Biomedical subjects
Publications and source records attributed to L Svensson.
Of 126 rotavirus-positive specimens, 7 could not be subgrouped (I or II). These strains showed a distinct reaction with a monoclonal antibody recognizing a common region on VP6, but they did not react with VP6 subgroup-specific monoclonal antibodies although they contained as much viral antigen as the subgrouped strains.
Among 274 neonates born at the maternity services of an urban hospital in India, 36.1% of the infants shed rotavirus in feces (as detected by ELISA) by 72 h of life. The excretion rate increased to 70.3% among the 120 infants who stayed for 5 days or more at the hospital. Diarrhoeal symptoms of mild and self-limited nature were observed only in 19.2% of the rotavirus excretors, the remaining being asymptomatic. Among the 98 infants who received supplement feeds, 49% acquired rotavirus infection as against 24.7% of the 150 exclusively breast fed infants (p less than 0.001). Viral RNA in the feces of all rota positive infants showed the same electropherotype, indicating infection from a common source. The mean percentage rotavirus inhibitory activity of cord sera in the infected and non-infected infants was 50.2 +/- 21.7 and 56.6 +/- 19.2 respectively (p greater than 0.05), suggesting that cord blood antibodies do not offer significant protection against neonatal rotavirus infection.
Among 600 rotavirus specimens collected in Finland during 1985-1987, 6 isolates were found to be related to serogroup C rotavirus by RNA profile analysis and solid phase immune electron microscopy (SPIEM). The group C isolates originated from 4 children (4.5, 4.5, 6.5 and 7 years old) with diarrhoea.
292 individuals were patch tested with twelve allergens, using a new patch test technique, TRUE Test (TT). As controls, the same allergens in standard concentrations in petrolatum were applied using the Finn Chamber technique (FC). The allergen doses used in TT were chosen according to results from a previous serial dilution patch test study. There were reactors to all twelve allergens. The concordance of positive reactions between TT and FC was 78%. 10% were indicated only with TT and 12% FC only. Irritant reactions occurred in the same order of magnitude for the two tests. Weak positive, uncertain, and irritant reactions observed with the different test methods used, indicate minor errors of allergen dosage in both. The investigation indicates that the TRUE Test method is simple to handle, is well standardized and gives good accuracy with the 12 allergens investigated.
The 41 serotypes of human adenoviruses are classified into six subgenera (A-F) with different tropisms. Enteric infections are caused in children by serotypes Ad40 and Ad41 of subgenus F. Serotypes Ad40 and Ad41 transform embryonic cells but cannot induce tumours in newborn hamsters. They differ from all other (established) human adenoviruses by being unable to replicate in conventional cell cultures. Ad40 and Ad41 grow in 293 cells (human embryonic kidney cells immortalized by transfection with the E1A, E1B regions of Ad5). In spite of the difficulty of isolating Ad40 and Ad41 they can be directly identified in stools by enzyme-linked immunosorbent assay (ELISA) and solid-phase immuno-electron microscopy. The amount of viral DNA in stool preparations is sufficient for identification by DNA restriction or dot-blot analysis. Adenoviruses have been associated with 7-17% of cases of diarrhoea in children. Ad40 and Ad41 cause diarrhoea throughout the year. Clinical features are watery stools, vomiting and moderately elevated temperature; respiratory symptoms are infrequent. The diarrhoea is protracted (mean 8.6 and 12.2 days for Ad40 and Ad41 respectively). Children with rotavirus diarrhoea vomited more frequently and had a higher temperature and diarrhoea of shorter duration. The impact of enteric adenoviruses in the aetiology of diarrhoea world-wide is not known but is accessible to investigation.
A commercial latex agglutination test for diagnosis of adenovirus in diarrheal disease (Adenolex, Orion Diagnostica, Finland) was evaluated by comparison with the results obtained by ELISA, electron microscopy (EM), and virus isolation. Fifty specimens originated from the diagnostic routine, and 50 were selected from a previous epidemiological study on the etiology of diarrheal disease in children. Thirteen of the 100 specimens reacted with the latex control, impairing interpretation of the results. Although the ELISA detected adenovirus antigen in 10(2) higher dilutions than the latex agglutination test, a total agreement was obtained between results by the two tests for 87 specimens including 42 positives. The two additional positives found by EM and virus isolation could not be diagnosed by the latex agglutination test. Of 37 specimens containing enteric adenoviruses (types 40 and 41), the agglutination test diagnosed all but 4 specimens containing type 41 virus. These four specimens were negative also by ELISA and adenovirus had been detected by virus isolation on the 293 cell line. The latex agglutination test gave positive results with nine specimens containing adenovirus types other than the enteric types 40 and 41. The latex agglutination test was found to be a rapid and simple method for the detection of adenovirus in diarrheal disease. Compared to ELISA and EM, the sensitivity was 100% and 95% respectively, and the specificity 100%.
