Biomedical subjects
Publications and source records attributed to H Rocha.
We report a severe fatal lepromatous leprosy case in an adult homosexual male 2 years after AIDS class IV was diagnosed. Multidrug therapy including thalidomide for erythema nodosum leprosum (ENL) was ineffective. The patient died with multiple large skin ulcerations due to multibacillary leprosy. Leprosy in AIDS patients may present as a severe uncontrolled disease, with extensive ENL unresponsive to therapy.
To evaluate the clinical effectiveness of intermittent intravenous cyclophosphamide in the treatment of severe systemic lupus erythematosus, 20 patients with systemic lupus erythematosus (SLE) and evidence of severe renal involvement or systemic vasculitis, consecutively admitted to the hospital were studied. Cyclophosphamide was administered intravenously at a dosage of 1.0 g/m2 monthly, during 6 months and maintained every 3 months during 12 additional months. Of 10 patients with active lupus nephritis, a reduction or disappearance of proteinuria and maintenance of normal renal function was recorded in 6. Improvement of renal function was observed in 4 out of 7 patients with renal insufficiency at initial evaluation; resolution of renal insufficiency was more frequently observed in patients with recent onset renal failure. At the end of the follow-up (18.0 +/- 14.5 months) disappearance or reduction of nephrotic range proteinuria was recorded in 6 out of 14 patients; there was progression toward renal failure in 4 patients (20%). Response to intravenous cyclophosphamide therapy was observed in 4 of 5 patients with severe extrarenal SLE. Side effects, recorded in 12 patients, were mild and transient and in no patient was the treatment discontinued. Four patients died during the follow-up, although in 2 of them the deaths were not attributable to therapy. Even though this was an open and uncontrolled study, intermittent, intravenous cyclophosphamide was an effective therapy for severe, steroid refractory SLE.
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The functional differentiation of mammary epithelial cells requires specific hormones, growth factors and chemical signals of the cellular environment. These signals consist in cell communication with the extracellular matrix and cell-cell interactions which through an intrincated mechanism lead to the events that trigger milk secretion. The mammary epithelial cells HC11 from the cellular line COMMA-1D were cultured in the presence of lactogenic hormones such as insulin, dexametazone and prolactin and further stimulated with the epidermal growth factor. In these conditions the cell differentiated, presenting quantitative changes in shape and volume on their organelle cell structure. These cells synthesize beta casein and the intermediary filaments of keratin demonstrated by immunoblotting as well as electronic micrographics.
To analyze the clinical course and response to therapy 15 patients (9 male and 6 female) with the hepatosplenic form of schistosomiasis mansoni and focal segmental glomerulosclerosis (FSGS) were prospectively studied (mean follow-up = 115.8 +/- 93.2 months). Nephrotic syndrome was the most frequent clinical presentation, followed by abnormalities of urinalysis. The clinical course was progressive: at final evaluation 9 patients (60%) had developed renal failure. Hypertension or/and renal insufficiency at initial evaluation and persistence of the nephrotic syndrome were associated with progression toward advanced renal failure. Response to immunosuppressive therapy was recorded in 30% of the patients; all responsive patients still had normal renal function at final evaluation. The treatment of the Schistosoma mansoni infection did not influence the clinical course of the renal disease. It is concluded that FSGS in patients with hepatosplenic schistosomiasis mansoni is a disease progressing to advanced stage independently of the presence of the parasite.
