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Biomedical subjects

M Havel

Publications and source records attributed to M Havel.

At least 55 records · Page 3Linked to original sources

[The course of atrial natriuretic peptide, aldosterone and antidiuretic hormone in normal pregnancy].

Atrial natriuretic peptide (ANP), consisting of 28 aminoacids, is a recently discovered cardiac hormone involved in blood-volume homeostasis. Pregnancy is associated with an increase in blood volume expansion, therefore an increase in ANP-concentration would have been expected. To test this hypothesis ANP, Aldosterone and Vasopressin, concentrations of 229 women with normal pregnancies at different gestational ages were measured and compared with values found in a non-pregnant control group of 24 women. Mean plasma ANP was increased during pregnancy, but significant differences were noted only after 36 weeks of gestation. Also plasma aldosterone increased significantly during pregnancy, whilst vasopressin levels showed no significant change compared to the non-pregnant group.

Adolescent↗

Beta 2-microglobulin. A reliable parameter for differentiating between graft rejection and severe infection after cardiac transplantation.

We investigated the role of beta 2-microglobulin as a noninvasive parameter to monitor acute rejection and severe infection in 45 consecutive heart transplant recipients. Endomyocardial biopsy revealed moderate (41 patients) or severe (three patients) rejection in 44 patients. Severe infections of bacterial septicemia (11 patients), bronchopneumonia (two patients), and viral infection (seven patients) were detected by a meticulous schedule of various clinical and laboratory tests. beta 2-Microglobulin levels in serum, generally corrected for serum creatinine, were significantly elevated in patients with infections (median, 6.3 mg/l; range Q10-Q90, 3.47-10.27 mg/l) compared with levels in patients with rejection (p less than 0.0001) or in patients in obviously good condition (p less than 0.0001). At the onset of acute rejection, the median corrected beta 2-microglobulin serum level was 1.56 mg/l (range Q10-Q90, -0.05-3.46 mg/l) and was significantly different from the control group (p less than 0.01). In addition, density function and empirical quantile analyses allowed us to define ranges of beta 2-microglobulin levels that would differentiate between rejection (2.05-3.46 mg/l) and infection (greater than 3.46 mg/l). With these values, sensitivity and specificity were 0.9 and 0.938 for detection of infection and 0.23 and 0.925 for detection of rejection, respectively. By means of beta 2-microglobulin, two cases of infection were misinterpreted as rejection (10%), and four of 44 rejections were mistaken for infections (9%). We conclude that measurements of beta 2-microglobulin may improve the management of heart transplant patients.

Adult↗

Diagnostic validity of multivariate combinations of biochemical analytes as markers for rejection and infection in the follow-up of patients with heart transplants.

The diagnostic validity of multivariate combinations of alpha 1-antitrypsin, alpha 2-macroglobulin, C-reactive protein, complement C3, complement C4, neopterin in serum, and neopterin in urine as markers for acute cardiac allograft rejection and for differential diagnosis of rejection and infections was investigated in the follow-up of 37 patients with heart transplants. Rejection was diagnosed by endomyocardial biopsy. Infections were classified as 'no infection', 'viral infection', and 'bacterial, fungal or mixed infections'. Although there are significant differences between the mean levels of analytes, multivariate discriminant analysis does not provide an adequate discrimination of rejection and infection states. In separate rejection diagnosis, multivariate combinations of analytes cannot replace endomyocardial biopsy. However, a multivariate combination of alpha 1-antitrypsin, alpha 2-macroglobulin, C-reactive protein, C3, C4 in serum, and neopterin in urine can be used as a screening procedure to reduce the number of endomyocardial biopsies.

Adolescent↗

[Orthotopic heart transplantation--experiences at the University Surgical Clinic II in Vienna (status: June 1986)].

