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Biomedical subjects

J Gram

Publications and source records attributed to J Gram.

At least 109 records · Page 6Linked to original sources
PubMed1990

[Diarrhea acquired abroad--traveller's diarrhea. Admissions to Medical Department C, Odense Hospital, during the period 1977-1988].

A total of 106 out of 267 patients admitted with acute gastroenteritis to Medical Department C, Odense Hospital, during the period 1977-1988 had acquired the condition abroad. This group was investigated retrospectively. During the period of investigation, the number of patients with "traveller's diarrhoea" increased but compurized constantly approximately 40% of the patients admitted with acute gastroenteritis. The patients were investigated routinely for pathogenic intestinal bacteria and parasites and the etiology could be determined in 72%. Salmonella infections were found in 50% and 1/5 of these were caused by Salmonella typhi or Salmonella paratyphi. Double and triple infections occurred. 51% of the infections were acquired in Asia and Africa although less than 7% of Danish package tours visit these regions. Five patients (5%) developed serious complications.

Adult↗
PubMed1990

Enhanced effective fibrinolysis following the neutralization of heparin in open heart surgery increases the risk of post-surgical bleeding.

The tissue-type plasminogen activator related fibrinolytic system was studied in 24 patients undergoing cardiopulmonary bypass surgery. The degradation of fibrinogen and fibrin was followed during and after surgery by means of new sensitive and specific assays and the changes were related to the blood loss measured in the chest tube drain during the first 24 postoperative hours. Although tissue-type plasminogen activator was significantly released into the circulation during the period of extracorporeal circulation (p less than 0.01), constantly low levels of fibrinogen degradation products indicated that a systemic generation of plasmin could be controlled by the naturally occurring inhibitors. Following extracorporeal circulation heparin was neutralized by protamine chloride, and in relation to the subsequent generation of fibrin, there was a short period with increased concentrations of fibrinogen degradation products (p less than 0.01) and a prolonged period of degradation of cross-linked fibrin, as detected by increased concentrations of D-Dimer until 24 h after surgery (p less than 0.01). Patients with a higher than the median blood loss (520 ml) in the chest tube drain had a significantly higher increase of D-Dimer than patients with a lower than the median blood loss (p less than 0.05). We conclude that the incorporation of tissue-type plasminogen activator into fibrin and the in situ activation of plasminogen enhance local fibrinolysis, thereby increasing the risk of bleeding in patients undergoing open heart surgery.

Adult↗
PubMed1990

Enhanced generation and resolution of fibrin in women above the age of 30 years using oral contraceptives low in estrogen.

Epidemiologic studies have suggested a relationship between the use of oral contraceptives and mortality from cardiovascular diseases in older women. Therefore we studied generation and resolution of fibrin in 28 healthy women above age 30 years, using oral contraceptives containing 30 to 50 micrograms of ethinyl estradiol. Thirty healthy nonusers served as control subjects. The oral contraceptive group had increased plasma concentration of thrombin-antithrombin III complexes (p less than 0.01), which indicated an enhanced generation of thrombin, increased plasma activity of tissue-type plasminogen activator (p less than 0.01), decreased plasma activity of plasminogen activator inhibition (p less than 0.01), and increased plasma concentration of fibrin degradation products (p less than 0.04). Interestingly, the ratio of thrombin-antithrombin III complexes/fibrin degradation products did not deviate significantly between groups. Twelve of the 28 women using oral contraceptives were light smokers, that is, less than 15 cigarettes per day. There were no differences in the determined variables between smokers and nonsmokers. Our study suggests that healthy women older than 30 years who use oral contraceptives containing 30 to 50 micrograms of ethinyl estradiol have an enhanced generation and resolution of fibrin, while the hemostatic balance is unaltered. These findings are unaffected by moderate cigarette smoking.

Adult↗
PubMed1990

A depression of active tissue plasminogen activator in plasma characterizes patients with unstable angina pectoris who develop myocardial infarction.

