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J Karjalainen

Publications and source records attributed to J Karjalainen.

At least 19 recordsLinked to original sources
PubMed1999

Disease-associated autoantibodies and HLA-DQB1 genotypes in children with newly diagnosed insulin-dependent diabetes mellitus (IDDM). The Childhood Diabetes in Finland Study Group.

The possible relation between HLA-DQ genotypes and both frequencies and levels of autoantibodies associated with IDDM was assessed by examining HLA-DQB1 alleles and antibodies to islet cells (ICA), insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tyrosine phosphatase-related IA-2 molecule (IA-2A) in 631 newly diagnosed diabetic children under the age of 15 years. ICA were found in 530 children (84.0%), while close to half of the subjects (n = 307; 48.7%) tested positive for IAA. GADA were detected in 461 index cases (73.1%), with a higher frequency in those older than 10 years (78.9% versus 69.2% in the younger ones; P = 0.006). More than 85% of the children (n = 541; 85.7%) tested positive for IA-2A. Altogether there were only 11 children (1.7%) who had no detectable autoantibodies at diagnosis. There were no differences in the prevalence of ICA or GADA between four groups formed according to their HLA-DQB1 genotype (DQB1*0302/02, *0302/X (X = other than *02), *02/Y (Y = other than *0302) and other DQB1 genotypes). The children with the *0302/X genotype had a higher frequency of IA-2A and IAA than those carrying the *02/Y genotype (93.8% versus 67.3%, P < 0.001; and 49.0% versus 33.6%, P = 0.002, respectively). The children with the *02/Y genotype had the highest GADA levels (median 36.2 relative units (RU) versus 14.9 RU in those with *0302/X; P = 0.005). Serum levels of IA-2A and IAA were increased among subjects carrying the *0302/X genotype (median 76.1 RU versus 1.6 RU, P = 0.001; and 50 nU/ml versus 36 nU/ml, P = 0.004) compared with those positive for *02/Y. Only three out of 11 subjects homozygous for *02 (27.3%) tested positive for IA-2A, and they had particularly low IA-2A (median 0.23 RU versus 47.6 RU in the other subjects; P < 0.001). The distribution of HLA-DQB1 genotypes among autoantibody-negative children was similar to that in the other patients. These results show that DQB1*0302, the most important single IDDM susceptibility allele, is associated with a strong antibody response to IA-2 and insulin, while GAD-specific humoral autoimmunity is linked to the *02 allele, in common with a series of other autoimmune diseases as well as IDDM. We suggest that IA-2A may represent beta cell-specific autoimmunity, while GADA may represent a propensity to general autoimmunity.

Adolescent↗
PubMed1999

Diabetes-associated autoantibodies in relation to clinical characteristics and natural course in children with newly diagnosed type 1 diabetes. The Childhood Diabetes In Finland Study Group.

We analyzed 747 children, younger than 15 yr of age, with newly diagnosed diabetes, for antibodies to glutamic acid decarboxylase (GADA), the IA-2 protein (IA-2A), insulin (IAA), and islet cells, to evaluate the influence of positivity for GADA, IA-2A, IAA, or multiple (> or = 3) autoantibodies at diagnosis, on the clinical presentation and natural course of the disease over the first 2 yr and to characterize autoantibody-negative patients. At diagnosis, 73.2% of the children tested positive for GADA, 85.7% for IA-2A, 54.2% for IAA, and 72.6% for multiple autoantibodies. Only 17 subjects (2.3%) had no detectable autoantibodies. The patients testing positive for multiple autoantibodies were younger than the remaining children (P < 0.001). A similar age difference was seen when comparing IAA-positive and -negative patients (P < 0.001). There was no significant difference between the GADA-positive and -negative subjects in the degree of metabolic decompensation at diagnosis, whereas those testing positive for IA-2A had reduced serum C-peptide concentrations (P = 0.003), and those positive for IAA had lower glycated hemoglobin values. The patients with no detectable autoantibodies had higher serum C-peptide levels (P = 0.007) at diagnosis than did the other subjects. The children initially positive for IA-2A had decreased serum C-peptide concentrations at 24 months (P = 0.045), and their daily insulin dose was higher at 18 (P = 0.005) and 24 months (P < 0.001). The patients who tested positive for multiple autoantibodies at diagnosis had decreased serum C-peptide levels (P < 0.001) and higher insulin doses (P = 0.005) at 12, 18, and 24 months. A lower proportion of them were also in clinical remission at 12 and 18 months (P = 0.01). Autoantibody-negative subjects needed less exogenous insulin at 6 and 18 (P = 0.01) and at 24 months (P < 0.001) than the other subjects, and a higher proportion of them were in clinical remission at 18 months (P < 0.001). We conclude that positivity for multiple diabetes-related autoantibodies is associated with accelerated beta-cell destruction and an increased requirement for exogenous insulin over the second year of clinical disease, indicating that multiple autoantibodies reflect an aggressive progression to total beta-cell destruction. Patients testing negative for diabetes-associated autoantibodies at diagnosis seem to have a milder degree of beta-cell destruction, but their metabolic decompensation is similar to that seen in other affected children, suggesting that they do represent classical type 1 diabetes.

