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Biomedical subjects

M L Larsen

Publications and source records attributed to M L Larsen.

At least 55 records · Page 3Linked to original sources

Association of IDDM and attenuated response of 2',5'-oligoadenylate synthetase to yellow fever vaccine.

Basal and yellow fever vaccination-induced 2',5'-oligoadenylate synthetase (2',5'A) activity was determined in blood mononuclear cells (peripheral blood lymphocytes [PBLs]) from insulin-dependent diabetes mellitus (IDDM) and matched control subjects. The live attenuated yellow fever vaccine represented a primary stimulus in all subjects. First, basal 2',5'A activity increased severalfold in response to yellow fever vaccination. In IDDM subjects, this increase was significantly lower (P = .025). Second, the 2',5'A activity increased proportionately to the higher basal 2',5'A activity in IDDM subjects. In control subjects, the increase in 2',5'A activity was not dependent on the basal activity. There was no relationship between basal or stimulated 2',5'A activity and age, sex, duration of IDDM, age at onset of IDDM, metabolic control, or HLA-DQ beta-chain gene polymorphism. There is a direct relationship between 2',5'A activity and latent viral infections associated with the presence of double-stranded RNA and with cellular interferons (IFNs) formed in response to viral infections. The higher basal 2',5'A activity (P = .05) in relation to the stimulated activity may therefore signify a latent infection or the presence of double-stranded RNA in PBLs of IDDM subjects. In vitro stimulation of PBLs showed increased IFN sensitivity in IDDM subjects. Analysis of 2',5'A activity is proposed to be a sensitive measure of the activation of the IFN system and the level of latent infectivity.

2',5'-Oligoadenylate Synthetase↗

Metabolic evaluation of non-insulin-dependent diabetes in primary health care--the clinical usefulness of glycated haemoglobin measurements.

To evaluate the clinical usefulness of measurements of glycated haemoglobin in the assessment of metabolic regulation in non-insulin-dependent diabetes mellitus (NIDDM) in primary health care, measurements of glycated haemoglobin, HbA1c, were compared with postprandial blood glucose measurements. 120 consecutive patients with NIDDM, following the routine control by their general practitioners, were offered a measurement of HbA1c. Approximately two-thirds of the patients had HbA1c values above the acceptable level, despite postprandial blood glucose values within the recommended intervals of good and acceptable metabolic control. Blood glucose values above 10.0 mmol/l, indicating poor metabolic regulation, were reflected in high HbA1c values. Measurements of HbA1c provide an index of metabolic regulation over time, which is otherwise not obtainable in the usual clinical setting, and HbA1c should be measured regularly to evaluate long-term metabolic control and the need for intensified therapy in patients with NIDDM.

Adult↗

The utility of glycated hemoglobin in identification of impaired glucose tolerance.

The purpose of this study was to investigate the ability of measurements of glycated hemoglobin HbAlc by a highly precise method to characterize impaired glucose tolerance (IGT). HbAlc was measured by an isoelectric focusing method (CV = 2.1% using mean of duplicates) in 100 consecutive persons referred to the laboratory by their general practitioners for an oral glucose tolerance test (OGTT) because of random blood glucose measurements within the uncertain range or positive urine tests for glucose. The patients were classified according to the most recent World Health Organization criteria in normals (n = 64), persons with IGT (n = 27) and diabetics (n = 9). HbAlc in persons with IGT was significantly higher (p less than 0.001) than in normals. It was possible to calculate a reference interval of IGT from 5.6-7.5% (mean +/- 2SD), but a considerable overlap with the reference interval of non-diabetics (5.2-6.8%) make measurements of HbAlc insufficient for diagnosis of IGT. Poor correlation was seen between plasma glucose measurements and HbAlc in persons with normal OGTT and IGT (r = 0.3). The question is, whether measurements of HbAlc provides additional information in IGT, identifying those with highest mean blood glucose concentrations in daily life, thereby being of value in itself in evaluation of glucose tolerance.