The balance between the coagulation system generating fibrin and its subsequent removal by the fibrinolytic system determines the fate of fibrin deposited in the vascular system. In a prospective study, selected haemostatic variables assessing this balance were determined in plasma samples from 20 consecutive patients admitted with unstable angina pectoris. Over a follow-up period of 6 years, eight patients developed myocardial infarction, whereas 12 patients did not. There was no significant difference between the two groups in the median plasma concentrations of thrombin-antithrombin III complexes reflecting the coagulant activity. The infarction group was characterized by a significantly lower median activity of tissue plasminogen activator in plasma euglobulins (P less than 0.05), a higher median concentration of tissue plasminogen activator antigen in plasma (P less than 0.05) and a tendency to higher plasma levels of antigenic and functional plasminogen activator inhibition. In all patients, the activities of tissue plasminogen activator inhibitor and of tissue plasminogen activator were significantly associated (rs = -0.4811, P less than 0.05). We conclude that a depressed fibrinolytic capacity attributable to a low tissue plasminogen activator activity is of pathogenetic importance for the development of myocardial infarction in patients with unstable angina pectoris.

Aged↗
PubMed1990

Interrelationship between coagulant activity and tissue-type plasminogen activator (t-PA) system in acute ischaemic heart disease. Possible role of the endothelium.

Patients with unstable angina pectoris (UAP; n = 20) and acute myocardial infarction (AMI; n = 34) were studied in the acute phase of ischaemic heart disease. We found significantly higher levels of thrombin-antithrombin-III (TAT) complexes, lower levels of systemic tissue plasminogen activator (t-PA) activity, and higher levels of plasminogen activator inhibitor (PAI) activity in the AMI patients compared to the UAP patients. In contrast to these specific changes, general acute phase reactants such as C-reactive protein, fibrinogen and von Willebrand factor did not differ significantly between the two groups. Studies of the relationship between coagulation (TAT-complexes) and fibrinolysis data revealed a significant positive correlation between plasma antigen concentrations of TAT-complexes and t-PA (P less than 0.02), and between TAT-complexes and PAI-I (P less than 0.002). These observations indicate a common pathophysiological mechanism underlying the changes in coagulation and fibrinolysis, suggesting that coagulation activity and t-PA-related fibrinolysis are interrelated processes in vivo, and probably take place at the level of the endothelial cell.

Acute-Phase Proteins↗
PubMed1990

The effect of carbonic anhydrase inhibition on calcium and bone homeostasis in healthy postmenopausal women.

Carbonic anhydrase localized in bone resorptive cells generates the protons necessary for bone resorption. Inhibition of the enzyme is a potential mechanism for decreasing bone resorption. Eight healthy post-menopausal women received oral acetazolamide 250 mg twice daily for 28 d. Bone resorption, evaluated by serum acid phosphatase activity and the renal excretion of hydroxyproline, was unaltered, as was bone formation estimated by serum levels of alkaline phosphatase and osteocalcin. The fasting renal excretion of calcium was increased, whereas serum ionized calcium was unchanged. The maximal renal reabsorption of phosphate decreased, but it was not an effect of PTH as it decreased significantly during the treatment period. In conclusion, no significant effect on biochemical markers of bone remodelling could be detected during the study period. The observed changes in calcium and phosphate metabolism may be secondary to the renal effect of acetazolamide.

Acetazolamide↗
PubMed1990

Investigations of coagulation system and fibrinolysis in patients with disseminated adenocarcinomas and non-Hodgkin's lymphomas.

Indicating activation of coagulation fibrinopeptide A (FPA) was elevated in 80.1% (mean = 10.5 ng/ml; P less than 0.01) and thrombin-antithrombin III complexes in 58.3% (TAT; mean = 5.3 ng/ml; p less than 0.05) in patients with adenocarcinomas (n = 57). In patients with non-Hodgkin's lymphomas (n = 30), however, elevation was observed only in 66.6% (FPA) and in 42.8% (TAT). Incidence of thrombosis is high only in the first group Local fibrinolysis explains elevated D-dimer in adenocarcinomas (1,818 ng/ml; p less than 0.01) and in non-Hodgkin's lymphomas (576 ng/ml; p less than 0.05). Significantly increased t-PA antigen was not committed by adequately increased t-PA activity in adenocarcinomas, because of high levels of the acute-phase protein, plasminogen activator inhibitor (mean = 25.3; p less than 0.01), indicating systemic hypofibrinolysis. Hemostatic disorder in patients with malignancy can be attributed to a combination of acute-phase reaction and an activation of coagulation.

Adenocarcinoma↗
PubMed1990

The possible role of oral epithelial cells in tissue-type plasminogen activator-related fibrinolysis in human saliva.

