Respiratory Syncytial Virus Infection in Infants with Congenital Heart Disease and Treatment with Human Leukocyte lnterferone

Between 1980 and 1986, we observed lower respiratory-tract infection caused by respiratory syncytial virus (RSV) in 19 infants and young children with various forms of congenital heart disease. Of these, seven patients who presented with a severe illness were treated with intramuscular injections of 0.5 to 1 times 10⁶ IU per day of human leukocyte interferon (IFN) for three to five days. Intrinsic IFN activity developed before treatment in three subjects. Viral isolation studies showed active RSV infection prior to treatment, and no infectious RSV was recovered one to four days after treatment. Although there were no obvious changes in the clinical course after IFN therapy, no deaths related to RSV infection occurred. Analysis of the different types of congenital heart disease showed that ventricular septal defect and/or patent ductus arter-iosus with pulmonary hypertension were associated with the most severe RSV illness. The therapeutic value of IFN may improve in this group of subjects if it is given without delay.     

Surgical treatment of limbal vernal keratoconjunctivitis by resection of a limbal lesion

PURPOSE: To report our experience managing a limbal mass associated with limbal vernal keratoconjunctivitis (VKC) by surgical excision. METHODS: A 16-year-old girl was referred to our hospital with the chief complaints of itching and photophobia in both eyes. She had a 2-year history of gradually enlarging limbal gelatinous masses on the temporal limbus in both eyes, which were diagnosed as limbal papillae of VKC. As the symptoms in her left eye were more severe, surgical resection of the limbal mass in her left eye was performed to relieve mechanical stress on the eyelid, followed by a free conjunctival autograft taken from the supranasal bulbar conjunctiva. RESULTS: After excision of the mass, ocular inflammation and other symptoms gradually disappeared. At 12-month follow-up, there was no recurrence of the mass. Findings in a histological examination of the excised limbal lesion were consistent with those of limbal papilla of VKC. CONCLUSION: In recalcitrant cases of limbal VKC, in which the symptoms are apparently caused by an elevated limbal mass, surgical excision of the limbal mass can be one of the therapeutic modalities, and it may facilitate resolution of the symptoms caused by chronic limbal VKC.     

Overview of lipophilic yeast Malassezia: the current status of the molecular diagnosis

The lipophilic yeast, genus Malassezia is a part of the normal cutaneous microflora of human and warm-blooded vertebrates. Species of the genera were re-classified to seven species; M. pachydermatis, M. globosa, M. furfur, M. obtusa, M. restricta, M. slooffiae and M. sympodialis. However, the means of species identification in conventional clinical laboratories have not been reported and the clinical significance of each species is not clearly understood. Species identifications of genus Malassezia which depend on the morphological, physiological characters are difficult and time-consuming. Recently, many molecular techniques have been developed for identification or typing of Malassezia. PCR-mediated methods, PCR-direct sequencing and nested-PCR using specific primers, are useful to identify the spices. The basic information obtained from these approaches have been contributing to the understanding of these pathogenic yeasts and related diseases.     

Longitudinal evaluation of anthracycline cardiotoxicity by signal-averaged electrocardiography in children with cancer

BACKGROUND: The aim of the present study was to investigate the detection of anthracycline cardiotoxicity by signal-averaged electrocardiography (SAE) in children with cancer. METHODS: There were 29 patients with a cumulative anthracycline (ATC) dose of 75-600 mg/m2. None of them had congestive heart failure. Patients underwent SAE just before (detection of chronic cardiotoxicity) and just after (detection of acute cardiotoxicity) ATC therapy. Echocardiography and Holter electrocardiography were performed at the same time. The rates of abnormal SAE, echocardiography, and electrocardiogram findings were calculated and compared for every 100 mg/m2 of ATC. RESULTS: The SAE showed a significantly higher detection rate for acute cardiotoxicity was at a cumulative ATC dose of less than 400 mg/m2 when compared with other methods (P < 0.05). The lowest dose at which acute cardiotoxicity was detected by SAE was 117.3 mg/m2. The detection of chronic cardiotoxicity by SAE was significantly higher at a cumulative ATC dose of 100-400 mg/m2 when compared with other methods (P < 0.05), and the lowest value showing toxicity was 373.3 mg/m2. The lowest ATC dose causing chronic cardiotoxicity was significantly lower in patients less than 2-years-old (120.0 +/- 28.3 mg/m2) than in the other age groups (P < 0.05). CONCLUSIONS: Acute and chronic ATC cardiotoxicity were detected by SAE at lower cumulative doses compared with other methods. The technique of SAE was a potentially useful method for detection of cardiotoxicity among those investigated and it provides useful information on subclinical cardiac dysfunction in patients receiving ATC therapy.     

Second Primary Cancers Following Non-Hodgkin's Lymphoma in Japan: Increased Risk of Hepatocellular Carcinoma

We evaluated the risk of development of second primary cancers, with particular reference to subsequent hepatocellular carcinoma (HCC), in 592 patients diagnosed as non-Hodgkin's lymphoma (NHL), at Osaka Medical Center for Cancer and Cardiovascular Diseases. During 1978–1994, 2,163 person-years of observation were accrued, and 27 of the patients developed a second primary cancer, yielding an observed-to-expected ratio (O/E) of 1.53 [95% confidence interval (CI) = 1.01–2.23]. Significant excess risk was noted for primary liver cancer (PLC; O/E=4.36, 95% CI=1.99–8.28; O =9) and non-lymphocytic leukemia (O/E=26.17, 95% CI=5.26–76.46; O=3). The excess risk of PLC was relatively constant within the first 10 years after the NHL diagnosis. Patients who received chemotherapy as the NHL treatment had a significantly increased risk of PLC (O/E=5.91, 95% CI =2.70–11.23; O=9). Their clinical reports indicated that all nine patients with PLC were diagnosed as HCC, and eight of them had clinical and/or histologic evidence of cirrhosis at the time of HCC diagnosis. None of the nine patients had a history of blood transfusion between the first NHL treatment and the diagnosis of HCC. These findings suggested that Japanese NHL patients might have an increased risk of developing HCC, and they indicated the importance of medical surveillance for liver malignancies, as well as subsequent leukemias. Possible explanations for the excess risk of subsequent HCC are discussed.     

