Biomedical subjects

J Ludvigsson

Publications and source records attributed to J Ludvigsson.

At least 145 records · Page 8Linked to original sources

PubMed1986

Plasma and erythrocyte concentrations of mercaptopurine after oral administration in children.

Plasma and erythrocyte concentrations of 6-mercaptopurine (6-MP) were determined by gas chromatography-mass spectrometry. Eleven children (9 with acute lymphatic leukemia) were studied after oral intake of 6-MP doses ranging between 31 and 128 mg/m2 body surface area. The concentrations of 6-MP in plasma were found to vary considerably between patients even after dose normalization to 75 mg/m2. After dose normalization the mean peak plasma concentration was 0.68 microM (range 0.12-1.38) and the area under the plasma concentration-time curve (AUC) was 1.37 microM.h (range 0.12-3.04). The mean time taken to reach the peak concentration was 1.3 h (range 1-2), and the half-life of elimination was 1.8 h (range 0.6-2.5). No patient had detectable 6-MP concentrations 12 h after dose intake. The concentrations of 6-MP tended to be higher in erythrocytes than in plasma. The mean peak concentration in erythrocytes was 131% and the AUC 145% of that found in plasma. The mean half-life of elimination from erythrocytes was 2.0 h (range 0.7-2.8). These data indicate that 6-MP can pass through all membranes rapidly to reach intracellular concentrations equal to or even higher than in plasma. In summary, marked interindividual differences in pharmacokinetics were found, probably due to highly variable bioavailability of oral 6-MP. Further studies are needed to determine whether measurements of plasma concentrations of 6-MP can be used to optimize maintenance treatment of childhood leukemia.

Administration, Oral↗

PubMed1985

Influence of metabolic control on the blood-retinal barrier in streptozocin diabetic rats.

One hundred and eight male Sprague-Dawley rats weighing 160-225 g were examined with vitreous fluorophotometry (VF). Fifty-five rats were made diabetic with streptozocin (43 with 65 mg/kg and 12 with 90 mg/kg); 53 nondiabetic rats served as controls. Fluorescein (7 mg/kg) was injected IV and VF was performed 60 min later. The diabetic rats had an abnormal blood-retinal barrier (BRB) after 4-7 days duration. The difference between the diabetic and non-diabetic rats was persistent up to 35 days (P < 0.02-0.001). The diabetic rats treated with 90 mg/kg streptozotocin had a more severe diabetes and a higher treated with 65 mg/kg (P < 0.05). The BRB function was normalized in 18 rats treated for 6-7 days with 5-6 IU long-acting insulin (P < 0.02). The results imply that streptozocin-diabetic rats have an abnormal BRB and that this abnormality seems to be related to the diabetic state and to be reversible after insulin treatment.

Animals↗

PubMed1985

Blood-retinal barriers in juvenile diabetics in relation to early clinical manifestations, HLA-DR types, and metabolic control.

Eighty-seven diabetics 8.5-26 years old (mean +/- SD 15.3 +/- 3.9) and 32 healthy non-diabetic controls 8-27 years old (13.9 +/- 4.3) were included in the study. They had had the disease for 2 months to 19 years (5.8-4.0 years). Seventy-two of the diabetic patients were HLA-DR type, 13 patients had DR 3 alone, 25 DR4, 33 DR 3,4 and 1 patient was neither DR 3 nor 4. The mean fluorescein concentration in the vitreous body 3.5-7 mm from the retinal surface at 60 min after intravenous administration of fluorescein was 15.5 +/- 11.9 ng/ml in the diabetics and 7.2 +/- 3.7 ng/ml in the non-diabetic controls (P less than 0.001). The diabetics still in partial remission had an almost normal blood-retinal barrier (BRB; 7.9 +/- 4.8 ng/ml) while about 55% of the diabetics beyond remission had impaired barrier function. Abnormal leakage was found in some patients who had had diabetes for less than 2 years and also before the onset of puberty. The incidence of abnormal leakage increased with increasing age and duration. There was a positive correlation between fluorescein leakage and the blood glucose level at the onset of diabetes (P less than 0.01). There was no statistically significant relationship between specific HLA-DR types and abnormal leakage. A defect BRB was significantly correlated with poor short-term metabolic controls, expressed as glucosuria index during the last week before examination with vitreous fluorophotometry. Prospective studies will show whether abnormal BRB gradually leads to irreversible retinopathy.

Adolescent↗

PubMed1985

Strategy for self-monitoring of diabetic control.

