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Biomedical subjects

P Forsberg

Publications and source records attributed to P Forsberg.

At least 37 records · Page 2Linked to original sources
PubMed1997

Compartmentalization of antigen specific cytokine responses to the central nervous system in CNS borreliosis: secretion of IFN-gamma predominates over IL-4 secretion in response to outer surface proteins of Lyme disease Borrelia spirochetes.

The neurological manifestations of Lyme disease have been proposed to be partly due to cytokine-mediated immunopathological mechanisms. In this study, the number of Borrelia-specific cells secreting interferon-gamma and interleukin-4 was determined in blood and cerebrospinal fluid from patients with CNS borreliosis (n = 23), other neurological diseases (n = 20), and in blood from healthy controls (n = 10), utilizing an ELISPOT-assay. Elevated specific secretion of IFN-gamma was found in CNS borreliosis, most pronounced in cerebrospinal fluid, whereas secretion of IL-4 was strikingly low. This may indicate that symptoms are due to side effects of the immune response, since IFN-gamma secretion in the absence of corresponding levels of IL-4 may be associated with tissue destruction.

Adult↗
PubMed1997

Problem-based medical education: development of a theoretical foundation and a science-based professional attitude.

Problem-based learning, combined with early patient contact, integration between different subject areas, elements of multiprofessional education, and special emphasis on the development of communications skills has become the basis for the medical curriculum at the Faculty of Health Sciences in Linköping. Critics have questioned the depth of the scientific and theoretical aspects of the curriculum. Through a series of specific measures in the organization of the curriculum and examinations, and due to the pedagogical principles involved per se, our claim is that students graduating at Linköping do possess the required theoretical knowledge and a scientific attitude to the practice of medicine, at least equivalent to that obtained in a more conventional medical curriculum. One such specific measure is that all students perform one field study and two scientific studies during the course of the curriculum. An investigation of student opinions regarding the value of performing scientific projects of their own have shown that these projects have had a positive impact on the students' general scientific attitude and their willingness to engage in future scientific work. The specific skills acquired, as confirmed by oral examinations, were largely determined by the scientific nature of the chosen field of study. Our graduates have not yet progressed far enough in their careers for comparisons to be made on the basis of the Swedish Licensing Board Internship Examinations, but continuing evaluations of students, graduates and licensed doctors emerging from the curriculum will provide future evidence as to whether our present evaluation is correct.

Attitude of Health Personnel↗
PubMed1995

Intrathecal production of specific IgA antibodies in CNS infections.

Cerebrospinal fluid (CSF) and serum from subjects with herpes simplex encephalitis, herpes zoster, mumps meningitis and neuroborreliosis were analysed for the presence of immunoglobulin A (IgA) and G (IgG) antibodies to the corresponding four antigens. Specific intrathecal IgA antibody synthesis as manifested by an elevated index was a frequent finding. Higher IgA index values than the corresponding IgG was seen in one third of the samples from subjects with herpes simplex encephalitis and herpes zoster. Correlation between specific IgG and IgA index was most pronounced for varicella-zoster virus (r = 0.66, P < 0.001). In subjects with mumps meningitis a strong intrathecal IgA and IgG antibody response to Borrelia burgdorferi was demonstrated. Specific herpes simplex and varicella-zoster virus IgA was not found to contain secretory component, thus contradicting an active secretion into the CNS compartment. In conclusion, our data indicate that specific IgA is intrathecally produced in herpes simplex encephalitis, herpes zoster and mumps meningitis but is a rare finding in neuroborreliosis.

Adult↗
PubMed1995

The outer surface proteins of Lyme disease borrelia spirochetes stimulate T cells to secrete interferon-gamma (IFN-gamma): diagnostic and pathogenic implications.

Late stages of borrelia Lyme disease infections may be difficult to diagnose because of unspecific symptoms and unreliable laboratory tests, being too unspecific or insensitive. The T cell immune response was thus evaluated in these patients by using a sensitive ELISPOT T cell assay that detects the secretion of IFN-gamma, i.e. a T helper 1 (Th1) response on the single-cell level. Three subcellular fractions of the Lyme borreliosis strain Borrelia afzelii were used for antigenic stimulation. The outer surface protein (Osp) fraction elicited the strongest response, discriminating between borrelia infections (n = 15) compared with other neurological diseases (n = 10) and normal controls (n = 12) (P = 0.0001). The more heterogeneous sonicated borrelia fraction also elicited a strong response, however, also in some of the controls. The flagellin fraction did not have a similar T cell-stimulating effect. When looking at subgroups of borrelia infections, central nervous system (CNS) infections (n = 7) revealed a lower T cell response in blood (P = 0.0128) compared with other borrelia manifestations (n = 8). Cerebrospinal fluid (CSF) lymphocytes were available from three patients with CNS borreliosis, and all showed a compartmentalization with higher responses to the Osp fraction in CSF compared with blood, also in the two patients without any intrathecal-specific antibody synthesis. The ELISPOT method is feasible for detecting a specific IFN-gamma T cell response in borrelia infections. This Th1 response may well be of pathogenic relevance.