We studied the fibrinolytic activities of the following subfractions of unstimulated human whole saliva on plasminogen-rich fibrin plates: (1) submandibular saliva, (2) parotid saliva, and (3) smears of buccal epithelial cells from ten healthy males. A cell-bound plasminogen activator could be demonstrated in the sediments of all three subfractions of whole saliva. The incorporation of antibodies (goat IgG) against human two-chain tissue-type plasminogen activator (t-PA) could quench the assessed fibrinolytic activities, whereas additional experiments suggested the absence of urokinase-like and F XII-dependent activators of fibrinolysis. The determinations in growth medium from buccal-epithelial cell culture of t-PA antigen by means of enzyme-linked immunosorbent assay showed the presence of t-PA. These clinical and experimental findings suggest that buccal-epithelial cells produce t-PA, while the activity of t-PA in parotid and submandibular saliva is very low.

Cells, Cultured↗
PubMed1990

The haemostatic balance in groups of thrombosis-prone patients. With particular reference to fibrinolysis in patients with myocardial infarction.

The concept of the haemostatic balance was reviewed, and its potential role in the regulation of tissue repair and the pathogenesis of thrombotic processes was surveyed. Physiological activation of coagulation appears to be dominated by effects of degenerated and injured cells of the vascular wall causing local release of thromboplastin and exposition of activating surfaces. Inhibition of coagulation impairs its progression and the non-thrombogenic nature of the normal endothelium is chiefly caused by the binding of inhibitory components (antithrombin-III, protein C) to specific receptor sites. Physiological activation of fibrinolysis appears to be triggered by and limited to the fibrin because of a specific affinity to fibrin of plasminogen and plasminogen activators. Systemic activation of fibrinolysis is prevented by primary (alpha 2-antiplasmin) and secondary (alpha 2-macroglobulin, alpha 1-antitrypsin) plasmin inhibitors. A plasminogen binding protein (histidine-rich glycoprotein), plasmin inhibitors and activator inhibitors appear to contribute to the regulation of the initial phase of fibrinolysis. A deviation from normal of the dynamic balance, regulating fibrin formation and resolution, may lead to a haemorrhagic and/or a thrombophilic state. Described were the optimization of selected methods for assessment of variables involved in the haemostatic balance. An overestimation of plasminogen concentrations in plasma may occur in patients with elevated levels of fibrinogen or fibrin degradation products, when using assays based on the activation of plasminogen by streptokinase followed by the hydrolysis of a synthetic chromogenic substrate. This source of error could be eliminated by presence of fibrinogen in excess in the plasminogen assay, thereby securing maximum stimulation of the plasminogen-streptokinase complex. The presence of cryoglobulin in plasma interferes with the assessment in euglobulins of plasminogen activator activities. Experiments indicate that tissue-type plasminogen activator adsorb cryoglobulins and that a cold-promoted activation of the factor XII-dependent proactivator system of fibrinolysis is related to the presence of cryoglobulins. Experiments supported the existence of an as yet not characterized factor XII-dependent proactivator. Strictly optimized procedures for the preparation of euglobulins for the accurate determination of plasminogen activators were recommended. The determination of plasminogen activator inhibition in plasma was optimized and simplified. The amidolytic assay of antithrombin-III was shown to be influenced by adsorption to laboratory utensils and aggregation of thrombin. This error could be corrected by protection with additives (Tween 80, polyethyleneglycol 6,000), which also improved the solubility of the chromogenic substrates in aqueous media. The role of thrombosis in myocardial infarction was reviewed.(ABSTRACT TRUNCATED AT 400 WORDS)

Antithrombin III↗
PubMed1990

Effects of methylamine and heparin on a rapid chromogenic assay of C1-esterase inhibitor in plasma.

We describe a rapid assay of C1-esterase inhibitor (C1-inh) activity in plasma. After adding purified C1s serine protease (EC 3.4.21.42) in excess to plasma, we determine the residual C1s activity towards a new chromogenic tripeptide, CH3CO-Lys(CbO)-Gly-Arg-pNA. Optimal conditions include the addition of methylamine (final concentration 0.12 mol/L) to reduce the potential inhibitory capacity of alpha 2-macroglobulin towards C1s and the addition of heparin (final concentration 3000 int. units/L) to enhance the reaction of C1s with C1-inh. The correlation with C1-inh antigen concentrations in plasma was excellent. The estimated interassay CV was 4.3%, whereas the intra-assay CV was 2.0% for activity concentrations within the range of normal individuals (means +/- 2 SD: 70-124%), 1.3% at lower concentrations. The method is more convenient, rapid, and precise than previous methods, and C1-inh activity in plasma can be assessed within 30 min. We found that concentrations of C1-inh in plasma were low during open-heart bypass surgery.