Adult↗

Heparin induces release of extrinsic coagulation pathway inhibitor (EPI).

Extrinsic pathway inhibitor (EPI) is a potent inhibitor of the factor VIIa-tissue thromboplastin complex. The effect of heparin on EPI activity was studied using a chromogenic substrate assay. Addition of heparin to test plasma or whole blood in vitro increased EPI activity. This increase in EPI activity was reduced by the addition of polybrene and/or antibodies to antithrombin (anti-AT). Polybrene was therefore added to the assay system. However, part of this effect (up to 20% of baseline value) was not abolished. After intravenous injection, EPI activity increased dose-dependently. The increase was about 200% of baseline value after 7500 U heparin, and was not reduced by the addition of polybrene and/or anti-AT. A slower and prolonged increase in EPI activity occurred after subcutaneous injections of unfractionated heparin and low molecular weight heparin (LMWH). Venous occlusion failed to increase EPI activity levels. Normal EPI values were observed in patients with severe liver cirrhosis and during warfarin treatment. Gel filtration of human endothelial cell culture supernatant revealed one inhibitory fraction with molecular weight about 43.000. We conclude that EPI probably is produced in endothelial cells and may be released by heparin.

Antithrombins↗

Heparin cofactor II, antithrombin and protein C in plasma from term and preterm infants.

The coagulation inhibitors heparin cofactor II (HC II), antithrombin (AT) and protein C (PC) were measured in healthy term and preterm infants in order to establish reference standards. The mean value for HC II in term infants was found to be about half of the adult values. Values below 25% in healthy infants may suggest hereditary deficiency states. One girl with congenital HC II deficiency was detected. Mean AT and PC levels were somewhat higher than HC II. Healthy preterm infants have significantly lower HC II and AT values than healthy term infants. Serial AT measurements have been used in monitoring seriously ill infants and used as a prognostic indicator. In a small number of unhealthy neonates HC II was reduced to an even greater extent than AT, and on recovery normalized more rapidly than AT.

Antithrombins↗

ELISA analysis of IgA subclass antibodies to dietary antigens. Elevated IgA1 antibodies in children with coeliac disease.

Enzyme immunoassays for the quantitation of IgA1 and IgA2 antibodies to dietary antigens were developed. Serum IgA1 antibodies to bovine serum albumin (BSA) were detectable in 2/30 healthy adults, in 3/26 healthy children, and at high levels in 8/11 children with coeliac disease, without relation to gluten exposure. IgA1 antibodies to ovalbumin (OA) and beta-lactoglobulin (BLG) at high titers were seen in one coeliac child but were otherwise low or absent. IgA2 antibodies to BSA were detectable in 28/48 healthy subjects and in 8/11 coeliac children. IgA2 antibodies to OA and BLG were measurable in a few samples from each group. IgA1 antibodies to the gluten component glycgli were found at low levels in 15/56 normal sera, and anti-glycgli antibodies of the IgA2 subclass in 14/48 sera from healthy persons, also at low levels. IgA1 anti-glycgli antibodies were measurable in 5/11 sera from CD patients on a gluten-free diet. Elevated levels of IgA1 anti-glycgli antibodies were detected in all sera from CD patients challenged with gluten, except in 1 patient with a markedly reduced serum IgA level. In contrast, the IgA2 anti-glycgli antibody levels were unaffected. Thus, increased levels of IgA antibodies to dietary protein antigens in childhood coeliac disease were observed only within the IgA1 isotype.

Adolescent↗

Acyclovir crystalluria.

Acyclovir crystals in the urine of a 28-year-old woman are described. The patient received intravenous acyclovir for herpes encephalitis. The crystalluria was accompanied by impairment of the renal tubules as evidenced by increased urinary beta-2-microglobulin excretion. Consecutive series of 60 patients on oral acyclovir and 20 patients on intravenous acyclovir were studied in order to define the frequency of acyclovir crystalluria. None of the patients studied had crystalluria, and none elevated serum creatinine levels. It is suggested that acyclovir crystalluria might be an early sign of acyclovir crystal nephropathy.

