Aldosterone Modulates Cell Proliferation and Apoptosis in the Neonatal Rat Heart

In the present study, we investigated whether and how the mineralocorticoid receptor antagonist spironolactone affects cardiac growth and development through apoptosis and cell proliferation in the neonatal rat heart. Newborn rat pups were treated with spironolactone (200 mg/kg/d) for 7 days. The cell proliferation was studied by PCNA immunostaining. The treatment with spironolactone decreased proliferating myocytes by 32% (P<0.05), and reduced myocytes apoptosis by 29% (P<0.05). Immunoblot and immunohistochemistry for the expression of p38, p53, clusterin, TGF-beta2, and extracellular signal-regulated kinase were performed. In the spironolactone group, p38, p53, clusterin, and TGF-beta2 protein expression was significantly decreased (P<0.05). These results indicate that aldosterone inhibition in the developing rat heart induces cardiac growth impairment by decreasing proliferation and apoptosis of myocytes.

Thyroid Function Studies in Patients Who Underwent Open Heart Surgery

PURPOSE: Alteration in the serum level of thyroid hormone can occur following open heart surgery due to major stress and hemodilution after extracorporeal circulation but these changes have been ignored. The purpose of this study is to evaluate the changes of thyroid hormone level after open heart surgery and if these changes influence the prognosis. METHODS: We evaluated 26 children who had undergone open heart surgery from Sept. 1994 to Jun. 1996 at Korea University Hospital. Five ml of blood were collected before surgery, immediately after surgery and 24 hours after surgery. The blood was centrifused and the serum stored at -40degrees C until examinations were made. Serum T3, T4, reverse T3 were measured by sensitive and specific radioimmunoassay. RESULTS: The mean T3 level was 1.49 +/- 0.50ng/ml (normal 0.08-2.0ng/ml) at pre op, 0.75 +/- 0.40ng/ ml immediately after surgery and 0.69 +/- 0.50ng/ml 24 hours after surgery. The mean T4 level was 10.73 +/- 4.40ug/dl (normal 6.1-11.8 microgram/dl) at pre op, 5.80 +/- 1.90ug/dl immediately after surgery and 5.60 +/- 2.10ug/dl 24 hours after surgery. The mean TSH level was 1.69 +/- 1.13uIU/ml (normal 0.25-4.0 uIU/ml) at pre op, 1.37 +/- 0.80uIU/ml immediately after surgery and 1.61 +/- 1.00uIU/ml 24 hours after surgery. Serum T3 and T4 levels in cardiac surgical patients were significantly reduced (P<0.01), and serum reverse T3 levels were significantly increased (P<0.05), and serum TSH levels were not significantly different in comparison with the preoperative state. CONCLUSION: We conclued that patients with congenital heart disease who underwent open heart surgery show euthyroid sick states like other severely ill patients. It is likely that reduction in T3 and T4 without increased TSH represents an adaptive response by the body to minimize catabolism when undergoing major stress.

The Efficacy of Routine Liver Function Test Follow Up in Epileptic Children

PURPOSE: Routine liver function test follow up is done in epileptic children receiving antiepileptic drugs to prevent hepatotoxicity induced by these drugs. But rarely seen are the abnormalities of liver function test, and seldomly are these abnormalities accompanied by the clinical manifestation. This study is carried out to assess the efficacy of routine liver function test follow up in epileptic children. METHODS: We determined the changes of the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, direct bilirubin, total protein, albumin, gamma-glutamyltransferase (gamma-GT) and alkaline phosphatase before and 3, 6, 12 months and 2 years after antiepileptic drug medication in 59 epileptic children who had been receiving carbamazepine (n=16), phenobarbital (n=14), valproic acid (n=10) and combination of these (n=19) for 2 to 5 years. RESULTS: 1) The difference in liver function test follow up according to the age and sex was not found and there was no statistical correlationship between drug medication time and the serum drug level. 2) AST and ALT had been within normal range for all the study period in any group. 3) Total bilirubin had been within normal range for all the study period in any group. Direct bilirubin had decreased for the first 6 months in valproic acid group, but the changes had been within normal range for all the study period. 4) Total protein and albumin had been within normal range for all the study period in any group. 5) gamma-GT had the increasing tendency for all the study period in valproic acid group, but the values had been within normal range for all the study period. 6) Alkaline phosphatase had decreased for the first 6 months in valproic acid group, but the changes had been within normal range for all the study period. 7) No clinically significant hepatic manifestation had developed during study period in any group. CONCLUSIONS: Our data suggest that routine liver function test follow up itself can not be the indicator of hepatotoxicity and that liver function test in need when accompanied by the development of clinical hepatic manifestation is more efficacious than routine liver function test follow up.

The Characteristics of Febrile Neutropenia Induced by Chemotherapy

PURPOSE: The development of fever in neutropenic cancer patients is frequently a sign of infection. Infection remains the major cause of death in the patient with cancer, primarily as a consequence of the profound alterations of normal host defences which result from the malignancy, its treatment or both. Fever in the patient with neutropenia is generally recognized as an indication of the need for prompt initiation of antibiotic therapy, but in spite of intensive efforts to identify infections in these patients and to institute appropriate antibiotic therapy, high mortality rate have continued to occur. This study was performed to identify the current etiologic agents, differences in frequency and/or type of infection in patients with hematologic malignacy as compared to those with solid tumor and to assess the period of neutropenia and treatment. METHODS: Between May 1994, and Feburuary 1994, we retrospectively evaluated 84 febrile episodes occurring in 46 patients with neoplastic diseases which were identified at Korea university hospital. Neutropenic fever has been defined as three episode of elevation of temperature above 38degrees C or a single elevation above 38.5degrees C in neutropenic patient (granulocyte<500/mm3) RESULTS: 1) Eighty-four episodes of fever and neutropenia were identified in 47 patients whose mean age was 6.6 years. 2) Thirty-three patients had leukemia or lymphma, representing 70.2% of the episodes of fever and neutropenia. 3) Microbiologically documented infection, clinically documented infection and unexplained fever accounted for 13%, 23%, 64% of the febrile episodes respectively. 4) Gastroenteritis and pharyngitis were the most common type of infection. 5) The common organism were Escherichia coli, Klebsiella pneumoniae, Staphyrococci aureus were common in decreasing order. 6) The mean duration of febrile neutropenia was 11.9 days in hematologic malignacy and 6.5 days in solid tumor. 7) The mean duration of receiving G-CSF was 13.1 days in hematologic malignancy and 5.8 days in solid tumor. 8) There was no significant difference in duration of neutropenia, times of receiving treatment and ANC level at fever in patients with MDI compared to CDI or UF. CONCLUSIONS: Gram negative bacilli are dominant pathogens of neutropenic fever in Korea university hospital.