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Biomedical subjects

A M Ehrly

Publications and source records attributed to A M Ehrly.

At least 19 recordsLinked to original sources

A prospective study on the incidence and clinical relevance of heparin-induced antibodies in patients after vascular surgery.

The heparin-platelet factor 4-antibody assay, polyanion-platelet factor 4-antibody assay and heparin-induced platelet activation test are used for laboratory diagnosis of the immune form of heparin-induced thrombocytopenia. Fifty consecutive patients receiving heparin treatment for more than 5 days after vascular surgery were prospectively screened for heparin-induced thrombocytopenia antibodies, thrombocytopenia (daily platelet counts), deep-vein thrombosis (color-coded duplex sonography), and arterial reocclusion (clinical assessment). None of the patients developed thrombocytopenia or thrombosis in association with formation of heparin-induced thrombocytopenia antibodies. Despite the absence of clinical evidence of heparin-induced thrombocytopenia, many patients formed heparin-induced thrombocytopenia antibodies: 34% of the patients were positive in the heparin-platelet factor 4-antibody assay, 28% in the polyanion-platelet factor 4-antibody assay, 14% in the heparin-induced platelet activation test, and 54% with any of these tests. Patients predominantly developed IgM (24%) and IgA antibodies (16%), whereas IgG antibodies were found in 12% of patients. Whereas the majority of patients with positive ELISA assays had IgM and IgA antibodies, patients with a positive functional assay (heparin-induced platelet activation test) predominantly had IgG antibodies. We conclude that a high percentage of patients develop heparin-induced antibodies after vascular surgery without any clinical symptoms of heparin-induced thrombocytopenia. None of the assays therefore is predictive of the clinical manifestation of heparin-induced thrombocytopenia in asymptomatic patients. Therefore, the diagnostic specificity of both antigen and activation assays for heparin-induced thrombocytopenia appears to be relatively low in the vascular surgery patient population.

Aged↗

[Current management of thromboembolism in pregnancy and puerperium].

Venous thromboembolism (VTE) remains the leading cause of maternal death. Today, various risk factors and conditions are known to increase the risk for VTE associated with pregnancy. Having identified the individual risk of a pregnant women, appropriate preventive measures can be taken. If VTE occurs during pregnancy, an appropriate immediate diagnostic work-up is essential in order to avoid further complications. For deep vein thrombosis (DVT) the diagnostic tool of choice is color-coded duplex-sonography, for pulmonary embolism (PE) perfusion/ventilation lung scan can be used. Integrating a detailed individual and family history, the presence of thrombophilia or other risk factors, a risk stratification can be undertaken. These risk categories are defined in the present paper and the appropriate treatment measures are described. As oral anticoagulants cross the placenta and may cause embryopathy in any trimester, oral anticoagulants should be avoided throughout pregnancy. Therefore, heparin is the anti-coagulant of choice for pregnant women, with low molecular weight heparins (LMWH) having distinctive pharmacological advantages over unfractionated heparins. Besides a potential for bleeding, the main side effects of heparin include heparin-induced thrombocytopenia which prompts for platelet monitoring, especially in the first weeks of heparin treatment, and, secondly, heparin-induced osteoporosis, which is a potential sequel of long-term heparin administration. Even though there are abundant reports in the literature on the use of LMWH in pregnant women, that show that they are safe and effective, LMWH are not specifically licensed for the use in pregnancy.

Anticoagulants↗

[Ambulatory treatment of an acute pulmonary artery embolism in fresh thigh vein thrombosis using low-molecular-weight heparin].

