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Biomedical subjects

A Mustonen

Publications and source records attributed to A Mustonen.

At least 19 recordsLinked to original sources
PubMed2002

Clinical, enzymatic, and molecular genetic characterization of a biochemical variant type of argininosuccinic aciduria: prenatal and postnatal diagnosis in five unrelated families.

A biochemical variant of argininosuccinate lyase deficiency, found in five individuals, is introduced. In comparison to classical patients, the variant cases of argininosuccinate lyase deficiency were characterized by residual enzyme activity as measured by the incorporation of [14C]citrulline into proteins. The five patients of different ethnic backgrounds presented with relatively mild clinical symptoms, variable age of onset, marked argininosuccinic aciduria and severe, but not complete, deficiency of argininosuccinate lyase. [14C]Citrulline incorporation into proteins, which is completely blocked in classical argininosuccinic aciduria, was only partially reduced in fibroblasts of these patients. Further investigation showed that previous standard conditions of the assay were not optimal. Higher concentrations of citrulline in the incubation medium strongly stimulated 14C incorporation in normal cells, but not in the patients; as a result, the relative incorporation level in the patients dropped to 6-28% compared to 18-75% of normal in the original procedure. Prenatal diagnosis was successfully performed in three of the families. Affected pregnancies were indicated by (partial) deficiency of [14C]citrulline incorporation in chorionic villi and/or increased levels of argininosuccinate in amniotic fluid. Analysis of the ASL gene in the five patients revealed a considerable allelic heterogeneity. Three novel mutations--R385C (2 patients), V178M and R379C--were detected in homozygous states, whereas one patient was compound heterozygous for the known mutations R193Q and Q286R. In conclusion, there are patients of different ethnic backgrounds who are characterized by residual activity of argininosuccinate lyase and who present with less severe clinical courses. In addition, we present an improved biochemical assay for accurate prenatal and postnatal diagnosis.

Adult↗
PubMed1999

The effects of two rewarming strategies on heat balance and metabolism after coronary artery bypass surgery with moderate hypothermia.

BACKGROUND: Postoperative hypothermia is common in cardiac surgery with hypothermic cardiopulmonary bypass (CPB). This trial was designed to evaluate whether rewarming over the normal bladder temperature (over 37 degrees C) at the end of hypothermic CPB combined with passive heating methods after CPB might result in a better heat balance, lower energy expenditure (EE) and decrease of disturbances in oxygen balance compared to only rewarming the patients to a bladder temperature of 35-37 degrees C. METHODS: A prospective, randomized controlled clinical study was performed in 38 patients scheduled for elective coronary artery bypass surgery. Twenty patients (group C) were rewarmed to a bladder temperature of 35-37 degrees C at the end of hypothermic (28 degrees C) CPB. Eighteen patients (group W) were rewarmed to a bladder temperature of 37-38.5 degrees C. RESULTS: At the end of CPB, the bladder temperature was 36.2+/-0.7 degrees C (mean+/-SD) in group C and 37.9+/-0.5 degrees C in group W. After half an hour's stay in the ICU, the mean body temperature (MBT) was 35.1+/-0.6 degrees C in group C and 36.6+/-0.7 degrees C in group W. During the following five hours, MBT increased to 37.4+/-0.8 degrees C in group C and to 38.0+/-0.6 degrees C in the other group. The peak value of EE in the ICU was 1.73+/-0.44 (group C) vs 1.35+/-0.29 (W/kg) (group W) (P=0.003). EE was significantly (P=0.044) higher in group C than in the other group between 1.5 and 5.5 h in the ICU. The increased energy expenditure due to heat production was associated with an increase in O2 consumption (VO2) 61.6+/-30.4% vs 25.2+/-24.1%, (peak values) compared to the basal values of the two groups measured before anesthesia (between groups P<0.001). Between 1.5 and 5.5 h in the ICU, group C had significantly higher VO2 (P=0.026), CO2 production (P=0.017), venous pCO2 (P<0.001) and minute ventilation (p=0.014) than group W. Venous pH was lower (P<0.001) in group C. The peak value of oxygen extraction was also higher (P=0.045) in group C. On the other hand, the lowest value of venous oxygen saturation was higher (P=0.04) in group W. CONCLUSION: With rewarming the patients at the end of CPB to a bladder temperature of over 37 degrees C combined with passive heating methods after CPB, it was possible to decrease EE and VO2 compared to the control group (rewarmed to bladder temperature of 35-37 degrees C) after coronary artery bypass surgery with moderate hypothermia.

