Myocarditis in beta-thalassemia major. A cause of heart failure.

BACKGROUND: Although acute pericarditis is a common complication of beta-thalassemia major, the prevalence and consequences of myocarditis in this disease have not been investigated. METHODS AND RESULTS: A prospective 5-year follow-up study was carried out in all patients with beta-thalassemia major in whom the diagnosis of acute infectious myocarditis could be established between 1977 and 1986. A similar number of age- and sex-matched control subjects with beta-thalassemia and normal left ventricular function and no evidence of myocarditis were also followed for 5 years. Of 1048 patients with beta-thalassemia major, 47 patients (age, 15 +/- 2.5 years) with precordial chest pain were diagnosed as having acute infectious myocarditis. Myocardial biopsy was diagnostic in 26 patients, border-line in 14 patients, and nondiagnostic in 7 patients. Acute heart failure with left ventricular dysfunction (left ventricular ejection fraction, 25 +/- 11%) developed in 11 patients (23.4%) with myocarditis, and 8 of them died within 1 month to 1 year after diagnosis. Thirteen patients with myocarditis (27.6%) developed chronic heart failure (left ventricular ejection fraction, 26 +/- 13%) within 3 +/- 1.3 years, and 10 of them died within 8 +/- 3 months. Left ventricular systolic and diastolic functions of the control subjects did not change significantly during the 5-year period (left ventricular ejection fraction, 63 +/- 11% versus 65 +/- 7%; P = NS). However, left ventricular restrictive abnormalities (early diastole/late diastole, > 2.2; deceleration time, < 110 milliseconds) combined with right ventricular dilatation (> 30 mm internal diameter) and right-sided heart failure developed in 3 patients with extremely high mean serum ferritin levels. No significant difference was found in mean levels of serum ferritin and pretransfusion hemoglobin between patients with and those without myocarditis. CONCLUSIONS: In patients with beta-thalassemia, myocarditis appears to be involved in the pathogenesis of left ventricular systolic dysfunction, being the main cause of death. Iron overload appears to provoke left ventricular restrictive abnormalities combined with right ventricular enlargement and dysfunction.

Expression of ras and c-myc oncoproteins and hepatitis B surface antigen in human liver disease.

One of the major antecedent factors preceding the development of hepatocellular carcinoma is chronic hepatitis B virus infection. Also, recent molecular studies have shown that activation of c-oncogenes might be responsible for the malignant transformation in some cases of hepatocellular carcinoma. We used immunohistochemical methods to investigate the correlation of ras and c-myc oncogene expression with the presence of HBsAg in human liver disease. Our material consisted of 23 chronic active hepatitis B needle liver biopsies and surgical specimens from 11 cases of cirrhosis, 23 hepatocellular carcinoma and 10 normal adult livers. Direct, three-step and streptavidin-biotin-complex immunoperoxidase techniques using polyclonal (anti-HBsAg) and monoclonal antibodies (anti-ras p21, anti-myc p62), were performed. Normal liver tissues were negative for all antibodies used. In HBsAg+ chronic active hepatitis B cases enhancement of c-myc, and less frequently of ras oncogene expression, was a common observation. Increased myc p62 and ras p21 expression was a finding not restricted to HBsAg+hepatocytes, which occasionally were negative for oncoprotein immunostaining. All HBsAg-chronic active hepatitis B cases were negative for ras p21 and myc p62 specific staining. Cirrhotic livers showed more frequently enhanced c-myc expression. Most of the immunostained cells were negative for HBsAg. HBsAg- cases of hepatocellular carcinoma more often showed ras p21 than myc p62 overexpression. HBsAg+ hepatocellular carcinomas presented only ras p21-positive immunostaining, which was not detected in HBsAg+ hepatocytes. Our recent data supports the view that continued expression of HBsAg in human liver disease is not necessary for the enhancement of ras and c-myc oncogene expression.

Detection of hepatitis-B virus-DNA and mutations in k-ras and p53 genes in human hepatocellular carcinomas.

Hepatitis B virus (HBV) infection is considered as one of the major risk factors in the development of human hepatocellular carcinoma (HCC). Recent studies have also suggested the implication of oncogene and onco-suppressor genes in liver carcinogenesis. We studied 41 cases of HCC for the presence of HBV DNA and point mutations in codon 12 of K-ras and codon 249 of p53. We used 'nested' PCR for the amplification of HBV because of the expected low incidence of the virus DNA in the samples. PCR was also used for the amplification of K-ras and p53 regions that contain the codons of interest, followed by RFLP analysis for the detection of point mutations. HBV DNA was amplified in 22 cases (53.7%), while 5 cases (12.2%) appeared to carry mutations in codon 12 of K-ras and 7 cases (17.1%) had mutations in codon 249 of the p53 gene. These results further support the correlation between HBV infection and HCC and also indicate an implication of K-ras and p53 genes in hepatocarcinogenesis.