HISTORY AND CLINICAL FINDINGS: A 39 year-old man presented with dyspnoea and calf pain. Aside from two long-distance flights there were no triggering events for deep vein thrombosis (DVT). 6 years before the patient had had a spontaneous DVT. Family history concerning DVT was negative. INVESTIGATIONS: The patient presented with tachypnoea but no significant dyspnoea at rest. Color-coded duplex scan revealed a free floating thrombus in the left femoral vein, lung perfusion scan exhibited perfusion defects on the right side with a high probability for pulmonary embolism (PE). Echocardiography showed no signs of right ventricular failure. Thrombophilia screening was normal including prothrombin and factor V gene analysis. TREATMENT AND COURSE: As the patient refused hospital admission, after informed consent he was treated on an out-patient basis with low molecular weight heparin (LMWH) with the dosage adjusted to body weight, despite of the pending licensing of most LMWH for PE. Compression therapy was initiated and patient education on self-injection was performed. On the second day, oral anticoagulation was initiated. The further course was uneventful and long-term oral anticoagulation was continued. CONCLUSION: LMWH is at least as safe and effective as unfractionated heparin for the treatment of DVT, and it had been demonstrated that out-patient treatment of patients with DVT is safe. For PE however, most LMWHs are not yet licensed in Germany, even though recent studies show that they are safe and effective in the same doses regimen. As data on out-patient treatment of PE are sparse, out-patient treatment of symptomatic PE seems not generally advisable at present, although--as shown in the present case--it is feasible under particular circumstances.

Adult↗

Involvement of erythrocyte aggregation and erythrocyte resistance to flow in acute coronary syndromes.

The objective of the study was to identify the relative importance of erythrocyte flow resistance and aggregation in acute and chronic coronary syndromes. 117 subjects in five groups were studied: (1) 34 patients shortly after acute myocardial infarction (AMI) before reperfusion therapy; (2) 27 patients with unstable and (3) 21 with stable angina pectoris (AP); (4) 14 age-matched control patients and (5) 21 healthy volunteers. Single erythrocyte transit times were measured using the Cell Transit Analyser. Shear dependent elongation and aggregation was measured by a modified computerized Myrenne aggregometer. Leukocyte count was increased in coronary artery disease (CAD), especially in acute syndromes (mean +/- SD for groups 1-5): 12.2 +/- 4.5; 10.0 +/- 5.4; 8.0 +/- 2.0; 8.0 +/- 3.7; 7.0 +/- 2.0 (pl(-1))). Platelets, hematocrit, fibrinogen, alpha2-macroglobulin did not differ between the groups. Plasma viscosity (mPas) was elevated in AMI and stable AP: 1.34 +/- 0.10; 1.30 +/- 0.09; 1.32 +/- 0.08; 1.27 +/- 0.07; 1.27 +/- 0.05. Erythrocyte filtrability was not different as was the shear dependent deformation. Aggregation parameters such as gammaTmin were elevated in CAD: 180 +/- 70; 159 +/- 60; 166 +/- 59; 115 +/- 43; 113 +/- 51 (s(-1)). Erythrocyte deformability, measured with two independent methods, does not appear to contribute to the pathophysiology of acute coronary syndromes. Erythrocyte aggregation and plasma viscosity were again found increased both in unstable and stable coronary disease. It is unlikely that increased red cell aggregation contributes to emergence of AMI.

Acute Disease↗

[Standardization of nailfold capillary microscopy in routine diagnosis].

BACKGROUND: Nailfold capillary microscopy is scientifically established and recognized as a diagnostic tool in clinical routine. It is, however, practiced in only a few centres. METHODS: But since a more widespread use of the method is to be expected for the near future, a consensus-meeting was held, where all German-speaking clinicians and scientists, involved in capillary microscopy, were invited. Here, the technical procedure and the most important morphological parameters were evaluated and defined according to practical clinical aspects. RESULTS AND CONCLUSION: The main task of the consensus-meeting was to develop a standard evaluation sheet, accompanied by an explanation sheet. This standard evaluation sheet focuses on semiquantitative registration of morphological parameters like density, dilation, avascular fields, perivascular edema, microbleeding, torsion, atypical capillaries and giant capillaries. This standard evaluation sheet is to be validated by determining the inter-observer-variance. Later-on an illustrated practical guideline will be published.

Capillaries↗

Plasma profiles of transdermal 17 beta-estradiol delivered by two different matrix patches. A four-way cross-over study in postmenopausal women.

