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Biomedical subjects

M Forsgren

Publications and source records attributed to M Forsgren.

At least 55 records · Page 3Linked to original sources
PubMed1995

Maternal enteroviral infection during pregnancy as a risk factor for childhood IDDM. A population-based case-control study.

Using the nationwide childhood-onset diabetes register in Sweden, we were able to trace children who contracted diabetes before the age of 15 years and who were born at a specific hospital in Sweden where maternal sera from delivery had been stored during the years 1969-1989. Sera obtained at delivery from 57 mothers of diabetic children were compared with sera from 203 mothers of control subjects who were delivered at the same hospital during the same time period. The sera were analyzed blindly using a group-specific enzyme-linked immunosorbent assay for enteroviral IgG and IgM antibodies before and after urea wash as an avidity test. On the same plates, IgG antibodies to herpes, mumps, and toxoplasmosis were analyzed. The mean absorbance values of enteroviral IgG antibodies against enteroviral antigens (echo30, coxsackie B5, and echo9) were significantly higher among mothers whose children later developed diabetes (P = 0.002, P = 0.02, and P = 0.04, respectively). When reduction in activity after urea wash, indicating recently formed antibodies, was compared, the differences were even more pronounced (P < 0.001 for all three antigens). No significant differences were found for antibodies against herpes (all types), herpes type 2, mumps, or toxoplasmosis. When IgM activity and/or a significant decrease in avidity index, an indication of recent enterovirus infection, was used as a risk exposure, the odds ratio standardized for year of birth (95% confidence interval) was 3.19 (1.39-7.30). We conclude that the results of this study indicate that enteroviral infection during pregnancy is a risk factor for childhood-onset diabetes in the offspring.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗
PubMed1995

Prevention of hepatitis B by immunization of the newborn infant--a long-term follow-up study in Stockholm, Sweden.

In order to assess the present hepatitis B immunization program in Stockholm, Sweden, 212 children of HBsAg carrier mothers were followed up 2-9 years after birth. In babies of HBeAg-positive mothers a combined passive and active immunization schedule with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine was used. Among 25 children to such mothers, 1 HBsAg carrier and 5 children with asymptomatic seroconversion were found. To newborns of HBeAg-negative/anti-HBe-negative mothers, only vaccine was given. Among 15 such children, no HBsAg carrier (but 1 child with an asymptomatic seroconversion) was found. In babies of HBeAg-negative/anti-HBe-positive mothers, immunization was withheld between 1983 and 1987. Among 90 such children, 1 HBsAg carrier and 8 asymptomatic seroconversions were detected. After 1987, newborns in this group were vaccinated whereafter 3 asymptomatic seroconversions were found among 82 children. We conclude that in low prevalence areas a screening program for HBsAg should be offered to pregnant women originating from hepatitis B endemic regions, since immunoprophylaxis gave long-term protection to most children at risk. Children born to HBeAg-positive mothers should receive vaccine in combination with HBIg, whereas for children of mothers lacking HBeAg, vaccination only seems sufficient, at least if a rapid vaccination schedule is used.

Carrier State↗
PubMed1994

Cytokines and other markers of intrathecal immune response in patients with herpes simplex encephalitis.

Sequential samples of serum and cerebrospinal fluid (CSF), from 9 patients with herpes simplex encephalitis (HSE), were analyzed for cytokines and soluble cytokine receptors. The response to herpes simplex virus was characterized by a vigorous compartmentalized immune response. The intrathecal response comprised three different phases: an acute stage (first week of illness), characterized by elevated CSF levels of interleukin (IL)-6 and interferon-gamma; an early convalescence stage (weeks 2-6 after onset of disease), associated with peaking levels of tumor necrosis factor-alpha and late markers of the specific T cell-mediated immune response, soluble IL-2 receptor, and soluble CD8 antigen (sCD8); and finally, a late convalescence stage, lasting months to years and associated with persistently increased levels of sCD8 in particular. These findings show the compartmentalization and kinetics of the inflammatory response in HSE and demonstrate persistence of the intrathecal inflammatory process, which may have implications for antiviral and antiinflammatory therapy.

Adult↗
PubMed1994

Molecular basis for serological cross-reactivity between enteroviruses.