In patients with cutaneous leishmaniasis in areas of Leishmania braziliensis transmission, ulcers may heal without therapy. In the present study, we evaluated the T cell responses of 10 subjects who two years earlier had a rapidly (less than three months) self-healing cutaneous disease. The immunologic responses of these cases were determined by intradermal skin test, measurements of antibodies, lymphocyte proliferative responses, and interferon-gamma (IFN-gamma) production in cultures stimulated with Leishmania antigens. These data were compared with those observed in 10 other patients with active cutaneous and mucosal leishmaniasis. Evidence of strong lymphocyte blastogenesis and IFN-gamma production was observed in eight of 10 patients with self-healing cutaneous leishmaniasis, with stimulation indices ranging from 32 to 506, and IFN-gamma levels ranging from 500 to 2,900 pg/ml. The mean +/- SD stimulation index of the lymphocyte proliferative responses (288 +/- 247) and the mean +/- SD of IFN-gamma production after stimulation with Leishmania antigen (970 +/- 960 pg/ml) in subjects with self-healing cutaneous leishmaniasis were similar (P > 0.05) to those observed in patients with mucosal disease (stimulation index = 308 +/- 282 and IFN-gamma level = 838 +/- 819 pg/ml). These responses were higher (P < 0.01) than those observed in patients with active cutaneous leishmaniasis (stimulation index = 50 +/- 82 and IFN-gamma level = 264 +/- 336 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult male rats were subjected to pyelonephritis by direct kidney intramedullary injection of 0.1 ml saline suspension of 10(5) E. coli. Animals were killed at intervals of 4, 10, 15, 30 and 60 days. Half of each kidney and bladder were cultured in proper bacteriologic media to demonstrate the existence of infection. The other halves were submitted to light microscopy and ultrastructural studies. Immunofluorescence methods were used for the study of connective matrix components, at the initial stage of the inflammatory process (4, 10 and 15 days). Infection was documented by bacteriologic, gross and microscopic findings in all groups following inoculation, and it lasted up to two months. Following the acute inflammatory reaction, fibronectin and type III collagen were deposited in the interstitium of kidneys. Small amounts of type I collagen were found later. Type IV collagen appeared in small quantities, associated with collapse of structures containing basement membranes. Fibronectin became concentrated in re-activated foci. The subsequent scarring and associated focal renal atrophy depended upon the extension of the acute lesion.
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T cell responses to lipophosphoglycan-associated protein (LPG-AP) and the rgp63 antigens were studied in subjects with either asymptomatic L. chagasi infection or cured visceral leishmaniasis. The [3H]-thymidine uptake of lymphocytes stimulated with LPG-AP and rgp63 (mean +/- SD) was 14275 +/- 5048 and 3523 +/- 1678 cpm, respectively, for subjects with asymptomatic L. chagasi infection and 20046 +/- 5102 and 5086 +/- 3500 cpm, respectively, for subjects cured of visceral leishmaniasis. The responses to LPG-AP in both asymptomatic and cured visceral leishmaniasis were higher (P < 0.01) than those observed with rpg63. LPG-AP induced IFN-gamma production in all subjects studied, while rgp63 did not induce lymphocyte proliferation or IFN-gamma production in the majority of the subjects tested. IFN-gamma levels in cultures stimulated with LPG-AP were 103 +/- 81 pg/ml in individuals with asymptomatic L. chagasi infection and 127 +/- 123 pg/ml in subjects cured of visceral leishmaniasis. IFN-gamma levels in cultures stimulated with LPG-AP from subjects with asymptomatic L. chagasi infection were comparable to those observed in subjects cured of visceral leishmaniasis (P > 0.05). These data indicate that LPG-AP is recognized and induces T cell proliferation and IFN-gamma production in subjects with protective immune response against Leishmania chagasi.
The study attempted to identify immunologic markers for progression of Leishmania donovani chagasi infection to disease in children in an area endemic for visceral leishmaniasis (VL). [3H]thymidine uptake of lymphocytes stimulated with L. donovani chagasi antigen from children with asymptomatic infection (25,286 +/- 11,648) and from children with self-healing subclinical infection (15,511 +/- 4681) was greater (P = .001) than that observed with lymphocytes from children who progressed to classic VL (4811 +/- 2984). The interferon-gamma (IFN-gamma) levels from asymptomatic and subclinically infected children (74 +/- 90 units/ml) were higher (P = .02) than those observed in children who progressed to VL (7 +/- 8 units/ml). Absence of lymphocyte blastogenesis and IFN-gamma production were associated with progression of infection to classic VL. In the presence of these markers, children should be closely followed to identify signs and symptoms that would permit early initiation of therapy.
