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Biomedical subjects

G Friman

Publications and source records attributed to G Friman.

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

New aspects of murine coxsackie B3 myocarditis--focus on heavy metals.

The magnitude of inflammatory lesions in the hearts of coxsackie B3 (CB3)-virus infected mice can be affected by the potentially toxic heavy metals cadmium (Cd), nickel (Ni) and methyl mercury (MeHg). The infection is associated with a changed distribution, such as Cd accumulation in the spleen and kidneys. New target organs for Ni during the infection were the heart, pancreas and lungs in which inflammatory lesions were present. This increased uptake was correlated with the disturbed function of immune cells and an increased inflammatory reaction. Ni and MeHg appeared to have a direct effect on immune cells that resulted in changed natural killer cell activity and decreased mobilization of macrophages, CD4+ and CD8+ cells into the inflammatory lesions. Although MeHg increased spleen T cell activity and gamma-interferon (IFN-gamma) levels, the inflammatory lesions in the heart increased. Another detrimental effect of MeHg treatment was evident by an increased calcium and decreased zinc content in the inflamed heart, which may partly explain the more severe inflammatory lesion. The host's response, CB3 infection, changed the distribution of each metal in a specific way, a fact which may subsequently result in altered target organ toxicity and resistance to the infection.

Animals↗
PubMed1995

The epidemiology of infectious myocarditis, lymphocytic myocarditis and dilated cardiomyopathy.

Infectious myocarditis is a common condition which often passes unrecognized, and the true incidence is thus unknown. Lymphocytic myocarditis has been recorded in 1.06% of 12,747 unselected routine autopsies performed over a 10-year period. Dilated cardiomyopathy (DCM) has an estimated frequency of 7.5-10% per 100,000 inhabitants per year. Overall, the enteroviruses, and particularly the Coxsackie-B viruses, predominate among viruses as the cause of myocarditis. As new molecular biological techniques have become available, the cytomegaloviruses (CMV) seem to have emerged as a more common cause of myocarditis than was previously recognized. Among the bacterial myocarditides, diphtheric myocarditis has become a serious threat in Russia and adjacent states during the 1990s. Among newly identified bacteria, Borrelia burgdorferi infection is accompanied by cardiac involvement in 1-8% of cases, where myocarditis with conduction disturbances is the most prominent feature. Chlamydia pneumoniae may be associated with myocarditis and sudden unexpected death. In AIDS, myocarditis with variable aetiology occurs in up to 50% of patients, although asymptomatic in most cases. In lymphocytic myocarditis and DCM, enteroviral-specific nucleotide sequences have been detected in about 30% of patients, and CMV-specific nucleotide sequences in 14%. Borrelia burgdorferi may occasionally be implicated in DCM. In this contribution we focus also on sudden unexpected death (SUD) in young athletes, since, in Sweden, an increased frequency of SUD has recently been observed in young orienteers and myocarditis was a common feature.

Bacterial Infections↗
PubMed1995

Infectious and lymphocytic myocarditis: epidemiology and factors relevant to sports medicine.

Myocarditis is a disease entity of permanent actuality and of special concern in the sports setting. This is because the probability of complications or sequelae increases if exercise is imposed. Myocarditis may pass unrecognized by the sufferer or be easily overlooked by the physician, especially in athletes, where electrocardiographic changes often exist normally. Furthermore, although the immune system of the conditioned individual may be more efficient than that of the sedentary individual, very strenuous and frequently repeated or long-lasting exercise may cause immunosuppression and an increased susceptibility to respiratory tract infections (RTI). Several causative agents of RTI can give rise to myocarditis as well. The true incidence of proven infectious myocarditis in society is unknown. Histopathologically defined myocarditis (lymphocytic myocarditis), on the other hand, has been found in about 1% of unselected routine autopsies. In general, the long-term prognosis in myocarditis is favorable but exercise stress may cause long-term sequelae or sudden death. It is thus essential to refrain from strenuous exercise during RTI.

Death, Sudden, Cardiac↗
PubMed1994

Changed distribution and immune effects of nickel augment viral-induced inflammatory heart lesions in mice.

