Alberto N. Raick

Histopatologia da leishmaniose tegumentar por Leishmania braziliensis braziliensis: 1. Padrões histopatológicos e estudo evolutivo das lesões

The Authors describe the histopathological findings observed in biopsies from 378 cases of Mucocutaneous Leishmaniasis, caused by Leishmania braziliensis braziliensis. All the patients lived in the locality of Tres Bracos, State of Bahia, an endemic area of Leishmaniasis in Brazil. Parasites were found in 63.7% of patients with cutaneous form and in 35.7% of cases with mucous lesions, although always in reduced number. Histopathologic findings allowed the caracterization of five different patterns: 1. Exsudative-cellular reaction, due to infiltraction of histiocytes, lymphocytes and plasm cells; 2. Exsudative-necrotic reaction, characterized by the association of necrosis with cellular infiltration; 3. Exsudative and necrotic-granulomatous reaction, corresponding to pattern described as chronic-granulomatous inflammation with necrosis; 4. Exsudativegranulomatous reaction, characterized a disorganized granulomatous reaction, without tissue necrosis; 5. Exsudative-tuberculoid reaction — in which a typical tuberculoid granuloma is formed. The follow-up study in 49 patients showed, in sucessive biopsies, changes in the histopathologic patterns in 63.2% of cutaneous forms and in 45.4% of the mucous forms. It was concluded that the exsudative-cellular reaction represents both the inicial and final pattern of Mucocutaneous Leishmaniasis lesion. The other four histopathologic patterns characterize intermediate forms found during the evolution of the disease.

Caso fatal de adiaspiromicose pulmonar humana

A fatal case of human pulmonary adiaspiromycosis is reported. The patient, a male farm laborer from Pernambuco, in the Northeastern part of Brazil, had moved to Planaltina, DF., one year prior the onset of his illness. The main clinical manifestations consisted in fever, myalgia, cough and dyspnea. After being sick for five weeks, the patient developed severe respiratory failure and died. Grossly, disseminated nodular lesions, a few millimeters in diameter, were observed throughout the lobes of both lungs. Microscopically, round structures, up to 600 /mi in diameter, with a thick membrane, identified as adiaconidia of Chrysosporium parvum var. crescens, were seen in the center of the nodular lesions. These adiaconidia appeared predominantly inside microabscesses or necrotic areas, both surrounded by a granulomatous reaction. The pulmonary alveoli not affected by the nodular lesions contained an inflammatory exudate composed of macrophages and neutrophils. The finding of several non-fatal cases of the disease in the area of the Federal District suggests that adiaspiromycosis is endemic in the Central Brazilian Plateau region, where the dry, warm and windy climate, particulary from August to October, may provide the appropriate environmental conditions for the dissemination of C. parvum conidia.

Histopatologia da leishmaniose tegumentar por Leishmania braziliensis braziliensis. 4. Classificação histopatológica

The Authors have analysed the histopathological alterations observed in 162 cases of Mucocutaneous Leishmaniasis from Tres Bracos, Bahia, of whom 131 (80,9%) had purely cutaneous lesions and 31 (19,1%) had only mucosal lesions. The clinical behavior of 5 histopathological forms was documented in relation to treatment. The best prognosis was associated with the exudative granulomatous histopathology, a phase where the a host mechanism to use the parasite is evident leading to necrosis and granuloma formation as a residual sign. Therapy in this phase merely hastened the process. In a further large group the lesions were classified as exudative cellular reaction (cutaneous forms), an exudative necrotic reaction and an exudative necrotic gra- nulomatous reaction. In these cases the mechanisms of host defense are still being developed and the effect of therapy is to reduce the time to healing. Cutaneous cases with an exudative tuberculoid reaction had a worse prognosis, although there was a favourable response to treatment if the patient was young, the lesion was of short duration and the intradermal leishmanin test was not exaggerated Lastly are a group of mucosal cases with an exudative cellular reaction where this infiltrate may be a manifestation of auto agression. These cases, also classified as exudative tuberculoid, occur in adult patients with longstanding lesions and an exaggerated leishmanin skin test. They have a poor prognosis. This study develops suggestions for a classification based on the histopathological picture which could be valuable in predicting prognosis and influencing the choice of treatment. This classification is strictly morphological and is easy for the pathologist to apply. It appears to, correspond to the clinical course of the illness and could aid the clinician in the initial case evaluation.

Pentavalent antimonial nephrotoxicity in the rat

Aspects of the renal function were assessed in rats treated with the pentavalent antimonials Glucantime (Meglumine Antimoniate, Rhodia) or Pentostam (Sodium Stibogluconate, Wellcome). In dose of 30 mg of Sbv (Glucantime or Pentostam) by 100 mg of weight by day for 30 days, renal functional changes were observed consisting of disturbances in urine concentrating capacity. Such disturbances were expressed by significantly low values of urine osmolality as compared to the basal values previous to the drugs. The decrease in urine osmolality was associated to a significant increase in urinary flow and in negative free-water clearance. There was no alteration in osmolar clearance and in fractional excretion of sodium. These observations suggest an interference of the drugs in the action of the antidiuretic hormone. The disturbance in urine concentration was reversible after a seven days period without the drugs administration. No significant histopathological alterations were observed in the kidneys of the rats treated with the drugs. On the other hand, the rats treated with a high dose of Pentostam (200 mg/100 grams of weight/day) showed the functional and the histopathological alterations of the acute tubular necrosis.

