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Biomedical subjects

B Persson

Publications and source records attributed to B Persson.

At least 433 records · Page 24Linked to original sources

Immunogenicity of monocomponent human and porcine insulin in newly diagnosed type 1 (insulin-dependent) diabetic children.

The aim of the present study was to compare the immunogenicity of monocomponent human insulin with that of monocomponent porcine insulin in newly diagnosed Type 1 (insulin-dependent) diabetic children. One hundred and thirty-five patients at diagnosis of diabetes (age 1-18 years, mean age 9.3 years) were randomly allocated to treatment with either Monotard MC + Actrapid MC or Monotard HM + Actrapid HM in a double-blind trial conducted in Sweden, Finland, Norway and Denmark. The human and porcine insulin groups were identical at diagnosis with respect to age, sex and measures of metabolic control. At all times the mean insulin antibody levels and the percentage of antibody-positive patients were lower in the human group compared with the porcine group. At 3 and 12 months, the insulin antibody values were significantly lower in the human group than in the porcine group (p less than 0.05, Wilcoxon's rank sum test). At 12 months, antibody values in the human group ranged from 0 to 1.2 U/l (mean 0.14 U/l) and in the porcine insulin group from 0-5.2 U/l (mean 0.63 U/l). It is therefore concluded that human monocomponent insulin has a lower immunogenicity than porcine insulin of the same purity in newly diagnosed diabetic children during the first year of insulin treatment.

Adolescent↗

Antihypertensive effects of chronic 5-hydroxytryptamine (5-HT2) receptor blockade with ketanserin in the spontaneously hypertensive rat.

The effects of chronic oral treatment with the 5-hydroxytryptamine (serotonin) receptor blocking agent ketanserin (17 mg/100 g dry food) on blood pressure, heart weight, peripheral vascular reactivity, baroreceptor sensitivity, central cardiovascular reactivity and central catecholamine turnover were investigated in the spontaneously hypertensive rat. Blood pressure measurements were performed in conscious rats 24 h after insertion of catheters. After 6 weeks treatment basal blood pressure was reduced (16%) compared to control rats (given identical food, except for ketanserin). Both heart weight and body weight were reduced (both to 93% of control values) leaving heart weight/body weight ratio unchanged. Pressor responses to phenylephrine and depressor responses to isoprenaline (after pretreatment with reserpine and atropin) were not different while the blood pressure increase to 5-hydroxytryptamine was inhibited, indicating that after 6 weeks treatment the blood pressure reduction is not directly related to alpha-adrenoceptor blockade. Cardiovascular response to stress (jet air), baroreceptor sensitivity (bradycardia to phenylephrine) and central catecholamine synthesis rates (accumulation of 5-hydroxytryptophan and dihydroxyphenylalanine after synthesis inhibition) were unchanged supporting earlier evidence that central mechanisms probably do not contribute to the hypotensive effects of ketanserin.

Animals↗

Dissolution test for felodipine tablets using chemical oxidation in situ to maintain 'sink conditions'.

A test model is described for the determination of the dissolution rate of the vasodilator, felodipine, a derivative of dihydropyridine that is practically insoluble in water. 'Sink conditions' are maintained by means of an oxidizing agent, ceric sulphate, which reacts rapidly with dissolved drug molecules in the dissolution fluid. A pyridine derivative is formed quantitatively in the oxidation reaction. The amount of dissolved felodipine is calculated from the concentration of the pyridine derivative, as determined by reversed-phase liquid chromatography. Dissolution rates depend on the concentration of the oxidizing agent so that high concentrations accelerate dissolution. The dissolution test suggested for 25-mg felodipine tablets is performed in 500 ml fluid that contains 5 mM ceric sulphate in 0.12 M sulphuric acid. The test is performed on single tablets with USP paddle equipment. Dissolution rates for nine different tablet compositions are correlated to such bioavailability parameters as maximum plasma concentration and total area under the plasma concentration-time curve. Interferences and limitations of the method are discussed.

Journal Article↗

Fatty acid composition of amniotic fluid lecithin and its relationship to amniotic fluid C-peptide in diabetic pregnancy.

Fatty acid composition in lecithin and C-peptide was analysed in amniotic fluid samples obtained from 28 normal and 24 insulin-treated diabetic women in the 34th to 39th week of pregnancy. The pattern of changes of fatty acid composition of amniotic fluid (AF) lecithin was essentially the same in pregnancies complicated by diabetes as in non-diabetic controls. However, at 36/37 weeks, the mean values for palmitoleic acid (16:1) were statistically higher in diabetic women (P less than 0.02), and the mean values for stearic acid (18:0) were higher for normals (P less than 0.02). The mean C-peptide value was more than twice as high (0.71 nmol/l) in the diabetic group than in the control group (P less than 0.01). The lecithin/sphingomyelin (L/S) and palmitic/stearic acid (P/S) ratios were equal in both groups. Neither in five diabetic patients with fetuses indicating marked hyperinsulinism (C-peptide greater than 1.0 nmol/l) nor in the remaining group of patients was there any relationship between C-peptide levels and the lecithin fatty acid composition.