Adolescent↗
PubMed1998

Autonomic modulation of QT intervals in post-myocardial infarction patients with and without ventricular fibrillation.

The autonomic nervous system plays an important role in the genesis of sudden cardiac death. The aim of this study was to evaluate spatial autonomic QT interval modulation at the myocardial level. Circadian patterns of QT intervals and heart rate variability (HRV) components and their hourly linear correlations were determined by Holter recordings in 15 healthy subjects (controls), in 15 post-myocardial infarction (MI) patients resuscitated from ventricular fibrillation (VF) (VF group), and in 15 matched infarction patients without a history of arrhythmia events (MI group). QT intervals were measured in modified leads V1 and V5 individually at same stable heart rates during each hour and related to hourly measures of HRV. Controls had highly significant correlations between QT intervals and the high-frequency component of HRV (parasympathetic modulation), and between QT intervals and low- to high-frequency ratio (sympathetic modulation) uniformly in both leads (r from 0.62 to 0.81, p <0.001). The MI group had impaired sympathetic modulation in V5 (r = 0.34, p = NS), but had uniform and exaggerated sensitivity to parasympathetic modulation. In the VF group the QT difference between V1 and V5 leads correlated with parasympathetic modulation (r = 0.401, p <0.05) and sympathetic modulation (r = 0.446, p <0.05). Thus, normal subjects exhibit spatially uniform autonomic QT modulation. Myocardial damage can result in abolished, exaggerated, or regionally discordant QT modulation, and this may generate arrhythmic vulnerability.

Adult↗
PubMed1998

Prediction of insulin-dependent diabetes mellitus in siblings of children with diabetes. A population-based study. The Childhood Diabetes in Finland Study Group.

An unselected population of 755 siblings of children with insulin-dependent diabetes mellitus (IDDM) was studied to evaluate the predictive characteristics of islet cell antibodies (ICA), antibodies to the IA-2 protein (IA-2A), antibodies to the 65-kD isoform of glutamic acid decarboxylase (GADA), insulin autoantibodies (IAA), and combinations of these markers. We also evaluated whether the histochemical ICA test could be replaced by the combined detection of other markers. 32 siblings progressed to IDDM within 7.7 yr of the initial sample taken at or close to the diagnosis of the index case (median follow-up, 9.1 yr). The positive predictive values of ICA, IA-2A, GADA, and IAA were 43, 55, 42, and 29%, and their sensitivities 81, 69, 69, and 25%, respectively. In contrast to the other three antibody specificities, GADA levels were not related to the risk for IDDM. The risk for IDDM in siblings with four, three, two, one, or no antibodies was 40, 70, 25, 2, and 0.8%, respectively. Combined screening for IA-2A and GADA identified 70% of all ICA-positive siblings, and all of the ICA-positive progressors were also positive for at least one of the three other markers. The sensitivity of the combined analysis of IA-2A and GADA was 81%, and the positive predictive value was 41%. In conclusion, combined screening for IA-2A and GADA may replace the ICA assay, giving comparable sensitivity, specificity, and positive predictive value. Accurate assessment of the risk for IDDM in siblings is complicated, as not even all those with four antibody specificities contract the disease, and some with only one or no antibodies initially will progress to IDDM.

Adolescent↗
PubMed1998

IA-2 antibodies--a sensitive marker of IDDM with clinical onset in childhood and adolescence. Childhood Diabetes in Finland Study Group.

