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Biomedical subjects

U Abildgaard

Publications and source records attributed to U Abildgaard.

At least 55 records · Page 3Linked to original sources
PubMed1994

Microheterogeneity of antithrombin III: effect of single amino acid substitutions and relationship with functional abnormalities.

Microheterogeneity of antithrombin III (AT-III) was investigated by crossed immunoelectrofocusing (CIEF) on eleven molecular variants. A normal pattern was found in five variants while two different abnormal CIEF patterns were found in the other four and two variants, respectively. Point mutations causing a major pI change (exceeding 4.0) of the amino acid substituted lead to alterations in the overall microheterogeneity. The variants thus substituted share a first type of abnormal CIEF pattern with alterations throughout the pH range, regardless of the location of the mutation (reactive site and adjacent regions or heparin binding region). Minor amino acid pI changes in these regions do not alter the AT-III overall microheterogeneity, whatever the resulting functional defect. However, if the mutation is placed in the region around positions 404 or 429, then even minor changes of the amino acid pI seem able to alter the overall charge, leading to a second type of abnormal CIEF pattern with the main alteration at pH 4.8-4.6. Neuraminidase treatment leads to disappearance of microheterogeneity except for the variants with the Arg393 to Cys substitution. Addition of thrombin induces CIEF modifications specifically related to the functional defect. A normal formation of thrombin-antithrombin complexes induces a shift towards the more acid pH range, whereas in the variants substituted at the reactive site the CIEF pattern is substantially unaffected by thrombin; variants substituted at positions 382-384 show a maximal thrombin-induced increase of the isoforms at pI 4.8-4.6. Therefore mutant antithrombins with different functional abnormalities but sharing a common CIEF pattern were well distinguished.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1993

[Coma from cerebral and metabolic causes].

The medical causes of coma fall into two main categories: intercranial diseases, and metabolic disturbances. The clinical examination should define 1) vital functions, 2) depth of coma, 3) whether cerebral signs are diffuse or local, 4) any signs of organ disease. The blood sugar level must be determined. Hypoglycemia may be the cause even if the signs point to another cause. Head injury and intoxication/poisoning must always be considered, even if a medical cause is suspected. Prolonged coma calls for repeated clinical and laboratory examination. Combinations of causes, e.g. organ disease plus intoxication should be considered.

Brain Diseases↗
PubMed1993

Increased plasma thrombomodulin in cancer patients.

Plasma samples from 35 patients with colorectal cancer, 16 patients with pancreatic cancer and 46 patients with various cancers in the terminal stage were analysed for soluble plasma thrombomodulin with an ELISA method. At time of diagnosis and before primary treatment, the patients with colorectal cancer had normal plasma TM levels. In the patients who developed disseminated disease, the mean plasma TM level increased significantly. In the patients with pancreatic cancer, the mean plasma TM level was increased already at time of primary treatment. The TM level increased further with progress of the pancreatic cancer. In the patients with various cancer types in the terminal stage, the mean TM was also significantly increased compared to healthy controls. Great individual variation in the plasma TM level was observed, as well as great variation of mean TM level between the various cancer types. There was no significant correlation between the TM levels and the levels of tissue factor pathway inhibitor, another endothelial coagulation inhibitor, which increased with progress of malignant disease. This may indicate different underlying mechanisms for the increased plasma levels.

Adenocarcinoma↗
PubMed1993

[Transesophageal echocardiography and endocarditis].

In 49 patients (34 men and 15 women with an average age of 51 years, range 21-81 years) with a total of 51 episodes of suspected or already demonstrated endocarditis, the diagnostic and therapeutic value of transthoracic echocardiography (TTE) was compared with transoesophageal echocardiography (TEE). It was demonstrated by operation, autopsy, or the course of the condition, that endocarditis was present in 34 cases, while 17 patients did not have endocarditis. The correct diagnosis was established in 19 out 51 cases (37%) by TTE and in 44 (85%) cases by TEE (p < 0.05). The number of ambiguous investigation results fell significantly from 30 (58%) with TTE to seven with TEE. A total of 14 cases of cavity formation related to endocarditis, rupture of fistulae, or perivalvular leakage from prostheses occurred. Three (21%) of these complications were demonstrated by TTE while TEE demonstrated all 14. After examination with TEE, treatment of the patients was changed in 20 cases (39%). It is concluded that: 1) TEE can confirm or exclude the diagnosis of endocarditis with much greater certainty than TTE, 2) TEE more than halves the number of ambiguous results of investigation and 3) TEE multiplies recognition of complications of endocarditis. Even although the results from the cardiological/thoracic surgical centre cannot be transferred to the primary hospital just like that, the results of these and other investigations suggest that TEE should be carried out when TTE cannot confirm or exclude clinically suspected endocarditis with certainty.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Adverse effect of warfarin in acute myocardial infarction: increased left ventricular thrombus formation in patients not treated with high-dose heparin.

