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Biomedical subjects

M Wimmer

Publications and source records attributed to M Wimmer.

At least 19 recordsLinked to original sources

Ascaris suum: protein phosphotyrosine phosphatases in oocytes and developing stages.

Protein tyrosine phosphatases were analyzed in oocytes of Ascaris suum. Phosphatases dephosphorylating modified acidic lysozyme were present in high-molecular-weight form (M(r) > 600,000) and as a 50- to 55-kDa protein in the soluble fraction. The low-molecular-weight form of the phosphatase cross-reacted with an antiserum raised against human T-cell protein tyrosine phosphatase and was not distinguishable from the 50- to 55-kDa protein tyrosine phosphatase previously described in the muscular layer of the adult worms (B. Schmid et al. 1996, Molecular and Biochemical Parasitology 77, 183-192). The low-molecular-weight form was also present on immunoblots of high-molecular-weight protein tyrosine phosphatase preparations after denaturing electrophoresis. The same or a similar form of the tyrosine phosphatase was also found in detergent extracts from the pelletal fraction. In addition, another tyrosine phosphatase of 180 kDa molecular mass that dephosphorylated myelin basic protein was also found in extracts from the soluble compartment as well as in detergent extracts from the pelletal fraction. It showed no cross-reactivity with antisera raised against soluble mammalian phosphatases and was resistant to inhibition by vanadate. While the activities of the myelin basic protein-dephosphorylating protein phosphatase remained fairly constant during early development of the oocytes, the activity of the enzyme dephosphorylating modified lysozyme in the pelletal fraction decreased to less than 10% of the initial activity between days 3 and 28 of incubation. Immunocytochemical studies of unfertilized and developing Ascaris eggs revealed association of protein tyrosine kinase and protein tyrosine phosphatase with the egg shell, in addition to their presence in the neighborhood of mitochondria. The amount of enzyme changed with the stage of development. In the larval stage (21 days) protein tyrosine kinase had increased in the chitin layer of the shell and in the nuclei while the relative amount of tyrosine phosphatase decreased in accordance with the biochemical data.

Animals

[Aortic coarctation--long-term follow-up in adults].

Surgical repair of coarctation of the aorta has been performed since 1945. Although surgical techniques have improved, problems such as restenosis and aneurysm at the operation site or hypertensive cardiovascular disease, still remain. To evaluate the long-term results after surgical repair of coarctation, 41 patients, 25 male and 16 female patients (mean age: 28 +/- 11 years, range 14-57 years), were studied 16 +/- 8 years after surgery (range 3-44 years). Mean age at surgery was 12 +/- 9 years (range 0.5-35 years). In 24 patients resection and end-to-end anastomosis had been performed, patch graft aortoplasty in nine patients, tube interposition graft in seven patients and one patient had undergone the subclavian flap technique. All patients were assessed by exact physical examination, the resting arm-to-leg systolic pressure gradient was measured by Doppler sonography, a bicycle exercise test and an echocardiogram were performed. Twenty-one patients reported postoperative symptoms such as dizziness (n = 12), headache (n = 3), cold legs (n = 10) and/or dyspnea (n = 8). In two patients the resting arm-to-leg pressure gradient was greater than 30 mm Hg, in two patients it was greater than 20 mm Hg. Gradient calculated by Doppler echocardiography ranged from 0 to 80 mm Hg (21 +/- 17 mm Hg) and showed poor correlation with the arm-to-leg pressure difference. The mean functional capacity was 89 +/- 18% (range 42-110%). In 18 patients exercise-induced hypertension was found, while in only eight patients arterial hypertension had already been known. To evaluate the morphology of the aorta MRI was performed in 28 patients. No aneurysm was found. In five patients a minimal lumen diameter as small as 9-11 mm was measured. Patients were divided into two groups according to their age at operation, group I: < 9 years (n = 19) and group II: > 9 years (n = 22). Resting blood pressure was significantly higher in group II (135 +/- 27 mm Hg vs 114 +/- 20 mm Hg, p < 0.009), anti-hypertensive medication (43% vs 11%, p < 0.04) and symptoms were more frequent in these patients (15/22 vs 6/19, p < 0.04). However at time of follow-up examination the age of patients of group II was significantly higher (33 +/- 12 vs 22 +/- 5 years, p < 0.0005). Between these two groups there was no difference in follow-up time and results of echocardiography or stress test. In conclusion, despite good long-term results after surgical repair of coarctation of the aorta, patients should be followed on a regular basis primarily in order to recognize systemic hypertension as early as possible and to improve the long-term outcome in these patients by antihypertensive treatment.