To study the relationship of IA-2 antibodies (IA-2A) to other autoantibodies and genetic risk markers in insulin-dependent diabetes mellitus (IDDM), 758 children and adolescents younger than 15 years of age (mean age 8.4 years) with newly diagnosed diabetes were analysed for IA-2A, GAD antibodies (GADA) and insulin autoantibodies (IAA) with radiobinding assays, for islet cell antibodies (ICA) with immunofluorescence and for HLA DR alleles by serology. IA-2A were detected in 85.9% of cases with no association with gender or age. An overwhelming majority of the patients (71.3%) tested positive for three or more antibodies, and 90.7% for at least two. Fifty-four subjects (7.1%) had one antibody detectable, whereas only 2.1% of the patients tested negative for all four. A higher proportion of patients was positive for IA-2A and/or GADA than for ICA alone (95.5 vs 84.2%, p < 0.001). The prevalence and level of IA-2A were increased in cases carrying HLA DR4/non-DR3 compared with other DR combinations. The results indicate that almost all patients with newly diagnosed childhood IDDM can be identified by screening with these four autoantibodies. The combination of IA-2A and/or GADA had a higher sensitivity for IDDM than ICA alone. The close association between IA-2A and HLA DR4, the strongest single allele predisposing to IDDM, suggests that IA-2A may be a more specific marker of beta-cell destruction than GADA, which have been shown to associate with the DR3 allele and thyroid autoimmunity.

Adolescent↗
PubMed1998

Hypertension in master endurance athletes.

OBJECTIVE: To determine whether long-term very vigorous endurance training prevents hypertension. DESIGN: Cohort study of master orienteering runners and controls. SETTING: Finland. SUBJECTS AND METHODS: In 1995, a health questionnaire was completed by 264 male orienteering runners (response rate 90.4%) who had been top-ranked in competitions among men aged 35-59 years in 1984, and by 388 similarly aged male controls (response rate 87.1%) who were healthy at the age of 20 years and free of overt ischemic heart disease in 1985. MAIN OUTCOME MEASURE: Self-report of medication for hypertension. RESULTS: In the endurance athlete group, the crude prevalence (8.7%) of subjects who had used medication for hypertension was less than a third of that in the control group (27.8%). Even after adjusting for age and body mass index, the difference between the groups was still significant (odds ratio for athletes 0.43, 95% confidence interval 0.25-0.76). CONCLUSIONS: Long-term vigorous endurance training is associated with a low prevalence of hypertension. Some of the effect can be explained by a lower body mass, but exercise seems to induce a lower rate of hypertension by other mechanisms than by decreasing body weight

Aged↗
PubMed1998

Islet cell antibodies are less predictive of IDDM among unaffected children in the general population than in sibs of children with diabetes. The Childhood Diabetes in Finland Study Group.

OBJECTIVE: To examine the controversial issue of whether islet cell antibodies (ICAs) have a higher predictive value for progression to clinical IDDM in first-degree relatives of patients with diabetes than in the general population. RESEARCH DESIGN AND METHODS: ICAs were analyzed with standard immunofluorescence in two population-based groups: 765 sibs of children with recent-onset diabetes and 1,212 unaffected Finnish children <20 years of age at initial screening. Those positive for ICAs were additionally tested for antibodies to GAD (GADAs) and the protein tyrosine phosphatase-related IA-2 antigen (IA-2As). Subsequently, these subjects were observed for the manifestation of clinical IDDM over the next 7 years. RESULTS: The frequency of both detectable ICAs and ICA levels > or =20 Juvenile Diabetes Foundation units (JDF U) was significantly higher among the sibs than in the general population (7.8 vs. 4.1% and 4.8 vs. 2.0%, respectively; P < 0.001). The prevalence of GADAs (37/60 vs. 3/48; P < 0.001) and IA-2As (31/60 vs. 0/48; P < 0.001) was increased among ICA-positive sibs compared with ICA-positive individuals from the background population. Over the next 7 years, 24 sibs (3.1%) and 3 unrelated children positive for ICAs (0.3%) progressed to clinical diabetes. The positive predictive value of ICAs was thus 6% in the general population and 40% among the sibs (P < 0.001), or 13 and 59%, respectively (P < 0.001), with an antibody cutoff level of 20 JDF U. The positive predictive value was related to the number of positive autoantibodies in sibs, which was 57% in those with three antibodies, 50% in those with two antibodies, and only 6% in those with ICAs alone. CONCLUSIONS: These data show that the frequency of multiple autoantibodies is substantially lower in ICA-positive children representing the general population than in ICA-positive sibs of children with IDDM. As a consequence, the predictive value of ICAs for IDDM is higher in sibs of affected children than in the general population. This finding must be taken into account when planning intervention trials aimed at preventing or delaying the manifestation of clinical diabetes in individuals from the general population who test positive for ICAs.

