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Biomedical subjects

J Gram

Publications and source records attributed to J Gram.

At least 73 records · Page 4Linked to original sources
PubMed1995

Procoagulant activity and intimal dysfunction in IDDM.

The biological activity of thrombin and coagulation factor Xa was assessed in 62 insulin-dependent diabetic patients. A group of non-diabetic subjects of comparable age and urinary albumin excretion rate (< 30 mg/24 h) served as control subjects (group 1, n = 14). The patients were divided into three groups according to urinary albumin excretion rate. In group 2, albumin excretion rate was less than 30 mg/24 h (n = 17), in group 3 albumin excretion rate was in the range 30-300 mg/24 h (n = 20) and in group 4 albumin excretion rate was greater than 300 mg/24 h (n = 25). Compared to non-diabetic control subjects an increase in the biological activity of factor Xa was observed in all groups of diabetic patients (prothrombin fragment 1 + 2 levels were 1.14 +/- 0.38 nmol/l in group 2, p < 0.005; 1.06 +/- 0.45 nmol/l in group 3, p < 0.05 and 1.03 +/- 0.31 nmol/l in group 4, p < 0.05 vs 0.75 +/- 0.34 nmol/l in group 1). No difference in the level of antithrombin III was seen between the groups. We reconfirmed the presence of intimal dysfunction in diabetic nephropathy demonstrated by elevated transcapillary escape rate of albumin in group 4 compared with group 2 (8.9 +/- 2.0% vs 7.0 +/- 1.9%, p < 0.05). An overall positive correlation between transcapillary escape rate and prothrombin fragment 1 + 2 was found (r = 0.36, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Cross calibration of QDR-2000 and QDR-1000 dual-energy X-ray densitometers for bone mineral and soft-tissue measurements.

Replacement of dual energy X-ray densitometry (DXA) equipment may be necessary in many labs with time, or new equipment may be added. In this context we compared patient scans between a Hologic QDR-1000W and a QDR-2000 (n = 29-43, depending on anatomic region) and between QDR-2000 single beam (SB) and fan beam (FB) modes (n = 40-62) as a quality control measure. A total of 83 subjects (79 females and four males) with a wide range of bone mineral densities (BMD) were studied. There was a linear relationship between results with the QDR-1000W and QDR-2000 in SB mode, and between SB and FB mode on the QDR-2000, but the magnitude of the coefficients and constants differed for the different anatomic regions. In SB mode the QDR-2000 underestimated whole body and forearm BMD by 3% relative to the QDR-1000W, even after cross calibration using a spine phantom. Femoral total BMD was slightly, but not significantly, underestimated. Thus, additional postanalysis correction had to be applied to forearm and whole-body scans. In FB with the QDR-2000, spine and whole-body BMD was underestimated by 3%, but femur total and neck BMD was overestimated by 2.2 and 2.8%, respectively, compared with SB scans on the same device. Soft-tissue composition with FB (enhanced analysis protocol) on the QDR-2000 differed greatly from that obtained using SB (standard protocol). Lean tissue mass was 4 kg lower and fat mass 4 kg higher in FB mode.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

Autosomal dominant osteopetrosis: bone mineral measurements of the entire skeleton of adults in two different subtypes.

Bone mineral content (BMC) and density (BMD) were measured by dual-energy X-ray absorptiometry in two subtypes of autosomal dominant osteopetrosis (ADO). Both types have been radiologically characterized by diffuse symmetrical osteosclerosis, but with characteristic differences. Increased thickness of the cranial vault is a typical finding in type I ADO, whereas endobones in the pelvis and end-plate thickening in the spine are obligate findings in type II. Eleven patients with type I from three kindreds, and seven patients with type II, one family participated in the study, and were compared with 18 age- and sex-matched normal controls. Whole-body BMC and BMD were measured, and regions of special interest were selected: head, axial, and appendicular skeleton. Moreover, lumbar spine and femoral neck scans were performed. Whole-body BMC and BMD, mostly reflecting cortical bone, were markedly increased in both types compared with normals. A pronounced osteosclerosis was present in the axial as well as the appendicular skeleton. Median BMD was markedly increased in the axial skeleton by 51% (44-56) and 42% (33-56), (median differences with 95% CI), respectively, for types I and II compared to normal controls, and in the appendicular skeleton by 48% (37-59) and 38% (16-45). No overlap between observed ranges of patients and controls was observed. A positive correlation between age and whole-body BMD was demonstrated in ADO, but not in the control group, indicating progressive osteosclerosis with age. Median BMD of the lumbar spine, which mostly reflects trabecular bone, showed increased densities in both types, 71% (51-84) and 59% (37-93), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