Adolescent

Myoadenylate deaminase deficiency, hypertrophic cardiomyopathy and gigantism syndrome.

We report a 20-year-old man with gigantism syndrome, hypertrophic cardiomyopathy, muscle weakness, exercise intolerance, and severe psychomotor retardation since childhood. Histochemical and biochemical analysis of skeletal muscle biopsy revealed myoadenylate deaminase deficiency; molecular genetic analysis confirmed the diagnosis of primary (inherited) myoadenylate deaminase deficiency. Plasma, urine, and muscle carnitine concentrations were reduced. L-Carnitine treatment led to gradual improvement in exercise tolerance and cognitive performance; plasma and tissue carnitine levels returned to normal, and echocardiographic evidence of left ventricular hypertrophy disappeared. The combination of inherited myoadenylate deaminase deficiency, gigantism syndrome and carnitine deficiency has not previously been described.

AMP Deaminase

Quality management and influential factors for the detection of single metastatic cancer cells by reverse transcriptase polymerase chain reaction.

The sensitive and specific detection of micrometastasis holds great promise for earlier staging of cancer patients. By amplification of tissue-specific gene expression, the reverse transcriptase polymerase chain reaction (rtPCR) readily detects single tumour cells in different tissues. An increasing number of rtPCR assays with possible relevance for routine laboratory diagnostic procedures is currently being reported in the literature. Interestingly, when used in the clinical setting, assays for the same target mRNA perform very differently, despite comparable sensitivities and specificities in-vitro. Using rtPCRs specific for carcinoembryonic antigen (CEA), prostate-specific antigen (PSA) and cytokeratin 18 (CK 18), we have started to systematically investigate, both experimentally and in clinical specimens, a number of factors that contribute to the varying and seemingly implausible test results. Here we have concentrated on sample collection modalities, assay stability and test reproducibility at the sensitivity limit. Our results demonstrate in detail that, at the maximum sensitivity required for micrometastasis detection, preanalytical and statistical influences increasingly become important for the consistency of the assay results. We conclude that the prerequisite for translating the results from highly sensitive and specific rtPCR assays into clinically relevant data is the thorough definition of assay procedures and the number of tests performed on a sample. Addressing questions of standardization and quality control management is a central aspect yet to be emphasized in assay development and application of routine laboratory rtPCR tests in oncology.

Carcinoembryonic Antigen

Effect of detailed fetal echocardiography as part of routine prenatal ultrasonographic screening on detection of congenital heart disease.

BACKGROUND: Cardiac abnormalities are frequently not detected by routine ultrasound screening examinations. Although detailed fetal echocardiography is more sensitive in detection of congenital heart disease, it is used only for high-risk cases. The main aim of this study was to assess the prenatal detection of congenital heart disease by detailed fetal echocardiography in an unselected, consecutive group of pregnant women. METHODS: Between Jan 1, 1993, and Sept 30, 1994, all women who attended our antenatal-care unit were routinely offered a detailed fetal echocardiography examination at 18-28 weeks' gestation. 3085 consecutive women were screened: 2181 were screening cases with no known risk factor for congenital heart disease; 540 had maternal risk factors for congenital heart disease, such as a family history or coexisting maternal disease; 364 had sonographically detected abnormalities. The examination included the four-chamber view, outflow-tract scan, and colour-flow mapping; doppler and M-mode investigations were also done when appropriate. FINDINGS: 46 cases of congenital heart disease were detected prenatally by echocardiography-15 in the group with no risk factors, three in the group with maternal risk factors, and 28 in the group with sonographic abnormalities. Postnatal assessments found six further cases of congenital heart disease that had not been detected prenatally, but these were all minor cases. There were no false-positive diagnoses (sensitivity 85.5%, specificity 100%). The incidence of congenital heart disease in screening cases with no risk factors and in those with maternal risk factors was low (6.9% per 1000, 5.6 per 1000) and similar to the expected overall incidence of 8.0 per 1000 livebirths in the general population. In the group with sonographic abnormalities congenital heart disease was found significantly more often (79.9 per 1000). INTERPRETATION: Inclusion of detailed fetal echocardiography as a screening examination has a substantial effect on detection of congenital heart disease since a major proportion of prenatally detectable cases occur in a low-risk population.

Adult

Protein phosphotyrosine phosphatases in Ascaris suum muscle.