The recognition sites for human antibodies which are cross-reactive between different types of enteroviruses were determined and characterized. Serum samples obtained from 58 patients with culture-confirmed enteroviral infections were analyzed in enzyme immunoassays against two sets of overlapping synthetic peptides covering residues 31 to 96 of poliovirus 1 VP1 (Mahoney strain) and residues 31 to 148 of coxsackievirus B1 VP1 (position based on alignment with poliovirus 1 VP1, Mahoney strain). A major antigenic region eliciting cross-reactive antibodies could be located to residues 37 to 51 of VP1. Furthermore, a single peptide covering residues 42 to 55 almost completely inhibited the binding of human antibodies to heat-inactivated enteroviruses, indicating that residues 42 to 55 of VP1 contain a major region eliciting cross-reactive antibodies. By using peptide analogs in which each residue within positions 42 to 55 of VP1 was sequentially substituted by Ala or Gly, we were able to determine the most essential residues for human antibody binding in 38 of the convalescent-phase patient serum samples. In a majority of the serum samples, the most essential residues for antibody binding were found to be Pro-42, Ala-43, Leu-44, Thr-45, Ala-46, Glu-48, Thr-49, and Gly-50. All of these residues are conserved, according to known enterovirus sequences, with the divergent echovirus 22 excepted. In conclusion, we could demonstrate that the essential residues for binding of cross-reactive antibodies are well conserved within the enterovirus family. These findings provide a molecular basis for the observed antibody cross-reactivity within the enterovirus group.

Amino Acid Sequence↗
PubMed1994

Prevalence of antibodies against hepatitis C virus infection among health care workers in Stockholm.

The prevalence of hepatitis C virus (HCV) markers was investigated among health care staff with a high rate of exposure to blood or needle-stick injuries. After screening sera in pools of 10 at a time and individual testing of all reactive pools, totally 6 of 880 (0.7%; 95% confidence interval, 0.25-14.8%) were positive for anti-HCV, a figure of the same order as that found among Swedish first-time blood donors. Among the seropositives, all of five evaluable had been exposed to blood and four of five to needle-stick injuries. Our data suggest that HCV, in addition to hepatitis B virus, may constitute an occupational hazard for health care workers in Stockholm, even though the risk appears to be low, and personal risk factors such as intravenous drug abuse or blood transfusion could not be ruled out as sources of the infection.

Adolescent↗
PubMed1994

Seroconversion after additional vaccine doses to non-responders to three doses of intradermally or intramuscularly administered recombinant hepatitis B vaccine.

Hospital staff members who failed to respond (anti-HBs < 10 IU/l) after 3 doses of a recombinant hepatitis B (HBV) vaccine (given either as 20 micrograms intramuscularly (n = 8) or 2 micrograms intradermally (n = 15)) received 1 or 2 additional doses by the same route as the initial vaccination. After the first additional dose, 12/23 responded with anti-HBs levels > or = 10 IU/l and after the second, another 2/5 responded, corresponding to a total response rate of 61%. No significant difference was seen in the response rate according to vaccination route, gender, age, or whether the vaccinee was a smoker or not. In this limited study some 50% of non-responders to 3 intradermal or intramuscular doses of recombinant HBV vaccine seroconverted after an additional 1-2 doses given by the same route as the initial vaccination, suggesting that additional doses can be administered by the same route as the initial one.

Adult↗
PubMed1994

Respiratory syncytial virus infection in hospitalized patients and healthy children in El Salvador.

Nasopharyngeal specimens from 42 children less than one-year old hospitalized with bronchiolitis or pneumonia in El Salvador were analyzed for the presence of subgroup-specific respiratory syncytial virus (RSV) antigens by the indirect immunofluorescence technique. The antigen RSV-A was demonstrated in 28 children, RSV-B in three, and in one child subgroup, specificity could not be determined. The male:female ratio in the RSV-infected children was 1.9:1. The most severe disease, requiring intensive care, was observed in two infants with RSV-B infection. Determination of serum IgG, IgA, and IgM antibodies in acute and convalescent sera showed that none of the tests alone had sufficient sensitivity for routine diagnostic purposes, although, in combination, they provided a correct diagnosis in 86% of the RSV-infected children. A seroprevalence study of IgG, IgA, and IgM antibodies in 206 healthy children showed that a primary RSV infection is usually acquired during the first year of life in El Salvador. These results also indicated that reinfections with RSV frequently occur during the first 3-4 years of life and suggest that the occurrence of serum RSV IgA antibodies may be a marker of reinfection.

Age Factors↗
PubMed1993

Screening for HIV-1 antibodies in pregnancy: results from the Swedish national programme.