Body Temperature↗
PubMed1999

When cooler heads prevail: peacemakers in a sports riot.

Male sports fans (N = 74) were asked to estimate the likelihood that they would intervene in a crowd disturbance in an attempt to stop the fighting. They also completed a battery of measures that included their attitude toward law and order, fight history, the false consensus effect, impulsivity, psychopathy, sensation seeking, anger, physical aggression and identification with their favorite team. Law and order, body mass, anger and the false consensus effect were positively related to peacemaking whereas sensation seeking was negatively related. A multiple regression analysis yielded a solution that accounted for 32.3% of the variance with anger and attitude toward law and order emerging as the best predictors.

Adult↗
PubMed1997

Improved prenatal diagnosis of the congenital nephrotic syndrome of the Finnish type based on DNA analysis.

Haplotype analysis and alpha-fetoprotein quantitation comprise a prenatal diagnosis of congenital nephrosis. Congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessive disease characterized by massive proteinuria and nephrotic syndrome from birth. Prenatal diagnosis of CNF has previously been based on the quantitation of alpha-fetoprotein (AFP) in the amniotic fluid and maternal serum, but an increased AFP is not specific for the disease. We have recently localized the CNF gene to the chromosome 19q13.1 region and observed a strong linkage disequilibrium to the genetic markers D19S610, D19S608, D19S224 and D19S220 in this chromosomal area. Four main CNF-haplotypes have been observed in Finnish kindreds. In the present study, linkage and haplotype analyses have been applied to prenatal diagnosis of six families with a history of CNF. The results diminish the risk of false positive diagnosis and abortions of healthy fetuses in families at risk.

Amniotic Fluid↗
PubMed1997

Postoperative symptoms at home following day-case surgery in children: a multicentre survey of 551 children.

The incidence and duration of postoperative symptoms in children at home following day-case anaesthesia and surgery was evaluated using a questionnaire completed by parents of 551 children aged 4 months to 13.4 years (mean 3.8 years). They also evaluated the instructions given in hospital for care at home. The incidence of all symptoms was highest at home on the day of the operation. No postoperative symptoms were reported in 79 (14%) children. The incidence of pain was 56% and the only significant predictor was the type of operation, tonsillectomy being the most problematic (mild pain in 38% and severe in 25%; pain lasted 7 days or longer in 33%). Analgesics were given to 78% of all the children reported to have pain on the day of the operation, to 60% the next day and later to 58%; 19 (3%) children were given more than two doses per day. The instructions given in hospital for the treatment of pain were considered inadequated by 12% of parents. Postoperative nausea and vomiting occurred in 13% of children. Predictors by multiple stepwise logistic regression analysis were emetic symptoms in hospital, pain at home, age > 5 years and administration of postoperative opioid (pethidine or fentanyl). Opioid given during anaesthesia (fentanyl or alfentanil) did not increase the incidence. Emetic symptoms were most common after tonsillectomy (31%). The highest incidences of emetic symptoms (37%), sedation (96%) and dizziness (41%) occurred in children who had been given fentanyl for postoperative pain. Undertreatment of nausea in hospital was evident as only two children had received anti-emetics, even though 61 were reported to have emetic symptoms. Administration of effective anti-emetics should be encouraged, as emetic symptoms in hospital were the most significant predictor of nausea and vomiting at home. Treatment of pain at home and instructions for treatment of pain need to be improved.

Adolescent↗
PubMed1997

Mutation analysis for prenatal diagnosis of hereditary tyrosinaemia type 1.

Hereditary tyrosinaemia type 1 is a rare but serious metabolic disorder with an autosomal recessive mode of inheritance. We describe the prenatal diagnosis of an affected fetus performed by DNA-mutation analysis and a subsequent pregnancy with a healthy child in the same family.

Amino Acid Metabolism, Inborn Errors↗
PubMed1996

Prenatal diagnosis of Batten's disease.

BACKGROUND: Batten's disease is the most common progressive encephalopathy of childhood in Western countries. The major mutation is a 1kb deletion, which is carried by 81% of Batten's disease patients. We report on the use of direct gene analysis in the prenatal diagnosis of this disease. METHODS AND FINDINGS: A Finnish woman with a son with Batten's disease came for genetic counselling for her current pregnancy. Electron microscopy of a chorionic villus sample gave suggestive findings. We used PCR to look for the intragenic microsatellite marker D16S298; 96% of Finnish Batten's disease patients carry allele 6 at this marker. The fetus and the affected son both carried the same high-risk genotype, 6/6. Both were homozygous for the 1 kb deletion. The pregnancy was terminated. Electron microscopy of the fetus showed typical Batten's disease changes. INTERPRETATION: We have successfully used direct gene analysis in the prenatal diagnosis of Batten's disease.

