Biomedical subjects
Publications and source records attributed to R Salonen.
We studied interferon (IFN) in the serum and CSF of 31 patients with multiple sclerosis. The sensitive IFN bioassay required only small volumes and detected IFN levels as low as 0.5 international units/ml (CSF) or 4 international units/ml (serum) of IFN. Two hundred twenty-eight paired CSF/serum samples were tested, and no IFN was found.
Interferon production after stimulation of lymphocytes with purified protein derivative, pokeweed mitogen, and phytohemagglutinin was studied in 39 patients with stable multiple sclerosis (MS) and 39 age- and sex-matched controls. Stable MS patients produced less interferon, and the number of subjects producing undetectable amounts of interferon was higher in the MS group (11/39) than in the control group (2/39). A tendency toward an association between low interferon production and HLA-Dw2 antigen was found in MS patients. There was no clear-cut correlation between interferon production and the duration of disease or disability of the patients. Although there was no systematic correlation of age with interferon production, patients older than 55 years tended to be very poor interferon producers.
Interferon (IFN) production by peripheral blood mononuclear cells after induction with one purified and three crude viral antigens was studied in 29 patients with stable multiple sclerosis (MS) and 29 healthy controls. Antiviral substance produced was characterized as interferon-alpha. MS patients produced significantly less IFN-alpha after induction with mumps and purified measles virus antigens and the same tendency was seen after induction with rubella virus antigen. However, when herpes simplex virus antigen was used as the stimulating agent, no difference was seen between MS patients and controls. The decreased ability to produce IFN-alpha was associated with the histocompatibility antigen Dw2. Control subjects positive for Dw2 also produced less IFN-alpha than Dw2-negative controls. In conclusion, we suggest that the observed impaired interferon-alpha production in MS is at least partially due to a high prevalence of Dw2 antigen in this disease.
A modification of yield reduction assay for interferon was developed. The standard micromethod of inhibition of cytopathogenic effect (CPE) of vesicular stomatitis virus (VSV) was first applied and the amount of virus antigen released to the supernatant was then measured by a competitive enzyme immunoassay technique. This assay was four times more sensitive than the CPE inhibition method and was able to detect 0.50-0.25 international units/ml of human interferon-alpha and was also applicable to interferon-gamma determinations. It is a suitable method when small volumes of samples containing low levels of interferon are tested.
The in vitro 3H-thymidine incorporation of peripheral blood (PB) and cerebrospinal fluid (CSF) lymphocytes from 11 mumps meningitis patients was studied after stimulation with non-specific mitogens and microbial antigens. Although corresponding viral antibodies were always found in the CSF of seropositive patients by a sensitive radioimmunoassay, their intrathecal synthesis was directed mainly against mumps virus. Most of the patients had PB lymphocytes that reacted on stimulation with phytohaemagglutinin (PHA) or pokeweed mitogen (PWM), but a smaller number of them had reactive CSF cells. Only four patients showed stronger responses to PHA in the CSF than in PB. Most patients had mumps-reactive lymphocytes in PB but only two of them in the CSF. In contrast, these patients more often had increased CSF cell reactivity when tested with purified protein derivative, measles, and herpes simplex virus antigens. The results could not be explained by a damaged blood-brain barrier alone but may reflect the immunological status of the brain compartment in these patients.
In a randomized cross-over trial on six healthy medical students, alcohol (lg/kg) ingested as whisky did not modify significantly the absorption of 200 mg of doxycycline (DC) given in two tablets. Cheap red wine with a clear taste of acetic acid postponed the absorption of DC for 2-3 hours without affecting its 24-hour AUC or urinary excretion significantly. Another similar trial with other wines on 8 healthy students suggested that good regular wines do not retard DC absorption irrespective of their tannic acid content. However, acetic acid may postpone DC absorption by possibly slowing the rate of gastric emptying.
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We describe a lethal malformation syndrome in 28 newborn infants from 18 families. The main manifestations were hydrocephalus (often with an unusual structure of the brain and the occipital bone), very small mandible, polydactyly, congenital heart defect, abnormalities of the respiratory organs, and (different from the Meckel syndrome) normal kidneys. Polyhydramnios and stillbirth or neonatal death were the rule. Autosomal recessive inheritance is evident. This syndrome is another in the group of rare recessive disorders which are found in Finland. Because of the 25% recurrence risk and possibilities for prenatal diagnosis, this syndrome should be recognized by paediatricians and, because of the frequent stillbirths, also by obstetricians and pathologists. The name hydrolethalus syndrome (hydramnios, hydrocephalus, lethality) may be of help in this.