OBJECTIVE: To determine the effectiveness of a national screening programme for HIV infection in pregnant women. DESIGN: Observational study. SUBJECTS: All pregnant women presenting to antenatal or abortion clinics. SETTING: Sweden, September 1987 to December 1991. MAIN OUTCOME MEASURES: Number and characteristics of infected women. RESULTS: By the end of the study period 510,000 tests had been performed and 54 women with HIV infection identified (1.06/10,000). Of the 33 women identified in Stockholm, 14 women (4.4/10,000) had attended abortion clinics and 19 antenatal clinics (1.8/10,000; p < 0.05). Three women had been intravenous drug users, one was infected through a blood transfusion, and 50 were probably infected sexually. Of the 20 women who attended antenatal clinics early enough to allow an abortion, 12 continued with their pregnancies. CONCLUSIONS: Testing of all women, not just those perceived to be at risk, probably contributed to the high uptake of HIV testing. With high uptake such screening provides valuable data on spread of HIV in the heterosexual population and presents opportunity for preventing transmission of HIV to children and partners.

Adolescent↗
PubMed1993

Encephalitis in immunocompetent patients due to herpes simplex virus type 1 or 2 as determined by type-specific polymerase chain reaction and antibody assays of cerebrospinal fluid.

A herpes simplex virus type 2 (HSV 2) etiology was sought in 93 consecutive cases of herpes simplex encephalitis (HSE) in immunocompetent post neonate patients. Antibodies to HSV 2 glycoprotein G antigen were determined by an enzyme-linked immunosorbent assay (ELISA) and HSV 2 DNA in cerebrospinal fluid (CSF) by a nested polymerase chain reaction (PCR) assay with primer pairs in the glycoprotein G gene. Evidence of HSV 2 infection was found in 6 patients; HSV 2 DNA was demonstrated in CSF and the intrathecal HSV 2 antibody response confirmed the findings. Five of the 6 patients with HSV 2 encephalitis presented a clinical picture, CSF, EEG, and CT findings characteristic of severe HSE. An atypically mild clinical course was seen in one patient. HSV 2 should be considered as an etiological agent in the viral diagnosis of HSE. With a combination of nested PCR assays for HSV 1 (primer pairs in the glycoprotein D gene) and HSV 2 in 10 microliters of CSF with no other preparation than freeze-thawing, HSV 1 or HSV 2 DNA was detected in 88 out of 93 (95%) of the first CSF specimens collected after the onset of neurological HSV disease. These findings extend and confirm previous results with PCR as a rapid and sensitive tool for early diagnosis of HSE.

Adolescent↗
PubMed1993

Diagnosis of enteroviral meningitis with IgG-EIA using heat-treated virions and synthetic peptides as antigens.

Two recently developed enzyme immunosorbent assays (EIA) for the detection of significant titre increases in enteroviral IgG-antibodies were evaluated as diagnostic tools in 127 etiologically well-characterized patients with aseptic meningitis. One assay was based on heat-treated virions (H-EIA) and one on synthetic peptides (P-EIA) as antigens. The sensitivities, with virus isolation as reference method, were 0.67 by H-EIA and 0.62 by P-EIA, which were higher than by a routinely used complement fixation test (CFT, 0.51) but somewhat lower than the sensitivities found by two previously presented IgM-assays, mu-capture EIA, and solid-phase reverse immunosorbent test (SPRIST). The specificities of the two IgG-EIA techniques and CFT were apparently high, whereas the two IgM-assays showed positive reactions in some non-enteroviral cases. A relatively rapid increase in enteroviral IgG-antibodies was apparent using H-EIA and P-EIA. The two IgG-EIA tests contributed with considerable additional etiological information since significant IgG-rises were obtained in 13 patients by H-EIA and in 19 by P-EIA, respectively, out of the 56 individuals in whom enterovirus isolation was negative and a non-enteroviral diagnosis was not found. Thus, detection of enteroviral IgG-antibodies by H-EIA and P-EIA seems to be a valuable alternative to CFT for the routine diagnosis of enteroviral meningitis. The IgM-assays, mu-capture EIA, and SPRIST, may allow a relatively rapid report of an enteroviral infection. However, since both the IgM-tests are hampered by incomplete specificities, a confirmation of positive results by an IgG-assay should be carried out.

Adolescent↗
PubMed1993

Modelling toxoplasma incidence from longitudinal seroprevalence in Stockholm, Sweden.

