[Chronic phase of Chagas disease. Clinical aspects and course of the disease]. / Fase crônica da doença de Chagas. Aspectos clínicos e evolutivos.

PURPOSE: To evaluate the clinical and evolutive aspects of chronic chagasic patients. METHODS: Three hundred chronic chagasic patients, 180 females, with age ranging from 19 to 81 years (55.6 +/- 13.1) were retrospectively studied. Patients were divided according to the following clinical types: indeterminated, cardiac (with the subtypes: arrhythmogenic, dilated and mixed), digestive isolated and digestive plus cardiac involvement. The following variables were analysed: prevalence of each clinical forms, symptoms, electrocardiographic pattern and clinical outcome. RESULTS: At the start of the study, 73 (24.3%) patients were in indetermined type, 106 (35.3%) in cardiac arrhythmogenic, 95 (31.6%) in mixed, 7 (2.3%) in dilated, 16 (5.3%) in digestive plus cardiac type and 3 (1%) in the pure digestive type. The most prevalent symptoms were dyspnea on efforts (57%), palpitations (41.33%) and chest pain (33%). The most frequent electrocardiographic pattern was right bundle branch block plus antero-superior fascicular block, in 30% of the patients. The average follow-up time was 7.8 +/- 6.1 years and the outcome was considered good in 20 patients (6.6%), stable in 214 (71.3%) and bad in 66 (23%). At the end of the follow-up, 9 patients have evaluated from the indeterminated to the cardiac and digestive types, and 19 (17.92%), from the arrhythmogenic to mixed cardiac subtype. The follow-up was lost in 79 patients (26.3%), most of them, probably dead. CONCLUSION: With a mean time of 7.8 years, 12.3% of the patients in the indeterminated type evolved to the cardiac and/or digestive type; right brundle branch block with antero-superior fascicular block was the most prevalent electrocardiographic pattern; the outcome was stable or good in the majority of these patients.

Cyclophosphamide affects the dynamics of granuloma formation in experimental visceral leishmaniasis.

We observed histopathological and ultrastructural hepatic changes following the intracardiac inoculation of Leishmania donovani amastigotes into inbred LHC hamsters (group I). Since granuloma formation is known to be T-cell-dependent, we also examined infected hamsters under cyclophosphamide immunosuppressive treatment (group ICy) and evaluated the production of interleukin-2 (IL-2) by their cells. Group I showed more intense hepatocyte and endothelial cell clasmatosis as well as hepatocyte degeneration and necrosis, deposits of connective tissue fibers, granulomas with multinucleated giant cells (MGCs) of foreign-body and Langhans' types and reduced production of IL-2 by spleen cells. In contrast, group ICy hamsters exhibited larger eosinophil and lymphocyte populations within sinusoids and peri-sinusoidal areas but showed no MGCs in granulomas. A striking decline in IL-2 production was noted. These results suggest that cyclophosphamide induces a delay in the natural evolution of L. donovani-induced granulomatous hepatic inflammation.

Nodular glomerulopathy associated with nonamyloidotic kappa light chain deposits and excess immunoglobulin light chain synthesis.

A nodular glomerulopathy characterized by mesangial deposits of monoclonal kappa light chains was detected by immunofluorescence in a renal biopsy from a patient with proteinuria and hypertension. These nodules lacked the tinctorial and morphologic features of amyloid. Ultrastructurally, the nodules contained electron-dense granular deposits as well as fibrils in parallel arrangement. The fibrils measured 110-140 A in diameter. They were consistent in size with amyloid fibrils. However, they differed in lacking the randomly oriented network of typical amyloid fibrils and more closely resembled fibrils intrinsic to mesangial matrix. The patient had no bone marrow or X-ray evidence of myeloma and no evidence of free monoclonal light chains in serum or concentrated urines. Biosynthetic studies of the patient's bone marrow cells demonstrated unbalanced immunoglobulin synthesis with excess production of monoclonal kappa light chains. These observations suggest that the observed glomerulopathy results from direct deposition of monoclonal light chains. Deposits with kappa light chain determinants have been found in 7 other patients with similar nodular glomerulopathies, 4 of whom had diagnosed clinical myeloma. The lesion of nonamyloidotic nodular glomerulopathy previously described in 19 patients, nor examined by immunopathologic techniques or not shown to contain light chain determinants, may have a similar pathogenesis.

Human C4-binding protein. Association with immune complexes in vitro and in vivo.

C4-binding protein (bp), a glycoprotein with specific binding affinity for the activated form of C4 (C4b), has recently been isolated from human serum and partially characterized. This report demonstrates that C4-bp is incorporated into soluble immune complexes after complement activation in vitro. The reaction requires Ca++ ions and the presence of C4 in serum. Immunopathological studies of various forms of glomerulonephritis revealed intense C4-bp deposition in glomeruli from patients with immune-complex type of pathogenesis. C4-bp deposition was in close correlation with that of C4. These observations, together with the in vitro association of C4-bp to immune complexes, support the notion that the deposits in glomeruli represent the local accumulation of immune complexes.