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Biomedical subjects

M Wimmer

Publications and source records attributed to M Wimmer.

At least 55 records · Page 3Linked to original sources

Angiotensin converting enzyme activity in children with congenital heart disease.

Serum angiotensin converting enzyme (ACE) activity was determined in 46 children with congenital heart disease with normal and abnormal lung perfusion: (1) congenital heart disease with normal pulmonary blood flow (12 patients); (2) congenital heart disease with increased pulmonary blood flow (18 patients); (3) congenital heart disease with decreased pulmonary blood flow (16 patients). There was no significant difference in serum ACE activity between the three groups. In group 2 serum ACE activity had a tendency to correlate inversely with both mean pulmonary arterial pressure (r = -0.43; P less than or equal to 0.05) and pulmonary vascular resistance (r = -0.48; P = 0.05). No further correlations between serum ACE activity and age, serum electrolytes, creatinine nor other haemodynamic data could be established.

Adolescent↗

The effects of acetylsalicylic acid on phosphoenolpyruvate carboxykinase activity and acinar heterotopy in livers from juvenile and adult rats.

Male and female juvenile as well as adult rats were treated with acetylsalicylic acid in order to examine the effect of the drug on over-all activity and activity distribution of phosphoenolpyruvate carboxykinase (PEPCK) in the liver acinus. Upon administration of acetylsalicylic acid PEPCK activity increased in juvenile males and adult females, but was reduced in juvenile females and adult males. The periportal-perivenous activity gradient along the sinusoidal length, which is flatter in untreated juvenile rats compared to the livers of adult rats, was distinctly steepened by acetylsalicylic acid treatment. Acetylsalicylic acid did not affect the gradient in adult rats.

Aging↗

The heterotopic effects of insulin and glucagon on the acinar activity pattern of phosphoenolpyruvate carboxykinase in male and female rat liver.

The effects of the administration of insulin and glucagon on the intraacinar heterotopy of phosphoenolpyruvate carboxykinase (PEPCK) were investigated in male and female rat liver. Insulin did not noticeably influence PEPCK activity or its acinar distribution, either in males or in females. But it affected the activities of glucose-6-phosphate dehydrogenase and malic enzyme. Glucagon in supraphysiological concentrations led to an induction of PEPCK activity. Despite high glucagon concentration along the whole sinusoidal length, the inducing effect of glucagon was most pronounced in the periportal and intermediary parts of the acinus; thus indicating that there is no direct interrelationship between local glucagon concentration and PEPCK activity. In both experiments blood glucose levels were kept fairly constant.

Animals↗

Experience with long-term nifedipine therapy in paediatric cardiological patients.

Clinical experience with long-term nifedipine treatment in 23 patients aged between 1 1/12 and 14 8/12 years is reported. The cardiopulmonary diseases comprised primary pulmonary diseases with pulmonary hypertension (n = 4), congenital heart defects with intracardiac shunts and pulmonary hypertension which either were inoperable as a result of an Eisenmenger reaction (n = 7) or presented a high surgical risk (n = 5), or defects in which pulmonary hypertension did not regress despite corrective (n = 1) or palliative surgery (n = 3), and congenital defects without pulmonary hypertension (n = 3). Subjective improvement with an increase in physical performance was clearly observed in 15 cases. Echocardiography and cardiac catheter examinations showed no progression of the pulmonary arterial diseases, except in 1 patient with severe primary pulmonary hypertension and an 11-year observation period with nifedipine treatment during the last 4 years. No complications occurred during the 4 corrective operations. A patient aged 14 8/12 years with the Down syndrome and atrioventricular septal defect developed easily controllable heart failure during 7-day administration of nifedipine without additional cardiotherapy. 4 children initially suffered from flushed face and scalp, in one case with headache; 2 children reported fatigue. Long-term treatment with nifedipine should begin with strict 7-day supervision in hospital and possibly additional digitalization. Success of the treatment was determined by an improved quality of life in patients with primary pulmonary hypertension and inoperable defects, and by a reduced perioperative risk and postoperative regression of pulmonary hypertension in patients with operable defects.