Age-stratified data on toxoplasma seroprevalence in pregnant women in Stockholm, Sweden for the years 1969, 1979 and 1987 provide the basis for an analysis of temporal patterns of Toxoplasma gondii infection, and estimation of the risk of maternal toxoplasmosis, in this population. A catalytic infection model, in which the rate or force of infection is assumed to be a function of time (and not, as is more usual, age), was employed to describe the observed changes in levels of toxoplasma seropositivity. A range of simple incidence functions (up to 3 parameters) were fitted using a method of maximum likelihood. The data were significantly better described by a linear or an exponential decay in the rate of infection through time compared with a constant level. More complex incidence functions gave no better data description. Thus, whilst there is strong evidence for declining incidence in Stockholm over the past 4-5 decades, the data do not allow discrimination between different possibilities for the nature of this decline. Based on these modelling results, best estimates of the force of infection in 1987 acting on susceptible women are within the range 0 to 0.0045/susceptible/year (95% confidence limits), yielding a possible risk of maternal toxoplasmosis of between 0 and 2.7 cases/1000 pregnancies. These values are shown to be significantly lower than estimates based upon an assumption of temporal stability in toxoplasma incidence, which may be of practical significance to public health policy.

Adolescent↗
PubMed1993

Tumor necrosis factor-alpha (TNF alpha) in cerebrospinal fluid from patients with meningitis of different etiologies: high levels of TNF alpha indicate bacterial meningitis.

The levels of tumor necrosis factor (TNF)-alpha in cerebrospinal fluid (CSF) were analyzed in 139 patients with meningitis and in 20 control subjects. Elevated concentrations were observed in 42 (82%) of 51 patients with purulent bacterial meningitis (18/24 Haemophilus influenzae, 13/14 Streptococcus pneumoniae, 7/7 Neisseria meningitidis, and 4/6 with other purulent bacterial etiology). In contrast, elevated levels were found in only 5 of 78 individuals with nonbacterial meningitis (2/8 with herpes simplex type 2, 3/3 with varicella-zoster virus). Thus, the positive and negative predictive values were 0.89 for indicating a purulent bacterial meningitis. Raised CSF TNF alpha levels were observed in 7 of 8 patients with purulent bacterial meningitis in whom the routinely used parameters did not unequivocally indicate the diagnosis. Moderately increased levels were seen in 5 of 6 patients with Mycobacterium tuberculosis meningitis and in 1 of 4 cases of Borrelia burgdorferi. Thus, the present study indicates that concentrations of TNF alpha in CSF usually can discriminate between purulent bacterial and nonbacterial meningitis. These findings may contribute diagnostic guidance with routinely used CSF parameters.

Diagnosis, Differential↗
PubMed1993

Persistent intrathecal immune activation in patients with herpes simplex encephalitis.

Neopterin and beta 2-microglobulin (beta 2M) levels were analyzed in sequential cerebrospinal fluid (CSF) and serum samples from 20 patients with herpes simplex encephalitis (HSE) and 30 patients with acute febrile encephalopathy of other cause (non-HSE). Markedly elevated acute phase CSF levels of neopterin and beta 2M were found in 19 HSE patients, but the levels were only moderately increased in most of those with non-HSE. Neopterin levels were analyzed in an additional 15 HSE patients who died within a month of the onset of neurologic symptoms and correlated with the clinical severity of the HSE. After HSE, but not after non-HSE, increased levels of neopterin and beta 2M persisted for a long time (> or = 13 years). Specific intrathecal IgG activity persisted in all but 2 HSE patients. These findings indicate that there is a vigorous acute inflammatory response and a long-term persistence of intrathecal cellular and humoral immune activity in HSE.

Adolescent↗
PubMed1993

Identification of group-common linear epitopes in structural and nonstructural proteins of enteroviruses by using synthetic peptides.

Synthetic peptides were employed in enzyme-linked immunosorbent assays to identify group-common linear epitopes in the structural and nonstructural proteins of enteroviruses. Nine linear epitopes were recognized by using sera from patients with heterotypic immunoglobulin G antibody responses to enterovirus infections. The most-reactive peptides were derived from conserved regions of the amino-terminal part of VP1, whereas peptides representing sequences from other conserved regions of VP1, as well as VP2, VP3, and VP4, and from a nonstructural region showed no or poor reactivity. These findings may be useful in the development of serological tests for the diagnosis of infections caused by a broad range of enteroviruses.