Two forms of protein tyrosine phosphatases were partially purified from the musculo-cutaneous layer of Ascaris suum. A 50-55-kDa soluble form of the phosphatase cross-reacted with antisera raised against human PTP-1B and TC-PTP. Like the enzyme of human origin the phosphatase from Ascaris exhibited a preference for anionic substrates (tyrosine-phosphorylated carboxymethylated and maleylated lysozyme) and was inhibited by micromolar concentrations of vanadate, molybdate, Zn2+, heparin, and poly(Glu4Tyr). As revealed by immuno-cytochemistry, the phosphatase was mainly localized and appeared equally distributed in the cytoplasm, apart from the myofibrils, possibly in loose association with cytoskeletal elements. A second tyrosine phosphatase of 180 kDa molecular mass was mainly found in detergent extracts from a microsomal fraction. It showed no cross-reactivity with antisera raised against soluble mammalian phosphatases and dephosphorylated a basic substrate (Tyr-phosphorylated myelin basic protein). It was resistant to common inhibitors of mammalian tyrosine phosphatases except Zn2+ and thiol reagents.

Animals

[Prenatal diagnosis of Bourneville-Pringle disease (cerebral tuberous sclerosis)].

An infant presented with prenatal marked fetal cardiac arrhythmia, not related to labour, and had intracardiac tumours. The association of cardiac tumours with tuberous sclerosis (Bourneville-Pringle disease) is described, using ultrasonic, radiological and electrocardiographic data, and reviewing the literature.

Arrhythmias, Cardiac

[Function and structure of families with chronically ill children].

In modern medicine especially the sick child often points out the limits of the psychosocial potentialities. This project investigates the function, structure, coping mechanisms, power and weakness of families with chronically ill children. We investigated 28 children from the nephrological ward and 55 patients from the cardiological department and also their families with the FAM III and compared the obtained T-scores with the results of the control-group (76 families, t-test, analysis of variance). Families with patients after renal transplantation (NTX) pointed out significant worse T-scores than the group with patients on CAPD or with preterminal renal insufficiency and CG (p < 0.05). Within the cardiological groups the differences were not statistically significant, on the other hand the group with patients before heart-operation and the group with patients after palliative heart-operation had better T-scores than the CT (p < 0.05). These results demonstrate that families with children suffering from a chronic renal or heart disease mobilize substantial resources to cope with these problems. By contrast the results of the families with patients after NTX or successful heart surgery are significant worse than the control-group and the other investigated patients groups. Our results come to the conclusion that especially after successful NTX or heart-surgery a psychosocial care of these families is necessary.

Adaptation, Psychological

Erythropoietin, erythropoesis and iron status in children after major surgical stress.

UNLABELLED: The aim of our study was to evaluate bone marrow stimulation and bone marrow response to post-operative anaemia in children after open heart surgery. In 16 children (age 5.7 +/- 0.9 years, weight 20.1 +/- 3.2 kg) serum erythropoietin, haematocrit, reticulocyte count, ferritin, transferrin saturation and C-reactive protein were assessed perioperatively after cardiopulmonary bypass for surgical repair of atrial septal defect. Erythropoietin increased seven fold from 14 +/- 6.2 (7-30) to 80 +/- 49 (20-171) mU/ml (P < 0.05) and the reticulocyte count a 1.7-fold from 11.1 +/- 3.1 (6-19) to 18.4 +/- 5.9 (10-31) / 1000 (P < 0.05). Transferrin saturation was inversely correlated to C-reactive protein. CONCLUSION: These findings suggest adequate bone marrow stimulation but an inadequate bone marrow response during the immediate perioperative period, caused by inhibition of erythropoesis by acute postoperative inflammation in children after open heart surgery.

Acute-Phase Reaction

[Balloon dilatation of postoperative and congenital aortic isthmus stenoses].