Base Sequence↗
PubMed1991

DNA-based prenatal diagnosis of the infantile form of neuronal ceroid lipofuscinosis (INCL, CLN1).

Eleven fetuses at risk for the infantile form of neuronal ceroid lipofuscinosis (INCL, CLN1) were studied using DNA markers and the results were compared with the results of electron microscopy (EM) of chorionic villus specimens from pregnancies in the first or early second trimester of pregnancy. In four cases, the prenatal diagnosis was made independently with both methods, and in seven cases, the EM diagnosis was confirmed postnatally or from autopsy material using RFLP analysis. The two methods gave concordant results in all cases. The DNA analysis based on RFLP haplotypes also for the first time facilitates reliable carrier diagnostics. RFLP analysis based on polymorphic markers closely linked to the INCL locus is now available for prenatal diagnosis of this fatal brain disease, whose biochemical background is totally unknown and for which no treatment is available.

Chorionic Villi Sampling↗
PubMed1990

Prenatal diagnosis of single gene disorders in northern Finland.

Prenatal diagnosis of single gene disorders is challenging because of the multidisciplinary diagnostic approach and the genetic counselling needed. Out of 3100 pregnancies of northern Finnish women studied for early detection of congenital defects or genetic disease, 110 were at risk for and 15 were unexpectedly found to carry a fetus with a single gene disorder. Seven of the 21 diseases studied were typically representative of inherited diseases in northern Finland. The diagnostic approaches used included fetal ultrasonography, analysis of the components of the amniotic fluid, fetal enzyme analysis, fetal karyotyping for the fragile X syndrome, and fetal DNA analysis. Altogether, 50 pregnancies were found to be affected; 11 of these were continued because the diagnosis was too late for termination, and seven because the parents wanted it. Prenatal diagnosis of severe hereditary disease can be enhanced by improving the detection of pregnancies at risk, and by developing methods for earlier fetal diagnosis.

Adult↗
PubMed1989

Low levels of mumps virus antigen induced interferon-alpha production in insulin-dependent diabetes.

The in vitro production of interferon-alpha was studied in cultures of peripheral blood mononuclear cells from children with insulin-dependent diabetes. Significantly lower levels (p less than 0.01) of interferon (median 64 IU/ml) were found in mumps antigen stimulated cultures of IDDM patients compared to control children (median 256 IU/ml) whereas no differences between groups were found in the amount of interferon induced by Coxsackie B pool antigen or live Sendai virus.

Antigens, Viral↗
PubMed1988

Insulin autoantibodies at the clinical manifestation of type 1 (insulin-dependent) diabetes--a poor predictor of clinical course and antibody response to exogenous insulin.

To study the possible clinical significance of the appearance of insulin autoantibodies prior to the diagnosis of Type 1 (insulin-dependent) diabetes, and their value in predicting the antibody response to exogenous insulin, we observed 46 newly diagnosed diabetic children and adolescents over the year following diagnosis for the occurrence and duration of clinical remission, daily insulin dose, metabolic control, residual B-cell function, insulin-binding antibodies and conventional as well as complement-fixing islet cell antibodies. Insulin-binding antibodies were determined using both monoiodinated human and porcine insulin. Sixteen children (34.7%) were positive for insulin autoantibodies upon diagnosis of Type 1 diabetes. These subjects were significantly younger (6.2 +/- 1.0 versus 10.8 +/- 0.8 years; mean +/- SEM, p less than 0.001), and their haemoglobin A1 levels were lower (14.1 +/- 0.6 versus 16.0 +/- 0.8%, p less than 0.05) at diagnosis than in the insulin autoantibody negative group. There were no significant differences in the occurrence and duration of clinical remission between insulin autoantibody-positive and -negative test groups. Daily insulin dose, haemoglobin A1 and serum C-peptide concentrations were of the same magnitude in both groups after the diagnosis, and no association could be found between the presence of insulin autoantibodies at diagnosis and persistently positive islet cell antibodies. In tests conducted 3 months after diagnosis, the group of patients with insulin autoantibodies showed significantly higher levels (p less than 0.05) of antibodies binding human insulin than the group negative for insulin autoantibodies, but no significant differences could be found between the insulin binding titres of the two groups in subsequent analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Evidence of an accelerated B-cell destruction in HLA-Dw3/Dw4 heterozygous children with type 1 (insulin-dependent) diabetes.