In a prospective non-randomized study, 229 patients with a verified first acute anterior myocardial infarction (AAMI) underwent echocardiography before discharge in order to study left ventricular (LV) thrombus formation. Antithrombotic therapy was given according to the routine of each centre. Patients receiving high-dose heparin had few LV thrombi, irrespective of warfarin therapy (6/32 vs 3/25, P ns). In patients not given heparin, however, a significantly higher prevalence of LV thrombi was found in a subgroup of patients treated with warfarin as compared to those who did not receive warfarin (8/13 vs 17/68, P 0.02). A similar, but non-significant difference was observed in patients given low-dose heparin (42% vs 27%, P ns). Within the non-heparin and low-dose heparin groups, age, infarct size, occurrence of Q-wave infarction, congestive heart failure and LV wall motion impairment did not differ between those treated or not treated with warfarin. In conclusion, high-dose heparin seems effective in the prevention of LV thrombosis irrespective of warfarin therapy after AAMI. The start of warfarin therapy in patients not receiving heparin was, however, associated with an increased prevalence of LV thrombosis.

Administration, Oral↗
PubMed1993

Identification of nine novel mutations in type I antithrombin deficiency by heteroduplex screening.

We have utilized DNA heteroduplex detection as a method for screening sequences of the antithrombin (AT) gene for the presence of mutations. Affected individuals from 41 kindreds with type Ia antithrombin deficiency were investigated. Heteroduplexes were detected in 12 cases; direct sequencing of the appropriate exons revealed nine cases with novel mutations, and two with previously described mutations. In addition, a new polymorphism in the 5' untranslated region was characterized. The defects included minor insertions and deletions which lead to the removal of intact codons or premature termination, and single base substitutions leading to premature termination or amino acid substitution. In all cases, the affected individuals were heterozygous for the defect and variant AT protein was not detected. In keeping with previous reports the defects associated with type Ia AT deficiency are extremely heterogeneous, the vast majority being point mutations. This study also demonstrates the efficiency of hydrolink gel electrophoresis as a method of screening for unknown mutations by heteroduplex detection.

Antithrombins↗
PubMed1993

Deep vein thrombosis: a 7-year follow-up study.

OBJECTIVES: To study the sequelae of deep venous thrombosis (DVT) in terms of symptoms and objective signs of deep venous insufficiency (DVI) and their relationship to the initial extension of DVT, and to assess the control legs in the same way. DESIGN: Follow-up study after an average of 89 (range 79-102) months. SETTING: Out-patient clinic, University Hospital, Oslo. SUBJECTS: Seventy-six patients with DVT 7 years previously. At follow-up 41 patients were dead and 10 were not available for restudy, thus twenty-five patients were studied in all. MAIN OUTCOME MEASURES: Symptom rating. Objective verification of DVI by invasive pressure recordings (DVI-I) and by the Doppler ultrasound technique (DVI-D). RESULTS: At follow-up, 42% of the patients had symptoms, half of these severe, while 68% had DVI. Eighty-two per cent of symptomatic patients and 60% of the asymptomatic patients had DVI. There were no more symptoms in proximal than in distal DVT, but slightly more DVI. Control legs had neither symptoms nor DVI. CONCLUSIONS: Seven years after DVT few patients had severe symptoms, although objective signs of DVI were common. Symptoms were no more frequent after proximal than after distal DVT. We found no symptoms or DVI in control legs.

Aged↗
PubMed1993

Heparin/low molecular weight heparin and tissue factor pathway inhibitor.

Tissue factor pathway inhibitor (TFPI) is the factor Xa (FXa)-dependent coagulation inhibitor. TFPI is released to the blood after injection of heparin or low molecular weight heparin (LMWH). The post-heparin anticoagulant effect is caused by this release of TFPI. Free TFPI has higher affinity for heparin than TFPI which is associated with lipoproteins. Heparin increases the rate of inactivation of FXa and of tissue factor-F VIIa by TFPI. Immunoblocking of TFPI reduces the anticoagulant effect of heparin in blood activated by tissue factor considerably. Both antithrombin and TFPI participate in the anticoagulant effect induced by heparinization of blood or plasma.