The aim of this study was to investigate the systemic bioavailability and plasma profiles of 17 beta-estradiol (CAS 50-28-2, E2) after the application of two types of matrix patches for the transdermal delivery of E2: MenorestTM (the test patch) with delivery rates of 37.5, 50 and 75 micrograms E2/day and a reference patch with a delivery rate of 50 micrograms E2/day. All 3 test patches were identical in composition, achieving different transdermal E2 delivery rates by variations in the surface area (11.0, 14.5 and 22.5 cm2). All 4 patches were each worn by 24 postmenopausal women over a 4-day period (i.e. 96 h), each of the 4 treatment periods being separated by a 7-day wash-out period according to a randomized, 4-way crossover design. Blood samples were collected before and 3, 6, 9, 12, 24, 34, 48, 58, 72, 84, and 96 h after each patch application. Plasma E2 concentrations were determined by a specific direct radioimmunoassay method. The following pharmacokinetic parameters were evaluated: AUC0-96h; Cmax, tmax, Cmin, Caverage. The course of the E2 plasma levels over the total test period (96 h) was relatively constant for all patches. For the test patch, a linear relationship between the pharmacokinetic parameters and the different patch areas (i.e. dosages of 37.5, 50, 75 micrograms E2/d) could be shown (correlation coefficient 0.99). The resulting Cmax values for the patch were: 44.2, 58.3, and 92.1 pg E2/ml, corresponding to Caverage values of 39.5, 45.5, and 70.6 pg E2/ml. The reference patch and the test patch, at a dose of 50 micrograms E2/d, were similar in terms of Cmax, while the Caverage, AUC0-96h and Cmin were significantly higher with the test patch. The systemic bioavailability of the reference patch was comparable to that of the test patch at a dose of 37.5 micrograms E2/d: AUC0-->96h 3017.5 +/- 1312.4 pg/ml.h for the reference patch and 3375.9 +/- 1254.7 pg/ml.h for the test patch. A physical model for the calculation of the course of the E2 levels was used to describe the experimentally determined data. However, in the evening, periodically higher E2 plasma levels were observed for all patches than in the morning. From these results it can be concluded that E2 plasma profiles produced by the test patch are reproducible, and in the physiological range consistent with the early to mid follicular level in the premenopausal woman over 4 days (96 h), correlating with the doses administered (37.5-50-75 micrograms E2/d). Additionally, the systemic bioavailability of the test patch at a dose of 37.5 micrograms E2/d is comparable to that of the reference patch at a dose of 50 micrograms E2/d.

Administration, Cutaneous↗

[Significance of hereditary thrombophilia for risk of thrombosis with oral contraceptives].

Oral contraceptives increase the natural incidence of venous thromboses of 1-2/10,000 women per year 3-to 4fold. Recent investigations have shown that during intake of desogestrel or gestodene containing formulations the risk is twice that with older low-dose ovulation inhibitors. This difference is larger in first time users than in women who had previously used an oral contraceptive. During pregnancy, the incidence of thromboses rises up to 10/10,000 women-years and post partum up to 40/10,000 women-years. In about 60 % of thromboses no causal explanation can be found. It is suggested that in 40 % of all cases an inherited thrombophilia is present. Among the hereditary types of thrombophilia, the resistance against activated protein C (APC-resistance) represents nearly 50 %, while altogether 15 to 20 % is based on a deficiency of antithrombin III, protein C or protein S. APC-resistance the prevalence of which is 3-5 % in the general population, increases the risk of thrombosis 8fold and in users of oral contraceptives 35fold. Protein C-deficiency (prevalence 0.1-0.5 %) increases the risk of thrombosis 9fold and in users of oral contraceptives 15fold, while antithrombin III-deficiency (prevalence 0.02-0.05 %) enhances the risk in pill-users 8fold. Ovulation inhibitors do not influence risk of thrombosis in women with protein S-deficiency. Antiphospholipid-antibodies the concentration of which may increase during treatment with oral contraceptives, represent a considerably enhanced risk of thrombosis, too. A positive family history (before age of 40 years) indicates an inherent thrombophilia. In these risk groups, the cost/benefit ratio of a selective screening is unfavorable, as at most 70 % of the hereditary thrombophilias can be diagnosed by laboratory analysis, and only very few patients will actually experience a thrombotic event: only 3 of 1000 carriers of APC-resistance will suffer from thrombosis during oral contraception per year. On the other hand, a negative result of laboratory tests does not exclude a hereditary thrombophilic disorder which as yet cannot be substantiated. It is not yet clarified whether a selective screening is superior to a careful assessment of individual and family history. A general screening cannot be justified because of the unfavorable cost/benefit ratio. If the individual or family history or pathological laboratory parameters indicate an enhanced risk of thrombosis, this risk has to be carefully weighed against the consequences of discontinuation of pill use. Those few individuals with risk factors who will experience a thrombosis, cannot be identified in advance. If in patients with thrombophilic disorders and/or other risk factors the use of oral contraceptives represents a particularly high risk, other contraceptive methods should be taken into consideration. If a patient with risk factors decides for the use of oral contraceptives, she has to be informed that in the case of symptoms indicating a thrombosis, the physician has to be consulted immediately. The earlier an appropriate therapy is initiated, the more effectively an acute pulmonary emboli or permanent damages, e.g. the post-thrombotic syndrome, can be prevented.