Adolescent↗
PubMed1997

Poor beta-cell function after the clinical manifestation of type 1 diabetes in children initially positive for islet cell specific autoantibodies. The Childhood Diabetes in Finland Study Group.

The prognostic significance of islet cell specific autoantibodies at the diagnosis of Type 1 (insulin-dependent) diabetes mellitus for the persistence of residual beta-cell function over the first 2 years of clinical disease was evaluated in a prospective population-based study. Seven hundred and eighty probands, aged 0.8-14.9 years, were examined for islet cell antibodies (ICA) and insulin autoantibodies (IAA), while 769 probands were studied for antibodies to glutamic acid decarboxylase (GAD65A). They were subsequently observed for 2 years. Lower serum C-peptide concentrations and higher requirement of exogenous insulin during the follow-up period were observed in the group of probands positive for at least one of the antibodies, especially for ICA or IAA. We conclude that the residual beta-cell function after the presentation of Type 1 diabetes is less in children initially positive for islet cell specific autoantibodies than in those testing negative at diagnosis. This might reflect possible heterogeneity in the pathogenesis of childhood diabetes. It also demonstrates that ICA and IAA negativity at the diagnosis of Type 1 diabetes is not associated with a smaller amount of functioning beta-cell mass, but the absence of antibodies probably reflects a slower beta-cell destructive process and a longer duration of preclinical disease.

Adolescent↗
PubMed1997

The presence of the gallbladder is associated with the severity of acute biliary pancreatitis.

CONCLUSION: The presence of the gallbladder at the onset of acute biliary pancreatitis is associated with increased severity of the disease. One possible explanation is that gallbladder contraction might induce bile reflux into the pancreatic duct during the transfer of a gallstone through the ampulla. BACKGROUND: In clinical practice there is an impression that the presence of the gallbladder in patients with biliary pancreatitis may be associated with increased severity of the disease, compared to patients who have undergone cholecystectomy. METHODS: To test this hypothesis, we studied 266 cases with biliary pancreatitis. Patients were divided into two groups: (A) those who had a gallbladder in situ at the onset of biliary pancreatitis (n = 234, 88%) and (B) those who had undergone previous cholecystectomy (n = 32, 12%). RESULTS: Pancreatitis was more severe in group A than in group B, according to Glasgow criteria (> or = 3 positive, 66/210 = 31% vs 4/29 = 14%, p = 0.04); development of complications (77/234 = 33% vs 4/32 = 13%, p = 0.01); and mortality (40/234 = 17% vs 1/32 = 3%, p = 0.03). Furthermore, serum C-reactive protein levels on admission were over 150 mg/L twice as often in group A as in group B.

Acute Disease↗
PubMed1997

Electrocardiographic findings in female endurance athletes.

OBJECTIVE: To determine the prevalence of aberrations in the resting electrocardiogram (ECG) in female athletes. DESIGN: Case-control study. PARTICIPANTS: Thirty female endurance athletes and 30 age-matched nonobese nonathletic control subjects. MAIN OUTCOME MEASURES: Different measurements based on resting ECGs. MAIN RESULTS: The athletes had lower heart rate (mean 53 +/- SD 7) than the controls (67 +/- 11; p < 0.0001), but no group difference was found in atrioventricular conduction (PQ interval). Cornell voltage (RaVl + SV3) reflecting left ventricular mass was higher in athletes (1.18 +/- 0.58 mV vs. 0.78 +/- 0.41 mV; p = 0.0030), but the deviations from normal limits were small. The index reflecting right ventricular mass (RV1 + SV5) was higher in athletes (0.58 +/- 0.23 mV) than controls (0.45 +/- 0.23 mV; P = 0.036) but did not exceed the criterion for right side hypertrophy. QRS duration was slightly prolonged in athletes (99 +/- 10 ms vs. 92 +/- 9 ms; p = 0.010), as were rate-adjusted QT intervals (p < 0.05). J-point elevations (p = 0.0062) and ST-segment elevations (p = 0.013) were seen more frequently in athletes, but were usually small. CONCLUSIONS: The female athlete's ECG differs less from control subjects than has been reported in male athletes. Extrathoracal anatomic considerations may explain some of the sex differences. However, when clear-cut ECG abnormalities are observed in female athletes, organic heart disease must be carefully excluded.