Adiaspiromicose pulmonar humana novo caso da forma disseminada

A case of disseminated pulmonary form of adiaspiromycosis is reported. This is the second case of the disease found in Brasilia, DF. The patient, a 42-year-old peasant, lived in Corrente - State of Piaui, where he certainly acquired the infection. He was admitted to the Social Security Hospital, in Brasilia, with fever, chills, dry cough and dyspnea. At that time, he had been sick for about ten months and the decision of seeking medical care in Brasilia resulted from an exacerbation of the symptoms that had occurred two months before. At a right thoracotomy for a lung biopsy, disseminated white nodular lesions, a few millimeters in diameter, could be observed on the lung surface. Microscopically, round structures, 300 microns or more in diameter, identified as adiaconidia of Chrysosporium parvum var. crescens were seen in the center of some of these lesions. The tisssue response to the causative agent consisted of microabscesses, surrounded by cells in palisading arrangement, and granulomas of the mixed and foreign body types. The two kinds of lesions were thought to represent evolutive stages of the inflammatory process, and to be related to different exposures to the conidia, on separated occasions. The suppurative lesions would be recent lesions, started some weeks or a few months before, while the others, in which the granulomatous reaction predominated, were possibly older lesions, with an evolutions of at least several months.

Histopatologia da leishmaniose tegumentar por Leishmania braziliensis braziliensis. 2. Resposta humoral tissular

The Authors analysed the humoral response in biopsy material from 90 patients with Mucocutaneous Leishmaniasis caused by Leishmania braziliensis braziliensis, utilising the immunoperoxidase method to identify IgA, IgG, IgM, C3 complement fraction and fibrin in the tissue. The presence of IgG, IgA and IgM was found in tissue plasma cells with a predominance of IgG and this was correlated significantly with the number of plasma cells in the lesion. The presence of immunoglobulins in the tissues stimulated the opsonisation of parasites and/or their antigens resulting in necrosis which represents one of the effective mechanisms to reduce parasite load. In ne- crotic areas and the walls of inflammed vessels immunoglobulins were deposited as well as the C3 fraction of complement and fibrin — immunocomplex fractions derived from the host. This tissue necrosis was interpreted as the result of the action of immunocomplexes in a region with equivalent or a smally excess of antigen (Arthus type reaction). The presence of parasite antigens expressed on the macrophage membrane in the initial phase of the lesion when in contact with tissue immunoglobulins, leads to the installation of an antigen-antibody reaction resulting in the appearance of necrosisin Mucocutaneous Leishmaniasis.

Histopatologia da leishmaniose tegumentar por Leishmania braziliensis braziliensis. 3. Reação celular nos tecidos