In visceral leishmaniasis (VL), patient's lymphocytes are not activated by leishmania Ag stimulation, and their sera exhibit a potent nonspecific suppressive effect on the responses of normal lymphocytes. Sera were obtained from 33 VL patients, eight patients with subclinical VL, and from 27 normal volunteers. Only sera from VL patients markedly reduced Con A-induced lymphocyte proliferative responses, as well as IL-2 or IFN-gamma production by normal lymphocytes. Addition of exogenous human rIL-2 to cultures containing VL patient sera partially reversed the normal lymphocyte proliferative capacity and restored IFN-gamma production. This phenomenon was consistent with the presence of greatly elevated levels of soluble IL-2R (sIL-2R) in VL patients' sera (4299 +/- 2351 U/ml), well above those of normal sera (180 +/- 94 U/ml), or of sera from patients with subclinical leishmania infection without immunosuppression (1002 +/- 281 U/ml). Furthermore, the removal of sIL-2R reduced VL serum suppressive activity as evaluated by effects on IL-2 and on IFN-gamma production. These data suggest the participation of high levels of sIL-2R in the serum-mediated suppression in VL.
Bacterial infections are often seen in patients with visceral leishmaniasis. To determine the incidence of such infection and the more common infectious agents, 30 consecutive patients with visceral leishmaniasis were followed throughout hospitalization. There were 24 episodes of bacterial infection in 18 patients (60%). The incidence of bacterial infections in these patients was 22.2/1000 days of admission. The proportion of patients becoming infected by time was significantly greater in the visceral leishmaniasis group than in controls (P less than .01). The skin, respiratory tract, and middle ear were the most common sites of infection, and Pseudomonas aeruginosa and Staphylococcus aureus were the most common agents. Low-grade-virulence bacteria (e.g., Serratia and Providencia species) were also isolated from some cases. Bacterial infections (mainly nosocomial) in patients with visceral leishmaniasis tend to be severe and can cause death. When bacterial infection is suspected in these patients, empiric antibiotic therapy should be started immediately, including coverage for P. aeruginosa and S. aureus, after appropriate diagnostic procedures are taken.
Schistosomiasis mansoni has been well documented as one of the causes of infectious glomerulopathy, with mesangiocapillary glomerulonephritis being the most frequent lesion observed in this condition. Twenty-one patients with hepatosplenic schistosomiasis mansoni and biopsy-documented mesangiocapillary glomerulonephritis (MCGN) were studied and compared with 19 patients with the idiopathic form of MCGN. Nephrotic syndrome was the most frequent clinical presentation in both groups. At the time of diagnosis nine patients with hepatosplenomegaly (4 with associated arterial hypertension) and 12 (8 with arterial hypertension) among the patients with idiopathic MCGN had renal insufficiency. At the end of the follow-up period 16 patients with hepatosplenic schistosomiasis and MCGN (75.2 months) and 15 with the idiopathic form (52.1 months) had renal failure. Also, when compared at 48 months of follow-up, no difference in renal function could be detected in both groups. No benefits related to anti-parasitic treatment in the schistosomiasis group and immunosuppression therapy in either group could be documented. The progression of the renal disease, as assessed by the reciprocal of serum creatinine versus time, and the survival curve, were not different between the two groups. It is concluded that MCGN in patients with the hepatosplenic form of schistosomiasis mansoni is a progressive disease not influenced by anti-parasitic or immunosuppressive therapy, and presents a clinical course similar to that of the idiopathic form.