From July 1987 to December 1992, 52 patients underwent balloon-angioplasty of aortic coarctation at three units of pediatric cardiology in Austria (Graz = 35 patients, Innsbruck = 15 patients, and Vienna = 2 patients). 35 patients had postoperative and 17 had native coarctation. Mean age at intervention was 7 10/12 years with 2 patients under 1 year and 5 patients over 18 years old. The mean relation balloon diameter-coarctation diameter was 2.6 +/- 0.9. The blood pressure gradient between upper and lower extremities decreased from a mean of 44 +/- 16 mm Hg to 15 +/- 13 mm Hg (p < 0.0001). The diameter of the stenosed segment was increased from 5 +/- 3 mm to 8.5 +/- 3.5 mm (p < 0.0001). Native coarctation showed a significantly better result in respect to decrease of the gradient (36 +/- 12 mm Hg) than did postoperative coarctations (25 +/- 19 mm Hg) (p < 0.03). 13 patients did not respond adequately to angioplasty. 10 patients out of this group had tubular narrowings and belonged to the group of postoperative coarctations, whereas localized stenoses in native coarctations gave the best results. Localized wall irregularities were found in 4 patients with native coarctation. Balloon angioplasty of postoperative and native coarctations in childhood and adolescence is a secure and effective means of treatment and should be considered as therapy of first choice. The best results can be found in the group of the circumscript type of stenoses in native coarctation, whereas long and tubular stenoses in the group of postoperative coarctations give less satisfying results.

Adolescent

[Comparison of surgical techniques and various suture materials for correction of aortic isthmus stenosis].

UNLABELLED: Clinical examination and Doppler ultrasound were performed in 31 children after repair of coarctation of the aorta. Median postoperative follow-up period was 4.5 years. The aim of our study was a comparison of different operation techniques and suture materials. In 16 infants subclavian flap repair had been performed using polydioxanone absorbable sutures (PDS) in 8 cases and polypropylene (Prolene) sutures in the other 8 cases. Resection and end-to-end repair had been carried out in 8 infants using PDS and in 7 using Prolene sutures. Doppler-echocardiographically derived gradients across the reconstructed aorta were significantly lower in infants operated with the subclavian flap technique (p < 0.05). The length of the arm on the side of the subclavian flap operation was shorter (median 1.2 cm), but there were no signs of ischaemic complications. Using PDS sutures the aortic arch and the aortic isthmus were each morphologically significantly wider in both operation techniques. Noninvasive two-dimensional echocardiography demonstrated good anatomical repair and no anastomotic aneurysm formation after aortic repair using polydioxanone. CONCLUSION: Regarding the doppler-echocardiographically derived gradients in the anastomotic region this intermediate follow-up study reveals better results using the subclavian flap technique; absorbable polydioxanone sutures favour normal growth of the anastomotic site without vascular complications.

Anastomosis, Surgical

The acinar heterotopy of phosphoenolpyruvate carboxykinase activity in rat liver under the influence of the oestrous cycle.

The acinar localization of phosphoenolpyruvate carboxykinase was investigated in livers from untreated female rats during the 4-day oestrous cycle. The results were correlated with plasma levels of insulin, glucagon and oestrogens. Total activity was highest in dioestrus and lowest in metoestrus. The highest activities were present in the periportal zone and decreased continuously towards the perivenous zone in all four phases of the cycle. This general pattern was modified under the influence of the cycle. The periportal-perivenous gradient was subject to cycle dependent changes, being steepest in proestrus. In addition to oestrogens the concentrations of plasma insulin also varied during the female cycle. Insulin was highest in oestrus and lowest in proestrus. Glucagon showed only minor variations. Oestrogen concentrations increased continuously from low values in oestrus to high values in proestrus. These changes were directly related to the changes in the slope of the activity gradient.

Animals

Quantitative EEG before and after open heart surgery in children. A significant decrease in the beta and alpha 2 bands postoperatively.

Quantitative EEGs of 30 patients undergoing open heart surgery were investigated before, 6 days, 11 days and 44 days after operation. The study was conducted in order to investigate whether quantitative EEGs can show postoperative changes in children after open heart surgery. In 28 children, no new neurological signs of cerebral involvement were seen postoperatively. The most striking feature in these children was a significant decrease in the beta and the alpha 2 bands 6 and 11 days postoperatively. The pattern in the delta band was dominated by an increase 6 days postoperatively. Except for a slight decrease in alpha 2 waves, all variables were restored to preoperative values at 44 days after the operation. We found a significant decrease in plasma sodium and chloride after surgery but children with no or slight declines (1-3 mmol/l) also showed increased slow activity postoperatively. Therefore we conclude that an organic brain syndrome, although usually mild and transient, is a general phenomenon after open heart surgery.

Adolescent

Anomalous origin of the left coronary artery: a review of surgical management in 13 patients.