Adult↗
PubMed1997

QT interval as a cardiac risk factor in a middle aged population.

OBJECTIVE: To evaluate the value of QT interval as a cardiac risk factor in middle aged people. METHODS: The association between QT interval and cardiac risk factors and mortality in a middle aged Finnish population of 5598 men and 5119 women was evaluated over a 23 year follow up. To adjust the QT interval confidently for heart rate, a nomogram was constructed from the baseline electrocardiograms separately for men and women. RESULTS: Nomogram-corrected QT interval (QTNc) prolongation was associated with elevated blood pressure and signs of cardiovascular disease; QTNc shortening was associated with smoking. Over 10% prolongation of QTNc predicted death in men with heart disease: adjusted relative risk (RR) was 2.17 (95% confidence interval 0.67-7.45) for sudden death; 2.12 (1.25-3.59) for total cardiovascular mortality; and 1.92 (1.23-3.00) for all cause mortality. In healthy men the increase in RR was not significant: sudden death, 1.48 (0.67-3.25); total cardiovascular mortality, 1.25 (0.92-1.70); all cause mortality, 1.21 (0.96-1.53). However, healthy men with long QTNc in the lowest heart rate quartile exhibited an RR of 2.75 (1.00-7.40) for sudden death. Over 10% shortened QTNc predicted cardiovascular death in men with heart disease who smoked; RR 3.72 (1.45-9.54). Non-smoking men with short QTNc had low mortality risks irrespective of possible signs of cardiovascular disease. The trends in mortality risks were similar but weaker for women. CONCLUSIONS: In a middle aged population, prolonged QT interval predicts cardiac mortality in men with signs of cardiovascular disease. In women and healthy men this risk is weak and may reflect subclinical heart disease. A shortened QT interval predicts death in men with heart disease who smoke.

Adult↗
PubMed1997

Left ventricular mass, geometry, and filling in endurance athletes: association with exercise blood pressure.

We studied whether left ventricular (LV) mass and concentricity [relative myocardial volume (RMV)] are associated with exercise blood pressure (BP) in athletes. LV structure and filling were evaluated by Doppler echocardiography and BP in maximal bicycle ergometry and isometric handgrip tests on 32 male endurance athletes and 15 age-matched controls. Indexed LV mass was 145 +/- 14 (SD) g/m in athletes and 93 +/- 20 g/m in controls. Mass was not associated with BP at rest or in low-grade exercise, but with heavier exercise loads this association strengthened in athletes, being maximal at peak exercise (r = 0.65 for mass and 0.58 for indexed mass; P < 0.001). Multivariate analysis indicated that BP at peak exercise accounted for 34% and the amount of training for an additional 11% of the variance in indexed LV mass. RMV was 21% larger in athletes. Only the increase in systolic BP during handgrip explained significantly (19%) the variance in RMV. LV filling velocities were not associated with mass, RMV, or BP. We conclude that in endurance athletes LV mass is associated with BP in heavy dynamic exercise and LV concentricity with BP response in static exercise.

Adult↗
PubMed1997

Do simple laboratory tests help in etiologic diagnosis in acute maxillary sinusitis?