Adolescent↗
PubMed1995

Lower values for immunoglobulin M in cerebrospinal fluid when sampled with an atraumatic Sprotte needle compared with conventional lumbar puncture.

Immunoglobulin M (IgM) has a very low concentration in cerebrospinal fluid (CSF) compared with serum, and therefore determinations of IgM in CSF are highly sensitive to pre-analytical errors caused by contamination with serum or interstitial fluid. Capillary attraction causes a thin layer of liquid containing serum proteins to be formed inside a conventional (Quincke) needle during penetration of tissue. To investigate this source of pre-analytical error, 35 patients had lumbar punctures using a 22 G atraumatic (Sprotte) or 25 G conventional (Quincke) needle according to a randomized scheme, and the IgM concentrations in CSF and serum were determined. The CSF IgM concentrations for samples taken with a Sprotte needle were significantly lower than those taken with a Quincke needle (P < 0.05), whereas the corresponding serum IgM concentrations and CSF erythrocyte counts did not differ significantly. The difference indicates that CSF IgM concentrations determined after conventional sampling may be falsely increased by contamination. We conclude that IgM concentrations in CSF samples taken with the atraumatic technique are more accurate, and recommend the use of this technique when CSF IgM is to be determined.

Diagnostic Errors↗
PubMed1995

Determination of total and herpes simplex virus specific monomeric and dimeric IgA in serum and cerebrospinal fluid by ultracentrifugation.

An improved method is described for differentiating between monomeric and dimeric total and herpes simplex virus (HSV) specific IgA by ultracentrifugation in sucrose gradient, using recovery and quantitative analysis of the fractions obtained. Calculation of monomeric and dimeric IgA was based on IgG as an internal standard. Intrathecally produced monomeric and dimeric IgA were judged by calculating IgA indices for each form. A new type of formula indicating relative over-production of dimeric compared with monomeric IgG (IgA dimeric-monomeric index) is suggested. The method was applied to serum and cerebrospinal fluid (CSF) from three patients with HSV encephalitis. The index for monomeric as well as dimeric IgA was high during the acute phase of the disease, indicating intrathecal synthesis of both molecular forms. One year after onset, there was no detectable HSV-specific IgA in CSF: both molecular forms, however, remained in serum. The amount of dimeric compared with monomeric IgA was high during the acute phase, and subsequently decreased after successful treatment. A new finding was the detection of HSV-specific IgA heavier than dimeric IgA in serum one year after onset of the disease. These components may be tetrameric IgA, or immune complexes containing IgA.

Antibodies, Viral↗
PubMed1994

Long-term findings in patients with facial palsy and antibodies against Borrelia burgdorferi.

Little is known about the long-term effects of Borrelia burgdorferi (Bb) infection in untreated patients with peripheral facial palsy. We investigated 12 patients with elevated serum Bb antibody levels, with a median follow-up time of 11 years, during which 3 of the 12 still exhibited intrathecal antibody production of antibodies against Bb flagellar antigen, and 2 of the 3 had normal serum Bb antibodies. Four of the 12 had elevated serum antibody titres at the late follow-up examination. Arthralgia, reported by 7 patients, was the single most common complaint. Four patients showed extensive oculomotor disturbances, which were not correlated to antibody titres or intrathecal antibody synthesis. In 1 of the patients with intrathecal Bb antibody production, most symptoms were eradicated by antibiotic treatment 6 years after the initial infection. We conclude that even several years after a Bb infection, intrathecal Bb antibody production can still occur in serum Bb IgG antibody negative patients with a history of facial palsy.

Adolescent↗
PubMed1993

Improved formulae for the judgement of intrathecally produced IgA and IgM in the presence of blood CSF barrier damage.

In order to discriminate between transsudated and intrathecally produced IgA and IgM in patients with blood cerebrospinal fluid (CSF) barrier (BCB) damage, we developed extended indices (IgA-EI and IgM-EI) for these immunoglobulins according to the general formula for extended index of a component X in CSF: X-EI = (CSF-X/serum-X)/(CSF-albumin/serum-albumin)a where a is a parameter specific for X. For IgA parameter a was found to be 1.15 and for IgM 1.9. A preliminary evaluation of IgA-EI and IgM-EI indicated lower false positive rates as compared to CSF IgA and IgM concentrations as well as 'conventional' IgA and IgM indices in cases with BCB damage, and essentially the same rates as for the hyperbolic formulae of Reiber and Felgenhauer. The importance of reliable sampling and analytical technique for IgM in CSF is discussed.

Adolescent↗
PubMed1992

Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome.