Adult↗

[Risk of thrombosis with oral contraceptives: value of a thrombophilia screening test].

Oral contraceptives increase the natural incidence of venous thrombosis of 1-2/10,000 women per year 3- to 4-fold. Recent studies have shown that desogestrel or gestodene containing formulations bear twice the risk of older low-dose ovulation inhibitors. During pregnancy, the incidence of thrombosis rises to 10/10,000 women-years and post partum up to 40/ 10,000. For 60% of thromboses no causal explanation can be found. In approximately 40% of the patients an inherited thrombophilia can be presumed. Among the hereditary types of thrombophilia, a resistance to activated protein C (APC-resistance) represents nearly 50%, while in 15 to 20% a deficiency of antithrombin III, protein C or protein S is found. APC-resistance, with a prevalence of 3-5% in the general population, increases the risk of thrombosis 8-fold and in users of oral contraceptives 35-fold. Antithrombin III-deficiency carries a comparable risk. Protein C-deficiency increases the risk of thrombosis 9-fold and in users of oral contraceptives 15-fold. Ovulation inhibitors do not influence the risk of thrombosis in women with protein S-deficiency. Anti-phospholipid-antibodies increase during treatment with oral contraceptives and represent a considerably enhanced risk of thrombosis. Inherent thrombophilia is suspected in a patient with a positive history or family history of thrombosis, especially with thrombosis before the age of 40 or with atypical localisation. Even in these risk groups, the cost-benefit ratio of selective screening is unfavorable, as today at most 70% of the hereditary thrombophilias can be diagnosed by laboratory analysis, and only very few of the patients will actually experience a thrombotic event: only 3 of 1000 carriers of APC-resistance will suffer from thrombosis during oral contraception. On the other hand, a negative result of laboratory tests does not exclude a hereditary thrombophilic disorder. At present, it is unclear whether a selective screening process is superior to a careful assessment of individual and family history. A general screening, however, cannot be justified because of the unfavorable cost/benefit ratio. If the individual or family history or pathological laboratory parameters indicate an increased risk of thrombosis, this risk has to be carefully weighed against the consequences of discontinuation of pill use. Those few individuals with risk factors who will experience a thrombo-embolic event, cannot be identified in advance. If oral contraceptives represent a particularly high risk in patients with thrombophilic disorders and/or other risk factors, other contraceptive methods should be considered. If a patient with risk factors decides on the use of oral contraceptives, she must be informed that in the case of symptoms indicating a thrombosis, a physician should be consulted immediately. The earlier an appropriate therapy is initiated, the more effectively pulmonary thrombo-embolism and permanent damage, such as the post-phlebitic syndrome, can be prevented.

Adult↗

[Kinetics of a new patch for transdermal administration of 17 beta-estradiol].