Adult↗

Ketanserin in combination with beta-adrenergic receptor blocking agents in the treatment of essential hypertension.

The antihypertensive properties of ketanserin, a 5-HT2 receptor antagonist, was investigated in combination with beta-adrenoceptor blockade. Ketanserin was given 40 mg twice daily to 10 hypertensive patients during 4 weeks in a double-blind placebo-controlled trial. Ketanserin significantly reduced supine and erect blood pressure compared to double-blind placebo, while no changes in heart rate were seen. When the blood pressure was assessed during 24 h at steady state conditions, the blood pressure reduction was maximal 1-2 h after tablet intake, corresponding to peak plasma concentrations of ketanserin. The blood pressure remained significantly reduced until next tablet intake (12 h). At steady state, on a 40 mg twice daily regimen, Css was 41.6 +/- 4.22, 36.9 +/- 5.19 and 39.8 +/- 4.81 ng/ml, Cmax 102.4 +/- 15.64 ng/ml and tmax 1.6 +/- 0.32 h. A slight sedation was observed in six patients. This side effect occurred 1-2 h after tablet intake and tended to subside with continued treatment.

Adrenergic beta-Antagonists↗

Plasma valine and urinary C-peptide in breast-fed and artificially fed infants up to 6 months of age.

Plasma branched-chain amino acids and urinary C-peptide-creatinine excretion was determined at 3, 4 1/2 and 6 months of age in a group of 50 infants who were either breast-fed or artificially fed and selected at random. The average concentrations of valine in plasma and C-peptide in urine as well as the ratio between C-peptide and creatinine in urine were 2-3 times higher (p less than 0.01) in artificially fed as compared to breast-fed infants at all the ages studied. Plasma valine values correlated significantly with the urinary C-peptide/creatinine ratio (r = 0.76, p less than 0.01), which suggests that the enhanced insulin response induced by the artificial formula is related to its protein content.

Amino Acids, Branched-Chain↗

Catecholamine surge and metabolic adaptation in the newborn after vaginal delivery and caesarean section.

The immediate postnatal metabolic adaptation and sympatho-adrenal activation were studied in infants delivered vaginally or by elective caesarean section. Vaginally delivered infants showed high catecholamine levels at birth compared to infants born by caesarean section under epidural or general anaesthesia. Umbilical arterial glucose levels were significantly higher in the vaginal group than in both caesarean section groups. At 30 min, all groups showed a marked decrease with several infants showing asymptomatic hypoglycaemia in the caesarean section group. C-peptide levels showed no difference at birth but later became significantly higher in the vaginal group. Although the levels of free fatty acids and glycerol were low at birth, they were significantly higher in the vaginal group. In all groups they increased substantially with time. Considering the marked differences in catecholamine levels, the differences in metabolic adaptation were unexpectedly small. This implies an attenuated metabolic response to sympatho-adrenal stimulation in the newborn.

Adaptation, Physiological↗

Sympatho-adrenal activity and metabolic adjustment during the first 12 hours after birth in infants of diabetic mothers.

Plasma adrenaline and noradrenaline concentrations at birth were the same in infants of diabetic mothers and controls after both vaginal and abdominal delivery. The infants delivered vaginally had significantly higher noradrenaline concentrations than those delivered by caesarean section. During the first 12 postnatal hours, the concentration of noradrenaline decreased to levels similar to those found in newborn infants with minor respiratory problems. No hypoglycemic values were recorded in infants of diabetic mothers at birth nor during the first twelve hours after birth. The C-peptide concentrations at birth were significantly lower in infants of diabetic mothers delivered vaginally as compared to those delivered by caesarean section. The FFA concentrations increased after birth possibly as a result of the lipolytic action of catecholamines released during labour and delivery. We have not been able to confirm the increased sympatho-adrenal activity previously reported in infants of diabetic mothers. We suggest that the difference is due to better metabolic control in the diabetic mothers during pregnancy and delivery in this study.

Adaptation, Physiological↗

Follow-up of children of insulin dependent (type I) and gestational diabetic mothers. Growth pattern, glucose tolerance, insulin response, and HLA types.