The possible association between residual B-cell function and specific HLA antigens in Type 1 (insulin-dependent) diabetes was studied in a cross-sectional series of 144 diabetic children and adolescents, as well as in a prospective series of 44 newly diagnosed diabetic subjects who were observed for the initial 2 years of their diabetes. In the cross-sectional study, the HLA-Dw3/Dw4 heterozygotes had a lower mean serum C-peptide concentration during 1980, 0.03 +/- 0.01 nmol/l (mean +/- SEM) vs. 0.09 +/- 0.01 nmol/l (p less than 0.02), as well as a lower 24-h urinary C-peptide excretion, 0.27 +/- 0.06 nmol/m2 vs. 1.34 +/- 0.19 nmol/m2 (p less than 0.05), than the other subjects. In addition, the Dw3/Dw4 heterozygotes had a clinical remission of shorter duration, 113 +/- 47 days vs. 203 +/- 22 days (p less than 0.05), and a higher mean glycosylated haemoglobin level during 1980, 14.8 +/- 0.05% vs. 13.7 +/- 0.2% (p less than 0.05), than those without the Dw3/Dw4 combination. In the prospective study the serum C-peptide concentrations were of the same magnitude in the Dw3/Dw4 heterozygotes and the other subjects during the first month. Subsequently the C-peptide concentrations in the subjects with the Dw3/Dw4 combination started to decrease 2 months earlier than in the other subjects. The Dw3/Dw4 children had a significantly lower serum C-peptide concentration at 21 months, 0.01 +/- 0.01 nmol/l vs. 0.13 +/- 0.02 nmol/l (p less than 0.01), and at 24 months, 0.03 +/- 0.01 nmol/l vs. 0.12 +/- 0.02 nmol/l (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Relation between insulin antibody and complement-fixing islet cell antibody at clinical diagnosis of IDDM.

To test the hypothesis that insulin-binding antibodies (IBAs) appearing in the circulation before insulin treatment are markers of beta-cell damage, we studied the prevalence of IBAs and both conventional (IF-ICAs)-and complement (CF-ICAs)-fixing cytoplasmic islet cell antibodies in 60 newly diagnosed diabetic children with a mean age of 9.5 yr. Seventeen (28.3%) had an insulin binding exceeding the upper range (2.8%) of that observed in 68 age-matched controls. The IBA-positive subjects were characterized by a younger age of onset [6.2 +/- 4.0 (SD) vs. 10.8 +/- 3.2 yr; P less than 0.001], lower glycosylated hemoglobin A1 levels (14.1 +/- 3.1 vs. 16.0 +/- 3.0%; P less than 0.05), lower serum C-peptide concentrations (0.12 +/- 0.07 vs. 0.20 +/- 0.17 nmol/L; P less than 0.05), and an increased frequency of HLA-Dw4 (9/13 vs. 11/37; P less than 0.05). There was no significant relation between IBAs and serum C-peptide concentrations after age adjustment by multiple regression analysis. Forty-three children (75%) were positive for IF-ICA and 38 (63.3%) for CF-ICA. Twelve IBA-positive diabetics (70.6%) had IF-ICA as well as CF-ICA in their serum. No association could be observed between IBA and either IF-ICA or CF-ICA, however. The results suggest that IBAs developing before diagnosis serve as an indicator of clinical and genetic heterogeneity within IDDM rather than as a marker of autoimmune beta-cell destruction.

Adolescent↗
PubMed1985

An analysis of epidemiological data in HLA-typed diabetic children.

To clarify the heterogeneity of Type 1 (insulin-dependent) diabetes mellitus, differences between patients with different HLA risk antigens were investigated with regard to sex, age at diagnosis, season of year and calendar year at diagnosis of the disease. The study consisted of 293 HLA-typed patients from the Department of Paediatrics, University of Oulu, Oulu, Finland. HLA-Dw2 was extremely rare among diabetic patients, whereas Dw3 and Dw4 were associated with increased risk in this as in other series. Male patients more often had the HLA-A1 antigen than females. On comparison of the Dw3 positive patients, boys more frequently had the combination A1,B8 than girls. A1,B8-positive patients were more often diagnosed during the warm months, in the late summer and autumn. Patients with both Dw3 and Dw4 were younger at diagnosis when compared with the rest of the patients. The results support the concept of heterogeneity in the pathogenesis of Type 1 diabetes associated with HLA-linked genetic determinants.

Age Factors↗