related antibody binding site as the PBC-MoAb. PBC-MoAb inhibited AMA binding to the inner membrane by more than 80% in 10 sera, 60-80% in 11 sera, and 40-59% in seven sera, with an average inhibition of 71%. Our observations strongly indicate that anti-mitochondrial autoantibody binding sites are restricted to a highly immunogenic epitope on the major PBC-specific antigen (NADH-ubiquinone reductase subunit I), and that the anti-mitochondrial monoclonal antibody obtained has a specificity identical with the human PBC-specific M2 type anti-mitochondrial autoantibody.

Antibodies, Monoclonal↗