Biological variation of serum and urinary magnesium in apparently healthy males.

The biological variations of serum (S-) magnesium and urinary (U-) magnesium concentrations and excretions have been investigated. Serum samples, 24-h and fasting urinary samples were collected from each of 60 supposedly healthy male volunteers. In addition, 12 volunteers collected additional samples 7 and 112 days after the initial sample. The reference interval for S-magnesium was 0.765-0.997 mmol l-1. The biological variation for S-magnesium was 3.2% within subjects and 7.4% between subjects. This indicated an index of indivduality of 0.5, which means that significant changes in S-magnesium can occur within the limits of the reference interval, and that serial determinations of S-magnesium might prove useful as an indicator of changes in whole body magnesium status. It is, on the other hand, unlikely that a single determination of S-magnesium can be used in assessing whole-body magnesium status in the individual. The reference interval for the 24-h U-magnesium excretion, corrected for surface area, was 1.306-4.762 mumol min-1 1.73 m-2. The 24-h U-magnesium excretion exhibited a biological within-subject variation of 36% and a between-subject variation of 26%. The 24-h U-magnesium excretion did not correlate with S-magnesium, and only slightly (r = 0.58) with the fasting U-magnesium/creatinine concentration. This, and the very large coefficients of variation, make it unlikely that the renal magnesium excretion can be used as a measure of whole body magnesium status, or that changes in the renal magnesium excretion can be used as a measure of changes in whole body magnesium status.

Adult↗
PubMed1995

The protein concentration of blood coagulation factor VII can be measured equally well in plasma and serum.

In the Northwick Park Heart Study, the coagulant activity of factor VII (FVII:C) has been identified as a risk marker of ischaemic heart disease. In the fasting state, the protein concentration of FVII (FVII:Ag) might be an even better risk marker, because of the low coefficient of variation of the antigen assay. Today, most analyses are performed in plasma samples, as it is unknown whether FVII, to some extent, is consumed during coagulation. In the present study, we have investigated, whether FVII:Ag can be measured equally well in plasma and serum. FVII:Ag was measured in 88 plasma and serum samples. Results were compared by means of linear regression, where y = 0.984 x +0.770, r = 0.96. No systematic variation existed between FVII:Ag in plasma and serum. The mean difference in FVII:Ag between plasma and serum was -1.17 (SD 11.92) arbitrary units, compared with a mean difference of 0.18 (SD 8.31) arbitrary units between duplicate measurements of the same plasma dilution. Our findings indicate that there is a good agreement between FVII:Ag in plasma and serum.

Adult↗
PubMed1995

Plasminogen activator inhibitor type-1 determines plasmin formation in patients with ischaemic heart disease.