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Prenatal diagnosis was performed in 81 cases at risk for the fragile X syndrome. There were 12 fra(X)-positive cases, two of which showed low expression in cultured amniotic fluid cells. FUdR and high thymidine were used for induction of fra(X) (q27.3) expression in all cases. In 21 cases linkage studies were performed, 7 with probes for the loci DXS52, DXS98 and DXS105, 13 with probes for DXS369 and DXS296, DXS304 or DXS374 and one with the probe Do33 for DXS465. In 11 of these cases linkage analysis gave risk figures higher than 95% or lower than 5%, all in concordance with the cytogenetic findings. Discordance was found in three cases studied earlier, the two cases with low expression mentioned above and one cytogenetically normal case, which were now restudied with the new probes. RFLP-studies and linkage analysis was also performed for 24 cytogenetically fra(X)-negative females having a 50%, 25% or 12.5% risk of being carriers according to pedigree data. In 15 cases the risk dropped to 1% or less. Six of these women were pregnant and had asked for prenatal diagnosis but after genetic counseling prenatal diagnosis was avoided.
Concentration of pregnancy-specific beta 1-glycoprotein (SP1) was studied in second and third trimester amniotic fluid from pregnancies with various fetal developmental disorders. The material consisted of 26 cases with chromosomal disorders and 19 cases with non-chromosomal fetal malformations. The SP1 concentration was elevated in two cases of Meckel's syndrome (mean +2.7-4.0 S.D.) as well as in one case of fetal triploidy (mean +22 S.D.), while it was normal in all other 14 different fetal disorders.
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A number of psychosomatic studies have suggested that alexithymia, impairment in identifying and expressing inner feelings, might somehow affect the course of various illnesses. However, none of these studies have distinguished between an impact of alexithymia on actual pathophysiological change versus an impact only on illness behavior. In the present study, a population-based random sample of 2297 middle-aged men from Eastern Finland was evaluated for alexithymia using the Finnish version of the self-report Toronto Alexithymia Scale (TAS). Although high TAS scores were associated with prior diagnosis of coronary heart disease (CHD), they were not associated with greater prevalence of ischemia on an exercise tolerance test. The results of B-mode ultrasonography of the carotid artery for those who had a CHD diagnosis showed that carotid atherosclerosis actually decreased significantly as alexithymia increased. An interaction analysis indicated that alexithymia was related to increased probability of being diagnosed with CHD only among those who had mildly or moderately progressed carotid atherosclerosis, and not among those with the most severe progression. Alexithymia was associated with higher perceived exertion, and to some extent, with more self-reported symptoms during the exercise tolerance test. The findings support the hypothesis that alexithymia relates to increased symptom reporting rather than pathophysiological changes in CHD. The results also suggest that alexithymic men may get diagnosed earlier, perhaps because of their different illness behavior.
We studied prospectively the association of hostility and anger suppression by the use of ultrasonographically assessed 2-year progression of carotid atherosclerosis (PCA) in a sample of 119 middle-aged men from eastern Finland. Based on measures of cynical distrust, impatience-irritability, anger-in, and anger-control, four variants of hostility-by-anger suppression model were tested with multiple regression analysis. In addition to the previously established risk factors (i.e., serum low-density lipoprotein cholesterol concentration, smoking, and old age), cynical distrust and anger-control significantly predicted PCA. There was about a two-fold accelerated PCA in the group with high cynical distrust and high anger-control even after we controlled for the established biological risk factors and possible confounding background variables. The impact of the independent variables on PCA seemed to be additive rather than synergistic. These results, based on a relatively small, but nonselected population sample, extend previous results of angiographic studies.
High plasma insulin has been shown to be associated with the risk of coronary heart disease in nondiabetic subjects in prospective population studies. Furthermore, insulin resistance measured by the euglycemic glucose clamp technique has been shown to be related to lipid and lipoprotein changes favoring atherosclerosis and to high blood pressure. No study, however, has demonstrated that insulin resistance per se is directly associated with atherosclerosis. With this aim, we studied 30 middle-aged nonobese subjects with asymptomatic atherosclerosis in the femoral or carotid arteries and 13 corresponding control subjects. Fasting blood glucose, insulin, and C-peptide levels were only slightly and nonsignificantly higher in subjects with atherosclerosis than in controls, and during the oral glucose tolerance test 1- and 2-hour glucose, insulin, and C-peptide levels were similar in both groups. During the euglycemic hyperinsulinemic (1,200 pmol/l) clamp studies, subjects with atherosclerosis had a 20% reduced whole-body glucose uptake (58 +/- 2 versus 71 +/- 4 mumol/kg/min, p = 0.004). Glucose oxidation, lipid oxidation, suppression of free fatty acid levels, and potassium disposal were similar in both groups. In contrast, nonoxidative glucose disposal was significantly reduced in patients compared with that in controls (37 +/- 2 versus 50 +/- 4 mumol/kg/min, p = 0.004). When glucose uptakes were matched during the hyperglycemic clamp studies, the rate of nonoxidative glucose uptake was normalized in the patients. These results provide the first direct evidence that asymptomatic atherosclerosis is associated with insulin resistance. This insulin resistance is characterized by reduced whole-body and nonoxidative glucose uptake. In contrast, glucose and lipid oxidation, potassium disposal, and suppression of free fatty acid levels during hyperinsulinemia did not differ between the subjects with and without atherosclerosis.