A radioimmunoprecipitation assay (RIPA) was used to study the serum antibody responses to individual polypeptides that developed after infection with viruses from human rotavirus subgroups I and II. Paired sera from eight children (1 to 8.5 years of age) were used in the study. Although all of the eight acute sera were negative by the complement fixation test, four of them were positive by RIPA, indicating a previous infection by rotavirus. A significant difference in the number of polypeptides immunoprecipitated was seen among the convalescent sera. The number of polypeptides immunoprecipitated was found to be related to previous infection experience. At most, ten different polypeptides were immunoprecipitated: seven structural polypeptides VP1 to VP7 and three non-structural polypeptides, NS1, NS2 and NS3. No sera immunoprecipitated VP8 or VP9. Acute sera positive by RIPA immunoprecipitated up to five polypeptides, VP1, VP2, VP3, VP4 and VP6. One of the non-structural proteins (NS2) was found to be particularly immunogenic, since antibodies to this polypeptide were detected in several convalescent sera. Among the structural proteins VP2 and VP6 were found to be the two immunodominant polypeptides which were recognized by all convalescent sera. Only three convalescent sera immunoprecipitated VP7, the major type-specific antigen responsible for inducing neutralizing antibodies. Three of four originally seronegative children with no reactivity in the convalescent sera to VP7 developed neutralizing antibodies to a single serotype. One child developed antibodies to two serotypes.
The antibody response to individual rotavirus polypeptides after vaccination with live attenuated heterologous rotavirus vaccines was studied with a radioimmunoprecipitation assay (RIPA). Following vaccination with bovine rotavirus strain RIT 4237 and rhesus monkey rotavirus strain RRV-1, an antibody response was demonstrated mainly against the inner capsid polypeptides VP2 and VP6 and to a lesser extent against VP3/VP4. There was no qualitative difference between the vaccines in the antibody response; both vaccines induced antibodies against the same polypeptides. Quantitatively the antibody response to RRV-1 was somewhat stronger. All prevaccination sera contained by RIPA low levels of rotavirus antibodies. The effect of these antibodies on the 'take' of the vaccines is discussed.
In order to examine an early ischaemia-induced local release of myocardial noradrenaline (NA), the left coronary artery of the isolated working rat heart was ligated for periods varying between 7.5 min and 30 min, followed by reperfusion for 5 min. As perfusion substrate, glucose, lactate or both were used. In part of the experiments, hearts were pre-labelled with [3H]NA. Already after 7.5 min of ischaemia, an increased efflux of endogenous NA was observed in the perfusate at reperfusion, concomitant with a decrease in tissue NA content. This effect was most pronounced with lactate as substrate. Qualitatively similar effects were seen on [3H]NA efflux from labelled hearts. The combination of glucose and lactate as substrate markedly reduced (compared with lactate alone) the efflux of NA, whereas no such reduction was observed on the efflux of creatine kinase (CK). It is concluded that ischaemia is associated with an early local release of NA. Furthermore, ischaemia may induce different effects on the metabolic processes of the myocyte as compared with the adrenergic nerve ending.
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The distribution of metoprolol and atenolol into ischemic and nonischemic myocardium was studied in anesthetized dogs, pigs, and cats. The beta-blockers were administered intravenously after coronary artery occlusion. Metoprolol was found to be significantly more efficiently distributed to the ischemic myocardium than atenolol in all three species. To investigate the functional implications of this difference in tissue distribution, the anti-ischemic effects of the two beta-blockers were studied in the 2-h period following coronary artery occlusion in anesthetized cats, in which heart rate was kept at a constant level. In this model, metoprolol (0.3 mg.kg-1 + 0.15 mg.kg-1.h-1) was found to attenuate or delay the developing ischemic process. This is shown by its significant reduction of (a) the decline of CK activity in ischemic myocardium, (b) the ST elevation in a precordial ECG lead, and (c) the decrease of arterial pressure and cardiac output. In contrast to metoprolol, atenolol (0.3 mg.kg-1 + 0.15 mg.kg-1.h-1) caused no significant anti-ischemic effect in this cat model. The difference in the effectiveness of the two drugs can most probably be explained by their differential distribution in the ischemic heart. Furthermore, the anti-ischemic effect of metoprolol shows that the presence of a beta-blocker in ischemic left ventricular myocardium can favorably affect the early phase of developing infarction.
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The molecular epidemiology of rotavirus infections was studied in children with acute gastroenteritis in Uppsala, Sweden, during 1981. Altogether 118 virus strains were investigated by analysis of the RNA migration pattern in silver-stained polyacrylamide gels. Six different electropherotypes were seen: two with "short" and four with "long" RNA migration patterns. Forty-two strains (36%) exhibited "short" patterns. The seasonal distribution showed that strains with "long" and "short" RNA patterns cocirculated in equal frequency during the first seven months of the year, until the predominant "short" RNA electropherotype suddenly disappeared. More than 11 RNA segments were seen in two stool specimens. A complete correlation was found between the electrophoretic migration of segments 10 and 11 and the serological defined subgroup specificity.
