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Biomedical subjects

R Puukka

Publications and source records attributed to R Puukka.

At least 19 recordsLinked to original sources

New method for the determination of pancreatic amylase evaluated.

We have carried out a multicenter evaluation of a new reagent carrier for Reflotron, specific for pancreatic amylase where the salivary isoenzyme is inhibited by two specific monoclonal antibodies. This new procedure combines easy handling with low imprecision (median CV less than 3%) in control material, serum, heparinized blood, and plasma) and close correlation (r = 0.991 to 0.999) with established manual and automated methods. The same close correlation was found with values obtained from either venous or capillary finger-stick blood. Salivary amylase up to 54 kU/L (37 degrees C) was inhibited to about 97%. Endogenous interference by hemoglobin, bilirubin, triglycerides, cholesterol, or hematocrit was found to be negligible within a wide range of interferent concentrations. Out of a panel of 28 commonly used drugs it was shown that only two (ascorbic acid and paracetamol), and then only at toxic concentrations, caused a deviation in amylase activity of greater than 10%. From the results of this study we conclude that this new method is suitable for highly precise and accurate measurements of pancreatic amylase in emergency and routine laboratories.

Amylases

Clinical significance of urinary C-peptide excretion in children with insulin-dependent diabetes mellitus.

In order to evaluate the accuracy of urinary C-peptide determination and the clinical significance of C-peptiduria for the early course of insulin-dependent diabetes (IDDM), the rate of urinary excretion of C-peptide was determined in 32 children and adolescents with IDDM and correlated with serum C-peptide concentration, urinary excretion of albumin and beta 2-microgloublin and with the glomerular filtration rate (GFR) measured in terms of the clearance of 99mTc-DTPA. The age of the subjects ranged from 9.1 to 17.1 years (mean 13.1) and the duration of diabetes from 0.3 to 11.9 years (mean 4.6). There was a good correlation between postprandial serum C-peptide concentration and the 24-hour urinary C-peptide excretion rate (r = 0.81; p less than 0.001). GFR and urinary albumin excretion were slightly elevated in the diabetic patients as compared with non-diabetic subjects (p less than 0.05 and p less than 0.001, respectively), but C-peptide excretion was unrelated to the degree of hyperfiltration or albuminuria, neither was there any correlation between the excretion rate of beta 2-microglobulin and C-peptide. Glycaemic control was poorer in the diabetic children who had only trace amounts of C-peptide in their urine (less than 0.05 nmol/m2/24 h) than in those with minimal (0.05-1.0 nmol/m2) or moderate 24-hour urinary C-peptide excretion (greater than 1.0 nmol/m2). It is concluded that urinary C-peptide excretion serves very well to reflect residual beta-cell function and is unrelated to the slight renal hyperfunction and albuminuria often seen in diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Reduced insulin removal and erythrocyte insulin binding in obese children.

To study the relationship between childhood obesity, weight loss, hyperinsulinaemia and the erythrocyte insulin receptor, we measured the plasma concentrations of immunoreactive insulin (IRI) and C-peptide and the binding of 125I-insulin to erythrocytes in 12 obese children with a mean age +/- SD of 11.4 +/- 2.5 years and a mean relative weight score +/- SD of 4.8 +/- 1.4 and 12 age-matched normal-weight children. Eight obese children were re-evaluated after 1 year's participation in a weight reduction programme. The obese children had higher fasting plasma concentrations of IRI (P less than 0.01) and C-peptide (P less than 0.05) and a lower C-peptide to IRI molar ratio (P less than 0.01) than the normal-weight children. The obese children had in addition a reduced erythrocyte insulin binding (P less than 0.05 or less) over the physiological range of circulating insulin concentration. There was a negative correlation (r = -0.60; P less than 0.01) between the insulin tracer binding and the relative weight. The weight reduction programme resulted in a decrease of 1.0 SD (P less than 0.05) in the mean relative weight score. At the end of the therapy the obese children had lower fasting blood glucose levels (P less than 0.05) and lower plasma IRI concentrations at 90 min (P less than 0.05) after an oral glucose load than at the onset of therapy. There were no significant differences between the insulin binding characteristics at the commencement and at the end of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose

Postnatal decrease in insulin binding to erythrocytes in infants of diabetic mothers.

