ABSTRACT
The aim of the study was to investigate whether nuclear immunopositivity for p53 is a factor of prognostic significance in astrocytomas of childhood and adolescence. Paraffin-embedded tissues of astrocytomas (10 WHO grade II, 11 WHO grade III) from 21 patients under 18 years of age, when operated for the first time, were studied immunohistochemically. We used a set of 6 different antibodies against p53, suitable for paraffin section (PAb1801, PAb240, DO-1, DO-7, BP53-12, CM-1). The intensity of the nuclear staining was scored and the percentage of stained nuclei counted. A tumor was scored positive if at least 10% of nuclei showed at least medium staining intensity with at least 1 primary antibody. No single antibody detected all cases designated immunopositive. This shows the advantage of using a set of antibodies. The time of survival in the immunopositive cases was significantly shorter, but immunopositivity was correlated with grade III (WHO). Comparing the time of survival between p53-immunopositive and -immunonegative grade III (WHO) astrocytomas no significant difference was found. We conclude that p53 immunoreactivity is not an independent unfavorable prognostic factor in astrocytomas of childhood and adolescence.
Subject(s)
Astrocytoma/metabolism , Tumor Suppressor Protein p53/analysis , Adolescent , Astrocytoma/physiopathology , Astrocytoma/surgery , Child , Child, Preschool , Female , Humans , Immunohistochemistry , Infant , Male , PrognosisABSTRACT
In order to estimate the role of the sympatho-adrenal system as a trigger in cardiovascular mortality risk after L-DOPA administration in patients with Parkinsons disease we performed the following experiments in normotensive Wistar-Kyoto-rats (WKY) and spontaneously hypertensive rats (SHR). L-DOPA was given orally in increasing doses (30, 100, 300 mg/kg b.w.). Haemodynamic parameters (BP, HR) were measured by tail cuff plethysmography and catecholamine concentrations in tissues assayed by high pressure liquid chromatography. Stressful situations were induced by experimental myocardial infarction. After administration of L-DOPA a dose-dependent increase in blood pressure in both WKY and SHR was observed with a prolongation in SHR. Significantly increased concentrations of dopamine in the hearts were measured in both strains. Noradrenaline stores in the heart of WKY were more filled than in the heart of SHR. Only in SHR high adrenaline concentration in the adrenal medulla were measured after L-DOPA administration. Circulating adrenaline concentrations were significantly enhanced after myocardial infarction in WKY and could be further elevated by pretreatment with L-DOPA. From the results obtained it is concluded that L-DOPA administration in WKY and SHR leads to exaggerate synthesis and massive release of catecholamines and in consequence to an enhanced cardiovascular mortality risk due to cardiotoxicity of catecholamines. It can be extrapolated that increased cardiovascular mortality risk seen in Parkinson patients treated with L-DOPA and benzerazide is probably associated with increased synthesis and release of catecholamines during stressful situations.
Subject(s)
Catecholamines/toxicity , Dopamine Agents/toxicity , Heart Diseases/physiopathology , Levodopa/toxicity , Animals , Catecholamines/blood , Catecholamines/metabolism , Dopamine/blood , Dopamine/metabolism , Epinephrine/blood , Epinephrine/metabolism , Heart Diseases/chemically induced , Hemodynamics/drug effects , Hypertension/genetics , Hypertension/physiopathology , Male , Myocardial Infarction/chemically induced , Myocardial Infarction/metabolism , Myocardium/metabolism , Norepinephrine/blood , Norepinephrine/metabolism , Rats , Rats, Inbred SHR , Rats, Inbred WKYABSTRACT
OBJECTIVE: Our purpose was to assess the prevalence, cause, and clinical significance of fetal tricuspid valve regurgitation in structurally normal hearts during indicated fetal echocardiographic examination. STUDY DESIGN: The prevalence of fetal tricuspid regurgitation was retrospectively evaluated in a group of 733 singleton fetuses referred for routine fetal echocardiography. RESULTS: The prevalence of this abnormality was 6.8%. Tricuspid valve regurgitation was most frequent in the group referred for fetal echocardiography to evaluate indomethacin exposure, followed by maternal diabetes. Factors associated with tricuspid valve regurgitation included ductal constriction, abnormal heart rhythm, atrial septal aneurysm, congestive heart failure, pericardial effusion, myocardial hypertrophy, and extracardiac malformations. Fetal tricuspid valve regurgitation was trivial in 80% (nonholosystolic, maximum velocity < 2 m/sec) and was significant in 20% (holosystolic, maximum velocity > 2 m/sec). Neonatal follow-up of tricuspid valve regurgitation was unremarkable. CONCLUSIONS: Fetal tricuspid valve regurgitation with normal heart anatomy was a frequent finding during indicated fetal echocardiographic examination and may indicate abnormal physiologic characteristics (increased preload or afterload, myocardial impairment, or arrhythmia). In the majority of cases (92%) the possible cause may be established. In other cases (8%) there may be "idiopathic" tricuspid valve regurgitation.