Amino Acid Sequence↗
PubMed1993

HIV-antibody testings among injecting drug users (IDUs) in the Stockholm area, 1984-91: information compiled from testing laboratories.

The available information about testings for HIV antibodies in injecting drug users (IDUs) carried out in Stockholm between 1984 and 1992 has been compiled. These testings were carried out mainly in special settings. The use of codes (the first 2 digits giving the age and the last 4 the 6 and checking figures in the individual's personal identity number) precluded exact identification of individuals; in most cases, however, complementary information made it possible to recognize patients at follow-up. The data indicated that 9,150 persons associated with current or previous drug addiction were tested. The first extensive testings were performed in 1985 and 1986. After this period, 4,500 persons were retested. 11% of the IDUs tested in 1984-85 were found to be HIV-antibody-positive. After 1988, 1% were estimated to seroconvert each year. While in the first phase the heroin users predominated among those infected, in later years the rates of newly diagnosed infections became similar for all types of IDUs. The age profiles of the IDUs tested were similar up to 1988, after which there was an indication that also younger persons had entered the scene. However, the infected IDUs discovered belonged mainly to the 'old' cohort born between 1950 and 1960.

Adult↗
PubMed1993

Detection of enteroviral RNA by polymerase chain reaction in cerebrospinal fluid from patients with aseptic meningitis.

An assay based on a 2-step (semi-nested) polymerase chain reaction (PCR) was developed and evaluated for detection of enterovirus-specific RNA in cerebrospinal fluid (CSF) from patients with aseptic meningitis of different etiology. The limit of detectability of enteroviral RNA was equivalent to about 0.25 tissue culture infective doses 50%. In samples, stored at -70 degrees C, analyzed without repeated thawing, enteroviral RNA was demonstrable in 21/22 CSF specimens from which an enterovirus had been isolated. Enteroviral RNA was shown to be degraded during freeze-thawing of the samples. In repeatedly freeze-thawed samples from 134 consecutive patients with aseptic meningitis, a lower sensitivity (34/48 = 0.71) was observed. In the latest phase of the study, comprising 35 consecutive patients, the PCR was performed in CSF stored at -20 degrees C without thawing. In this material, the PCR yielded positive results in 19 patients, whereas enteroviruses were isolated from 6 cases only. In the total clinical material of 169 patients, 67 (40%) were found positive by PCR, whereas an enterovirus was isolated from CSF in 54 (32%) cases. All the 13 isolated enterovirus serotypes found in the study were demonstrable by PCR, indicating that the assay is broad-reacting within the enterovirus group. The specificity appeared to be high, since all of 21 patients with non-enteroviral diagnoses were negative by the PCR test, except 1 with an Epstein-Barr virus infection. As serological evidence of enteroviral etiology was found in this patient, a dual infection seemed probable. This study indicates that enteroviral RNA can be detected in CSF by a 2-step PCR in meningitis caused by enterovirus and that the technique has the potential to become a screening method for routine diagnosis of enteroviral meningitis.

Adolescent↗
PubMed1993

Clinical manifestations and antibody prevalence of Lyme borreliosis and tick-borne encephalitis in Sweden: a study in five endemic areas close to Stockholm.

Five populations, including 903 individuals living in 5 different areas close to Stockholm, were studied with regard to clinical manifestations and antibody prevalence of Lyme borreliosis (LB) and tick-borne encephalitis (TBE). The study areas involved 4 groups of islands in the Baltic Sea and 1 island in Lake Mälaren. Serum samples from each individual were tested for antibody activity to Borrelia burgdorferi using a sonicated whole spirochete antigen in an ELISA, and to TBE-virus (TBEV) by ELISA and haemagglutination inhibition. A history of LB was reported by 1-21% and antibodies to Borrelia burgdorferi were found in 7-29% of the participants from the various areas. An increasing seroprevalence with age was seen. In sera from 3 different control groups, including 502 individuals living in non-endemic areas, antibodies to Borrelia burgdorferi were detected in 1-2% and from 1 control group including 150 individuals living in the city of Stockholm, in 9%. A history of TBE was reported by 0-6% of the individuals and in non-immunized individuals seropositivity was seen in 4-22%, depending on the area investigated. No antibody activity to TBEV could be detected in sera from persons in the 3 control groups living in non-endemic areas, whereas 5% of the controls from Stockholm were found to be positive. The prevalence rates of antibodies to TBEV in persons vaccinated against TBE were 40%, 53% and 79% after 1, 2 and 3 injections, respectively.

Adolescent↗