Treatment of diabetes must aim at normal metabolism. Sporadic measurements of any known parameter is not a sufficient guarantee but continous regular self-monitoring is necessary. At least in insulin dependent diabetes it seems reasonable that we should monitor the free insulin levels, but that still belongs to the future. As blood glucose gives us a good reflection of the hormonal and metabolic balance, this is a relevant parameter to follow. Glycosylated proteins, mainly hemoglobin, give only retrospective information of moderate value for the practical management of the disease. Furthermore, one should be aware of the different weak points of glycosylated hemoglobin which does not tell the only, total truth about glucose balance. Self-monitoring of blood glucose is a very valuable tool, especially when used in a systematic way. To get information covering the whole day every day tests for glucosuria have still a place, especially among children and young adults with rather short duration of diabetes. With a sensible approach it is possible to get good compliance among most patients. A combination of blood and urine glucose selfcontrol creates opportunities for a good metabolism in diabetes.

Adolescent↗

PubMed1985

Islet cell antibodies in insulin-dependent (type 1) diabetic children treated with plasmapheresis.

Plasma levels of islet cell cytoplasmic and cytotoxic antibodies were determined in 10 children with insulin-dependent diabetes mellitus (IDDM) treated with plasmapheresis shortly after diagnosis, and in 9 children with IDDM treated by conventional means alone. Islet cell cytoplasmic antibody (ICA) titers were determined by indirect immunofluorescence using unfixed sections of human pancreas, and islet cell cytotoxic antibody levels were determined in a complement-dependent antibody-mediated cytotoxicity (C'AMC) assay using a human fetal cloned insulin-producing cell line (JHPI-1) as target. Before plasmapheresis, ICA was present in 7 out of 10 children and C'AMC was positive in 4. Four successive treatments with plasmapheresis did not consistently decrease plasma levels of ICA or C'AMC. ICA was present in 15 out of the total 19 children at diagnosis, and titers of ICA decreased in 12 out of 15 subjects by at least 1 degree of dilution (1:3) at 18-30 months follow-up, whether or not they had been treated with plasmapheresis; C'AMC was positive in 6 out of the 18 children at diagnosis and decreased in 2 out of 6. Plasma levels of C-peptide did not differ at diagnosis but remained higher in the plasmapheresis treated diabetic children at 3 and 18-30 months follow-up. Neither ICA titers nor C'AMC levels correlated with plasma C-peptide responses at 18-30 months. It is concluded that plasmapheresis decreases ICA and C'AMC but is followed rapidly by a rebound effect, and does not affect the rates at which these islet cell antibodies decrease with increasing duration of IDDM.

Adolescent↗

PubMed1984

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↗

PubMed1984

Insulin antibodies in diabetic children treated with monocomponent porcine insulin from the onset: relationship to B-cell function and partial remission.

Insulin antibodies expressed as insulin binding capacity of IgG were determined in 50 Type 1 (insulin-dependent) diabetic children who have been treated with monocomponent porcine insulin from the onset of the disease. During the follow-up period of 0.5-5.5 years (mean +/- SD: 3.2 +/- 1.6 years), 26 out of 50 patients (52%) developed detectable insulin antibodies. These patients had significantly lower maximal C-peptide responses to a standardized breakfast 9 months after onset of diabetes (mean 0.24 pmol/ml, p less than 0.001) than those without insulin antibodies (mean 0.47 pmol/ml). In addition, patients with antibodies showed both significantly higher insulin requirements at 9 months (p less than 0.05), and shorter remissions (p less than 0.01) than those without. It is concluded that even 'small' amounts of insulin antibodies may be biologically significant and have negative effects on B-cell function and metabolic balance.

Adolescent↗

PubMed1984

Human lymphocyte antigen DR types in relation to early clinical manifestations in diabetic children.

Human lymphocyte antigen (HLA)-DR-typing was performed in 117 insulin-dependent diabetics with age at onset between 0.5 and 17 years (mean +/- SD, 9.0 +/- 3.9); 115 of 117 patients were DR3- and/or DR4-positive. DR4 was very common, seen alone or in combination with other DR types in 82.9% of the patients. Only two children were DR2-positive, but they also were DR4-positive. A comparison between DR3 and DR4 patients showed that DR4 patients manifested a seasonal variation of onset (most common onset during spring and autumn), had more severe signs and symptoms of the disease at onset, and were less likely to have a partial remission than patients with DR3. The results support the hypothesis that insulin-dependent diabetes mellitus is a genetically heterogeneous disease.

Adolescent↗

PubMed1984

A prospective analysis of islet-cell cytotoxic antibodies in insulin-dependent diabetic children. Transient effects of plasmapheresis.