The aim of the present study was to find out whether plasminogen activator inhibitor type-1 (PAI-1) controls the formation of plasmin in patients with ischaemic heart disease. We examined PAI activity, PAI-1 antigen, tissue type plasminogen activator (t-PA) activity, t-PA antigen, plasmin-alpha2-antiplasmin complex (PAP-complex) and fibrin degradation products D-dimer in 62 patients before (unstimulated) and after infusion of 1-desamino-8-D-arginine vasopressin (DDAVP; stimulated). DDAVP was used in a standardized dose to trigger the release of t-PA from the vascular endothelium. We observed that under basal conditions (unstimulated) median plasma t-PA activity for the whole group of patients was 86.5 mIU/ml (0-900), and after stimulation 2550 mIU/ml (0-6800), P < 0.0001; median plasma concentration of t-PA antigen was 14.7 ng/ml (7.0-115.5) under basal conditions, and after stimulation 34.1 ng/ml (15.8-58.6), P < 0.0001; median plasma PAI activity was 16.9 IU/ml (1.5-144.8) under basal conditions, and after stimulation 3.1 IU/ml (0-118.5), P < 0.0001; median plasma concentration of PAI-1 antigen was 21.5 ng/ml (8.1-132.2) under basal conditions, and after stimulation 14.9 ng/ml (4.8-149.0), P < 0.0001; the median plasma concentration of PAP-complex was 469.5 ng/ml (185.0-1802.0) under basal conditions, and after stimulation 695.5 (243.0-2292.0), P < 0.0001; median plasma concentration of D-dimer was 298.0 ng/ml (103.0-948.0) under basal conditions, and after stimulation 296.5 ng/ml (97.0-917.0), P < 0.0008.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Plasminogen activator activity and plasma-coagulum lysis measured by use of optimized fibrin gel structure preformed in microtiter plates.

We introduce a new fibrin plate assay performed in microtiter plates. By means of spectroscopic studies we optimized the structure of the fibrin gel and then used the optimized fibrin gel to determine plasminogen activator activity. Plasminogen activator solutions were applied on top of the fibrin gel, and the absorbance of the gel was recorded at 405 nm. After incubation for 17 h at 25 degrees C, the absorbance was measured again. The difference in absorbance was proportional to the concentration of plasminogen activator, such that the dose-response curves were linear when the difference in absorbance was plotted as a function of the logarithmic concentration of plasminogen activator. We assayed both tissue-type and urokinase-type plasminogen activator activity. The intraassay CV was < 4.7% (n = 20); the interassay CV was < 3.1% (n = 15). Using the optimized procedure, we modified the assay for determination of plasma-coagulum lysis time in human plasma. We established a reference interval for lysis time in apparently healthy subjects of 75 to 201 ks. Patients with deep vein thrombosis showed significantly (P = 0.013) higher values.

Adult↗
PubMed1995

Does low protein concentration of tissue-type plasminogen activator predict a low risk of spontaneous deep vein thrombosis?

Many reports have demonstrated an abnormal fibrinolysis in a subset of patients with deep vein thrombosis. We have studied systemic global fibrinolytic activity and protein concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) in plasma of 25 young patients with a previous instance of spontaneous deep vein thrombosis documented by phlebography and in 50 healthy controls. The two populations were comparable with respect to a number of base-line variables (age, height, weight, etc.), while the patients had significantly lower fibrinolytic activity (p < 0.02), and significantly higher protein concentrations of t-PA (p < 0.0001) and PAI-1 (p < 0.0006). We used probit scale plots to identify the consequence of different cut-off points to separate patients from controls. Reasonable separation could be obtained for t-PA with a cut-off point of 5.2 ng/ml and for PAI-1 18 ng/ml. The sensitivity and specificity for these cut-off points were for t-PA 73% (95% confidence interval 63%-84%) and for PAI-1 67% (confidence interval 55%-77%). The negative predictive value with a cut-off point t-PA concentration of 5.2 ng/ml was 85% (95% confidence interval 70%-94%). We observed a significantly negative association between concentration of t-PA and fibrinolytic activity (rs = -0.47; p < 0.005) and also between PAI-1 and fibrinolytic activity (rs = -0.78; p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Regulation of tissue-type plasminogen activator-mediated fibrinolysis by plasminogen activator inhibitor type-1 in patients with ischaemic heart disease: possible unfavourable effect of diuretics.