To clarify the role of insulin receptors in the macrosomia and the tendency to hypoglycemia in infants of mothers with insulin-treated diabetes mellitus (IDM) we studied insulin binding in erythrocytes from mixed umbilical blood and from peripheral venous blood collected when the infants were 3-14 days old. Normal infants were matched for gestational and postnatal age. The IDM infants were macrosomic, with significantly higher birth weights relative to gestational age than the control infants. Plasma free insulin concentrations in cord blood were 15-fold higher in the IDM than in the normal infants and more than 3-fold higher in the peripheral venous blood at the median age of 4 days. Hypoglycemia occurred in 12 of the 17 IDM and in none of the normal infants. In umbilical blood insulin binding to erythrocytes was similar in the IDM and normal infants. In both groups insulin binding decreased during the first postnatal weeks, but the decrease was significantly greater in the IDM than in the normal infants. The decrease in insulin binding to erythrocytes was a consequence of decreased receptor affinity as well as decreased receptor concentration in the IDM infants, but was mainly due to decreased receptor concentration in the normal infants. We conclude that insulin binding to its erythrocyte receptor in cord blood in IDM infants is similar to that in normal infants in spite of the simultaneous gross hyperinsulinemia in the IDM infants. The resulting increase in insulin action would then contribute to the tendency toward hypoglycemia and may be partly responsible for the macrosomia in IDM infants. The marked postnatal decrease in insulin binding in IDM infants is a possible explanation for their diminishing risk of hypoglycemia after the first few days of life in spite of persisting hyperinsulinemia.

Birth Weight

Maternal residual beta-cell function and the outcome of diabetic pregnancy.

Preservation of own insulin production (residual pancreatic beta-cell function) has been shown to have a beneficial effect on glycemic control in insulin-dependent diabetic subjects, and its total lack has been suggested to be an independent risk factor during diabetic pregnancy. We studied the influence of residual beta-cell activity on the glucose control and the outcome of pregnancy in 29 diabetic women by sequentially measuring gestational postprandial plasma C-peptide (CPR) levels, diurnal blood glucose curves and blood glycosylated hemoglobin (Hb A1c) and by analyzing the morbidity and mortality of the offsprings. The 9 diabetics with moderate own insulin secretion (CPR levels over 1.0 microgram/l, White classes B and C, later referred to as group I) had significantly better glucose control than the remaining 20 subjects with lower CPR values (White classes C, D and NF, later referred to as group II) (figure 1, table I). There were two intrauterine deaths, both in group II. These deaths (one caused by multiple congenital contracture syndrome and the other by severe intrauterine growth retardation without any evident cause) could not be straightly connected with diabetes. Respiratory distress syndrome was seen in group II only. There was no other significant difference in the neonatal morbidity between the two groups (table II). All mothers of RDS infants were in White class NF where the birthweight was also smaller than in classes B and C. These were the only differences in neonatal morbidity between the White classes (table III). In conclusion, moderate residual beta-cell function seemed to be clinically important in maintaining strict glucose control during gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose

Correlation between umbilical vein blood flow and umbilical blood viscosity in normal and complicated pregnancies.

Umbilical vein blood flow (UVBF) was studied during the last 24 h before delivery using a combination of real-time and Doppler ultrasonic equipment in 64 normal and pathological pregnancies and the results were correlated with the values of whole blood viscosity taken from the umbilical vein after delivery. UVBF was reduced in the subgroup with chronic fetal distress (n = 14) (P less than 0.001) and the hypertensive pregnancies (n = 17) (P less than 0.05), whereas umbilical blood viscosity was increased only in the subgroup with chronic fetal distress (P less than 0.01) as compared with the normal pregnancies (n = 24). A significant positive correlation was observed between the umbilical blood viscosity and haematocrit values in all the groups of patients. UVBF and blood viscosity had a significant negative correlation in chronic fetal distress (P less than 0.001) and in hypertensive pregnancies (P less than 0.05), but not in normal or diabetic pregnancies (n = 9). Thus haemoconcentration leading to increased fetal blood viscosity may act as an aetiological factor in the reduction of UVBF in developing fetal distress.

Blood Viscosity

Levels of some purine metabolizing enzymes in lymphocytes from patients with Down's syndrome.