The immunopathology in primary Epstein-Barr virus (EBV) infections and in chronic fatigue syndrome was studied by examining serum levels of interleukins (IL) and of soluble T cell receptors in serum samples. Serum samples were from patients during and 6 months after primary EBV-induced infectious mononucleosis and from patients with chronic fatigue syndrome and serologic evidence of EBV reactivation. Markers for T lymphocyte activation (soluble IL-2 and CD8) and for monocyte activation (neopterin) were significantly elevated during acute infectious mononucleosis but not in patients with chronic fatigue syndrome. Interferon-alpha, IL-1 beta, and IL-6 levels were not significantly increased in any patient group but inferferon-gamma levels were significantly increased during the acute phase of infectious mononucleosis. The levels of IL-1 alpha were significantly higher than in controls both in patients with infectious mononucleosis and in those with chronic fatigue syndrome. In the latter, the lack of most markers for lymphocyte activation found in patients with infectious mononucleosis makes it less likely that EBV reactivation causes symptoms.

Adolescent↗
PubMed1992

Comparison of seven formulae and isoelectrofocusing for determination of intrathecally produced IgG in neurological diseases.

Seven different formulae and agarose isoelectrofocusing (AIF) using immunolabelling for IgG were compared for their ability to discriminate between intrathecally produced IgG and transudated IgG in cerebrospinal fluid. All reference limits were set to a specificity of 97.5% (reference group, n = 211). The probability of a positive test (p+) was evaluated for 112 patients with multiple sclerosis (MS), 42 with meningitis, 114 with noninflammatory diseases affecting the central nervous system (CNS), 23 with Guillain-Barré syndrome, and 56 with various diseases not affecting the CNS. Agarose isoelectrofocusing had the best diagnostic sensitivity (93%) for MS, combined with a low p+ (0-19%) for other diseases. Among the formulae, the IgG extended index and Reiber's hyperbolic formula were equivalent, giving high (75-79%) diagnostic sensitivity for MS combined with low p+ (4-22%) for other diseases. All other formulae, although sensitive for MS, had a higher rate of false positive results.

Algorithms↗
PubMed1991

Acute peripheral facial palsy: CSF findings and etiology.

CSF and serum were examined in acute and convalescence phase from 56 patients with acute idiopathic peripheral facial palsy. CSF protein analysis, viral and borrelia serology were performed. Borrelia infection was found in 9/56 cases and was often associated with inflammatory CSF findings. One patient each had serological evidence for a recent or ongoing infection with herpes simplex, varicella zoster, adeno, influenza B, echo and Epstein-Barr virus, but none had specific intrathecal antibody synthesis; 11 patients had a serological pattern compatible with a reactivated Epstein-Barr virus infection. Eleven patients displayed mononuclear CSF pleocytosis. Four of them had a borrelia infection. A disturbed blood-brain barrier was observed in 19 patients. Intrathecal immunoglobulin synthesis as indicated by elevated IgM-indices was found in 16 patients and by IgG indices in three. Nine patients had oligoclonal IgG bands in serum and CSF, three exclusively in CSF. It is concluded that patients with facial palsy often have inflammatory CSF findings, indicating a generalised central nervous system affection, and not only a mononeuritis. The importance of viral infections in the pathogenesis is still obscure. Borrelia is the most common infectious cause of facial palsy.

Adolescent↗
PubMed1989

An improved formula for the judgement of intrathecally produced IgG in the presence of blood brain barrier damage.

In order to develop a better formula for discrimination between transsudated and intrathecally produced IgG, we studied the relation between cerebrospinal fluid (CSF) IgG, serum IgG, CSF albumin, and serum albumin for patients with blood brain barrier (BBB) damage. From this study we derived a new formula, IgG extended index = (CSF IgG/serum IgG)/(CSF albumin/serum albumin). Applying this index on 152 patients with BBB damage, but not expected intrathecal IgG synthesis, yielded 14 patients (9.2%) with increased (greater than 1.24) IgG extended index. In comparison, 'conventional' IgG index was increased in 34 of the patients (22%). The diagnostic sensitivity for 68 patients with multiple sclerosis (MS), did not differ significantly between the two formulas (81 and 87%, respectively). A formula for the estimation of 24 hours IgG production was also developed, but this formula was not better than IgG index. Children (0.5-16 yr) had similar IgG patterns as adults.

Adolescent↗
PubMed1989

Mononuclear cell types in cerebrospinal fluid and blood of patients with multiple sclerosis. Quantitation by immunoenzyme microassay with panel of monoclonal antibodies.

Phenotypic distribution of mononuclear cells in cerebrospinal fluid (CSF) and peripheral blood from patients with multiple sclerosis (MS) and, for reference, patients with acute aseptic meningoencephalitis (AM), and in blood only from healthy controls, was studied with an immunoenzymatic microassay enabling analysis even in the presence of a normal CSF cell count. In MS, increased CD5+ (pan-T) cell proportion in CSF compared with blood was not reflected by changes of CD4+ or CD8+ cells, while in AM, an increase of CD4+ cells was registered. Therefore, a population of CD5+, CD4-, and CD8- cells may be anticipated to exist in CSF of patients with MS. Numbers of OKB7+, OKM1+, or HLA-DR+ cells did not distinguish between MS and AM. Proliferating cells expressing transferrin receptors (OKT9+ cells) were generally few or absent in CSF and not useful as a marker of disease activity in either MS or AM.

Acute Disease↗