Enhanced Antitumor Efficacy of a Combination of CPT-11, a New Derivative of Camptothecin, and Cisplatin against Human Lung Tumor Xenografts

The objective of this study was to evaluate the antitumor efficacy of combined use of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carhonyloxycamptothecin (CPT-11) and cisplatin (CDDP). The antitumor activities of CPT-11, CDDP and their combination against 3 human lung tumor xenografts were estimated using congenitally athymic BALB/c ( nu/nu ) mice. The doses were 47 mg/kg for CPT-11 and 6 mg/kg for CDDP on days 1, 5 and 9. In combination therapy, half of the single dosage of each agent was used. The doses were administered intraperitoneally. The antitumor activity and toxicity were evaluated in terms of the tumor volume and body weight change of mice, respectively. The combination therapy resulted in a statistically significant tumor regression compared to the use of only CPT-11 or CDDP in two tumor xenografts out of three. The toxicity of the combination therapy was no higher than that of CPT-11 or CDDP alone. These results suggest that the antitumor activity of the combination of CPT-11 and CDDP is superior to that of CPT-11 or CDDP alone.     

Effects of human neonatal serum on DNA synthesis in suckling and adult rat hepatocytes in primary culture

The effect of human neonatal serum on DNA synthesis in suckling and adult rat hepatocytes in primary culture was investigated to characterize growth regulating factors of the liver in neonates and to confirm whether the stimulatory factor is human hepatocyte growth factor (hHGF). Neonatal serum stimulated DNA synthesis of both adult and suckling rat hepatocytes. The stimulatory effect was dose-dependent up to 20% in volume. The molecular weight of the stimulatory substance in neonatal serum was between 12 500 and 25 000, as estimated by gel filtration. Its activity was stable after heating at 56°C for 20 min, but was lost after heating at 90°C for 30 s, and easily passed through S- or heparin-Sepharose columns. The concentration of hHGF quantified by ELISA was too low to stimulate DNA synthesis in vitro. Biological and biochemical properties of the growth stimulatory activity in neonatal serum differed from that of hHGF. The presence of other growth factors in human neonatal serum for suckling and adult hepatocytes was suggested.     

Tc-99m MDP bone scintigraphy of myositis as a manifestation of chronic graft-versus-host disease after non-myeloablative peripheral stem cell transplantation

A 27-year-old man developed polymyositis as a manifestation of chronic graft-versus-host disease (GVHD) after non-myeloablative peripheral blood stem cell transplantation (PBSCT). Bone scintigraphy showed intense, striped, and heterogeneous accumulation of Tc-99m methylene diphosphonate (MDP) in the soft-tissue of his lower limbs, while faint activities were seen in the right upper limb. Tc-99m MDP scintigraphy was very useful for accurate and objective evaluation of the severity of the muscle injury and the extent of polymyositis caused by chronic GVHD.     

Possible synergic effect of angiotensin-I converting enzyme gene insertion/deletion polymorphism and angiotensin-II type-1 receptor 1166A/C gene polymorphism on ischemic heart disease in patients with Kawasaki disease

ACE I/D and AT1R 1166A/C polymorphisms are considered to comprise individual risk factors for the development of coronary disease. We sought to demonstrate that the ACE I/D and AT1R 1166A/C polymorphisms affect coronary artery stenosis in patients with Kawasaki disease (KD). We examined 147 healthy controls and 281 Japanese children with KD. The patients were further divided into group N (n = 246, no ischemia) and group I (n = 35, severe coronary artery stenosis with myocardial ischemia), and we studied the genotype of ACE I/D and AT1R 1166A/C polymorphisms. We also examined ACE activity in patients with acute KD. We did not detect any prevalent genotypes of the ACE and AT1R polymorphisms between controls and KD patients. However, the prevalence of the D allele in the ACE polymorphism and of the C allele in the AT1R polymorphism tended to be higher in group I than in group N (odds ratios, 2.00 and 2.32, respectively). In addition, the presence of the D and/or C alleles significantly increased the relative risk of developing myocardial ischemia (odds ratio, 2.71; p = 0.038). During the convalescent phase of KD, ACE activity was increased despite significant attenuation during the acute phase. These results suggested that the renin-angiotensin system is associated with the formation of severe coronary artery stenosis and myocardial ischemia.     

Functional aortic stenosis diagnosed in fetal period

We report a case of fetal congenital heart disease prenatally diagnosed as critical aortic valve stenosis at 25 weeks of gestation. Fetal echocardiography demonstrated severe mitral regurgitation, aortic valve stenosis, hypocontractility of the left ventricle, and showed retrograde flow in the aortic arch like HLHS (hypoplastic left heart syndrome). However, soon after delivery, improvement in the baby's hemodynamics and myocardial contractility were recognized without any treatment.