We determined the effects of plasmapheresis on cytotoxic antibodies to islet cells in 10 children (aged 11-16 yr) with newly diagnosed insulin-dependent diabetes mellitus (IDDM), as well as the plasma levels of antibodies over the next 30 mo and their relation to serum C-peptide concentrations. Complement-dependent, antibody-mediated cytotoxicity (C'AMC) in plasma was measured in a 51Cr release assay using monolayers of the rat islet cell line RINm5F. Cytotoxic antibodies decreased in most IDDM subjects treated by plasmapheresis four times within 2 wk of diagnosis; however, the decreases were small and lasted less than 2-3 days. Thus, both before and after plasmapheresis, 7 of the 10 IDDM children were C'AMC-positive (51Cr release greater than 2 SD above mean for 13 healthy children). After 18-30 mo, only 2 of the original 7 IDDM children with C'AMC-positive plasmas were still positive, and 1 of the original 3 IDDM children without significant cytotoxicity had become positive. Meal-stimulated serum C-peptide responses, measured from diagnosis to 18-30 mo later, did not correlate with C'AMC values. We conclude that (1) plasmapheresis has only transient effects on islet-cytotoxic antibody levels in children with IDDM; (2) these antibodies decrease in most, but not all, subjects over the first 18 mo after diagnosis; and (3) the level of cytotoxic antibodies in IDDM plasma at diagnosis has no predictive effect on residual B-cell function.

Adolescent↗

PubMed1984

Determination of glucosuria, an obsolete form of self-monitoring in diabetes?

During the last few years we have got improved and cheaper test materials for blood glucose determination. Self-monitoring of blood glucose has become common and urine tests have appeared more obsolete and useless than ever. Before we abandon urine tests we wanted to compare blood and urine glucose and also evaluate the opinion of our patients. A comparison of 301 parallel blood and urine glucose determinations showed a good correlation. In only 5.0% of the samples was the blood glucose above 10 mmol/l without glucosuria and in 9.7% of the samples the blood glucose was below 10 mmol/l but still with glucose in the parallel urine test. Anonymous questionnaires were answered by 94 juvenile diabetics aged between 7-25 yr. Carelessness or "cheating" had sometimes occurred in 10-20% of them. An overwhelming majority preferred daily urine test and a sporadic blood test to regular blood glucose monitoring. Urine tests seem to have a place together with blood glucose determinations in the management of juvenile diabetes.

Adolescent↗

PubMed1983

HLA-D region beta-chain DNA endonuclease fragments differ between HLA-DR identical healthy and insulin-dependent diabetic individuals.

The human HLA-D histocompatibility region encodes class II antigens each of which consists of two polypeptide chains (alpha and beta) inserted in the plasma membrane. These molecules are implicated in the regulation of the immune response but several human diseases are also found to be associated with certain HLA-DR antigens. The occurrence of insulin-dependent (type I) diabetes (IDDM) is strongly associated with HLA-DR3 and/or 4 (ref. 5). The class II antigens, however, show a marked genetic polymorphism associated with the beta-chains which seem, from hybridization studies, to be encoded by several genes. We have therefore used the beta-chain cDNA probe, pDR-beta-1 (refs 8, 10) to test whether there are differences in hybridization pattern between DNA from healthy individuals and diabetic patients, after digestion with restriction endonucleases. Among the HLA-DR 4 and 3/4 individuals, the IDDM patients showed an increased frequency of a PstI 18 kilobase (kb) fragment. A BamHI 3.7 kb fragment, frequent among controls (30-40%), was rarely detected in the IDDM patients (0-2%). These differences may be related to susceptibility to develop the disease.

DNA Restriction Enzymes↗

PubMed1983

Plasmapheresis in the initial treatment of insulin-dependent diabetes mellitus in children.

Several factors indicate that autoimmune mechanisms may play a part in the aetiology of insulin-dependent diabetes mellitus. At the onset of the disease in 10 children (aged 11-16 years) plasmapheresis was performed four times over one to two weeks. Seventeen age-matched children with the same clinical features served as controls. The C-peptide concentrations at onset were the same in the two groups, but after one month the children treated with plasmapheresis had significantly higher values. This difference became even more pronounced after three, nine, and 18 months, both during fasting and at the maximum response to a standardised meal. The study group also had a significantly more stable metabolism, longer partial remission, and no higher insulin requirement. Of the 10 treated children islet-cell cytoplasmic antibodies were present in seven before plasmapheresis and in nine during treatment. The antibodies remained detectable in five and six out of nine patients at one and six months respectively after plasmapheresis. Although the mechanisms are obscure, plasmapheresis performed at the onset of insulin-dependent diabetes mellitus may help to preserve beta-cell function.

Adolescent↗

PubMed1983

Haptoglobin concentrations in children aged 9-10 years and its correlation to indirect parameters of erythrocyte turnover.