1. The production of lymphokines capable of activating macrophages to kill leishmania was evaluated in seven visceral leishmaniasis patients. 2. Macrophages from healthy donors cultivated in vitro with supernatants from lymphocyte cultures of visceral leishmaniasis patients were infected with L. d. chagasi or L. m. amazonensis. After infection the number of amastigotes per 100 cells was counted. 3. The supernatant from visceral leishmaniasis lymphocytes did not significantly reduce the number of intracellular amastigotes of L. donovani chagasi (89 +/- 27%) in relation to controls (culture containing medium alone). In contrast, supernatants of mucocutaneous lymphocyte cultures decreased the percentage of infection to 26 +/- 11%. The supernatant of antigen-stimulated lymphocyte cultures from visceral leishmaniasis patients also did not inhibit L. mexicana amazonensis growth. The supernatant of visceral leishmaniasis lymphocytes stimulated with PHA reduced the number of intracellular amastigotes to 62 +/- 23% in relation to controls. 4. The inability of lymphocytes from visceral leishmaniasis patients to proliferate when stimulated with leishmania antigens and to activate macrophages to kill leishmania may represent a fundamental defect and lead to the acquisition of the disease.
We have characterized the T-lymphocytes in the skin lesions of 10 patients with cutaneous leishmaniasis and in the nasal lesions of seven patients with mucosal leishmaniasis, with the immunoperoxidase and monoclonal antibody techniques. There was predominance of cells with helper phenotype (Leu 3A+ 3B) over suppressor phenotype (Leu 2a) in the lesions of both groups. The helper/suppressor (H/S) ratio in the skin lesions was 1.6 +/- 0.5 and in the nasal lesions of mucosal leishmaniasis was 1.7 +/- 0.8. The H/S ratios in the peripheral blood of patients with cutaneous leishmaniasis (2.1 +/- 0.8) and in patients with mucosal leishmaniasis (1.6 +/- 0.8) were comparable and similar to the ratios in the skin and nasal biopsies. The percentage of T-cells and macrophages expressing the Dr antigen in the cutaneous group (69.5 +/- 13.7) was not significantly different from the mucosal patients (90.3 +/- 5.7). We conclude that the immunopathology of the skin lesions in cutaneous leishmaniasis is similar to the nasal lesions of mucosal leishmaniasis.
In this study, renal function of 52 workers of a primary lead smelter located in Northeast Brazil was compared to a reference group of 44 otherwise similar workers of a paper mill. Renal dysfunction, defined by a serum creatinine level greater than or equal to 1.5 mg/dl, was found in 17 (32.7%) workers at the lead smelter, the exposed group, but in only 1 (2.3%) individual from the reference group. Workers from the exposed group also showed significantly higher mean serum uric acid levels. Renal dysfunction of workers from the exposed group was statistically associated with duration of the employment at the smelter and with age, but not with the levels of lead and zinc protoporphyrin in blood and delta-aminolevulinic acid in urine. The two groups presented similar rates of arterial hypertension. However, arterial hypertension was much more strongly associated with renal dysfunction in the lead workers.
Although several aspects of the association between S. mansoni infection and renal disease are well known, the influence of the anti-parasitic therapy on the clinical course of the glomerulopathy remains undefined. With the aim of studying this aspect, 16 patients with glomerulopathy associated with schistosomiasis mansoni were evaluated (proteinuria and levels of BUN and creatinine) before therapy, 1 week, 1 month, 2-3 months and 6 months after therapy of the parasitic infections. During the follow-up of such cases no benefit could unquestionably be demonstrated in the patients. Also, no permanent deterioration of renal function related to anti-parasitic therapy could be documented. It is concluded that the treatment of the S. mansoni infection, once the consequent glomerulopathy is clinically apparent, does not influence the clinical course of the disease.
Three cases are described showing that Leishmania donovani can cause progressive disease in immunocompromised hosts. The first patient was receiving corticosteroid therapy for ulcerative colitis and the second corticosteroids and cyclophosphamide for proliferative glomerulonephritis; in the third patient, leishmaniasis occurred after a long episode of hepatosplenic schistosomiasis and salmonella bacteraemia which was treated with chloramphenicol. In two cases, the patients had moved away from areas of L donovani transmission many years before the progressive disease occurred, consistent with long-term survival of the organism in normal hosts. L donovani should be added to the growing list of opportunistic microbial infections.