Over the last decades, surgical management of anomalous left coronary artery originating from the pulmonary artery (ALCAPA) has seen a considerable evolution. Between 1965 and 1992, 13 children with age at operation ranging between 2 months and 11 years (mean 23 months) underwent one of 5 different surgical procedures: ligation (n = 3), direct aortic reimplantation (n = 7), subclavian (n = 1) or internal mammary (n = 1) artery anastomosis, or modified aortic implantation (Vigneswaran-procedure, n = 1). There were 3 early and one late deaths resulting in an overall mortality of 30.7%. Mortality was 66.7% in the ligation group, and 20% in the revascularization group (28.6% in the subgroup with direct aortic implantation). The one late death occurred 6 months after ligation. Follow-up ranges between 3 months and 21 years, mean 7.3 years. All but one survivors are in NYHA functional class I. Following operative correction, there was clear improvement in left ventricular performance. Our data give reason to suggest ALCAPA to be more frequent than considered so far. Early surgery is recommended in all patients with ALCAPA, regardless of age or symptomatic status. Reestablishment of a two-coronary system is considered the procedure of choice. All survivors require long-term follow-up controls of early recognition of residual or progressive cardiac problems.

Austria

Long-term hemodynamic effects of nifedipine on congenital heart disease with Eisenmenger's mechanism in children.

The hemodynamic effect of long-term nifedipine medication was studied in 10 children, 3-12 years of age, five with ventricular septal defect and five with complete atrioventricular septal defect; all had Eisenmenger's reaction, seven also had Down's syndrome. They underwent heart catheterization prior to and during 1-4 years of nifedipine therapy. Fick's principle was used to calculate the ratio of pulmonary arterial pressure to aortic pressure (PAP/PAO), the ratio of pulmonary flow to aortic flow (QP/QS), as well as the ratio of pulmonary vascular resistance to aortic vascular resistance (RP/RS). In the seven children under 8.8 years, nifedipine caused a significant drop in PAP/PAO (p less than 0.004), a slight increase in arterial O2 saturation, a significant increase in QP/QS (p less than 0.02), and a decrease in RP/RS (p less than 0.02). The nifedipine effect was age related. On nifedipine, breathing oxygen resulted in, independent of age, a significant increase in QP/QS (p less than 0.003) and a significant decrease in PAP/PAO (p less than 0.04) and in RP/RS (p less than 0.003). Direct O2 consumption measurements before and during oxygen breathing in six patients demonstrated no significant change in RP, RS, QP, or QS indices. Nifedipine had a relaxing effect on the pulmonary vascular bed, especially in the younger child with Eisenmenger's mechanism. On nifedipine therapy, O2 produced a more complex hemodynamic reaction that was not restricted to the pulmonary circulation alone.

Child

Two-dimensional and Doppler echocardiographic follow-up after the arterial switch operation for transposition of the great arteries.

An echocardiographic follow-up examination was performed in 20 children who underwent an arterial switch operation from November 1984 to October 1990. The age at the time of operation ranged from 1 to 54 days, the weight ranged from 2.5 to 4.5 kg body weight. The time interval from the day of operation and the examination ranged from 3 to 74 months. M-mode echocardiography showed hypokinetic left ventricular function in 6 patients (30%). Abnormal segmental left ventricular wall motions were found in 6/16 patients (37.5%). Doppler echocardiographic examination at the site of the pulmonary anastomosis revealed an instantaneous gradient less than 20 mmHg in 9 patients (45%), a gradient between 20 and 60 mmHg in 9 patients (45) and a gradient greater than 60 mmHg in two patients (10%). The location of the stenosis was just below the bifurcation in 17 patients (85%) and seemed to be related to stretching of the pulmonary trunk during the Lecompte maneuver. One patient (5%) had a supravalvular aortic stenosis with a gradient of 43 mmHg. Color-flow mapping revealed mild aortic regurgitation in 8 patients (40%) but moderate regurgitation in one patient (5%). Three patients (15%) showed mild mitral regurgitation, all of them also had hypokinetic left ventricular function.

Child, Preschool

[Heart transplantation in childhood].

This report presents 5 children, in whom a heart transplantation was performed at the II. Chirurgische Universitätsklinik of Vienna. At the time of transplantation the age of the children was 2, 3, 6, 10, and 14 years. The preoperative diagnosis was dilative cardiomyopathy in two patients, hypertrophic cardiomyopathy, right ventricular decompensation after atrial repair of TGA and a tumor of the heart in the other patients. Three children are alive and well. One child suffered from severe postoperative complications and 1 child died because of rejection of the heart. Indication, follow-up, complications of the therapy and the position of heart transplantation in children are discussed.

Adolescent