Low serum haptoglobin values are often found in children. Nine different parameters were studied in 125 healthy children aged 9-10 years to get indirect information on erythrocyte turnover and its possible relation to the low mean plasma haptoglobin level in childhood. The mean LD activity was higher than in adults. The mean carboxyhaemoglobin per cent saturation (COHb %) and the mean serum haptoglobin concentrations were lower than in adults. No significant correlation was found between serum haptoglobin and serum iron, serum bilirubin and COHb %. Significant correlation at low r-values was found between serum iron, serum bilirubin and COHb %. The low serum haptoglobin levels often seen in children seemed not to be caused by an increase in erythrocyte turnover.

Adolescent↗

PubMed1983

Methodological aspects on C-peptide measurements.

It is rather difficult to draw conclusions from reported C-peptide values, as the methods for determination differ, and C-peptide may be measured in serum or in urine with the patient fasting or after stimulation. We have followed prospectively 49 children with IDDM with regular determinations of serum C-peptide fasting and after a standardized breakfast. A subgroup of seven patients have been studied more thoroughly with 24-hour-profile of serum C-peptide, C-peptide excretion in urine, and stimulation by i.v. glucose + i.v. arginine. Our results indicate that the stimulation of the beta cells usually reaches a maximum around a blood glucose level of 10-12 mmol/l leading to a curve linear relationship between serum C-peptide and blood glucose. Thus a simple quotient is not so useful but the degree of stimulation should be stated and actual blood glucose value noticed. Stimulation with a standardized breakfast gives roughly the same information as maximal stimulation with i.v. glucose + arginine, and little extra information is found by a 24-hour-profile. Urinary C-peptide may give valuable information if it is related to the actual degree of metabolic balance. It can be of special interest in patients with very low serum C-peptide levels.

Adolescent↗

PubMed1983

Prospective and retrospective studies of zinc concentrations in serum, blood clots, hair and urine in young patients with insulin-dependent diabetes mellitus.

Two main diabetic groups were investigated, viz, one consisting of 19 diabetic children with newly diagnosed insulin-dependent diabetes mellitus (IDDM) (median age 10 years) where a prospective study was made, and one where a retrospective examination was performed of 73 patients (median age 14 years) with a mean duration of IDDM of 7 years; 83 healthy school children (median age 13 years) served as controls. In both groups of diabetic children more zinc was excreted in the urine than in the controls. At onset of IDDM, serum and blood clot zinc concentrations were reduced with a gradual increase towards normal within 1 month of insulin therapy. The zinc concentrations in hair did not differ from those of the controls. No correlation were found between zinc levels in serum, blood clots, urine and hair on one hand and the concentrations of albumin and glucose in serum and urine on the other.

Adolescent↗

PubMed1983

Immunoglobulin from insulin-dependent diabetic children inhibits glucose-induced insulin release.

Immunoglobulin was separated from islet cell antibody positive plasma of six children with newly diagnosed insulin-dependent (type I) diabetes mellitus. The dynamics of insulin release in response to glucose and partially purified antibodies were determined in dispersed rat islet cells perifused on small columns of Biogel P-2 beads. After perifusion at 5.5 mmol/L D-glucose in the presence of healthy control immunoglobulin, the rate of insulin release increased in a biphasic manner after stimulation with 30 mmol/L D-glucose. In cells exposed to diabetic immunoglobulin, 30 mmol/L D-glucose had little, if any, effect on insulin release. These results suggest that islet cell antibodies in insulin-dependent diabetes may interfere with the insulin release mechanisms in the pancreatic B-cells.

Adolescent↗

PubMed1983

Blood carboxyhaemoglobin per cent saturation in children.

The carboxyhaemoglobin per cent saturation (COHb %) was determined in healthy non-smoking subjects, aged 5-37 years, in order to establish age-dependent reference values for COHb %. A gas chromatographic method using gaseous carbon monoxide (CO) as a standard was used to determine the CO content in blood. The mean COHb % for children below 15 years of age was significantly lower than for older children and adult men. The mean COHb % of children, aged 15-16 years, was significantly increased compared to adult men.

Adolescent↗

PubMed1982

Plasma and urine carnitine in children with diabetes mellitus.

L-Carnitine is essential for the transport of long chain fatty acids into mitochondria and, hence, in ketoacid production. Total, free and acylcarnitine in plasma and urine have been determined in 52 children and adolescents with insulin-dependent juvenile diabetes and compared with 72 controls. The subjects were divided into three age groups 8-10, 11-15 and 16-20 years. The plasma, total and free carnitine were significantly lower in diabetic patients than in controls in all age groups. Acylcarnitine was significantly higher in the diabetic patients than in the controls in the two younger age groups. No sex-related differences in plasma carnitine and its derivatives were found in the two younger groups. A statistically significant correlation coefficient was noted between glycosylated hemoglobin and the plasma acyl/free carnitine ratio, 2 p less than 0.05. The daily urinary excretion and renal clearance of carnitine and its derivatives showed few significant differences between the diabetic and the control subjects.

Adolescent↗