Antigens↗
PubMed1990

Specific, sensitive, precise, and rapid functional chromogenic assay of activated first complement component (C1) in plasma.

We present a new functional assay for the first complement component (C1) in plasma, based on its activation by inhibition of the C1-esterase inhibitor (C1-inh) when monospecific antiserum to C1-inh is added to the plasma. After maximal activation, we can determine the concentration of activated C1 by using an amidolytic rate assay with a chromogenic substrate. We have optimized the assay conditions with respect to incubation time, concentration of antiserum to C1-inh, ionic strength, and pH. Our method determines specifically the concentration in plasma of free activated C1, not complexes of activated C1 with C1-inh, and is not influenced by the concentration of C1-inh in the test sample. Concentrations of C1 correlated significantly with activities determined by a hemolytic assay (r = 0.55, t = 4.09, P less than 0.001). The estimated interassay CV was 5% and the intra-assay CV was 1%. The sensitivity, imprecision, and practical test performance of our assay are superior to those of conventionally used hemolytic assays.

Adult↗
PubMed1989

[The effect of liver cirrhosis on activation of the coagulation and fibrinolysis system and on coagulation inhibitors].

The activation of coagulation and fibrinolysis as well as coagulation inhibitors in the blood of patients with compensated (n = 25) and decompensated (n = 25) liver cirrhosis were studied. Protein C (PC) was decreased in a more pronounced manner than antithrombin III (AT III) in liver cirrhosis. Thereby, PC proved to be a highly sensible indicator of liver cell dysfunction. Decreased levels of PC activity (PC ratio activity/antigen 0.82) in decompensated liver cirrhosis suggest production of dysfunctional, undercarboxylated PC. We observed increased blood concentrations of fibrinopeptide A (FPA) (p less than 0.05) in both groups of patients compared to healthy volunteers (n = 25), while D-Dimer was increased only in patients with decompensated liver cirrhosis (p less than 0.01). Comparing both groups of patients. D-Dimer was significantly different with higher levels in decompensated liver cirrhosis (p less than 0.01). The ratio D-Dimer/FPA was significantly increased in decompensated liver cirrhosis compared to both other groups. These observations indicate that efflux from the extravascular space, e.g. ascitic fluid, contributes to the high contents of fibrin degradation products (D-Dimer) in patients with decompensated liver cirrhosis. In summary we conclude that patients with liver cirrhosis have enhanced activation of both coagulation and fibrinolysis but that the balance is not significantly displaced.

Aged↗
PubMed1989

Drug consumption in elderly diabetics.

The drug use in 228 persons with diabetes was studied and compared with that of sex- and age-matched non-diabetic controls--all of whom were found by the screening of a well-defined Danish population aged 60-74 years. Ninety per cent of the diabetics had non-insulin-dependent diabetes mellitus (NIDDM), as evaluated by a glucagon-C-peptide test. Information on daily use of prescribed and non-prescribed drugs was obtained by questionnaires and interviews. More than 80% of the diabetics used drugs daily, compared to 55% of control subjects (P less than 0.00001). Among subjects using drugs diabetics, on average, used 70% more defined daily doses (DDD) than controls, even when antidiabetics were excluded. There was no difference in the number of drug users among subgroups of diabetics when divided according to antidiabetic treatment but tablet-treated diabetics, on average, used 20% fewer DDD than other diabetics. Cardiovascular drugs were the most commonly used drugs. Diabetics in all antidiabetic treatment groups used significantly more cardiovascular drugs than non-diabetics. Diabetics treated with oral antidiabetics used fewer cardiovascular drugs than insulin- and diet-treated diabetics. The estimated cost of drug therapy was more than 2.5 times higher for diabetics than for the control group. Our results reflect the increased morbidity among elderly diabetics and emphasise, together with other aspects of costs of diabetes in the elderly, the need for allocating resources for the prevention of NIDDM instead of the treatment of its complications.

Aged↗
PubMed1989

Rise of plasma t-PA fibrinolytic activity in a group of maturity onset diabetic patients shifted from a first generation (tolbutamide) to a second generation sulphonylurea (gliclazide).