Since 1984 27 heart transplantations (HTX) were carried out in 25 patients at the 2nd Department of Surgery, University of Vienna. The classic orthotopic technique of Lower and Shumway was used in all cases. Routine immunosuppression consisted of azathioprine and cyclosporin-A. In order to treat the main complications successfully, i.e. rejection and infections, we were compelled to establish an extensive follow up regimen. The early recognition of acute rejection was based on the findings obtained by cutaneous as well as epicardial ECG leads, in conjunction with cytoimmunological monitoring on the basis of RIA measurements of the serum levels of Neopterin and gamma-Interferon. Furthermore, we recorded some parameters of ventricular performance, such as the isovolumetric relaxation time and the radiologically measured heart volume. An endomyocardial biopsy was carried out to secure the diagnosis. Pulsed doses of methylprednisolone were used for the treatment of rejection, facultatively combined with ATG in the absence of improvements. Infections were pinpointed by comprehensive serum tests and various blood, sputum and urine cultures. The management consisted of treatment with the requisite antibiotics. Of 25 primarily transplanted patients 15 patients are still alive. 5 persons, amongst them 2 children, have survived already for more than 1 year. 6 patients died at an early stage. In 3 cases the cause of death was intractable infection. In 1 case multi-organ failure occurred and 1 patient died due to acute organ failure. 4 patients died at a late stage and acute severe rejection was responsible in all these cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Cyclosporin-A induced heart failure after orthotopic heart transplantation.

Two patients suffering from dilated Cardiomyopathy (CMP) had to undergo orthotopic heart transplantation (HTX). In both cases, the postoperative period was without any complications. The immunosuppression consisted of Cyclosporin-A and Azathioprine including a one week prophylactic treatment with Antithymocyte Globuline (ATG). Four months postoperatively, they developed clinical signs of heart failure. The endomyocardial biopsies showed rejection at stage I according to Billingham's grading plus a fine interstitial fibrosis. Therefore, the Cyclosporin treatment was suspended and replaced by conventional immunosuppression consisting of Prednisolone and Azathioprine. Acute heart failure was managed by catecholamines in combination with aggressive diuretic therapy. After three weeks, both patients recovered. 12 weeks later, one died because of an acute rejection episode. The other is in good condition, with conventional immunosuppression at the present time. A vascular process caused by Cyclosporin-A as the pathogenic mechanism is considered. The absence of rejection signs in the biopsies as well as the remarkable improvement of heart failure after withdrawal of Cyclosporin-A support this possibility.

Coronary Disease↗

Tolerability of a new vitamin K1 preparation for parenteral administration to adults: one case of anaphylactoid reaction.

The efficacy and tolerability of a conventional vitamin K1 preparation containing polyoxyethylated castor oil as solubilizer were compared with those of a new compound containing mixed micelles as solubilizer in 30 patients. A statistically significant increase in the thrombotest was detected after treatment in both groups. No hematological or chemical toxicity was observed during the observation period. One patient had an anaphylactoid reaction after intravenous injection of the mixed micelles preparation. Intradermal testing yielded positive results. The authors conclude that intravenous administration of vitamin K preparations should be reserved for acute emergencies.

Adult↗

[Measuring cyclosporin in immunosuppressive treatment following liver and heart transplantation].

