Search

1 Pethidine is commonly used in single doses as an analgesic in obstetrics. Plasma concentration-time profiles of pethidine after intramuscular administration of 1.5 mg/kg body weight to 16 pregnant women during labour were investigated. There was only a two-fold variation in peak plasma concentration (300-650 ng/ml). The mean (+/- s.d.) value of the apparent plasma half-life of pethidine was 3.4 (+/- 1.0) h which is not different from that in healthy controls. norpethidine plasma levels were not measurable (less than 10 ng/ml). 2 The placental transfer transfer of pethidine was studied at delivery in samples from the umbilical cord vessels and from a maternal peripheral vein. In another 14 patients serial determinations of pethidine concentration were made in foetal scalp blood and maternal venous blood simultaneously during the different stages of labour. The foeto- maternal drug ratio varied between 0.35 and 1.5 with a positive correlation between ratio and dose delivery time interval. The concentration of pethidine in umbilical cord plasma or blood varied between 60 and 400 ng/ml with dose-delivery time intervals of 30 min to 10.5 h. The foetal concentration of pethidine reached a peak-plateau value between 1-5 h after dose. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.

SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.

In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.

Lumbar epiduval analgesia with bupivacaine was given to 37 women for uncomplicated labor. After the blcokade serial determinations of pH and bupivacaine concentration were made in fetal scalp blood and maternal venous blood and there was continuous monitoring of the fetal heart rate. Fetal scalp blood pH was within normal limits and no pathologic FHR tracings were elicited by the blockade, although a temporary decrease of the baseline fetal heart rate irregularity was seen in about one-fifth of the cases. Fetal drug concentrations were low and about one-fourth of corresponding maternal values. After reinjection of bupivacaine the degree of drug accumulation was fairly similar in fetal and maternal blood.

Administration of prostaglandin synthetase inhibitors to pregnant does and dams in late gestation was followed by in utero contraction of the fetal ductus arteriosus when studied by the whole-body freezing method. In the rat this contraction was well established within 6 h and persisted up to 36 h following 15 mg/kg indomethacin p.o. No effect was observed in the 18 d rat fetus but fetuses at 20 d and 22 d of gestation responded significantly to indomethacin. Doses of indomethacin approaching clinical usage (2.5 mg/kg also caused a positive response in utero. The rat was found to be sensitive also to sodium salicylate and in the rabbit both indomethacin and sodium salicylate were effective. Exposure in utero to prostaglandin synthetase inhibitors with resulting contraction of the ductus may seriously disturb cardiac function in the fetus.

Lumbar epidural analgesia with bupivacaine was administered to 33 women for relief of pain during labor. At delivery blood samples were drawn from the umbilical cord vessels and from a maternal peripheral vein. Blood samples were also collected from the noenate and its mother, 1, 4, and 20 hours after delivery. Analyses of bupivaccaine concentrations were carried out in all samples with a gas-chromatographic technique. The drug concentration in the umbilical vein (UV) was usually higher than the corresponding umbilical artery value (UA), but with increasing time interval between the last bupivaccaine infection and delivery the UA/UV drug concentration ratio rose. After delivery the rate of drug decline in blood was similar in mother and newborn infant. The clinical condition of the infant was unrelated to the drug concentration in the umbilical cord vessels.

Diabetic mothers affect their offspring during pregnancy, sometimes giving rise to the complete symptoms of diabetic fetopathia with the typical appearance of the child high birth weight, hyperinsulinism, etc. Some of these traits have also been reported to appear in the infants some time before the onset of diabetes in the mother, but no prospective study of infants born to truly prediabetic mothers has yet been reported. Thus it is not possible to say whether or not the previously reported effects are related to an undetected, subclinical diabetes in the mother. A prospective study of the insulin reponse to glucose during pregnancy [9] has been previously published, which included 11 women with a low insulin response to glucose infusion (GIT) - a prediabetic type of insulin response according to the definition of Cerasi and Luft [5] - and a control group of 14 women with a high insulin response to glucose infusion. In the following the neonatal findings in these 13 infants of low insulin responders (ILR) aand 14 infants of high responders (IHR) are reported...

It has earlier been postulated that a low insulin response to a glucose infusion is characteristic for the prediabetic individual (Cerasi & Luft 1967c). There is also evidence that some infants of individuals with low insulin response might have a carbohydrate metabolism that is in some respects similar to that of newborn infants to diabetic mothers (Edström et al. 1974). In the present study 15 infants to low insulin responders (ILR) and 22 infants to high insulin responders (IHR) were subjected to an intravenous glucose load (IVGTT) at 2-24 h age. A significant difference in glucose tolerance was found between the groups, the mean k-value for the ILR being 1.39 plus or minus 0.41 and that for the IHR 1.05 plus or minus 0.09 (P smaller than 0.05). No mothers were found to have a gestational diabetes (with the possible exception of one low insulin responders) but during late pregnancy the mean k-value at IVGTT in the low responders decreased from non-pregnant values (the mean difference being 0.41 plus or minus 0.20, P smaller 0.025) while the high responders did not show a corresponding decrease (mean difference 0.12 plus or minus 0.25, P greater than 0.05). No other differences between the groups of infants that could influence the k-value could be found apart from the mothers being low or high insulin responders. Our findings show that a low insulin response in the mothers might effect the glucose tolerance of the foetus even in the absence of continuous maternal hyperglycaemia in late pregnancy.

This is the first part of a study dealing with the predicted effect of early renal function changes on later development of diabetic nephropathy. Renal function was studied by the clearance method in 128 children with insulin dependent diabetes mellitus after 0, 2, 5 and 10 years duration of the disease. The glomerular filtration rate (GFR) and filtration fraction were significantly increased after 0-5 years, but after 10 years the GFR did not differ from that of controls, which finding might indicate an earlier onset of diabetic nephropathy in children. Renal plasma flow did not differ significantly from that of controls. Increased fractional sodium excretion in cases of recent onset might indicate inadequate adaptation of the proximal tubules to the increased filtered load or to inadequate insulin therapy. An inverse correlation was found between GFR and metabolic control as evaluated clinically and by glucosylated haemoglobin concentration, i.e., poor metabolic control corresponded with high glomerular filtration rates.