BACKGROUND: Impaired endogenous tissue-type plasminogen activator (t-PA)-mediated fibrinolysis may be involved in the evolution of myocardial infarction. t-PA-mediated fibrinolysis is believed to depend on the amount of active t-PA present in the circulation. Accordingly, we investigated the possible mechanisms responsible for impaired t-PA-mediated fibrinolysis in patients with ischaemic heart disease. METHODS: Forty-five survivors of acute myocardial infarction were examined 8 weeks after discharge from hospital. Intravenous infusion of 1-desamino-8-D-arginine vasopressin (DDAVP; 0.4 micrograms/kg bodyweight) was used to stimulate the endogenous fibrinolytic system, and blood samples were collected before and after infusion. We compared the response of the t-PA-plasminogen activator inhibitor type-1 (PAI-1) fibrinolytic system in patients with preinfusion levels of active t-PA below or at the detection limit of the assay with that in patients with higher preinfusion levels of active t-PA. RESULTS: All patients responded to DDAVP infusion with an increase in plasma concentration of t-PA antigen. This response did not differ between the two groups. In contrast, the preinfusion levels of PAI activity were significantly higher in patients with undetectable plasma levels of active t-PA compared with patients with higher levels of active t-PA (22.3 versus 12.8 IU/ml; P < 0.01). Subgroup analyses demonstrated that patients treated with diuretics had significantly higher plasma concentrations of PAI-1 antigen (28.5 versus 17.9 ng/ml; P < 0.03) and a trend towards higher PAI activity (24.0 versus 14.6 IU/ml; P = 0.07) compared with patients not receiving diuretics. CONCLUSION: Our study strongly suggests that a high plasma level of PAI-1, the main inhibitor of t-PA, is responsible for impaired t-PA-mediated fibrinolysis in patients with ischaemic heart disease, and that treatment with diuretics may be associated with an unfavourable effect on the fibrinolytic system.

Aged↗
PubMed1994

Body composition in active acromegaly during treatment with octreotide: a double-blind, placebo-controlled cross-over study.

OBJECTIVE: In active acromegaly body composition is characteristically altered by an increase in lean body mass and a corresponding reduction in fat mass. These changes are induced by an excessive secretion of GH and insulin-like growth factor I (IGF-I). Growth hormone is an anabolic hormone and leads to stimulation of protein synthesis and an increased lipolysis in adipose tissue. Treatment with the somatostatin analogue, octreotide, has been shown to reduce GH levels causing reduced hormonal effects on target tissues. We have studied changes in body composition during short-term reduction in GH level by octreotide in active acromegaly. DESIGN: Octreotide was compared to placebo in a double-blind, cross-over trial. Dual-energy X-ray absorptiometry scanning was employed to calculate body composition. Relations between body composition parameters and clinical signs of acromegaly (finger circumference and foot volume) were studied. PATIENTS: Twelve patients with active acromegaly, confirmed by lack of GH suppression during oral glucose loading, were included. All had pituitary adenomas diagnosed by computed tomography. MEASUREMENTS: Serum GH and IGF-I. Lean body mass, fat mass and total weight, foot volume and finger circumference. RESULTS: Four weeks of octreotide treatment caused a 75% decrease in GH levels (n = 10), a reduction in IGF-I from 476 +/- 51.9 (mean +/- SEM) to 233 micrograms/l +/- 46.3 (P < 0.005) and a corresponding decrease in both body weight (2.51 kg +/- 0.41) (P < 0.005) and lean body mass (2.44 kg +/- 0.48) (P < 0.005). No significant changes in fat mass were observed. These findings were paralleled by significant reductions in foot volume (44.50 ml +/- 17) (P < 0.05) and finger circumference (1.3 mm +/- 0.3) (P < 0.05). CONCLUSIONS: Short-term octreotide therapy reduces growth hormone levels leading to a significant reduction in lean body mass as assessed by dual-energy X-ray absorptiometry. Alterations in lean body mass were positively correlated with reductions in foot volume. Thus, simple clinical tests may be valuable in judging the effects of treatment in active acromegaly.

Absorptiometry, Photon↗
PubMed1994

A new automated method for continuous registration of factor VII activation in vitro. Activation is accelerated by the concentration of factor VII and the activity state of the protein.

When a plasma sample is exposed to tissue factor, single-chain factor VII (FVII) is gradually converted to the active two-chain form (FVIIa). In the present study, we have constructed a measurement system, which allows continuous registration of the activation of FVII to FVIIa in vitro. In this system, FVII activation follows parabolic kinetic after an initial lag-phase. The slope of the linear phase is a measure of the protein concentration of factor VII (FVIItotal), while the length of the non-linear phase represents the velocity of FVII activation. The time required for complete activation of FVII is inversely related to both FVIItotal and the relative amount of FVIIa in the sample. In future studies, this new measurement system will make it possible to study the process of FVII activation in different samples, and to examine how varying concentrations of exogenous added components affect the activation process in vitro.