A novel patch containing 17 beta-Estradiol exhibits improved kinetic profiles compared to the currently available leading transdermal product. The blood concentrations produced by the newly developed matrix patch are stable over 3 to 4 days, thus avoiding the occurrence of 17 beta-Estradiol peaks in the blood. In an additional clinical study an almost linear relationship could be identified between the patch size (Test patch: 7.25, 14.5 and 29.0 cm2) and the obtained 17-estradiol bioavailability (judged on AUC, cmax, c(ave), Cmin). These results are corroborated by the additional in vitro experiments. An almost constant drug delivery rate of 48 micrograms +/- 15 micrograms/day of 17 beta-Estradiol per 13.85 cm2 patch over 4 days can be detected through excised human skin. No statistically significantly different transdermal flux rates of 17 beta-Estradiol were detected in 3 different batches of the transdermal drug delivery system in vitro. Statistical evaluations were performed with the 3-Way-Anova test on the 0.05 significance level. This newly developed product presents a kinetically optimized transdermal 17 beta-estradiol patch for hormone substitution therapy.

Administration, Cutaneous↗

Microcirculatory long-term effects after hypervolaemic and isovolaemic haemodilution in patients with intermittent claudication.

OBJECTIVE: The aim of the present study was to clarify the possible long term effects in the course of different haemodilution regimes according to the tissue oxygen supply in the lower limb muscle of patients with intermittent claudication. METHODS: In order to simulate the situation of intermittent claudication muscle tissue pO2 measurements were performed before and after a standardized pedal ergometric test. Muscle tissue pO2 readings were performed using micro-pt-needle electrodes at a work load of 5.7 +/- 0.2 Watt. We performed hypervolaemic haemodilution as well as isovolaemic haemodilution intraindividually and in order to compare these different regimes we have chosen the situation, when the haematocrit had returned to the pretreatment values. RESULTS: Observing 4 weeks after the end of isovolaemic haemodilution the red blood cell aggregation is significantly decreased, whereas the other haemorrheological variables remained unchanged. Furthermore muscle tissue pO2 values are increased at rest without improvement of the exercise-induced muscle tissue pO2. In contrast there is no effect on haemorrheological variables as well as muscle tissue oxygen supply at rest and after pedal ergometric exercise test after the end of hypervolaemic haemodilution. CONCLUSIONS: Our results suggest no benefit in the course of a long-term hypervolaemic haemodilution therapy in patients with intermittent claudication. In contrast after isovolaemic haemodilution there was found an increase in muscle tissue oxygen supply at rest without changing of the exercise-induced pattern. In our opinion isovolaemic haemodilution is to prefer in the course of long-term haemodilution therapy.

Blood Gas Monitoring, Transcutaneous↗

Muscle tissue PO2 during moderate altitude exposure in patients with peripheral arterial occlusive disease.

OBJECTIVES AND METHODS: In 10 patients with peripheral arterial occlusive disease (intermittent claudication) and in 10 healthy volunteers serving as controls, muscle tissue pO2, transcutaneous pO2, arterial pO2 and rheological parameters were measured before and during breathing (for 20 min) of an oxygen reduced gas mixture simulating an altitude of about 8500 feet (2600 m, approximately 116 mm Hg pO2). Oxygen pressure values were determined by means of a polarographic method according to Ehrly and Schroeder using atraumatic micro-pt-needle electrodes. RESULTS: Tissue oxygen tension in the tibialis anterior muscle of patients with peripheral arterial occlusive disease decreased significantly from 6.5 mm Hg to 2.4 mm Hg (medians). The pooled histograms were markedly shifted to hypoxic values. The controls showed a decrease from 20.8 to 12.2 mm Hg and a strong shift to the left. Transcutaneous pO2 measured in the diseased leg decreased from 53.4 +/- 11.6 to 36.1 +/- 9.3 mm Hg (controls 57.1 +/- 9.9 to 39.7 +/- 8.9 mm Hg), arterial pO2 decreased from 80.2 +/- 15.1 to 60.0 +/- 10.4 mm Hg (controls: 86.5 +/- 16.0 to 64.7 +/- 13.6 mm Hg) and pulsoximetrically determined O2-saturation from 95.0 +/- 2.5 to 90.0 +/- 5.5% (controls: 96.1 +/- 2 to 92.0 +/- 4.2%). CONCLUSIONS: Exposure of patients with intermittent claudication to moderate altitude led to a marked decrease of tissue pO2 values in the diseased legs without any evidence of clinical worsening, especially no rest pain. It may be discussed if rest pain in ischaemic legs is due to low pO2-values or to disturbed microcirculatory perfusion.