The Authors analyse the histopathological alterations observed in 378 cases of Mucocutaneous Leishmaniasis from Tres Bracos, Bahia, of whom 307 (81,4%) were only cutaneous, 54 (14,2%) only mucosae and in 17 (4,4%) both integuments were involved simultaneously. A cellular infiltration of lymphocytes and plasma cells was invariably present in all forms and during healing. In mucosal cases, this reaction may have an important role in maintaining an auto agression in the presence of few or no parasites. The plasma cell is a constant ele-ment in well developed lesions but not present in healing lesions. Its presence almost always denotes a tendancy to relapse. Mast cells were observed in both cutaneous and mucosal lesions but predominate in the former. Its number was significantly greater in those with an exudative and necrotic granulomatous reaction where necrotic phenomena are marked. Eosinophils were significantly associated with mast cells suggesting the existence of association between these cells in the modulation of the inflammatory response. Two types of granulomatous reaction were observed: a disorganized one, often related to tissue necrosis, and an organized, tuberculoid type granuloma. The first type is interpreted as of post necrotic origin resulting in a reduction in antigenic load with maintenance of antibody levels, creating the conditions to establish a granuloma similar to that observed in immunocomplex lesions with excess of antibody. The other type of rection was the granuloma of epithelioid cells, which tend to arise in two groups of patients. In young patients, with short time cutaneous lesions and normal positive leishmanin skin tests, this type of granuloma perhaps similar to the specific hypersensibility granuloma described by EPSTEIN (1977). In the other group of patients, the leishmanin skin test was always exaggerated. In these cases the hypersensitive granuloma is associated with a cellular hypersensivity, perhaps amplified by sequestration of antigen, reforcing the antigenic stimulus of the granuloma. As a result, treat- ment of this group is more difficult and the prognosis worse in consequence.The Authors analyse the histopathological alterations observed in 378 cases of Mucocutaneous Leishmaniasis from Tres Bracos, Bahia, of whom 307 (81,4%) were only cutaneous, 54 (14,2%) only mucosae and in 17 (4,4%) both integuments were involved simultaneously. A cellular infiltration of lymphocytes and plasma cells was invariably present in all forms and during healing. In mucosal cases, this reaction may have an important role in maintaining an auto agression in the presence of few or no parasites. The plasma cell is a constant ele-ment in well developed lesions but not present in healing lesions. Its presence almost always denotes a tendancy to relapse. Mast cells were observed in both cutaneous and mucosal lesions but predominate in the former. Its number was significantly greater in those with an exudative and necrotic granulomatous reaction where necrotic phenomena are marked. Eosinophils were significantly associated with mast cells suggesting the existence of association between these cells in the modulation of the inflammatory response. Two types of granulomatous reaction were observed: a disorganized one, often related to tissue necrosis, and an organized, tuberculoid type granuloma. The first type is interpreted as of post necrotic origin resulting in a reduction in antigenic load with maintenance of antibody levels, creating the conditions to establish a granuloma similar to that observed in immunocomplex lesions with excess of antibody. The other type of rection was the granuloma of epithelioid cells, which tend to arise in two groups of patients. In young patients, with short time cutaneous lesions and normal positive leishmanin skin tests, this type of granuloma perhaps similar to the specific hypersensibility granuloma described by EPSTEIN (1977). In the other group of patients, the leishmanin skin test was always exaggerated. In these cases the hypersensitive granuloma is associated with a cellular hypersensivity, perhaps amplified by sequestration of antigen, reforcing the antigenic stimulus of the granuloma. As a result, treat- ment of this group is more difficult and the prognosis worse in consequence.

Imunofluorescência indireta no pênfigo foliáceo endêmico. contribuição para sua padronização

The aim of the present research was to standardize the indirect immunofluorescence reaction for Endemic Pemphigus Foliaceus (Fogo Selvagem). We found that fresh human skin was the ideal substrate and could proceed from foreskin, head, neck, or anterior abdominal wall. PBS pre-washing of the skin preceding the incubation with the serum should be avoided since the antigenicity might be diminished. TAS-calcium pre-serves the Pemphigus antigenic properties of the skin and shall be preferred as the diluent for the sera. Albumin-coated slides are useful because they increase the adherence of the skin sections. The conjugate appropriate dilution is convenientely determined by the radial immunodiffusion test (Ouchterlony method). So far as the correlation between the antibody titer and the clinical activity is concerned, we concluded that a titer of 160 or more was of bad prognosis, since it was associated with the generalized form of the disease or with cases of the localized form refractory to the usual therapy. Nevertheless, this assumption needs confirmation by further studies involving an appropriate clinical approach.O proposito da presente investigacao foi padronizar a reacao de imunofluorescencia indireta para Penfigo Foliaceo Endemico (Fogo Selvagem). Verificamos que a pele humana normal e o substrato ideal e que pode proceder de prepucio, cabeca, pescoco ou da parede abdominal anterior. A lavagem previa da pele precedendo a incubacao com o soro deve ser evitada pois a antigenicidade pode ser diminuida. O TAS-calcio preserva as propriedades antigenicas da pele e deve ser preferido como diluente para os soros. Lâminas cobertas com albumina sao uteis porque aumentam a aderencia dos cortes de pele. A diluicao apropriada do conjugado e convenientemente determinada pelo teste de imunodifusao radial (metodo de Ouch-terlony). Com referencia a correlacao entre titulo de anticorpos e atividade clinica, concluimos que um titulo igual ou maior do que 160 era de mau prognostico pois estava associado a forma generalizada da doenca ou a casos de forma localizada refratarios a terapeutica usual. Contudo, esta obervacao requer confirmacao atraves de estudos que envolvam uma abordagem clinica apropriada.The aim of the present research was to standardize the indirect immunofluorescence reaction for Endemic Pemphigus Foliaceus (Fogo Selvagem). We found that fresh human skin was the ideal substrate and could proceed from foreskin, head, neck, or anterior abdominal wall. PBS pre-washing of the skin preceding the incubation with the serum should be avoided since the antigenicity might be diminished. TAS-calcium preserves the Pemphigus antigenic properties of the skin and shall be preferred as the diluent for the sera. Albumin-coated slides are useful because they increase the adherence of the skin sections. The conjugate appropriate dilution is convenientely determined by the radial immunodiffusion test (Ouchterlony method). So far as the correlation between the antibody titer and the clinical activity is concerned, we concluded that a titer of 160 or more was of bad prognosis, since it was associated with the generalized form of the disease or with cases of the localized form refractory to the usual therapy. Nevertheless, this assumption needs confirmation by further studies involving an appropriate clinical approach.