We have used the myocarditic coxsackievirus B3 (CB3) infection in Balb/c mice to investigate immunotoxic effects of a ten-week low-dose (0.002 M) administration of nickel chloride (NiCl2) prior to infection. This dose did not influence CB3-induced mortality. Whole-body autoradiography of [63Ni] during the disease showed the pancreas, lungs and myocardium to be new target organs in this disease. Seven days after the inoculation, impulse counting of these organs showed the infection-induced increase of [63Ni] to be 5-fold (P < 0.01) in the pancreas, 2.2-fold (P < 0.05) in the lungs and 1.3-fold (P < 0.05) in the heart. Nickel tended to increase spleen B- and T-cell activities, but thymocyte activity was unaffected. The activity of spleen natural killer (NK) cells decreased by 30% (P < 0.05), whereas blood-cell activity in fact increased by 51% (P < 0.05). The inflammatory and necrotic lesions in the ventricular myocardium seven days after the inoculation covered 3.31% of the tissue section area in infected control mice. This damage was increased by 43% (to 4.74% of the tissue section area) in nickel-treated mice. The response pattern of lymphocyte subsets in situ in myocardial inflammatory lesions was elucidated by an immune histochemical staining technique. The number of cytotoxic T-cells, helper T-cells and Mac 2+ cells (macrophages) in these lesions decreased by 46% (P < 0.05), 41% (P < 0.05) and 27% (not significant), respectively, with the nickel treatment. The number of helper T-cells was negatively correlated to the size of the inflammatory area (r = -0.529, P < 0.02). The results indicate that nickel may contribute to the progression of target organ pathology in infection-induced diseases of an autoimmune and/or inflammatory character, such as diabetes and myocarditis.

Administration, Oral↗
PubMed1994

Immune responses and resistance to viral-induced myocarditis in mice exposed to cadmium.

The effects of 10 weeks of treatment with cadmium (Cd) on the immune function and resistance to coxsackievirus B3 (CB3)-induced myocarditis in female Balb/c mice were investigated. A 2mM dose of Cd in the drinking water did not influence mortality due to the CB3 infection. The inflammatory and necrotic lesions in the ventricular myocardium seven days after inoculation (2.94% of tissue section area) were not increased by Cd (2.82% of tissue section area). The response pattern of lymphocyte subsets in situ in myocardial inflammatory lesions was elucidated by an immune histochemical staining technique. With Cd treatment the number of cytotoxic T cells and B cells in these lesions decreased by 22% (n.s.) and 21% (p < 0.05), respectively. Spleen weight and the lymphoproliferative response to the B-lymphocyte mitogen increased by 19% (p < 0.05) and 23% (n.s.), respectively. The titers of neutralizing antibodies increased by 22% (n.s.) with Cd treatment. However, the activity of spleen T lymphocytes and spontaneous cell-mediated cytotoxicity (NK-cell) was unchanged. Thymus weight and WBC count in peripheral blood tended to decrease. Thus, Cd exposure seems to result in a decreased maturation and mobilization of T and B lymphocytes, but increased humoral immune host responses.

Animals↗
PubMed1994

[Myocarditis. Epidemiology, etiology and clinical aspects].

The term myocarditis covers a diversity of pathological conditions. Aetiologically, the best documented is acute infective myocarditis, predominantly caused by enteroviruses, particularly Coxsackie B. However, there are many possible sources of infection, and the management of immunosuppressed patients requires careful deliberation. Research into the pathogenesis of viral myocarditis has made formidable advances and provided detailed knowledge of the mechanisms responsible for myocardial damage. Microbiological techniques have yielded evidence of the involvement of Coxsackie viruses in the development of dilated cardiomyopathy. Nowadays, the term myocarditis has a strictly histopathological definition which is clinically applicable only in the few cases where endomyocardial biopsy is performed. The diagnosis, acute infective myocarditis, can usually be made with reasonable certainty on the basis of ECG findings and the serum concentrations of biochemical markers. Physical diagnostic procedures, particularly echocardiography, can provide useful supporting evidence. Prognosis is generally good in cases of acute infective myocarditis, whereas that in other forms of myocarditis varies from case to case. To date, antiviral agents have no established place in the treatment of viral myocarditis. Where diagnosis is based upon endomyocardial biopsy (e.g., in lymphocytic myocarditis), immunosuppressive therapy generally has no significant effect.

Acute Disease↗
PubMed1993

Comparative tolerability and kinetics during long-term intake of Lariam and Fansidar for malaria prophylaxis in nonimmune volunteers.