Selective suppression of the immune system in graft recipients is now achieved in most cases by treatment with cyclosporine A. Due to large individual differences in absorption, utilization and metabolisation of this drug, therapeutic blood levels (immunosuppression/toxicity) can be maintained only by frequent measurements of the cyclosporine concentrations in blood samples and dosage readjustments. In the present study, we measured cyclosporine in whole blood samples from 37 patients (23 liver and 14 heart transplant recipients) using an high pressure liquid chromatographic method for native cyclosporine A which has been developed in our laboratory and a radioimmunoassay method (cyclosporine A + metabolites). By comparison of the results of HPLC and RIA-measurements (n = 520) we found a relatively stable metabolization rate (RIA/HPLC-ratio) of 4.23 +/- 1.30 for heart transplant recipients. In contrast RIA/HPLC ratios were highly variable in liver graft recipients ranging from 1.3-9 for the same patient in the posttransplant period. The liver recipients could be classified into two groups according to their mean RIA/HPLC-ratios: for 11 patients we observed a mean ratio of 2.65 +/- 0.35, for another 12 patients one of 4.35 +/- 0.75. Lower metabolisation rates seem to be associated with low donor age. No direct correlation was found between changes in RIA/HPLC-ratios and liver function, rejection and infection periods. Rejection treatment with high doses of methylprednisolone had no systematic influence on cyclosporine metabolisation in our patients. Since cyclosporine metabolites, at least those ones which are most abundant, have less immunosuppressive and toxic effects we recommend measurements of cyclosporine blood concentrations with any HPLC-method specific for the unchanged drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗

Reversed-phase high-performance liquid chromatographic separation of steroids with the beta-crotonate side chain.

An isocratic high-performance liquid chromatographic separation of some ethyl 3-stereoidyl crotonates [ethyl-24-nor-20(22)-cholen-23-oate derivatives] was developed. The separations were achieved by reversed-phase chromatography (Separon Si C18) using methanol, methanol-water, methanol-0.1 M formic acid and ethanol-0.01 M aqueous phosphoric acid mixtures as mobile phases. The steroidal crotonates were detected at 230 and 240 nm.

Butyrates↗

Neopterin and interferon gamma serum levels in patients with heart and kidney transplants.

The main problem in the follow-up of patients receiving organ allografts is the early differential diagnosis of rejection episodes and infections. Serum levels of interferon gamma, a marker of T-lymphocyte activity, were determined with an immunoradiometric assay, specific for biologically active interferon gamma and sufficiently sensitive (20 U/l) for the determination of circulating interferon gamma. Neopterin, a pteridine released from stimulated macrophages, was determined by radioimmunoassay. Both rejection crises and infections are accompanied by distinct increases of serum neopterin (median values 124 and 128 nmol/l; N = 98). Interferon gamma levels are elevated for a short period one or two days earlier, the maximal values during infections (median 430 U/l, range 120-1220 U/l, N = 25) being higher than those during rejection episodes (median 120 U/l, range less than 20-330 U/l, N = 73). Each rise of interferon gamma was followed by an increase of neopterin, but not every neopterin increase was preceded by a interferon gamma peak. Neither of these parameters showed an increase during deterioration of kidney function due to cyclosporin toxicity. The determination of interferon gamma, a lymphokine involved in the activation of alloreactivity, reflecting T-cell stimulation, and the measurement of neopterin, a secretory product of activated macrophages, allows the simple, quick and reliable monitoring of the immune status of transplant recipients.

Adolescent↗

Time course of alterations in muscle transfers with microneurovascular anastomoses. An experimental study in the rectus femoris muscle of the rabbit.

The time course of alterations in muscle transfers with microneurovascular anastomoses was studied in 17 rabbits. The left rectus femoris muscle was transferred to the right side. For comparison, in some animals the right rectus femoris muscle was transferred from the right to the left side, but without vascular repair. Two, seven, 14, 21, and 30 days after transfer, the electric excitability, macroscopic appearance, histology, histochemistry, ultrastructure, and activity of muscle enzymes were assessed. In the transfers with microneurovascular anastomoses, almost all muscle fibers survived. Alterations were limited to those typical of a denervation-reinnervation process. Contrary to this, only a few atrophic fibers survived in the periphery of the transfers without vascular repair. By far, the greater central part underwent necrosis. A considerable amount of connective tissue developed. These results clearly show the functional superiority of microsurgically vascularized muscle transfers over those without vascular anastomoses. Excellent functional recovery is possible because the process of complete degeneration and consecutive regeneration, with inevitable augmentation of connective tissue, is prevented by the performance of vascular anastomoses.

Anastomosis, Surgical↗