The activities of a number of purine metabolizing enzymes of erythrocytes and lymphocytes were determined in 18 subjects with Down's syndrome and in 18 age- and sex-matched control subjects. An increase of adenosine deaminase activity (adenosine or deoxyadenosine as substrates) was found in erythrocytes (P less than 0.001) as well as in lymphocytes (P less than 0.001) of Down's syndrome subjects compared to controls. The purine nucleoside phosphorylase activities in lymphocytes and plasma urate concentrations were also significantly higher in Down's syndrome subjects than in controls (P less than 0.001 and less than 0.02, respectively). Adenine phosphoribosyltransferase activities and hypoxanthine-guanine phosphoribosyltransferase activities in lymphocytes were identical in the two groups. In all subjects studied there were positive correlations between the erythrocyte adenosine deaminase activities, lymphocyte adenosine deaminase or deoxyadenosine activities, and plasma urate concentrations (P less than 0.05 in all cases), and between lymphocyte nucleoside phosphorylase and lymphocyte adenosine deaminase or deoxyadenosine deaminase activities (P less than 0.01 and less than 0.05, respectively). The results suggest that increased activities of some purine metabolizing enzymes found in both erythrocytes and lymphocytes may contribute to increased purine degradation and hyperuricemia in subjects with Down's syndrome. In addition, the increased adenosine deaminase and nucleoside phosphorylase activities may be related to the immunological dysfunction found in subjects with Down's syndrome.

Adenine Phosphoribosyltransferase

Residual B-cell function and glycaemic control in diabetic pregnancy.

Serum C-peptide immunoreactivity (CPR), mean blood glucose and blood glycosylated haemoglobin Hb A1c were measured in 23 insulin-dependent diabetic women at 11-12, 23-24, 33-34 and 37-38 gestational weeks in order to elucidate changes in residual B-cell function during pregnancy and their influence on the glycaemic control. CPR values generally increased at the 23-33 gestational weeks, with a significant difference between the mean of the peak values and the mean of the values at the first admission. When the subjects were divided into two groups on the basis of the residual B-cell function at the first admission, the glycaemic control during pregnancy was significantly better in those with higher residual B-cell activity. The overall prevalence of marked residual B-cell activity was higher than previously reported in non-pregnant insulin-dependent diabetic subjects. The results indicate clinically important enhancement in residual B-cell function during pregnancy. The mechanism of this improvement is poorly known although the more strict management of diabetes during gestation may be an important factor.

Adult

Erythrocyte insulin binding in preterm newborn infants.

To characterize the erythrocyte insulin receptor in newborn infants we studied the binding of 125I-insulin to the erythrocytes from 42 preterm infants (14 at birth, 14 aged 2-7 days, and 14 aged 8-16 days) with a mean gestational age of 34.1 wk, and from 32 term infants (16 at birth and 16 aged 2-7 days). The insulin binding to cord blood erythrocytes from preterm infants was significantly higher than that of cord blood cells from term infants and to postnatal cells from preterm as well as term infants. The erythrocytes from preterm infants aged 2-7 days bound more insulin than cells from preterm infants aged 8-16 days. The maximum insulin binding (specific insulin binding at tracer concentration of insulin) correlated negatively with the gestational age both at birth and over the 1st postnatal wk. In the preterm infants there was a strong negative correlation between the maximum insulin binding and postnatal age. The enhanced insulin binding to cord blood erythrocytes from preterm infants was due to both an increased receptor concentration and a high affinity for insulin. The increased affinity persisted over the 1st wk of life. In preterm infants older than 1 wk the insulin binding characteristics were basically similar to those in term newborn infants. In all infants studied the receptor concentration seemed to be postnatal age dependent while the receptor affinity was gestational age dependent. No correlation was found between the insulin binding data and the plasma concentrations of immunoreactive insulin or C-peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose

Evidence of delayed beta-cell destruction in type 1 (insulin-dependent) diabetic patients with persisting complement-fixing cytoplasmic islet cell antibodies.