One hundred and five healthy nonimmunes in Colombia took part in a randomize, double-blind comparison of 250 mg of Lariam (L) (active ingredient: mefloquine) on alternate weeks or one tablet of Fansidar (F) (active ingredients: sulfadoxine and pyrimethamine) weekly for malaria prophylaxis during at least six months. Volunteers also gave blood for determination of drug concentrations after six months and/or 24-27 months of prophylaxis. Twenty-five volunteers withdrew involuntarily when they lost their jobs in the company. Two who took L withdrew due to moderate diarrhea and mild nausea or headache, weakness, drowsiness and anxiety. One volunteer stopped taking F due to severe unilateral hypostatic eczema and slight S-T depressions on the ECG. The rest completed at least six (range 6-36) months of prophylaxis. The mean half-life for L was 26 days. The AUCs in the time interval 0-14 days for L varied between 19.3-31.5 mumol x days/l. For the main metabolite, the corresponding range was 28.8-81.3 mumol x days/l. The range of trough concentrations at day 0 and 14 were 0.95-2.01 mumol/l for L and 1.69-5.62 mumol/l for the metabolite. No differences in tolerability and efficacy were noted between L and F. Our kinetic results do not indicate that enzymatic induction or inhibition would be important during long-term prophylaxis with mefloquine. This favors a continued use of the drug for very long periods of time (= years).

Adult↗
PubMed1993

Is juvenile diabetes a viral disease?

The purpose of this review is to discuss recent literature data concerning the etiology and pathobiology in insulin-dependent diabetes mellitus as well as present our own experience from all children up to 15 years of age in Uppsala County, Sweden presenting with juvenile (type I) diabetes since 1976. Chronic enterovirosis is an emerging concept in apparently immunologically competent patients. By means of new serological and DNA-based methods, a persistent enteroviral (Coxsackie virus A, B and ECHO virus) infection can sometimes be demonstrated after an acute primary infection, which is often subclinical. There are several indications that these viruses can contribute to the development of illnesses with a pathogenesis as yet not fully understood, e.g. dilated cardiomyopathy, type I diabetes, and possibly some cases of the so-called chronic fatigue syndrome. In type I diabetes, many pieces of evidence including epidemiology, genetic analysis of the host susceptibility genes, cytokine analysis and new seriological evaluation suggest an infection to be the starting point for the beta cell destruction. These etiological agents most likely belong to the enteroviral group of picornaviruses. Later events may well involve all parts of the immune system launching a selective autoimmune 'suicidal attack' on the cells necessary for glucose homeostasis.

Animals↗
PubMed1993

High yield production of an inactivated coxsackie B3 adjuvant vaccine with protective effect against experimental myocarditis.

Dilated cardiomyopathy, perhaps chronic postviral fatigue syndrome as well as juvenile diabetes could be triggered by enteroviral infections. The frequency of sudden death after myocarditis and its relationship to enteroviral infections is disputed. Neonatal enteroviral disease is rare, but can be severe. It is also possible that enteroviruses pose a threat to immunocompromised patients, like bone marrow transplant recipients. Consequently, the emergence of chronic enteroviral diseases as a concept, prompted our attempts to produce an enteroviral vaccine. 1. Live attenuated enterovirus strains were previously in some cases shown to be suitable as vaccine candidates. We obtained neutralizing antibody titres ranging from 40-2560 against Coxsackie B3 virus (RD strain). Animals were protected to 90% against challenge infection. 2. Inactivated whole vaccine. We used beta-propiolactone to inactive Coxsackie B3 virus. 74% of the animals survived if the vaccine was prepared with Quil A matrix as adjuvant. The neutralisation antibody titres varied from < 5 to 320. By comparison aluminium hydroxide (p = 0.06) and Freund's adjuvant were inferior (p < 0.01). 3. Subunit vaccines. We have previously used the ISCOM (immunostimulatory complex) technology to produce a Coxsackie B3 subunit vaccine. High levels of neutralizing antibodies were obtained (512)-comparable to natural infection. All animals survived challenge infection after two booster doses with 16 nanogram of the ISCOM preparation. Limiting for this technique was the availability to include sufficient amount of antigenic protein material. In addition to neutralizing antibodies a cellular response might be obtainable. In conclusion we have shown that vaccine can be made against Coxsackie B3 virus with good protective effect and significant neutralisation antibody titre.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1993

Effects of the antiviral WIN 54954 and the immune modulator LS 2616 on cachectin/TNF and gamma-interferon responses during viral heart disease.

