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Biomedical subjects

G Friman

Publications and source records attributed to G Friman.

At least 91 records · Page 5Linked to original sources

The anti-inflammatory effect of LS 2616 and poly I:C in coxsackievirus B3 induced murine myocarditis.

We have studied the effects of immunotherapy in coxsackievirus B3-induced myocarditis in male BALB/c mice. A single i.p. injection of the synthetic interferon inducer poly I:C conferred an almost total protection from lethality when administered at 0 h or 24 h after infection. Poly I:C treatment at 48 h after infection, as well as daily i.p. injections of the quinoline-3-carboxamide LS 2616, a new stimulator of NK-cell activity, gave no protection from lethality. The inflammatory lesions and necrosis in the ventricular myocardium 7 days after virus inoculation (3.1% of section area) were reduced in the poly I:C (24 h) treated group (1.0% of tissue section area). A less pronounced reduction was seen in the LS 2616 and poly I:C (48 h) treated groups (1.7 and 1.9% of tissue section area, respectively). The response patterns of the studied lymphocyte subpopulations were different with these two compounds, TIB+ (pre-B)-cells increased with poly I:C treatment (49%), but decreased with the LS 2616 treatment (65%). The Lyt 1+ (pan T)-cells responded similarly. Poly I:C (24 h) and LS 2616 treatment tended to increase the number of class II expressing cells (1.9- and 2.9-fold, respectively). The titer of neutralizing antibodies to coxsackievirus B3 was significantly increased in the LS 2616 treated group (1:80) but not significantly so in the poly I:C treated groups (1:40) as compared to the infected and non-infected control groups (1:20 and less than 1:5, respectively).

Adjuvants, Immunologic↗

IgM against Coxsackie B viruses in children developing type I diabetes mellitus--a seven-year retrospective study.

IgM antibodies to coxsackievirus type B 1-5 (CB 1-5) have recently been observed in sera from children with newly diagnosed insulin-dependent diabetes mellitus (IDDM). In the present study IDDM patients below 15 years of age diagnosed between 1978 and 1984 inclusive in two different areas (counties) of Sweden, Uppsala and Linköping, were studied at the onset of their disease. The incidence of IDDM per 100,000 children below the age of 15 years varied between 11.1 and 40.8, with a mean of 26.3 in Uppsala and 23.0 in Linköping. CB-IgM was determined by a mu-antibody capture radioimmunoassay (RIA) and was found in the sera of 40% (range 15-76%) of the Uppsala patients and 30% (0-57%) of the Linköping patients. The IDDM onset peaked in January, August and October, and these months also displayed the largest numbers of CB-IgM-positive cases. There seemed to be a relation between IDDM incidence and CB-IgM positivity, but not during the whole period. IgM antibodies against CB2 and CB3 predominated during the first part of the study period, whereas during the last two years IgM antibodies against all five serotypes were demonstrated. It is concluded that if CB virus infection is involved in the pathogenesis of IDDM in children, this may be the case in less than half of the patients, though with seasonal and annual peaks and nadirs and also changes of serotypes that may reflect the natural epidemiology of these viruses.

Adolescent↗

Urinary excretion of 1-methylhistidine: a qualitative indicator of exogenous 3-methylhistidine and intake of meats from various sources.

In order to investigate whether the urinary excretion of 1-methylhistidine (1MH) might serve as an objective indicator of meat ingestion and exogenous 3-methylhistidine (3MH) intake, healthy subjects were fed an ovolactovegetarian diet. At five-day intervals they were given meat of different origin and 24-hour urinary excretions of 1MH and 3MH were determined. After beef intake there was a marked increase of 3MH and 1MH excretion. The elimination curves were found to follow first-order kinetics and to indicate similar elimination rates. 1MH was present in ten different types of meat analyzed. A strong linear relationship was found between increase in 3MH and 1MH excretion and the amount of chicken, pork, or plaice ingested. IMH may serve as an objective indicator of meat and exogenous 3MH intake, since it is present in meat, and, regardless of source, shows similar dose-independent kinetics, and has similar half-life to 3MH.

Adult↗

Matching of host genotype and serotypes of Coxsackie B virus in the development of juvenile diabetes.

