Ras oncogenes and p53 tumor suppressor gene analysis in cardiac myxomas.

Although ras oncogenes and p53 tumor suppressor gene mutations are implicated in the development of several human tumors, little is known about their role in the pathogenesis of primary cardiac tumors. Paraffin-embedded tissue from 19 cardiac myxomas were investigated for the presence of ras oncogenes and p53 tumor suppressor gene abnormalities. Immunohistochemical analysis was used to identify the accumulation of p21-ras and p53 proteins. A polymerase chain reaction was used to amplify exons 1 and 2 of the ras genes and exons 5 to 8 of the p53 gene. The PCR products were analyzed by single strand conformation polymorphism analysis and by direct DNA sequencing. Three of 19 myxomas showed strong positive staining for the ras p21 protein. In contrast, nuclear p53 was not detectable in any of the myxomas. Among the ras p21 immunopositive myxomas, 2 were heterozygous for a missense point mutation of the K-ras, Gly 12Asp. Further screening of the remaining myxomas showed no mutation or even silent polymorphism in any exon of the ras and p53. The results suggest that although genetic alterations of ras oncogenes and p53 are uncommon events in cardiac myxomas, ras mutations may be involved in the pathogenesis of a subgroup of this type of tumor.

Old ectopic pregnancy remnants with morphological features of placental site nodule occurring in fallopian tube and broad ligament.

Placental site nodule (PSN) is an asymptomatic benign proliferation of intermediate trophoblast from a previous gestation that failed to involute. It is most commonly found in the endometrium or endocervix; however, placental site nodule has recently been reported to occur at sites of ectopic gestation. This is the first case of PSN in the broad ligament in direct contact with the fallopian tube. The patient underwent surgery for an adenocarcinoma of the opposite tube. Microscopically and immunohistochemically, the lesion showed the characteristics of a proliferation of intermediate trophoblast.

Intracystic pressure and viability in hydatid disease of the liver.

BACKGROUND: Knowledge on the viability of hydatid cysts of the liver during operation is important to the surgeon may dictate the peri-operative therapeutic manoeuvre undertaken. PATIENTS AND METHODS: A prospective study was performed on 23 patients with 28 hydatid cysts of the liver to assess whether intracystic pressure (ICP) could predict viability of protoscoleces. All patients received albendazole (10 mg/kg body weight/day) for 5 days pre-operatively. The ICP was measured from the apex of the cyst, after laparotomy, using a 16-G needle connected to a water manometer. After manometry, the cyst contents were aspirated and the viability of protoscoleces assessed by their flame cell activity, motility and ability to exclude 5% aqueous eosin. RESULTS: The median ICP was 54 +/- 21 cmH2O for 17 viable cysts and zero for 8 non-viable cysts, while 1 additional non-viable cyst and 2 sterilized cysts had high ICP (sensitivity, 100%; specificity, 72%; accuracy, 89%). The median diameter of the viable cysts was 9.3 +/- 3.5 cm and the non-viable cysts 10.7 +/- 2.6 cm. In the right lobe were located 12 viable and 8 non-viable cysts and in the left lobe, 5 viable and 3 non-viable cysts. No significant difference in diameter or ICP were noted between the hepatic lobes. CONCLUSIONS: These findings suggest that the measurement of ICP is a simple, cheap and reliable method for assessment of the viability of hydatid cysts of the liver.

Germ line mutation analysis in families with multiple endocrine neoplasia type 2A or familial medullary thyroid carcinoma.

The RET proto-oncogene has been identified as the multiple endocrine neoplasia type 2 disease gene. An association between specific RET mutation and disease phenotype has been reported. We present the phenotype-genotype of 12 Greek families with multiple endocrine neoplasia type 2A (MEN 2A) or familial medullary thyroid carcinoma (FMTC). Seventy members were studied and DNA analysis for RET mutations was performed in fifty-eight of them. Exons 10, 11, 13, 14 and 16 of the RET proto-oncogene were analyzed by single strand conformation polymorphism analysis, direct DNA sequencing and/or restriction enzyme analysis. No mutations of the RET proto-oncogene were identified in 1 of 9 families with MEN 2A and in the 3 families with FMTC. In 7 MEN 2A families, the mutation was demonstrated in codon 634 and in 1 family it was demonstrated in codon 620. There was a low frequency, about 8%, of hyperparathyroidism associated with MEN 2A. The specific causative mutations for pararthyroid disease were C634R or C634Y. Among the MEN 2A individuals there was one case with de novo C634R mutation and one case, C634Y, with cutaneous lichen amyloidosis which predated by 24 years the diagnosis of MEN 2A. In 2 children who were MEN 2A gene carriers, microscopic medullary thyroid carcinomas were found. These data show a low frequency of hyperparathyroidism in our cases and provide further evidence that individuals with C634R as well as with C634Y mutations of the RET proto-oncogene could be at risk for parathyroid disease. Cutaneous lichen amyloidosis could be an early feature of MEN 2A. Additionally, direct DNA testing provided an opportunity to resect medullary thyroid carcinoma at an early stage.

Perioperative benzimidazole therapy in human hydatid liver disease.

Primary treatment of liver hydatidosis is surgical, but the recurrence rate is about 10%. To minimize the risk of recurrence, 67 consecutive patients with liver hydatidosis were prospectively treated by mebendazole or albendazole for 5 days before surgery. During the operation the viability of the protoscoleces was assessed. Seventeen patients who had viable protoscoleces at the time of the operation received the same benzimidazole one extra month postoperatively, while the remaining 50 patients who had dead protoscoleces didn't receive postoperative therapy. None of the patients developed recurrence of the disease after a follow-up period of 15-67 months (average 41 months). These results suggest that a 5-day preoperative benzimidazole therapy either combined or not with a monthly postoperative course according to the viability of the protoscoleces at the time of operation, may erase the risk of recurrence after surgical treatment of the liver hydatidosis.

Trimetazidine for prevention of hepatic injury induced by ischaemia and reperfusion in rats.

OBJECTIVE: To assess the effect of trimetazidine (an anti-anginal drug that acts as a scavenger of oxygen free radicals) in the protection of hepatocytes after a 90 minute period of warm ischaemia followed by reperfusion in rats. DESIGN: Prospective study. MATERIAL: 80 Wistar rats. INTERVENTIONS: 20 Rats were given a single dose of trimetazidine 2.5 mg/kg intravenously 30 minutes before the induction of ischaemia; 20 received the same dose intraperitoneally twice a day for five days before the experiment and one dose intravenously 30 minutes before; 20 were given a single dose of 2.5 mg/kg intravenously after reperfusion had been started; and 20 acted as controls. All rats underwent liver biopsy through a laparotomy incision on postoperative days 2, 7, and 21, and the activities of liver enzymes in their blood were measured before induction of ischaemia and two, seven, 14, and 21 days afterwards. OUTCOME MEASURES: Histological changes and serum enzyme activities. RESULTS: The amount of centrilobular necrosis of hepatocytes, and the activity of hepatic enzymes were greatest on day 2, as was the reduction in superoxide dismutase activity in the erythrocytes. A single dose of trimetazidine, whether given before or after the ischaemic episode, gave significant protection to hepatocytes, but pretreatment for five days was even more effective. CONCLUSION: Trimetazidine protected rats' livers from injury after a period of warm ischaemia and reperfusion.