The effects of the anti picornaviral drug WIN 54954 (5-(5-(2.6-dichloro-4-(4.5-dihydro-2-oxazolyl)phenoxy)pentyl)-3-me thyl- isoxazole) and the immune modulator LS 2616 (Quinoline-3-carboxamide) on plasma cachectin/TNFa and g-interferon (IFN-g) responses were investigated during the clinical course of a myocarditic coxsackievirus B3 (CB3) infection in the mouse. Virus as well as inflammatory and necrotic lesions were found in the hearts on days 4 and 7 post inoculation (p.i.), respectively. This was demonstrated using in situ virus RNA hybridization and immune histological techniques with monoclonal antibodies against lymphocyte subsets. The CB3 infection increased TNFa levels during the first three days of disease. This response was suppressed by WIN 54954 and LS 2616. IFN-g was decreased in infected mice in the late phase of the disease (day 11). Therapy, however, was protective, and WIN 54954 even tended to increase the IFN-g response at day 5, corresponding to the time when viremia peaks. These results indicate that cytokines may serve as prognostic markers in the therapy of infectious diseases and also that WIN 54954 and LS 2616 are both possible candidates for treatment of coxsackievirus infections in man. It is suggested that a combined antiviral and immune stimulatory treatment could be of future value.

Adjuvants, Immunologic↗
PubMed1993

Therapy of coxsackie virus B3-induced myocarditis with WIN 54954 in different formulations.

The antiviral efficacy of WIN 54954 was demonstrated in vivo in a Coxsackie B 3 virus (Woodruff strain) induced myocarditis mouse model. The model was selected because of the high mortality rate during the first week, which was convenient for antiviral therapy regimen studies. The antiviral component WIN 54954 was found to inhibit the early virus-induced mortality almost completely if treatment was started at the same time as virus was inoculated. However, there was still a late mortality, occurring at 1-2 months after virus inoculation. Non-infected mice which were treated with the drug did not show any such late effects. However, drug treatment in non-infected mice did not cause any mortality. When therapy was delayed for one day, 85% survived for 3 weeks as compared to 100% mortality after just over 3 weeks in the infected control group (p < 0.05). With a delay of 4 days after viral inoculation, a therapeutic effect was still noted. Thus, mortality was virtually abrogated when the compound was given early, but the effect vanished with time of delay. Different preparations of the WIN 54954 substance were tried, and it was found that a fat emulsion containing several nutrients (Nutrodrip) was superior to other used formulations. We conclude that the use of the antiviral drug WIN 54954 in treatment of enteroviral associated diseases is of great value if therapy is started early. Thus therapy is almost fully effective within 24 hours of infection, but the beneficial effects decline with time. Nutrodrip oil emulsion was found superior as vehicle as compared to other formulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Genotypic and serotypic profile in dilated cardiomyopathy.

Eighteen consecutive patients, admitted with a diagnosis of dilated cardiomyopathy (DCM), to the Cardiology Section, Department of Internal Medicine, University Hospital, Uppsala, Sweden were enrolled into the study. All patients suffered signs of cardiac incompensation of variable duration. Patients were defined by conventional clinical investigations including chest X-ray, ultrasound, g-camera, catheterization and endomyocardial biopsy with histological evaluation by a specially trained pathologist. Angiography was performed to exclude ischemic heart disease. Several patients were diagnosed as having a specific reason for the cardiac insufficiency, like pheochromocytoma, SLE, ethylism, ischemic heart disease and hypertrophic cardiomyopathy. In this group all 7/7 had negative serology against Coxsackie B viruses. In the other group of idiopathic CM, no other etiology could be found. Serological analysis in this group showed high IgM titres against Coxsackie viruses in 6/8 patients. EDTA-blood was taken for tissue-typing using DNA probe hybridisation. 6/12 patients had DQB1:4 using the newest nomenclature, vs 17% in the control population. The reversed picture was observed for DQB1:2, occurring in 1/12 patients, vs 19% in the normal population, thus indicating a protective value of this genotype, which to our knowledge has not been described before. The results indicate a dual dependence of (host) genotype and (virus) serotype according to the Doherty-Zinkernagel hypothesis. Thus, it would also be in agreement with the virus-immune hypothesis suggested more than 20 years ago to explain the enigmatic pathogenesis of DCM.