The aim of the present study was to evaluate whether the results of such simple hematologic tests as erythrocyte sedimentation rate (ESR), white blood cell count (WBC) and C-reactive protein (CRP) could give any useful information about the causative agents in 176 patients with acute maxillary sinusitis (AMS). The great majority of tests (82%) showed values which were within normal limits. This may be due to the fact that 22% of AMS cases were culture negative for bacteria and about 60% of culture positive cases had Haemophilus influenzae as the etiologic agent. Significantly raised test values were seen in connection with Streptococcus pyogenes in the majority of cases, less frequently with Streptococcus pneumoniae and rarely with Haemophilus influenzae. We conclude that none of the evaluated routine blood tests are particularly sensitive indicators of the specific etiology of AMS in general. However, elevated CRP values (> 40 mg/l) associated with AMS should alert the physician to the suspicion of Streptococcus pyogenes or Streptococcus pneumoniae in etiology, since both, if left untreated, may lead to sinus empyema. With CRP or other evaluated tests Haemophilus influenzae- or Branhamella catarrhalis-positive AMS cannot be distinguished from a purely viral disease.

Acute Disease↗
PubMed1997

Serological findings in patients with acute syndromes fulfilling the proposed criteria of adult onset Still's disease.

In order to analyse possible triggering or contributing infections and HLA-B27 frequency in patients with acute febrile joint syndrome fulfilling the proposed criteria of adult Still's disease (AOSD), we studied prospectively the serological findings of 25 patients. They were aged 15-62 years and diagnosed between 1978-1992. We then compared results with a control group consisting of 119 healthy persons. Positive viral or bacterial serology was found in 12 patients (48%) in the AOSD group compared with 13 cases (11%) in the control group (p < 0.001). Fourfold or higher viral antibody rise was found in two patients and bacterial antibody rise in three patients. High stable viral antibody titre was observed in one patient and high stable bacterial antibody titre in six patients. HLA-B27 was not overrepresented in the study group (12%) compared with a healthy Finnish population (14%). We conclude that many different bacterial and viral infections may trigger or contribute to AOSD.

Acute Disease↗
PubMed1996

Serious cardiovascular side effects of large doses of anabolic steroids in weight lifters.

Pathological cardiovascular manifestations are reported in four male patients, who had taken massive amounts of anabolic steroids while undergoing many years of strength training. One patient was referred because of ventricular fibrillation during exercise, one because of clinically manifest heart failure, and one because of arterial thrombus in his lower left leg. The fourth patient was persuaded to attend for a check-up because of a long history of massive use of anabolic steroids. All four patients had cardiac hypertrophy. Two of the patients had symptoms and signs of heart failure, and one of these two had a massive thrombosis in both right and left ventricles of his heart. After cessation of the use of anabolic steroids in the other patient with heart failure, left ventricular wall thickness reduced quickly from 12 to 10.5 mm, and fractional shortening increased from 14% to 27%. Endomyocardial biopsy revealed increased fibrosis in the myocardium in two of the three cases. HDL-cholesterol was 0.58 mmol.l-1 and 0.35 mmol.l-1 in the two patients still using multiple anabolic steroids at the time of investigation. The cardiovascular findings described in the present paper should warn all physicians and athletes about the possible serious acute and long-term side effects of the massive use of anabolic steroids.

Adult↗
PubMed1996

Islet cell autoimmunity and progression to insulin-dependent diabetes mellitus in genetically high- and low-risk siblings of diabetic children. The Childhood Diabetes in Finland (DiMe) Study Group.

Insulin-dependent diabetes mellitus (IDDM) risk was evaluated in 765 siblings based on prospective observation of islet cell antibodies (ICAs) and insulin autoantibodies (IAAs) as a function of the degree of HLA identity to the proband and HLA-DR alleles. Twenty-eight (3.7%) siblings progressed to IDDM over a median observation period of 5.8 years. ICAs had higher sensitivity than IAAS (100% vs. 33% , P < 0.001), whereas persistent ICA positivity and double ICA/IAA positivity defined the highest actuarial risk (47% and 70%). Diabetes manifested after a mean of 3.2 years from the detection of ICAs in those siblings who were initially ICA negative and, importantly, the risk was equal to that of the siblings constantly positive from the first sample obtained. Although the combination of HLA identity and ICAs at or above 80 Juvenile Diabetes Foundation units carried the highest positive predictive value (77%), the high-risk HLA markers were insufficient to predispose siblings with low ICA levels to IDDM and low-risk HLA markers did not provide complete protection against high ICA levels and from subsequent IDDM. These results emphasize ICAs as the primary tool for risk evaluation in siblings followed by restricted HLA subtyping to reduce the population to be subjected to clinical intervention trials.

Actuarial Analysis↗