Adolescent↗

[Secondary immunopathogenesis in myocarditis, diseases of the heart muscles and infarct-associated arrhythmia in childhood and adulthood].

In histologically proven or clinically diagnosed perimyocarditis in children and adults alterations in cellular and humoral effector mechanisms are demonstrable: OKIaI-positive B- or activated T-lymphocytes are increased in the peripheral blood, whereas natural killer cell activity is reduced. Antibodies are directed to the membranes of isolated human atrial myocytes and, to a lesser extent with lesser specificity, to endothelial cells and to the extracellular matrix. AMLAs are of diagnostic relevance if they belong to the IgM class, indicating a recent humoral immune stimulation and, if they fix complement, indicating a functional property which is complement associated lysis of target cells. Immunohistological studies demonstrate fixation of immunoglobulins to the autologous biopsy specimens, which are diagnostic only if they also belong to the IgM class and fix complement. In acute rhythm disturbances in the context of a recent "common cold", similar humoral immune reactions can be found in children, which are compatible with a secondary immunopathogenesis after viral illness involving the myocardium.

Adult↗

[L-carnitine therapy and myocardial function in children treated with chronic hemodialysis].

Six out of 14 chronically hemodialysed children with significantly decreased serum carnitine levels were substituted with L-carnitine (15-30 mg/kg/day-Biocarn) up to normal and above normal carnitine levels. None of these patients were digitalised. During the time of investigation plasma carnitine levels were investigated monthly and, simultaneously, three echocardiographic parameters in M-mode were quantitatively und qualitatively determined: shortening fraction (SF-%), ratio of left ventricular pre-ejection/ejection time (LVPT/LVET) and velocity of circumferential fibre shortening (Vcf). Carnitine substitution produced measurable changes in echocardiographic parameters, and a significant quantitative improvement in left ventricular function and performance: after 6 months of carnitine substitution a 24% improvement was seen, after 18 months a 44% mean improvement. No side effects of carnitine were observed; the compatibility was good. Beside these positive effects all patients reported decreased dialysis-associated spasms and polyneuropathic symptoms and increased somatic ability.

Administration, Oral↗

Reactivity of monoclonal islet cell antibodies on normal hyperplastic and neoplastic thyroid C-cells.

Thyroid C-cell reactivity to 15 monoclonal antibodies raised against a series of pancreatic islet cells (H[human]ISL,B[bovine]ISL and R[rat]ISL) was evaluated using an indirect immunoperoxidase technique on frozen thyroid sections. Of the monoclonal anti-islet cell antibodies, five reacted specifically with bovine C-cells or human hyperplastic and neoplastic C-cells but not with follicular cells. Two monoclonal antibodies of the bovine series showed strong immunoreactivity with C-cells and only a weakly positive immunostaining of follicular cells. Five monoclonal antibodies reacted with both thyroid C-cells and follicular cells, whereas 3 monoclonal anti-islet cell antibodies did not strain any cell type of the thyroid. In human medullary carcinomas, calcitonin- and somatostatin-producing neoplastic cells were immunoreactive with the same monoclonal antibodies as were normal human C-cells. The protein bands identified by the monoclonal antibodies in human medullary carcinomas had the same molecular weight as those from pancreatic islet extracts. Our study demonstrates the presence of similar differentiation antigens on thyroid C-cells and pancreatic islet cells; this further illustrates common modes of differentiation and specialisation of these embryologically different members of the dispersed neuroendocrine system. The crossreactivity of seven of the monoclonal antibodies investigated with follicular epithelium of the thyroid suggests the existence of common antigenic determinants in different endocrine organs and may partly explain the multiple organ autoimmune response found in patients with polyendocrine diseases.

Animals↗

Phosphoenolpyruvate carboxykinase activity patterns in the liver acinus of diabetic and diabetic and estrogen treated rats.