Adult↗
PubMed1993

Altered distribution of heavy metals and lipids in coxsackievirus B3 infected mice.

This report presents evidence that a micro-organism common in our environment, coxsackievirus B3 (CB3) and the host responses it causes, can change the body distribution of heavy metals and lipids. The present results show that the distributions of intravenously injected 109Cd, 63Ni and 14C-Cholesterol are changed during infection, in a way that is specific for each of the studied compounds. Increased accumulation of 109Cd in the spleen and kidneys, 63Ni in the pancreas and ventricular myocardium, and 14C-Cholesterol in the heart and pancreas was observed during CB3 infection. This may affect the development of inflammatory lesions and subsequently result in altered and/or increased target organ toxicity as well as lipid accumulation. Thus, risk assessment in exposed populations may have to be evaluated depending on individual nutritional and exposure status.

Animals↗
PubMed1993

The epidemiology of viral heart disease.

The enteroviruses, especially the Coxsackie B viruses, predominate as causative agents in myopericarditis and may be involved in the pathogenesis of dilated cardiomyopathy. Some studies suggest that these and other viruses might be implicated even in atherosclerosis and myocardial infarction. True incidence data of myopericarditis in the population at large are hardly feasible, since the disease is most often mild or subclinical. The long-term prognosis is favorable even in a majority of hospital-treated patients. A recent histopathological study of unselected autopsy cases employing the "Dallas criteria" for a diagnosis shows a myopericarditis incidence of 1.06 per cent. A link between myopericarditis and dilated cardiomyopathy is supported by findings of enteroviral RNA in biopsies and explanted hearts in the latter condition. A partly new panorama of viral heart disease is emerging in heart transplant recipients and AIDS patients.

Humans↗
PubMed1992

Coxsackie B virus IgM in children at onset of type 1 (insulin-dependent) diabetes mellitus: evidence for IgM induction by a recent or current infection.

Thirty-five children with newly-diagnosed Type 1 (insulin-dependent) diabetes mellitus and their 47 siblings were investigated for the presence of IgM antibodies to Coxsackie B virus serotypes 1-5 (CBV 1-5) with the aid of mu-antibody-capture radioimmunoassays. When a high cut-off value was used, 16 (46%) diabetic children and 16 (34%) siblings showed CBV-IgM. Of the siblings of diabetic patients positive for CBV-IgM, 11 (44%) were CBV-IgM-positive; the corresponding figure for the siblings of negative patients was five (26%). With a lower cut-off value, leading to a "borderline titre", the frequency of IgM positivity increased in both the patients and siblings. When the borderline titres were included, the number of IgM-positive patients was 19 (54%) and the corresponding number of siblings was 29 (62%). Of the siblings of positive patients, 27 (93%) showed CBV-IgM, and of the siblings of the negative patients, two (11%) were CBV-IgM-positive. Sixteen (89%) siblings of IgM-negative patients remained negative. Regarding the serotypes of CBV to which IgM was directed, CBV 4 was most frequent, followed by serotypes CBV 3, CBV 2, CBV 5 and CBV 1. There was a striking similarity between the individual diabetic child and his or her sibling(s) concerning this specificity of IgM. It is concluded that within most families with a newly-diagnosed diabetic child positive for CBV-IgM the same serotype(s) of the virus circulates and that the intrafamilial spread of virus is considerable. The results strongly indicate that the IgM detected was CBV-specific and caused by a recent or current CBV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

A common viral infection can change nickel target organ distribution.

The autoradiographic distribution of the toxic heavy metal nickel (Ni) was studied at 4 and 7 days post-coxsackievirus B3 (CB3) infection in Balb/c mice. The distribution of the iv injected 63Ni was studied 10 min, 4 hr, and 24 hr after administration. Results clearly show that the site of 63Ni accumulation is greatly changed during this viral infection. This newly discovered distribution was mainly visible as a greatly increased accumulation in the pancreas and the wall of the ventricular myocardium. Healthy animals showed almost no 63Ni accumulation in these tissues. These results for the first time show that an invading microorganism can change the distribution of an environmental pollutant.

Animals↗