Thirty-six consecutive paediatric patients (0-16 years old) with recently contracted juvenile diabetes (IDDM) during 1982-84 were included in the study. Sera were assayed for recent or current Coxsackie B virus (CBV) infection using a specific and sensitive IgM RIA. Eighteen patients (50%) had IgM against CBV 1-5. The patients were also assayed for restriction fragment length polymorphism (RFLP) patterns with DNA probes coding for HLA-DR and DQ beta chains. The CBV-positive patients (n = 18) had either RFLP patterns associated with HLA-DR 3 or 4 or HLA-DQ patterns III or IV beta. Two of the CBV negative patients had neither HLA-DR 3 nor DR 4 and four of them had neither DQ patterns III nor IV. Eleven out of 18 CBV-positive patients had HLA-DQ III and DR 3 (61%) versus 5 out of 18 (28%) of the CBV-negative patients. All 11 patients with serology positive for CBV 2, 3, and 5 had HLA-DR 4 and DQ IV patterns. This was significantly (P less than 0.01) different from all five CBV 4-positive patients, who in contrast all had HLA-DR 3 or HLA-DQ III patterns. CBV 1-positive patients (n = 2) all had HLA-DR 3, 4, and HLA-DQ III, IV patterns. Thus CBV 4 seems to be significantly associated with a different host genetic constitution from at any rate CBV 2, 3, and 5, and possibly CBV 1.

Adolescent↗

Role of surgery in infective endocarditis.

One-hundred-and-thirteen patients with endocarditis and valvular insufficiency were studied retrospectively with special regard to indications for operation and the optimum time for cardiac valve surgery. Thirty patients (group I) had acute, 63 (group II) subacute and 20 (group III) prosthetic valve endocarditis. Group I: Eleven patients underwent surgery in the acute stage, 8 while bacteremic; 5 of the latter died perioperatively. Of the 19 patients treated medically, 16 died. Group II: All patients underwent operation in a bacteria-free state. The mortality was 5%. Group III: Eight patients had early (less than 60 days postoperatively) and 12 late endocarditis. Total mortality was 40% (71% early and 25% late mortality). Ten patients underwent reoperation, with a mortality of 20%, compared with 60% in the medically treated group. The results support the indication for early operation in acute endocarditis with progressive cardiac failure and renal failure and prosthetic valve endocarditis, even during bacteremia.

Acute Disease↗

High frequency of Coxsackie-B-virus-specific IgM in children developing type I diabetes during a period of high diabetes morbidity.

Twenty-four consecutive children with newly diagnosed insulin-dependent (type I) diabetes mellitus (IDDM) were investigated for a history of infectious disease. Thirteen of the 24 (54%) patients reported symptoms of acute infection within two months before diabetes was diagnosed. The mean age was 8.5 years and 15 (63%) of the patients were girls. No clear seasonal variation in onset was seen. Coxsackie B (CB)-virus-specific IgM responses were detected by reverse radioimmunoassay (RIA) in 16 of the 24 (67%) patients on the day of diagnosis of IDDM. The highest titre was usually recorded at that time, but with some the highest titre was found with a second serum obtained three to seven weeks after diagnosis. Thereafter the titres declined, and after six months IgM was detected only in a few patients. Thirteen patients displayed monotypic IgM responses, whereas three patients showed ditypic responses. Among the former, IgM was recorded against Coxsackie B4 (CB4) in four, B5 (CB5) in three, B1 (CB1) in two, B2 (CB2) in two, and B3 (CB3) in two patients. The ditypic responses were against CB2 and CB3, CB3 and CB4, and CB5. No CB-virus-specific IgM was detected in sera, found during the same period, from age-matched nondiabetic children without evidence of infection. In neutralisation (NT) tests, antibodies to the homotypic virus were found in 12 of the 16 diabetic patients showing CB-virus-specific at the time of diagnosis. A significant rise in NT titre was demonstrated in three of these patients. No significant clinical difference was noted between IgM positive and IgM negative patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Does fever or myalgia indicate reduced physical performance capacity in viral infections?

To study prospectively the effects of a brief febrile viral infection on parameters of muscle and circulatory function, seven volunteers were inoculated with sandfly fever virus and two control subjects with sterile saline. During but not after fever, decreased isometric and dynamic strength and endurance were recorded in various muscles. Impairment could not be explained by altered activities of relevant muscle enzymes in serum or muscle tissue or by altered muscle ultrastructure, but correlated with the severity of perceived symptoms, including myalgia, as rated by each subject. Compared to baseline, cardiac stroke volume was lower during and after fever. During fever, an increased heart rate maintained cardiac output at pre-inoculation values, whereas cardiac output fell in early convalescence. This decrease in cardiac output correlated significantly with the severity of fever. Thus, in brief viral infections a transient impairment of muscle performance capacity is correlated to subjective symptoms such as myalgia, rather than to fever, whereas a decreased cardiac output following such infections seems to be associated with the fever reaction.

Adult↗

The first human case of domestic Q fever in Sweden.

A case of Q fever in a 56-year-old man is reported. The patient had visited Mallorca six months prior to the present disease. Except for that he had not been outside Sweden for several years, thus being the first known case of Q fever acquired in this country.

Humans↗

An incidence peak of juvenile diabetes. Relation to Coxsackie B virus immune response.