Amino Acid Sequence↗
PubMed1993

Multicentre evaluation of commercial kit methods: plasminogen activator inhibitor activity.

In order to study the analytical performance of different commercial kits for determination of plasminogen activator inhibitor (PAI) activity we distributed eight selected split samples to 11 European laboratories experienced with haemostasis testing. Three different laboratories were involved in the production of data from each of the commercial kits tested. A considerable variation of PAI activity results reported from the laboratories testing the same commercial kits was observed. The range of reported results could in individual samples exceed the median value indicating an interlaboratory variation of more than 100%. When we harmonized the results reported from different kits in different laboratories by means of an international standard from National Institute for Biological Standards and Control (NIBSC) we still observed that the results produced by some kits deviated systematically from results produced by other kits. Also, the harmonized results were used to estimate the overall coefficient of variation (CV) of PAI activity determined in various laboratories by different kits. We observed an inverse correlation between the PAI activity level and the CV with a CV of about 100% for low PAI activity levels and a CV of about 16% for high PAI activity levels. The high imprecision of the kits in the low concentration range of PAI activity indicates that unspecific factors in plasma may interfere with determination of active PAI. This was confirmed by the evaluation of the results from one of the plasma samples, which was PAI-1 depleted. The laboratories involved in the testing reported for this sample a mean value of 6.1 IU/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Preservation↗
PubMed1993

Multicenter evaluation of commercially available methods for the immunological determination of plasminogen activator inhibitor-1 (PAI-1).

In order to evaluate the comparability of data obtained with various available kits for the immunological determination of PAI-1 antigen in plasma and in order to investigate the underlying cause of observed differences, e.g. problems of specificity or of proper calibration of the provided standard, a multicenter study was organised in the framework of the Subcommittee of Fibrinolysis of the Scientific and Standardization Committee. Eight different plasma samples were distributed among 16 laboratories: a pooled normal plasma, NIBSC 87/512, PAI-1 antigen depleted plasma, PAI-1 depleted plasma supplemented with 59 ng/ml active PAI-1 and four different individual plasma samples. A considerable variation in absolute values is observed between the various kits, e.g. in pooled normal plasma a value is found ranging between 7.4 and 28 ng/ml. Harmonization of all data relative to the PAI-1-depleted plasma supplemented with an exact amount of active PAI-1 (59 ng/ml), followed by a statistical analysis using a two way analysis of variance, revealed that 6 out of 7 kits yielded values that were not significantly different with coefficients of variation around 30%. Correlations between the values obtained with these kits yielded slopes between 0.75 and 1.44 with correlation coefficients between 0.973 and 0.999. Values obtained with one kit appeared to be significantly different (even after harmonization) from the other kits (p < 0.001 to p < 0.05). Comparison of PAI-1 antigen with the PAI activity values in the analysed samples suggests that one kit may deal with a problem of a difference in reactivity between active and latent PAI-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1993

Depression of factor XII-dependent fibrinolytic activity in survivors of acute myocardial infarction at risk of reinfarction.

Defective fibrinolysis may constitute a risk for the development of myocardial infarction in patients with ischaemic heart disease. We studied prospectively the factor XII-dependent plasminogen proactivator system in 49 survivors of an acute myocardial infarction. Blood samples were collected 8 weeks after hospital discharge. The factor XII-dependent fibrinolytic activity in the specimens was determined on fibrin plates after complete immuno-inhibition of the urokinase-like and the t-PA related fibrinolytic systems. During the subsequent follow-up period of 2.4 years, 10 patients developed recurrent myocardial infarction, whereas the remaining 39 patients did not. The reinfarction group of patients had a significantly lower median factor XII-dependent fibrinolytic activity (24.9 blood activating units (BAU).ml-1) than the patients without a relapse (41.9 BAU.ml-1, P < 0.02). Plasma concentrations of factor XII did not deviate significantly between the groups (P > 0.05), whereas the median plasma concentrations of prekallikrein was slightly lower in the reinfarction group (90%) than in the non-reinfarction group of patients (105%, P < 0.02). These observations point to an association between a depressed factor XII-dependent fibrinolytic activity and an enhanced risk of reinfarction in patients with a previous episode of acute myocardial infarction.

