We report results obtained with sera from 58 chronic chagasic patients that were evaluated for effects on heart rate and atrioventricular (AV) conduction in isolated rabbit hearts and screened for the presence of muscarinic and beta-adrenergic activity. We show that sera from 26 patients decreased heart rate, while 10 increased it and 22 had no effect. Additionally, sera from 20 of the 58 patients blocked AV conduction. Muscarinic activation seems to be involved in both effects, but is not the only mechanism, since atropine did not antagonize the decrease in heart rate in 23% of sera or AV block in 40%. Sera from patients with complex arrhythmias were significantly more effective in depressing both heart rate and AV conduction. Sera that induce increases in heart rate seem to operate exclusively through beta-adrenergic activation. Two of these sera, evaluated with respect to intercellular communication in primary cultures of embryonic cardiomyocytes were able to block gap junction conductance evaluated by a dye injection technique after 24-h exposure. The mechanisms underlying this uncoupling effect are currently being investigated.

We report a healthy, 73-year-old Japanese woman who presented with primary cryptococcosis on the skin of both cheeks. She had initially developed an erythematous, partly ulcerated lesion on the right cheek 2 weeks earlier following an injury. There was no regional lymphadenopathy, and chest X-rays were normal. Histopathological findings showed granulomatous cell infiltration. Periodic acid Schiff staining revealed spores that were identified by the indirect immunoperoxidase staining method as Cryptococcus neoformans. The isolate was identified as C. neoformans var. neoformans serotype D. The skin lesions healed in 1 month without antifungal therapy. A literature review indicates that this serotype tends to produce cutaneous lesions without systemic involvement.

Fifty-three patients with invasive transitional cell carcinoma of the renal pelvis and ureter were studied for p53 protein overexpression by immunohistochemistry. Overexpression of p53 protein was observed in 19 patients (35.8%). There was a significant correlation between overexpression of p53 protein and histologic grade (p < 0.01). However, there was no correlation found between p53 immunoreactivity and pathologic stage. By univariate survival analysis, a significant difference in cumulative survival was observed between stage pT2 and stage pT3 or pT4 tumors (p < 0.05). The difference in survival between patients with p53-positive and negative tumors did not reach statistical significance (0.05 < p < 0.1). Multivariate analysis revealed that pathologic stage had an independent prognostic value (p < 0.05). The independent prognostic value of p53 protein overexpression did not quite reach statistical significance (p = 0.07). p53 protein nuclear overexpression appears to be a relatively weak prognostic indicator for patients with invasive transitional cell carcinoma of the renal pelvis and ureter.

The protozoan parasite Trypanosoma cruzi causes Chagas' disease, a major cause of cardiac dysfunction in Latin Americans. Chagas' disease exhibits both acute and chronic phases, and each may be characterized by cardiac conduction disturbances. In acutely infected cultures of rodent heart cells, synchronized spontaneous beating becomes less regular, and coupling between cells is reduced. The basis of this decreased conduction is apparently in localization of the gap junction protein (Cx43) inside infected cells. Although total Cx43 is normal in infected cells, little is recognizable at appositional membranes. Electrophysiological properties are also altered by this infection. Action potentials are shortened, resting Ca2+ levels are elevated, and response to alpha-adrenergic agonists was altered, compared to controls. Humoral factors may contribute to the conduction defects in chronic Chagas' disease. Sera from chronically infected rabbits produced ECG abnormalities in Langendorff-perfused rabbit hearts. These findings indicate that chagasic infection may modify ion channel function in the heart, and we suggest that these changes may be manifested in the conduction disturbances that characterize this disease.

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