The acinar activity pattern of phosphoenolpyruvate carboxykinase (PEPCK) was investigated in livers of streptozotocin diabetic male and female rats and in addition in livers of diabetic males, which had undergone estrogen treatment. In all diabetic animals blood glucose levels were supranormal and liver PEPCK activity was increased. This increase in activity was greatest in estrogen treated diabetic males and lowest in diabetic females. Plasma insulin levels were reduced after the application of streptozotocin to otherwise normal male and female rats. Yet, in males treated in addition with estrogens the plasma insulin levels reached the normal range again. The PEPCK activity showed a heterotopic distribution along the acinus. The periportal to perivenous gradient was steeper in males compared to females in the untreated as well as in the diabetic state. The application of estrogens to males resulted in a further steepening of the gradient.

Animals↗

Sex differences of the influence of T3 on the topical distribution of phosphoenolpyruvate carboxykinase activity in the liver acinus.

Phosphoenolpyruvate carboxykinase (PEPCK) activity was investigated in livers of triiodothyronine (T3) treated male and female rats with special regard to its intraacinar localization. In untreated controls of both, male and female rats, the activity was heterotopically distributed within the acinus with highest values in the periportal zone, and with lowest values in the perivenous zone. This periportal to perivenous activity gradient revealed to be under the influence of T3. Application of T3 resulted in a relative increase of PEPCK activity which was much greater in the livers of females than in males. The extent of T3-induced augmentation of PEPCK activity was dependent on the intraacinar position. In both sexes greatest relative activation was found in the perivenous zone. In female animals, the perivenous activity of T3 treated livers was comparable to that observed in the periportal zone of controls.

Animals↗

Effects of starvation and refeeding a high carbohydrate diet on the intra-acinar distribution pattern of phosphoenolpyruvate carboxykinase activity in the liver of male and female rats.

Phosphoenolpyruvate carboxykinase activity in rat liver was shown to be heterotopically distributed within the acinus under varying feeding conditions. Highest values of PEPCK activity were found in the periportal zone of the acinus from where it decreased continuously towards the perivenous zone. 84 h of starvation resulted in an increase of activity, which was most prominent in the perivenous zone, but nevertheless resulted in a steeper gradient. Refeeding of starved rats with a high carbohydrate diet for 6 nights led to a decrease in PEPCK activity which was most prominent in the periportal zone, but almost negligible in the perivenous zone, resulting in a further change in the activity gradient. Sex-dependent differences for total PEPCK activity were found i) in controls, where the activity was lower in females, ii) after starvation, where the induction was much higher in females, and iii) after refeeding of starved rats, where the activity in females remained higher compared to that of the controls. Differences in the intra-acinar localization of the activity in dependence of the sex were registrated in the control group and in starved rats. Livers from female rats contained a higher periportal/perivenous ratio compared to males. In starved and starved and refed animals the periportal/perivenous ratios were almost the same in both sexes.

Animals↗

Growth and nutritional intake of infants with congenital heart disease.

Poor weight and length gain of infants with congenital heart disease is generally considered to be related to inadequate nutritional intake, but no longitudinal data on growth and nutritional intake of such infants are available. We compared weight, length, subscapular and triceps skinfold thickness, energy and protein intake (24-h dietary intake records) as well as serum prealbumin and albumin of infants with cyanotic heart disease (n = 8) or isolated left-to-right shunt (n = 8) with those of healthy infants aged (n = 8) 45-365 days. Weight, length, and combined (subscapular and triceps) skinfold thickness of the two groups with congenital heart disease (CHD) were significantly less from 183 through 365 days of age. However, energy and protein intake was similar to that of the control group from 45 through 365 days of age. Normal serum prealbumin and albumin in the infants with CHD ruled out protein-calorie malnutrition. It is concluded that a low level of food intake was not the main cause of inadequate growth and of small subcutaneous fat stores in these two small, but homogeneous, groups of infants with CHD.

Body Height↗

Histological grading of therapy induced regression in squamous cell carcinomas of the oral cavity. A morphological and immunohistochemical study.