Fifty-three children of insulin dependent (IDM) and 20 children of gestational diabetic mothers (IGDM) representing 80 and 91%, respectively, of all surviving infants of diabetic mothers born between 1969 and 1972 at Sabbatsberg's hospital, Stockholm, participated in the follow-up study. The first follow-up examination was performed when the children had reached approximately 5 years of age and included measurement of height and weight, insulin response to intravenous glucose, and HLA typing. When the children were approximately 11 years old, a search was performed in the national register for type I diabetes in children in order to ascertain the frequency of type I diabetes mellitus in the total series (n = 88). The majority of children had a normal height for age and desirable weight for height. At the first follow-up all children had normal glucose disappearance rates (kt) and the insulin response including the early insulin response to glucose were not different between IDM and IGDM groups. The frequency distribution of HLA antigens (A, B, C) was not different from normal and there was no association between HLA B 8 and/or B 15 and early insulin response or kt values. At the second follow-up, two children of type I diabetic mothers had acquired type I diabetes, both were HLA B 15 positive, had normal kt values at the first follow-up, one with low, one with a high early insulin response. The frequency of type I diabetes in offspring of insulin dependent diabetic mothers was 3%.

Adolescent↗

Follow-up of children of insulin-dependent and gestational diabetic mothers. Neuropsychological outcome.

Ninety-four infants of 28 weeks gestation or more were born to 85 women, 64 type I and 21 gestational diabetics, between 1969-1972 at Sabbatsberg's Hospital, Stockholm. Perinatal mortality rate was 6.3%. The follow-up study was conducted when the children were approximately 5 years of age and included a physical and a neurological evaluation, IQ determination of mother and child, and an interview of mother by a psychologist. Fifty-three infants of insulin-dependent (IDM) and 20 infants of gestational diabetic mothers (IGDM) (83%) participated, 3 families could not be traced and 12 were unwilling. The group lost to follow-up (13 IDM, 2 IGDM) had more perinatal complications including congenital malformations than the follow-up group. All children had normal physical and neurological development. IQ was normal, the majority were above 100, the average in IDM was 115 (range 98-144) and 112 in IGDM (range 95-133). No obvious relationship was found between maternal acetonuria during pregnancy, infant birthweight, blood glucose during first hours after birth or neonatal complications and IQ of the children. A correlation (r = 0.364, p less than 0.01) was found between maternal and child IQ. Mothers exhibiting emotional disorders (anxiety, depression) had significantly higher life stress scores based on 29 stress variables and reported more frequently about conduct and behavioural disorders in their children than mothers without emotional disturbances.

Adult↗

Amniotic fluid C-peptide and phosphatidyl glycerol in diabetic pregnancy.

The concentrations of C-peptide and phosphatidylglycerol in the amniotic fluid were determined in 36 pregnant diabetic women. Twenty-one patients who were being treated with insulin for gestational diabetes as well as 15 patients who were insulin dependent were studied. All patients were subjected to a program of strict metabolic control, and amniocentesis was performed at gestational week 36-37. Phosphatidyl glycerol was present in the amniotic fluid in 15 cases and absent in 21. The mean concentration of C-peptide did not differ whether phosphatidyl glycerol was present or absent. (C-peptide: 0.56 +/- 0.06 and 0.43 +/- 0.05 nmol/l respectively). Although the mean value for amniotic fluid C-peptide in both groups was close to that in diabetic pregnancies with an uneventful neonatal outcome, it was significantly higher than that in non-diabetic pregnancies, indicating minor fetal hyperinsulinemia. The level of C-peptide in the amniotic fluid showed a correlation to the subsequent birthweight of the infant (r = 0.50; p less than 0.01). It is concluded that with rigorous metabolic control of the pregnant diabetic patient, the presence or absence of phosphatidyl glycerol, as an index of fetal lung maturity, is apparently not related to the level of C-peptide in the amniotic fluid.

Amniocentesis↗

Spiral artery lesions in relation to metabolic control in diabetes mellitus.

Decidual and intramyometrial spiral arteries from 18 insulin-dependent diabetic and 18 non-diabetic women were compared histologically. All women were normotensive and none had signs of pre-eclampsia. None of the infants in either group had intra-uterine growth retardation. Metabolic control in the diabetic women was assessed by pregnancy glucose level from the last trimester of pregnancy and by C-peptide in amniotic fluid and cord blood as a measure of the fetal beta-cell function. The intramyometrial and decidual parts of the spiral artery were normal in the non-diabetic group. None of the diabetic patients showed pathological changes in the intramyometrial part of the spiral artery. Two of the 18 diabetic patients had pathological changes (intramural fibrosis) in the decidual portion of the spiral artery. These two women had signs of diabetic angiopathy (White's class D and F) and in one of them, the background diabetic retinopathy progressed markedly during pregnancy. The pregnancy glucose level was above normal (greater than 6.2 mM/l) in 3 of 18 diabetics. The C-peptide values in amniotic fluid and cord blood were above normal in 11 of 17 and in 5 of 17, respectively. Both patients with spiral artery lesions had pregnancy glucose levels in the upper range, 5.86 and 5.98 mM/l, respectively and the highest value of C-peptide in the amniotic fluid and cord blood, suggesting exaggerated fetal beta-cell function.