All new cases of insulin dependent diabetes mellitus (IDDM) in children below 15 years of age were recorded prospectively during a 21-year period 1964-1984 in a defined uptake area with a relatively constant child population. The total number of children recorded was 222-111 boys and 111 girls. The number of new cases varied between 4 cases in 1968 and 20 in 1984; in 1983 seventeen new cases were recorded. Specific IgM antibodies against Coxsackie B virus (CBV), types 1-5 were measured by a reverse radioimmunoassay (RIA) technique in 24 consecutive patients collected during the period March 1982-January 1984, some of whom represented the recent period of a very high incidence of diabetes. Sixteen patients (67%) exhibited CBV IgM responses, strongly suggesting a current or recent CBV infection. The titres declined during the first few months of diabetes and seemed to be absent after the first half-year period. Among age-matched non-diabetic children scheduled for elective procedures during the same period, no cases with CBV-IgM antibodies were detected. Only three of the 16 IgM-RIA-positive patients showed a significant rise in the neutralising antibody titre against the same Coxsackie B type. It is concluded that CBV may play a pathogenetic role in induction of IDDM, and possibly more frequently so during periods with a high incidence of diabetes, at least in children below 15 years of age.

Adolescent↗

Studies of biochemical markers in cerebrospinal fluid in patients with meningoencephalitis.

Several biochemical markers in the cerebrospinal fluid (CSF) of 120 patients with serous meningoencephalitis (SM) of viral origin were compared with those of 74 patients with viral or bacterial infections accompanied by neck stiffness but no CSF abnormality (i.e., meningism). CSF adenylate kinase was higher (P less than 0.025) in SM and correlated with lactate concentration (r = 0.37; P less than 0.01). CSF hypoxanthine was lower (P less than 0.001) in SM, whereas CSF xanthine was similar in the two conditions. The xanthine/hypoxathine ratio correlated with the CSF leukocyte count (r = 0.32; P less than 0.01), and especially with the mononuclear cell count (r = 0.45; P less than 0.001). CSF adenylate kinase correlated with fever in SM (r = 0.28; P less than 0.01). CSF urate and protein displayed a mutual correlation in both conditions (r = 0.26 and P less than 0.05 for SM; r = 0.55 and P less than 0.001 for meningism). These results support the hypothesis of impaired brain cell metabolism, probably of ischemic nature, in viral meningoencephalitis, causing leakage of adenylate kinase into the CSF, where hypoxanthine may be reutilized by mononuclear leukocytes.

Adenylate Kinase↗

Qualitative and quantitative bacteriological studies in infected surgical wounds treated with Debrisan or saline.

In a study of methods for the evaluation of clearing of wound infection, local treatment with Debrisan (10 wounds) or saline (11 wounds) was examined clinically and bacteriologically. No correlation was found between clinical course and numbers of bacteria found in wound biopsies or swabs. Biopsy results varied greatly between sites in the same wound. In wounds with established infection, biopsies or wet swabs yielded little more information than conventional dry swabs. Debrisan seemed to offer no advantage over saline as regards clearing of infection in this small patient group.

Bacteriological Techniques↗

Variations in serum myoglobin after a 2-min isokinetic exercise test and the effects of training.

Serum-myoglobin was measured after the completion of three different types of exercise i.e., dynamic, isometric, and isokinetic. The maximal rises in serum-myoglobin levels were 20%, 70%, and 300%, respectively. On the basis of this finding a 2-min isokinetic test was developed and standardized for the purpose of studying conditions in vivo that may affect myoglobin leakage from skeletal muscle cells. Fourteen healthy men performed the 2-min isokinetic test. Blood lactate increased on average eight times with maximal levels obtained 4 min after completed work. S-Myoglobin levels obtained 4 min after completed work. S-Myoglobin was raised approximately five times after 2 h. The rise in S-myoglobin was significantly (P less than 0.01) related to the loss in muscle strength (torque decline) during the test. After a training period of 3 weeks comprising 4 min of maximal isokinetic exercise three times a week the rise in S-myoglobin after a 2-min isokinetic test was reduced from on average 240 micrograms X 1(-1) to 96 micrograms X 1(-1) (P less than 0.001). The rise in blood lactate was not related to the variations in S-myoglobin or affected by training. The 2-min isokinetic exercise test is an easily standardized exercise test which in combination with measurements of serum-myoglobin should prove valuable in the study of conditions affecting leakage from muscle cells.

Adenosine Triphosphate↗

The effect of exercise and fasting on the myocardial protein and lipid metabolism in experimental bacterial myocarditis.