Aged↗

[The effect of co-dergocrine mesylate on erythrocyte deformability of hyperosmolar blood in vitro].

Addition of low doses of co-dergocrine mesilate (CAS 8067-24-1), a drug containing a mixture of hydrated ergot alkaloids to hyperosmolar blood in vitro leads to a dose-dependent increase in erythrocyte filterability through a 8 mu filter system. The concentrations of co-dergocrine mesilate used in the present experiments ranged from 0.04675-6.0 mg/100 ml blood. Blood samples were incubated for 90 min at 37 degrees C, measuring temperature was 37 degrees C. It could be shown that the drug-induced increase in erythrocyte filterability was not dependent on the presence of leucocytes. At higher osmolarity values, when the erythrocytes were more rigid, higher concentrations of codergocrine mesilate were needed in order to obtain a comparable improvement in red cell deformability.

Ergoloid Mesylates↗

Hematocrit dependent changes of muscle tissue oxygen supply in the lower limb muscle of patients with intermittent claudication.

Hematocrit dependent changes of muscle tissue oxygen supply at rest and after exercise were detected in 23 patients with chronical arterial occlusive disease stage IIb according to Fontaine. In these patients with a concomitant high hematocrit a stepwise isovolemic hemodilution by vena esection and subsequent infusion of 10% hydroxyethylstarch solution (200/0.5%) was achieved intraindividually. Measurements of muscle tissue oxygen pressure (pO2) values in the lower limb muscle using a standardized pedalergometric exercise test as well as pain free walking distance with a treadmill were performed. Improvement of muscle tissue pO2 supply after pedalergometric exercise as well as muscular performance on the treadmill were found at an average hematocrit value of 40.50%, whereas muscle tissue oxygen supply and pedalergometric performance were markedly reduced at hematocrit 50.60% as well as 33.75%. Thus it is likely that an improvement of muscle tissue oxygen supply in severe intermittent claudication can be achieved by isovolemic hemodilution to hematocrit values about 40-41%.

Blood Viscosity↗

Exercise-induced variations in muscle tissue oxygen pressure in claudicants: effects of buflomedil.

The amount of oxygen actually supplied to the ischemic muscle tissue of patients with intermittent claudication was quantified before and after a standardized pedal ergometric test. Muscle tissue pO2 was measured with micro-platin needle electrodes directly in the lower limb muscles at rest and 3, 10, 20 and 60 min after a 4-min work load. Time-dependent variations in the behavior of pO2 values as well as changes in the shapes of pooled pO2 histograms make it possible to monitor the effect of therapeutic measures. In claudicants (stage IIb) with ascertained occlusions or stenosis of the femoral artery or the pelvis region, it was demonstrated that the delayed increase in tissue pO2 after exercise could be improved by the infusion of 400 mg buflomedil. Comparison between the time-related pooled histograms confirmed improvement of oxygen supply under the influence of this drug.

Adult↗

[Effect of stepwise hypervolemic versus isovolemic hemodilution in patients with intermittent claudication on muscle oxygen pressure during exercise].

In patients with intermittent claudication and concomitant high hematocrit values a stepwise hypervolemic hemodilution versus isovolemic hemodilution (intravenous infusion of 500ml 10% hydroxyethylstarch solution (HES)(mean molecular weight 200.000/substitution degree 50%) or vensection and subsequent infusion of 10% HES (200/0.5)) were performed intraindividually. Measurements of muscle tissue oxygen pressure (pO2) values using a standardized pedalergometric exercise test as well as the pain free walking distance using a standardized treadmill were performed. Optimal results of muscle tissue oxygen pressure (pO2) behaviour after pedalergometric exercise test as well as muscular performance on the treadmill were found using isovolemic hemodilution at an average hematocrit value of 40.60%. In contrast, hypervolemic hemodilution at a comparable hematocrit level (40.50%) induced a "retarded reactive hyperoxia" and only a moderate increase of painfree walking distance.

Adult↗