Adult↗

Villous structure in different parts of the cotyledon in placentas of insulin-dependent diabetic women. A morphometric study.

Placentas from 13 insulin-dependent diabetic mothers and 10 non-diabetics were compared by means of photographic planimetry. The material was investigated in fresh state and obtained from three well-defined areas within a cotyledon, central, intermediate and lateral regions. Length and area of the villi in each region were calculated. The non-diabetics showed a consistent organization of the cotyledon, with increasing villous length towards the periphery. The surface areas increased with increasing length. In placentas of diabetic mothers, this organization was disrupted. The villi were of even length throughout the cotyledon. The average length of a villus in the diabetic group did not differ from the average length in the control group. Despite this fact, the average surface area in the diabetic was greater than that in the controls. This increased surface area was due to increased branching of peripheral villi in the diabetic group. The degree of blood glucose control of the diabetic mothers was assessed by the day-to-day variation in maternal blood glucose levels ( MODD ) for periods 12th to 32nd week and 32nd week to term and by "pregnancy glucose value", i.e. the mean of four consecutive daily blood glucose levels from the 32nd week of gestation to term. Only MODD values based on blood glucose values from 12th to 32nd week of gestation were correlated to the villous surface area. The greater the blood glucose variability, the greater was the surface area.

Adolescent↗

Experience with ketanserin, a serotonin (S2) antagonist, in longterm treatment of essential hypertension.

Ketanserin ia a quinazoline derivative which acts selectively on serotonin (S2) receptors. The compound has been shown to possess antihypertensive properties. BP and HR were measured blindly on 14 patients with essential hypertension during one year. Ketanserin 40 mg, once or twice daily, reduced BP (and HR to a slight extent) largely unchanged from 14 days after initiation of therapy. Response rate varied from 57-77% at the regular control visits. During the one year follow up period the reduction in supine SBP was 9 +/- 3% (p less than 0.001) and DBP was 12 +/- 1% (p less than 0.001). The only side effect was a slight sedation that passed with time. It is concluded that ketanserin is effective in the chronic treatment of hypertension and may offer a new alternative to existing pharmacotherapy.

Adult↗

The Kockum study: twenty-two-year follow-up. Coronary heart disease in a population in the south of Sweden.

The Kockum study of risk factors for coronary heart disease (CHD) consists of 464 individuals, one third white collar workers, one third heavy workers and one third well trained firemen, all of whom have now been followed for 22 years. Important risk factors for CHD seem to be heredity, smoking, stress, lack of physical activity, diabetes mellitus hypertension, high body weight, ECG abnormalities, hypercholesterolemia, hypertriglyceridemia and baldness. In addition to the common risk factors, baldness seems to be of importance. A high cholesterol value predisposes for an increased death rate not only due to CHD but also to malignant disease. A Cox analysis shows a markedly decreased life expectancy in multirisk factor patients caused not only by CHD but also by cancer.

Adult↗

Fetal maturation in strictly controlled diabetic pregnancy.

In 56 strictly controlled diabetic pregnancies, altogether 60 amniotic fluid samples were analysed for their content of lipid-carrying cells and the presence of phosphatidylglycerol. The outcome of the amniotic fluid tests was examined for its association to macrosomia and to minor neonatal complications such as hypoglycaemia, hypocalcaemia, respiratory disturbances and hyperbilirubinaemia. The predictive value of these tests was nil, since all cases of neonatal complications occurred in the group showing maturity in tests at week 37. At term, phosphatidylglycerol was detected in 80% of the pregnancies, a finding corresponding to our observations in non-diabetic pregnancies. Lipid-carrying cells were present in quantities indicating maturity (greater than or equal to 10%) in 65% of the pregnancies at term, compared with 87% in non-diabetic pregnancies, suggesting a somewhat disturbed skin maturation secondary to the maternal diabetic state. The failure of these tests to predict neonatal complications indicates that other factors may be of more importance for the occurrence of these disorders than those aspects of final functional maturation of the fetus that are reflected in these two particular maturity tests.

Adult↗