During treatment with tolbutamide 10 maturity onset diabetic patients had no detectable activity of tissue-type plasminogen activator (t-PA) determined on two occasions 3 months apart. All 10 patients responded on the change in treatment to gliclazide with an increase in activity of t-PA. However, after 12 months of treatment the t-PA activity in one of the 10 patients returned to the baseline level, whereas the remaining nine patients had a sustained increased t-PA activity compared to the period during treatment with tolbutamide. The concentration in plasma of t-PA antigen under basal conditions and after stimulation (venous occlusion) increased significantly during the period of treatment with gliclazide. The plasma concentrations of plasminogen activator inhibitor remained unchanged throughout the study. In contrast to these findings seven patients with marked activities of t-PA during treatment with tolbutamide retained unchanged levels of the variables reported above after a change in treatment to gliclazide. Serum glucose, HBA1c, apolipoproteins A and B, and triglycerides remained constant throughout the study, whereas serum cholesterol showed a decrease in both groups of patients after 3 months (P less than 0.05) as well as after 12 months (P less than 0.05) of treatment with gliclazide. There was no significant relationship between serum cholesterol concentrations and plasma concentrations of t-PA antigen indicating that the increase in t-PA antigen was independent of the metabolic state of the patients.

Aged↗
PubMed1989

Depressed plasma fibrinolytic activity in a group of patients with connective tissue diseases.

In various connective tissue disorders, a depressed fibrinolytic activity of the blood, attributed a contributory role in the development of disease, has been reported. We have determined selected fibrinolysis variables of the blood in 16 patients (7 patients with mixed connective tissue disease, 4 with systemic lupus erythematosus, 3 with rheumatoid arthritis and 2 with systemic sclerosis) and in 16 apparently healthy, age- and sex-matched controls. A significantly reduced mean activity of the intrinsic derived, urokinase-like plasminogen activator was found in the patient group. None of the other variables, including the extrinsic plasminogen activator (t-PA), differed from the control group. Possible implications of our findings in relation to the patho-physiology of these connective tissue diseases are discussed.

Adolescent↗
PubMed1989

Circadian variation of fibrinolytic activity among Eskimos in Greenland.

Recent studies on circadian variation of blood fibrinolytic activity have suggested a relation between a depressed morning fibrinolytic activity and the frequent onset of myocardial infarction at that time in Caucasians. We have obtained blood samples from 10 Eskimos with an interval of 4 h during 24 h and studied the extrinsic tissue-type plasminogen activator-related fibrinolysis. We observed a significant change in the activity of tissue-type plasminogen activator (t-PA; p less than 0.01) and in the activity of plasminogen activator inhibitor (PAI; p less than 0.001) during 24 h. The activity of t-PA increased more rapidly and the activity of PAI decreased more rapidly during the morning hours in Eskimos compared to reported patterns in Caucasians. A significant negative correlation between PAI and t-PA (r = -0.79, p less than 0.0001) suggested that PAI contributes to the regulation of t-PA activity in the blood. Whether the observations are of importance for the low prevalence of myocardial infarction in Eskimos remains to be further studied. However, our observations demonstrate that it is of utmost importance to standardize the collection of blood samples in order to obtain reliable information on the fibrinolytic system in Eskimos.

Circadian Rhythm↗
PubMed1989

Increased concentrations of heparin cofactor II in diabetic patients, and possible effects on thrombin inhibition assay of antithrombin III.

We compared concentrations of antithrombin III (AT-III) in plasma, as determined by an immunological method and by a functional thrombin inhibition method, in the presence of heparin in 160 blood samples from Type I diabetics. Although the correlation was highly significant (P less than 0.001) between the results obtained by the two methods, our data demonstrated that results by the thrombin inhibition assay, 121 (SD 15)%, expressed as percentages of the results for a normal plasma pool, were significantly (P less than 0.001) higher than by the immunoreactive method, 104 (SD 15)%, indicating an overestimation of functionally active AT-III. Concentrations of functionally active AT-III determined by a factor Xa inhibition assay, 105 (SD 13)%, were in the same range as immunoreactive AT-III. Addition of IgG antiserum to normal pooled plasma quenched only about 90% of the AT-III activity determined by the thrombin inhibition assay, but all of the AT-III activity determined by a factor Xa inhibition assay. These results demonstrate that the factor Xa inhibition assay is more specific for the determination of AT-III than the thrombin inhibition assay. We suggest that the high concentrations of heparin cofactor II, 117 (SD 17)%, might have caused an overestimation of AT III in this group of patients with diabetes Type I, and should not be overlooked in other clinical situations.

Antithrombin III↗