Cholesterol↗
PubMed1993

Reactive coagulation induced by plasmin in patients treated with recombinant tissue-type plasminogen activator.

BACKGROUND: We and others have demonstrated that administration of thrombolytic agents causes the generation of thrombosis-promoting agents. At present, we have studied whether formation in vivo of excessive amounts of plasmin is responsible for the activation of coagulation in patients treated with recombinant tissue-type plasminogen activator. METHODS: Modified crossed immunoelectrophoresis was used for determination of the plasminogen-binding form of alpha 2-antiplasmin. Enzyme-linked immunosorbent assay methods were used for determination of hemostatic reaction products. RESULTS: The association between the generation of hemostatic reaction products and the exhaustion of the plasminogen-binding form of alpha 2-antiplasmin (PB alpha 2AP) was studied in 21 patients with acute myocardial infarction and 11 patients with unstable angina pectoris who were given a 3-hour, 100-mg intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA). We observed in all patients a fall in blood concentrations of PB alpha 2AP (P < 0.01) after 2.25 hours of treatment and, simultaneously, a significant increase in fibrin degradation products (P < 0.01), D-dimer (P < 0.01), fibrinogen degradation products (P < 0.01), prothrombin fragment 1 + 2 (P < 0.01), and thrombin-antithrombin III complexes (P < 0.01). When we evaluated individual data, we observed high concentrations of the reaction products when the PB alpha 2AP concentration after 2.25 hours of treatment was lower than 25% of the pretreatment values. Also, we observed highly significant associations between the increase in the plasma concentrations of fibrin degradation products and thrombin-antithrombin III complexes (rs = 0.72; P < 0.01), the increase in plasma concentrations of fibrin degradation products and prothrombin fragment 1 + 2 (rs = 0.63; P < 0.01), the increase in plasma concentrations of D-dimer and thrombin-antithrombin III complexes (rs = 0.78; P < 0.01), and the increase in plasma concentrations of D-dimer and prothrombin fragment 1 + 2 (rs = 0.79; P < 0.01). CONCLUSIONS: Generation of excessive amounts of plasmin is the main factor in producing the procoagulant response in patients who receive thrombolytic therapy with rt-PA, and intravenous heparin does not abolish this response. Plasmin inhibitors might be used in relation to thrombolytic therapy as indirect "antithrombotics."

Aged↗
PubMed1993

Different membrane expression of CD11b and CD14 on blood neutrophils following in vivo administration of myeloid growth factors.

During the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) or granulocyte-macrophage CSF (rhGM-CSF) we studied the early and late changes of membrane antigen density on neutrophils. RhG-CSF and rhGM-CSF both caused an early transient reduction in blood neutrophilic granulocyte-concentration within the first 30 min after treatment followed by a marked later increase during the subsequent 24 h. During the early neutropenia quantitative flow cytometry showed an associated marked increase in the density of membrane CD11b from 169 x 10(3) before to 568 x 10(3) A.U. per cell induced by rhGM-CSF but a non-significant change by rhG-CSF, suggesting that different mechanisms may be responsible for the transient neutropenia. The subsequent neutrophil granulocytosis was followed by a significantly (P < 0.05) increased density of the CD14 antigen from 6.1 x 10(3) before to 15.9 x 10(3) A.U. per cell during treatment with rhG-CSF, but not by rhGM-CSF administration. These results demonstrate that the two cytokines may affect the function of neutrophilic granulocytes in different ways. The increased expression of CD11b could explain some of the side-effects during treatment with rhGM-CSF. The upregulation of CD14 induced by rhG-CSF may be clinically relevant, as CD14 is an opsonic receptor for lipopolysaccharide binding proteins, acting in the defence against Gram-negative bacterial infections.

Adult↗