A generally nonlethal Salmonella typhimurium infection in weanling rats produced bacterial myocarditis and myocardial hyperplasia. Myocardial lesions were characterized by focal infiltrates of inflammatory cells (predominantly mononuclear), segmental myocyte necrosis, and incipient fibrosis. Although bacterial infections are infrequently associated with myocarditis, the S. typhimurium infection in young rats produced a new experimental model of diffuse myocardial inflammatory foci. Biochemical changes in the myocardium included great increases in total myocardial contents of protein (23%), RNA (39%) and DNA (43%) and several lipid fractions (35-55%) as well as in tissue activities of acid hydrolases, such as cathepsin D (124%) and beta-glucuronidase (135%), all of which contrasted with the relatively limited areas of histologic involvement (1.5%). To study the effects of additional stress in this model infection, some rats were exercised by forced running in wheels for 2 hours and others were fasted for 24 hours before samples were obtained. The short period of forced exercise in this infection caused an additional increase of myocardial protein content (47%) but with no additional change in histology. The expected fasting-induced degradation of protein as well as an infection-associated increase in myocardial lipids were each prevented when rats were fasted during ongoing acute infection. Protein degradation, as reflected by heightened acid hydrolase activities, seemed to occur at a similar rate regardless of other stresses, whereas the rate of myocardial protein synthesis appeared to be alterable.

Animals↗

Sequential metabolic alterations in the myocardium during influenza and tularemia in mice.

Mice with generalized influenza or tularemia of similar lethality were studied in an effort to compare biochemical responses of the myocardium during infections of viral and bacterial etiology. A progressive loss of body weight characterized the course of both infections. Accompanying this, the myocardial content of protein and the activities of lactate dehydrogenase, citrate synthase, and cytochrome c oxidase all decreased. However, myocardial protein degradation appeared earlier and was more pronounced in influenza, and the protein changes were accompanied by a rapid decline of myocardial RNA. Activation of acid hydrolases, such as cathepsin D and beta-glucuronidase, occurred in tularemia but not in influenza, whereas leakage of beta-glucuronidase into the plasma occurred in both infections. Conversely, there was a considerably greater activation of myocardial catalase in influenza. These findings suggested that different control mechanisms or metabolic pathways were operative in the degradation of myocardial constituents in influenza as compared with tularemia. The absence of histological signs of myocarditis in either infection appeared to exclude any direct local effects of an inflammatory process on myocardial cells. Since the infections were of comparable lethality (based upon the inoculated dose of organisms), the observed differences in pattern and extent of metabolic responses of the myocardium to these infections may be attributed to different pathophysiological mechanisms evoked by the different microorganisms.

Animals↗

Modifying effects of exercise on clinical course and biochemical response of the myocardium in influenza and tularemia in mice.

For a study of the interactions of strenuous physical exercise (daily swimming to exhaustion) and a viral as compared with a bacterial infection with regard to the clinical course and the biochemical response of the myocardium, influenza and tularemia of similar lethality were used in mice. In both infections, expected infection-induced catabolic alterations in the ventricular myocardium were evident 2 days before median lethality was achieved, with a more pronounced wasting in influenza than in tularemia. Exercise before inoculation (preconditioning) was beneficial in that the catabolic effects of both infections were limited and lethality in influenza was reduced. Thus, the myocardial protein-degrading effect of influenza did not occur with preconditioning, and oxidative tissue enzyme activities decreased less. In tularemia, cytochrome c oxidase activity was fully preserved with preconditioning, and activation of catalase was less pronounced. Exercise during ongoing infection counteracted the infection-induced decrease in the activities of glycolytic and oxidative enzymes in tularemia, but lethality and bacterial counts in the spleen were uninfluenced. Conversely, exhaustive exercise in influenza increased lethality and had no significant effect on cardiac enzymes. These exercise models caused no major alterations in activation of lysosomal enzymes (beta-glucuronidase and cathepsin D).

Animals↗

Effects of Streptococcus pneumoniae, Salmonella typhimurium and Francisella tularensis infections on oxidative, glycolytic and lysosomal enzyme activity in red and white skeletal muscle in the rat.

Since opinions differ as to whether the oxidative and glycolytic capabilities of skeletal muscle are altered in acute infection, enzyme activities in oxidative, glycolytic and degradative (acid hydrolases) pathways and total protein and DNA were determined in skeletal muscle of rats infected with Streptococcus pneumoniae, Salmonella typhimurium or Francisella tularensis. Studies were performed separately in red (slow twitch) and white (fast twitch) muscle tissue because these fibers function during different types of exercise. In the salmonella- and tularemia-infected rats, the intramitochondrially located oxidative enzymes of muscle were decreased to 56-83% of controls whereas the glycolytic enzyme situated in the cytosol showed an earlier and more pronounced loss of activity, 30-75% of controls. In the pneumococcal infection, only reduced glycolytic activity was significant. DNA concentrations were unchanged in any infection. Reductions during tularemia were statistically correlated with whole-cell protein degradation, while that of the glycolytic enzyme was parallelled by activation of lysosomal enzymes. Red and white muscle tissues responded similarly, in contrast to several other pathologic states that involve a catabolic component of muscle with a predominant response (or damage) in one or the other fiber type.

Animals↗