Epididymitis from Enterobius vermicularis: case report.

A rare case of epididymitis caused by Enterobius vermicularis, a pinworm, is reported. A 52-year-old man underwent resection of the right epididymis and histological examination confirmed the diagnosis of pinworm infection by discovering parts of the body of the oxyurid in various sections.

Acute amiodarone-induced hepatitis.

Two fatal cases of amiodarone-induced acute, confluent, necrotic hepatitis are described. The patients, aged 28 and 60, had received a high loading dose of amiodarone. After the first and second day respectively following the administration of amiodarone, the patients developed jaundice, hepatomegaly, high serum transaminases, a prolonged prothrombin time and low cholesterol concentration. They died of hepatic coma and acute renal failure on the fourteenth and fourth day respectively. Needle liver biopsy, performed immediately after death, revealed lesions of acute drug-induced hepatitis with confluent and bridging necrosis. It is proposed that rapid administration of a high loading dose of amiodarone can cause acute confluent necrotic hepatitis. The mode of administration and the dosage of the drug should be re-considered.

Expression of ras and myc oncogenes in human hepatocellular carcinoma and non-neoplastic liver tissues.

An immunohistochemical assay was used to assess expression of ras p21 and myc p62 oncogene products in human hepatocellular carcinoma (HCC) and non-neoplastic liver tissues. The monoclonal antibodies Y13 259 and Myc1-9E10, specific for ras p21 and myc p62 oncoproteins, were employed on paraffin-embedded sections. Most HCCs showed enhanced ras p21 and myc p62 expression, as indicated by staining intensity. Cirrhotic livers revealed increased myc p62 and occasionally increased ras p21 expression. HBsAg+ hepatocytes showed intense immunostaining for ras p21. Fibrotic, cholestatic, fetal and normal adult liver did not present enhancement of oncoprotein production. We suggest that combined over-expression of ras and myc oncoproteins may be important for the malignant phenotypic alteration in human HCC.

Cirrhotic process, liver cell carcinoma and extrahepatic malignant tumors in idiopathic haemochromatosis. Study of 71 patients treated with venesection therapy.

A detailed morphological study concerning the liver of 71 patients suffering from idiopathic haemochromatosis was carried out. These patients were subjected to long-term venesection therapy, which lasted from 1 to 12 years. The mean duration of therapy was 7 years for each patient. The material consisted of needle biopsies of the liver. Three to seven biopsies were performed in each patient; the initial biopsy, the biopsy following venesection therapy, and the follow-up biopsies. In 30 cases the follow-up was performed in autopsy material. It was found that the final histological appearance of the liver remained unchanged in 44 (62%) cases, became worse in 23 (32%) cases, and improved in 4 (5%) cases. However, the change for the worse is generally retarded and consequently the mean survival of the patients is increased. Two out of 4 cases that showed improvement (i.e. changing from cirrhosis to fibrosis) are strongly supported by the fact that the follow-up study was performed in autopsy material after 2-5 needle liver biopsies. A high incidence of hepatocellular carcinoma (18%), as well as of a malignant neoplasia in another organ (8.4%), was noted in spite of the long-term venesection therapy. It follows therefore that the longer survival of patients with idiopathic haemochromatosis increases the possibility of hepatocellular carcinoma or of a malignancy in another organ.

Large Brunner's glands adenoma. A case report.

A rare case of a large Brunner's glands adenoma is reported. Usually, these neoplasms are small, exceeding 1 cm only in a few cases. Although the tumor was considerably large (6.5 cm), it did not cause obstruction of the upper digestive tract and bleeding was the first clinical symptom. Diagnosis was established after endoscopy with biopsies, which excluded malignancy. Local surgical excision of the neoplasm, which is the treatment of choice in such cases, was successfully performed.

Osteoid osteoma of the terminal phalanges.

Four cases of osteoid osteoma of the terminal phalanx--a very rare location--are presented. The clinical picture of cell cases is essentially the same, gradual swelling of the terminal phalanx with enlargement of the nail and pain, particularly at night and relievable by aspirin. The treatment was operative and of double value. 1. The osteoid osteoma is removed; 2. Cosmetic result is obtained by reduction of the size of the terminal phalanx.