Forty-four children with Type 1 (insulin-dependent) diabetes (aged 0.7-16.7 years) were observed from diagnosis for cytoplasmic islet cell antibodies and serum C-peptide concentrations. Islet cell antibodies were analysed by indirect immunofluorescence for both conventional IgG and complement-fixing antibodies. Thirty-seven children (84%) were found to be positive for conventional islet cell antibodies at diagnosis, and 21 (48%) remained positive over the observation period. Twenty-six patients (59%) were positive for complement-fixing antibodies at diagnosis and eight remained so during the follow-up period. The serum C-peptide concentrations increased significantly during the first 3 months after diagnosis, after which there was a gradual decrease in the levels. Those children who remained positive for complement-fixing antibodies over the observation period had significantly higher serum C-peptide concentrations on several occasions during the second year and had also a higher integrated serum C-peptide concentration over the initial 2 years than those who became negative for complement-fixing antibodies. These observations suggest that the continuous production of complement-fixing islet cell antibodies in those patients who are positive for these antibodies at diagnosis presupposes the preservation of a sufficient amount of functioning beta cells for antigenic stimulation. These results support the view that the complement-fixing islet cell antibodies reflect ongoing destructive processes in the beta cells.

Adolescent

Physical fitness of children and adolescents with insulin-dependent diabetes mellitus.

The physical working capacity (PWC170) of 84 children and adolescents with insulin-dependent diabetes mellitus (IDDM) and of 94 non-diabetic subjects was measured by a submaximal progressive exercise test. The age of the diabetic subjects ranged from 6.3 to 18.8 years and that of the control subjects from 8.5 to 18.8 years. The PWC170 of diabetic boys was lower than that of non-diabetic boys (p less than 0.01) while no difference was observed between diabetic and non-diabetic girls. PWC170 was inversely related to age (p less than 0.01) and concentration of hemoglobin A1 (p less than 0.025) in diabetic boys but not in diabetic girls. No relationship was observed between PWC170 and duration of diabetes in either boys or in girls. The results indicate that good physical fitness in boys is associated with a better metabolic control. Hence the study indirectly supports previous observations that physical activity improves the metabolic control of IDDM.

Adolescent

Pancreatic islet cell function and metabolic control in an infant with permanent neonatal diabetes.

A girl with typical clinical manifestations of neonatal diabetes was observed for 16 months with consecutive evaluations of pancreatic beta- and alpha-cell function and metabolic control. At the diagnosis both the plasma immunoreactive insulin (IRI) and C-peptide concentrations were inappropriate for the contemporaneous hyperglycemia. During the follow-up, the C-peptide fell twice below the detection limit but the beta-cell function recovered partially on both occasions. Based on 24-hour urinary C-peptide excretion, the endogenous insulin secretion was less than 10% of that in non-diabetic infants. When diagnosed the patient had plasma immunoreactive glucagon (IRG) and glucagon-like immunoreactivity (GLI) concentrations below the reference range for normal neonates. The IRG normalised within the first month, while the GLI increased to a level exceeding the reference range. Hemoglobin A1 had already risen at the time of diagnosis and subsequently rose to a level indicating poor metabolic control. The findings indicate an immature function of both beta- and alpha-cells at the diagnosis with the alpha-cells maturing within the first month. The recovery of the beta-cell function, after two failures in this patient with permanent neonatal diabetes, suggests that the beta-cell damage was at least partially reversible.

Diabetes Mellitus, Type 1

Erythrocyte insulin binding in normal infants, children and adults.

To establish normal insulin binding criteria, we studied the binding of insulin to erythrocytes from normal subjects of different ages. Insulin binding to cord erythrocytes and to erythrocytes from infants aged 2-7 days was significantly higher at tracer and physiological insulin concentrations than was binding to cells from children aged 1-15 years and adults. In infants aged 1-12 months the maximum insulin binding to erythrocytes was significantly higher than that to erythrocytes from children, and in addition, it correlated negatively with age. An increase in receptor concentration was found in cord erythrocytes whereas an increased receptor affinity for insulin was found in erythrocytes from infants. Insulin binding characteristics in erythrocytes from prepubertal and pubertal children were basically similar to those in women. Erythrocytes from men bound significantly higher amounts of insulin than did those from women. This difference was associated with changes in receptor affinity for insulin. There was no correlation between the insulin binding characteristics and the circulating concentration of insulin or C-peptide. The increased erythrocyte insulin binding at birth persisted over the neonatal period. There was an overall negative correlation between the maximum insulin binding and age in the subjects studied, but the major decrease in erythrocytes insulin binding occurred during the first year of life past the neonatal period. These observations stress the importance of using age-matched controls in studies on erythrocyte insulin binding in disease states.