Blood Coagulation↗
PubMed1992

Effect of tissue factor pathway inhibitor (TFPI) in the HEPTEST assay and in an amidolytic anti factor Xa assay for LMW heparin.

Both the HEPTEST and amidolytic anti factor Xa assays are currently being used for heparin activity detection in plasma from patients receiving standard heparin or low molecular weight heparin (LMWH). In this study we have investigated the influence of recombinant and endogenous Tissue Factor Pathway Inhibitor (TFPI) on these assays. The HEPTEST determinations were performed on an ACL 300 R Clottimer using the APTT program which resulted in a longer incubation time with factor Xa than recommended by the manufacturer. rTFPI added to plasma prolonged the HEPTEST clotting time markedly, but had only a little effect in the amidolytic assay. Antibodies against TFPI (anti-TFPI) abolished these effects. The effect of adding rTFPI and Logiparin was additive. When anti-TFPI IgG was added to samples of normal plasma, a statistically significant shortening of the HEPTEST clotting time was seen. When anti-TFPI was added to plasma samples from volunteers who had received Logiparin by subcutaneous or intravenous injection, then the HEPTEST clotting time was shortened considerably. For some samples the clotting time was halved. These experiments show that the HEPTEST clotting time is prolonged not only by heparin-antithrombin III, but also by TFPI released by heparin injection.

Amides↗
PubMed1992

[A cerebrovascular unit. Experiences after 8-years of activity].

The authors review experience gained from developing and running a non-intensive stroke unit during the years 1983-91. The number of patients treated per year has increased from 65 to 149. The average length of stay in hospital has dropped from 21 to 15 days. About 87% of the patients had verified stroke, 7% had transient ischemic attacks (TIAs). Other intracranial diseases were found in 3.3%. The mortality rate was low (5%) 48% of the patients were transferred to a rehabilitation centre, 37% were discharged to their homes, with or without out-patient care, and 10% were discharged to nursing homes. Early and systematic investigations and multi-disciplinary rehabilitation in a specialized stroke unit increases the quality of care for patients suffering from stroke. A shorter stay in hospital gives a bonus in the form of reduced health expenditures.

Cerebral Hemorrhage↗
PubMed1992

Elevated levels of thrombin-heparin cofactor II complex in plasma from patients with disseminated intravascular coagulation.

An ELISA assay for quantitation of the thrombin-heparin cofactor II complex (T-HC II) in plasma was developed. Plasma was incubated with immobilized, specific antibodies to human thrombin. The second, biotinylated antibody was directed against human HC II. The assay was insensitive to thrombin-antithrombin complex (TAT) and to uncomplexed HC II. In plasma samples from 31 normal individuals (aged 21-68, mean 43.3 years), the T-HC II ranged 0.3-6.1 ng/ml; median 1.5, mean 2.0, and SD 1.6 ng/ml. In plasma samples from 13 patients with disseminated intravascular coagulation (DIC), T-HC II ranged 0.4-30.0 (median 13.5) ng/ml. In plasma samples from 6 patients in which the clinical suspicion of DIC was not verified, T-HC II complex ranged 1.4-14.3 (median 3.6) ng/ml. In plasma samples with elevated T-HC II levels, TAT was usually elevated, and on the average more than was T-HC II. These results indicate that HC II contributes significantly to the inactivation of in vivo generated thrombin.

Adolescent↗
PubMed1992

Renal effects of alpha-adrenoceptor blockade during furosemide diuresis in conscious rats.