Squamous cell carcinomas in the oral cavity and the oropharynx were diagnosed in 84 patients. After verification by biopsy, 79 of these patients were treated preoperatively with mitomycin C and 5-fluro-uracil, radiated and operated 3-5 weeks later. The effectiveness of adjuvant preoperative radio-chemotherapy was evaluated histologically. Serial sections of the entire tumor specimen were investigated and the percentage of vital cancerous tissue in the total tumor area was assessed. Regression was classified into four grades. Grades I and II were regarded as good response to adjuvant preoperative radio-chemotherapy, while grades III and IV stood for bad or no response. Morphologically questionable residual tumor infiltrates could be clarified by immunohistochemical methods with antibodies against vimentin, desmin and Lu-5. The histological assessment of the regression grade of operated tumor specimens allows a clinically relevant, morphologically exact and reproducible evaluation of the effect of preoperative radiochemotherapy.

Adult↗

The effect of sex hormones on the acinar distribution pattern of phosphoenolpyruvate carboxykinase activity in rat liver.

The intra-acinar distribution pattern of phosphoenolpyruvate carboxykinase activity (PEPCK) was investigated in microdissected samples of livers from normal, castrated, castrated and estradiol- or testosterone-treated, and uncastrated and testosterone- or estradiol-treated male and female rats. The total PEPCK activity showed a marked sex dependency, with 1.8 times higher activity in males. The intra-acinar distribution profiles were also sex-dependent. The periportal-to-perivenous gradient was steeper in males. Castration resulted in an approximation of PEPCK activity and its acinar distribution pattern between the sexes due to a reduction in males and an increase in females. Estrogen treatment of castrated males had no further effect on PEPCK activity and its acinar gradient, whereas in ovariectomized animals the activity was reduced to levels near normal. Testosterone treatment of castrated male or female animals led to a marked increase in enzyme activity with a concomitant steepening of the acinar gradient. Administration of estradiol to normal male rats also led to a reduction in activity, together with a change in the acinar activity gradient. Testosterone treatment of normal females resulted in an induction of PEPCK activity which was most prominent in the periportal zone. The most drastic changes were observed in the perivenous zones. In all experiments a periportal-to-perivenous activity gradient persisted thus marking the periportal zone as the area with highest gluconeogenic capacity.

Animals↗

[Value of myocardial scintigraphy of coronary anomaly in the differential diagnosis of pediatric cardiomegaly].

The differentiation between anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) and other causes of cardiomegaly and thereby the decision to operate, as opposed to undertaking conservative therapy is often extremely difficult in clinical practice. Electrocardiographically, signs of myocardial infarction can be missed in ALCAPA, other forms of dilative cardiomyopathy (DCMP) often showing similar clinical features. Up to now aortography alone can make a clear-cut distinction between these two entities. In order to determine the diagnostic value of thallium-201 myocardial scintigraphy in ALCAPA, we investigated 18 children, 7 of them with angiographically or autoptically established ALCAPA and 11 patients with DCMP. The coronary artery anomaly was diagnosed on the basis of the typical myocardial perfusion defects in only 3 of the relevant 7 patients. In 9 of the 11 patients with DCMP ALCAPA was excluded by the homogeneous perfusion pattern or small focal reduction in thallium-201 activity in the left ventricular muscle mass. In view of the overall disappointing results of this method in achieving a specific diagnosis in ALCAPA, all patients with DCMP with or without suspected fibroelastosis should undergo invasive diagnosis with aortography.

Adolescent↗

[Immunosuppressive treatment of chronic myocarditis].

6 children aged 9 months to 13 8/12 years developed reduced physical capacity, failure to thrive, dyspnoea on effort and heart failure after viral infection. Bed rest and anticongestive therapy did not reduce the severe heart failure. Immunosuppressive therapy with prednisolone 2 mg/kg/d and azathioprine 2 mg/kg/d was added on the assumption of chronic myocarditis (n = 4) or endocardial fibrosis (n = 2). 3 of the 6 children showed a considerable improvement in heart size, ECG and systolic heart function. Interruption of immunosuppressive therapy due to side effects in one child led to cardiac deterioration, which was reversed by renewed prednisolone therapy. Two patients died of progressive congestive heart failure. Heart transplantation was successfully performed in the now 14 year-old girl who was suffering from terminal dilated cardiomyopathy. Since there is no specific test for selecting patients who are likely to benefit from immunosuppressive therapy we feel this regimen would be justified in hopeless cases of congestive cardiomyopathy who have not responded to conventional therapy with anti-congestive drugs.