Adolescent

Basal insulin secretion and erythrocyte insulin binding in preterm and term newborn infants.

To study the ontogeny of the insulin secretion and the erythrocyte insulin receptor we measured plasma immunoreactive insulin and C-peptide concentrations and the binding of [125I]-insulin to the erythrocytes in cord blood from 16 preterm and 16 term infants. 20 normal-weight adults were also studied. The C-peptide concentrations and the molar ratio of C-peptide to insulin were lower in the newborn infants than in the adults. The immunoreactive insulin correlated positively with birth weight in the term infants. The insulin binding to erythrocytes from the newborn infants was increased when compared to the adults. Erythrocytes from the preterm infants bound more insulin than the cells from the term infants. There was a strong negative correlation between insulin binding and gestational age. In the term infants, plasma C-peptide correlated negatively with the insulin binding. The increased binding to erythrocytes from the term infants was due to an increase in the receptor concentration. The high insulin binding in the preterm infants was a result of both an increased receptor concentration and affinity. These data suggest that the basal insulin secretion is similar in preterm and term infants and that the clearance of insulin is decreased in newborn infants. The increased insulin binding in newborn infants may be a mechanism by which the growth stimulatory effect of insulin in fetal life is mediated.

Adult

Erythrocyte adenosine deaminase, purine nucleoside phosphorylase and phosphoribosyltransferase activity in patients with Down's syndrome.

The erythrocyte adenosine deaminase, nucleoside phosphorylase, hypoxanthineguanine phosphoribosyltransferase and adenine phosphoribosyltransferase activities and plasma urate concentrations were measured in 20 cases of Down's syndrome and in 20 age- and sex-matched control subjects. The mean erythrocyte adenosine deaminase and adenine phosphoribosyltransferase activities and plasma urate concentrations were significantly higher in Down's syndrome subjects than in controls (p less than 0.001, p less than 0.01 and p less than 0.001, respectively). In all subjects studied there was a positive correlation between the erythrocyte adenosine deaminase activity and plasma urate concentration (r = 0.488, p less than 0.005). The concentrations of the erythrocyte adenine nucleotides, AMP, ADP and ATP, did not differ in Down's syndrome (n = 10) from those of control subjects (n = 10). The results suggest that the increase of plasma urate concentrations is a consequence of the increase in adenosine deaminase activity in Down's syndrome patients.

Adenine Nucleotides

Haemoglobin Hijiyama: a haemoglobin variant found in connection with glycosylated haemoglobin estimation in a Finnish diabetic boy.

A variant of haemoglobin A, named earlier haemoglobin Hijiyama, was found in three generations of a Finnish family in connection with the determination of glycosylated haemoglobin of a diabetic patient. The biochemical abnormality is in the beta-chain at residue 120 where lysine is replaced by glutamic acid. In the heterozygote carriers of the abnormal haemoglobin there was no apparent association with clinical or haematological abnormalities. By isoelectric focusing in thin-layer polyacrylamide gels, haemoglobin Hijiyama could be distinguished with high specificity from haemoglobin A as well as from other haemoglobin variants earlier found in Finland. The glycosylated haemoglobin fractions (haemoglobin A1 and haemoglobin Hijiyama 1) in the diabetic patient sample could be determined by colorimetric and electrophoretic methods.

Child

99mTc-DTPA--a useful clinical tool for the measurement of glomerular filtration rate.

The single injection 99mTc-DTPA clearance was compared with the inulin clearance performed with the constant infusion technique in 22 subjects. There was a good correlation between these two methods (r = 0.968, p less than 0.001). Although the single injection technique calculated by one compartment model is not accurate enough for research purposes, it seems to work well in routine clinical practice for the measurement of glomerular filtration rate using 99mTc-DTPA as a tracer substance. The performance is simple, it needs only a few blood samples, nor does it need any urine collection, the radiation dose is low and it seems to be more accurate than the endogenous creatinine clearance.

Adolescent