Clearance experiments were performed in conscious rats in order to investigate whether intravenous infusion of the non-selective alpha-adrenoceptor antagonist phentolamine could block compensatory sodium reabsorption during furosemide-induced volume contraction. By measuring inulin clearance, urinary excretion rates of sodium and water, and lithium clearance, the effects on proximal and distal nephron segments were dissociated. The renal effect of intravenous infusion of 0.3 mg/kg/hr phentolamine (n = 6) was compared with time control animals (n = 9). Furosemide was administered as constant intravenous infusion (7.5 mg/kg/hr) with simultaneous phentolamine infusion at four dose levels: 0 (n = 9), 0.3 (n = 6), 1.0 (n = 7) and 3.0 mg/kg/hr (n = 6). Phentolamine infusion reduced norepinephrine-induced increase in blood pressure at all three dose levels (n = 5). Phentolamine infusion induced transient antidiuresis and a prolonged antinatriuretic response. Compared with rats given furosemide only, phentolamine attenuated dose-dependently the diuretic and natriuretic peak response to furosemide. This effect was associated with dose-dependent reductions in mean arterial pressure. The reduced natriuretic response was due to a reduced fractional sodium excretion in the distal nephron segment (at all doses of phentolamine) and a reduction of the glomerular filtration rate (1.0 and 3.0 mg/kg/hr phentolamine). The fractional lithium excretion (FELi) increased to 65 +/- 3% at 0.3 mg/kg/hr phentolamine during the natriuretic peak response of furosemide, while it only increased to 52 +/- 3% during furosemide alone. At steady-state conditions (120-180 min. after start of furosemide infusion) after infusion with furosemide plus 0.3 mg/kg/hr phentolamine the animals were still volume-depleted, but the compensatory tubular Na reabsorption in the proximal tubules was inhibited (FELi = 48 +/- 2% versus 39 +/- 1% in rats given furosemide alone). During furosemide infusion plasma epinephrine increased 700% and plasma norepinephrine increased 50%. These results are compatible with increased systemic sympathetic nervous activity and a contributory role of proximal tubular alpha-adrenoceptors in mediating compensatory sodium reabsorption during acute furosemide-induced volume contraction.

Adrenergic alpha-Antagonists↗
PubMed1992

Pleiotropic effects of antithrombin strand 1C substitution mutations.

Six different substitution mutations were identified in four different amino acid residues of antithrombin strand 1C and the polypeptide leading into strand 4B (F402S, F402C, F402L, A404T, N405K, and P407T), and are responsible for functional antithrombin deficiency in seven independently ascertained kindreds (Rosny, Torino, Maisons-Laffitte, Paris 3, La Rochelle, Budapest 5, and Oslo) affected by venous thromboembolic disease. In all seven families, variant antithrombins with heparin-binding abnormalities were detected by crossed immunoelectrophoresis, and in six of the kindreds there was a reduced antigen concentration of plasma antithrombin. Two of the variant antithrombins, Rosny and Torino, were purified by heparin-Sepharose and immunoaffinity chromatography, and shown to have greatly reduced heparin cofactor and progressive inhibitor activities in vitro. The defective interactions of these mutants with thrombin may result from proximity of s1C to the reactive site, while reduced circulating levels may be related to s1C proximity to highly conserved internal beta strands, which contain elements proposed to influence serpin turnover and intracellular degradation. In contrast, s1C is spatially distant to the positively charged surface which forms the heparin binding site of antithrombin; altered heparin binding properties of s1C variants may therefore reflect conformational linkage between the reactive site and heparin binding regions of the molecule. This work demonstrates that point mutations in and immediately adjacent to strand 1C have multiple, or pleiotropic, effects on this serpin, leading ultimately to failure of its regulatory function.

Adolescent↗
PubMed1992

Comparison of low molecular weight heparin vs. unfractionated heparin in gynecological surgery. II: Reduced dose of low molecular weight heparin.

In a double blind, randomized trial the hemorrhagic complications of a reduced dose of low molecular weight heparin (LMWH) (Fragmin, KabiPharmacia) were compared to those of the conventional dose of unfractionated heparin (UH). 2500 anti-XaU of LMWH was given once daily and UH in a dose of 5000 anti-XaU twice daily. During a one year period 141 patients undergoing gynecological surgery were included in this study. The patients were examined clinically for hematomas and for deep venous thrombosis (DVT) on the third and fifth day. Venography was performed when DVT was suspected. No patients developed clinical DVT. One woman in the LMWH group had pulmonary embolism 3 days after the prophylaxis was stopped. Two women in the LMWH group died, one from a stroke on day 2, one from cancer on day 39. There was no significant difference in serious bleeding complications between the two regimens, 20% in the LMWH group and 14% in the UH group. Even with the reduced dose of LMWH the mean plasma concentration of heparin in the LMWH group was higher (mean 0.14 anti-XaU/ml) than in the UH group (0.029 anti-XaU/ml) 3 hours after injection on the 2nd postoperative day. A reduced dose of LMWH (2500 anti XaU once daily) does not cause more bleeding complications than the conventional heparin regimen to prevent thrombosis, as was the case in our previous study with 5000 anti XaU of LMWH once daily.

Double-Blind Method↗