In a prospective 1-year study, 144 children attending or admitted to hospital and 272 children outside hospital with acute gastro-enteritis and 200 controls were investigated by a broad panel of diagnostic methods for enteropathogenic agents in the faeces and for related antibody responses. Enteropathogens were identified in 77% of the inpatients, 63% of the outpatients and 8% of the controls. Rotavirus and Yersinia enterocolitica were detected significantly more often among inpatients. Altogether, viral, bacterial and parasitic agents were found in 58%, 14% and 1% of diarrhoeal patients, respectively. The isolation of more than one pathogenic agent was uncommon (6.5%). Rotavirus (45%) and enteric adenoviruses 40 and 41 (7.9%) predominated among the viruses, while Campylobacter jejuni (4.8%) was most common among the bacteria. Clostridium difficile and/or its cytotoxin, which were found in 14% of the children with gastroenteritis and in 15% of the controls, were significantly associated with antibiotic therapy but not with gastro-intestinal illness. Diarrhoeal infections of unknown aetiology exhibited a seasonal peak in the autumn. The duration of excretion of enteropathogens was investigated. Rotavirus particles were detectable by solid-phase immune electron microscopy for 14-25 days after the diarrhoea had ceased. Transmission of rotavirus and bacterial pathogens within families was studied also.
The permeability properties of the small intestinal mucosa was investigated in nine previously healthy children with acute diarrhoea due to rotavirus. The investigation was performed after intake of a mixture in water of polyethyleneglycol molecules (PEG 400 and 1000) ranging from 282 to 1250 dalton in molecular weight. The 6-h urinary recovery of the PEGs was determined with high performance liquid chromatography and used to assess the permeability characteristics of the intestine. The patients served as their own controls and were investigated in the same manner after recovery 3-5 weeks later. A significantly lower urinary recovery of PEG was noted for all molecular sizes (326-1206 dalton) during acute diarrhoea in comparison with the results obtained after recovery (p less than 0.001-0.1). There was also a relatively lesser change in the urinary recovery of larger PEG molecules during infection, as reflected by a higher recovery ratio between 1074 and 370 dalton PEGs. The results indicate profound changes in the permeability characteristics of the intestine during acute rotavirus diarrhoea.
During a prospective 1-year study rotavirus isolates from 169 children with gastroenteritis were investigated by polyacrylamide gel electrophoresis. A total of 118 (70%) of the strains analyzed contained sufficient viral nucleic acid to give visible electrophoretic patterns; 36% were identified as strains belonging to subgroup 1 (short patterns), and 64% were identified as strains belonging to subgroup 2 (long patterns). The two subgroups cocirculated at equal frequencies during the first 7 months of the year, after which subgroup 1 rotavirus completely disappeared. Subgroup 2 rotavirus occurred throughout the year. No significant differences between the subgroups in relation to age or sex distribution were observed. Fever and temperatures exceeding 39 degrees C were significantly more frequent in children who shed rotavirus subgroup 1. Diarrhea and vomiting occurred at similar rates in both groups of patients, but were more pronounced in children who shed rotavirus subgroup 2. One of three dominant electropherotypic variants of subgroup 2 rotavirus was found to be associated with more intense symptoms, higher rates of hospitalization, and a significantly higher frequency of respiratory symptoms; the clinical picture may indicate that this rotavirus electropherotype has higher virulence.
The concentrations of adrenaline, noradrenaline and cortisol in blood sampled at routine attempts at catheterization of the adrenal and renal veins, the inferior vena cava and the azygos and hepatic veins were measured in six patients with a phaeochromocytoma and six patients with hypertension due to other causes. In the non-tumour patients the adrenaline and noradrenaline concentrations, compared with normal values for peripheral venous blood, were abnormally high in five out of seven samples from the site of the left adrenal vein but in only one out of seven from the right side. In all the adrenal vein samples with an abnormally high catecholamine concentration the cortisol level was also elevated, and it was at least 100 per cent higher than in samples from the inferior vena cava. This suggests that a high catecholamine concentration linked with an elevated cortisol level is merely an indication of correct adrenal vein sampling and is not necessarily evidence of a tumour. In successful attempts of sampling adrenal venous blood (cortisol levels increased), concentrations of adrenaline and noradrenaline of up to 100 and 20 nmol/l, respectively, can be regarded as normal. From a retrospective analysis of catecholamine levels in the six tumour patients it is clear that owing to the variability of venous drainage from the right adrenal gland, the technique of adrenal venous blood sampling may be unreliable and even misleading in attempts to locate a phaeochromocytoma. This is also true in patients with generally elevated catecholamine levels.
Specimens for the isolation of microorganisms were obtained from the cervical canal in 83 and from the placenta in 86 of 90 women delivered by cesarean section. In addition, the placentas from 87 of these women were examined histopathologically. No correlation was found between the isolation of a given microorganism from the cervical canal and infectious disease in mothers and/or neonates. Isolation of microorganisms from the placenta was correlated with rupture of the membranes occurring six or more hours before surgery and, in women with intact fetal membranes, was correlated with uterine activity. Chorioamnionitis histopathologically was associated with maternal and/or neonatal infections and prematurity. Microorganisms were not isolated significantly more often from the placenta in cases with chorioamnionitis than without. The value of cervical and placental cultures in predicting intrauterine infection is questionable.