Adolescent↗

A bioluminescent assay for the determination of phosphoenolpyruvate carboxykinase activity in nanogram-sized tissue samples.

A highly specific and sensitive assay for the determination of phosphoenolpyruvate carboxykinase (PEPCK) in nanogram-sized tissue samples is described. This test system is based on the stoichiometric transformation of phosphoenolpyruvate into ATP. In a subsequent step ATP is quantified by bioluminescent techniques. The applicability of this assay system is shown by measurements in liver samples with normal and high PEPCK activity levels.

Adenosine Triphosphate↗

Hemodynamic effects of nifedipine and oxygen in children with pulmonary hypertension.

Fourteen patients, 2 to 20 years old were investigated. Two had primary pulmonary hypertension, 11 had congenital heart disease and post-tricuspid shunts, and 1, a 20-year-old patient, was investigated after he had undergone surgical correction of truncus arteriosus I. Pulmonary arterial pressure, pulmonary flow index, peripheral systolic blood pressure and heart rate were measured before, and several times after intrapulmonary injection into the pulmonary artery of 0.5 microgram nifedipine/kg. Six patients were given an additional dose of 1 microgram nifedipine per kilogram into the pulmonary artery and hemodynamic measurements were repeated. In eight children, receiving 100% oxygen via a breathing mask, nifedipine effects were compared with oxygen effects. After 10 minutes under oxygen, the same hemodynamics were determined as after nifedipine. In addition, in four of these children aortic pressure and arterial oxygen saturation were also measured. Maximal effects occurred within 4 minutes. 0.5 micrograms nifedipine per kilogram caused a slight reduction in mean pulmonary arterial pressure (p less than 0.05), as well as increase in pulmonary flow index (p less than 0.005). However, no significant change in heart rate or in systolic blood pressure was observed. 1 microgram nifedipine per kilogram IP had almost the same effects. No adverse side effects occurred, besides mild headaches in one child. A comparison of nifedipine injected into the pulmonary artery with oxygen breathing in congenital heart disease combined with pulmonary hypertension, is reported for the first time. Nifedipine had a more pronounced and beneficial effect with a selective action on the pulmonary vascular bed.

Adolescent↗

Exercise testing after surgical repair of coarctation of the aorta.

After repair of coarctation, exercise testing was performed in 20 patients with an isolated coarctation (group I) and in 26 with additional congenital cardiac malformations (group II). Ages at time of operation were significantly different in both groups (7.9 +/- 6.0 years in group I; 4.6 +/- 3.8 years in group II; p less than or equal to 0.01). Simultaneous blood pressures were obtained from upper and lower limbs at rest and after exercise. There was no significant difference regarding the systolic blood pressures at rest (122.5 +/- 15.6 mmHg in group I versus 119 +/- 15.8 mmHg in group II). Seven (14%) of the patients were hypertensive; five of them had blood pressure gradients between arms and legs of 15-45 mmHg. But the gradients at rest were found to be significantly different in both groups (9.0 +/- 10.5 mmHg in group I; 18.5 +/- 16.1 mmHg in group II; p less than or equal to 0.05). Six patients, all in group II, had gradients greater than or equal to 30 mmHg at rest. After exercise there were no significant differences in systolic blood pressure and gradients in both groups. Values for blood pressures and gradients at rest and after exercise showed a positive correlation (blood pressure r = 0.76, p less than or equal to 0.001; gradient r = 0.44, p less than or equal to 0.01). Thus exercise testing can provide valuable information about blood pressure and gradient changes during physical activity, but angiography is required to reveal restenosis or residual stenosis.

Adolescent↗