Acyclovir↗

Liver transplantation in a 48-year-old female with primary biliary cirrhosis.

In 1983, a Danish female with primary biliary cirrhosis underwent orthotopic liver transplantation (OLT). The transplantation took place in Groningen under a Danish-Dutch cooperation, at this writing, and more than four years after transplantation, the patient is still alive. The quality of her life has been dramatically improved, making possible her return to work. Liver tests, liver function, and biopsies are normal and without signs of development of primary biliary cirrhosis in the transplanted liver. Liver transplantation is now frequently performed at several centres throughout the world with an increasing success rate. In Scandinavia, centres have been established in Norway, Finland, and Sweden, whereas in Denmark the organisation of a programme for liver transplantation is still being discussed. Because of the extremely high costs, liver transplantation has to be approved medically and politically, and the brain death criteria have to be accepted before it can be considered as a generally accepted modality of treatment.

Female↗

Monitoring of heparin therapy: should heparin assays also reflect the patient's antithrombin concentration?

Chromogenic substrate (CS) assay of heparin may be performed with or without addition of antithrombin (AT) to the test plasma. Both types of assay are used for monitoring of heparin therapy, reflecting either heparin activity (heparin act), or heparin concentration (heparin conc) when AT is added. In plasma samples from 43 patients treated with intravenous heparin for DVT, the ratio between heparin act and heparin conc varied from 0.36 in patients with AT plasma concentration below 0.50 U/ml, to 0.85 in patients with AT above 1.00 U/ml (mean ratio 0.61). A formula expressing heparin act as a function of AT and heparin concentration in the test plasmas of the patients was used to calculate heparin act of the total material comprising 280 patients. Mean heparin act and heparin conc were both significantly correlated to clinical outcomes (bleeding complications, pulmonary embolism and phlebography score). For monitoring heparin therapy, guidelines for plasma heparin activity or concentration ("therapeutic ranges") are requested. When using a heparin act assay, the heparin dose needed in patients with low plasma AT concentration to reach a fixed therapeutic range, may imply undue risk of bleeding. On the other hand, when a heparin conc assay indicate plasma heparin conc within therapeutic range, antithrombotic activity may still be inadequate in patients with low plasma AT concentration.

Antithrombins↗

Effects of cisapride on gastroparesis in patients with insulin-dependent diabetes mellitus. A double-blind controlled trial.

Fourteen insulin-dependent diabetics with symptoms and signs of delayed gastric emptying were treated with a new prokinetic agent, cisapride. In a placebo-controlled cross-over trial no significant differences from placebo was found regarding overall symptomatic effects and effects on gastric emptying of a mixed solid/liquid isotope marked test meal. Solid emptying was most markedly delayed in diabetics compared with healthy controls, but the emptying rate was not correlated to the severity of symptoms as observed for liquid emptying. During active treatment with cisapride the amelioration of symptoms was correlated to increased emptying rates assessed by combined measure of liquid/solid gastric emptying.

Cisapride↗

Plasma heparin cofactor II, protein C and antithrombin in elective surgery.

The coagulation inhibitors heparin cofactor II (HC II), protein C (PC) and antithrombin (AT) were measured in 14 patients undergoing uncomplicated abdominal, orthopedic or vascular surgery. Marked transient decrease of all the inhibitors was found after all surgical procedures, most prominently in vascular surgery. The greatest mean reduction was in HC II. The fall in PC and AT showed a pattern similar to that of albumin. In contrast to some earlier suggestions our results indicated that, except for HC II, the reduction probably was not due to consumption. Redistribution, hemodilution and, probably, reduced synthesis were the most important contributing factors. Serial measurements of the three coagulation inhibitors may be of prognostic value, but the present study's observed mean decrease of c. 25% in abdominal and 50-62% in vascular surgery must be borne in mind. Still lower inhibitor levels suggest consumption and a complicated postoperative course.

Adult↗