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Nineteen patients suffering from allergic rhinitis and bronchial asthma were studied for bacterial allergy with Staphylococcus aureus, Kelbsiella pneumoniae and Diplococcus pneumoniae. Allergy skin tests, provocative tests and the Migratory Inhibition Factor were employed. The correlation indicates to the authors that bacterial allergy is more important than bacterial "infection" as a cause of allergic rhinitis and asthma in many instances. This is often overlooked by practicing allergists.

Sixty-one patients with superficial candidiasis, confirmed on entry by clinical examination and mycological culture, were treated with a single daily application of a 1% bifonazole gel over a period of 4 weeks. Patients were seen every week during treatment and then followed-up for 2 weeks. An overall assessment of response to treatment, based on the clinical and mycological culture findings at the 14-day follow-up visit, showed that the results were very good in 49 and moderate in 9 patients, with only 3 patients being considered as failing to respond. Local tolerance was very good, but burning was reported by 1 patient, burning and itching by 1, and ardor and irritation by one. All these side-effects occurred at the start of treatment and they subsided without interruption of bifonazole treatment.

Twelve strains of Nocardia isolated from sputa, bronchial washings and pleural fluids, were studied. The classification was based on the following characteristics: a) acid-fastness; 2) ability to disolve crystals of tyrosine and xantine; 3) hydrolysis of casein; 4) growth in dilute gelatin medium (0.4%) and 5) galactose acidification. Direct cultivation of the clinical material in Czapek liquid culture medium without carbon source and containing a paraffin rod (pariffin-bait technic), as well as the routin T.B. sputum digestion and concentration with NaOH solution followed by its cultivation in Loewenstein's medium, were employed for the isolation of Nocardia. The sensitivity of the strains to tuberculostatic drugs was investigated using the Canetti's method, as was the ability to growth in Sabouraud and lactrimel culture media supplemented with 100 mug/ml of rifamycin. Finally the pathogenicity test was carried out by intraperitoneal and intramuscular inoculation in guinea-pigs. All the strains were classified as Nocardia asteroides. Seven starins were isolated from patiens with lung conditions of no nocardial etiology. The diagnosis of nocardiosis of the lung was demonstrated in the remaining five patiens by microscopical observation of Nocardia in clinical specimens, by the repeated cultures obtained from these materials and, finally, by the fact that an improvement of the clinical symptomatology was obtained by sulfa administration.

Results are presented of treatment with miconazole, orally and intravenously, in patients with paracoccidioidomycosis. Twenty-eight male patients aged from 34 to 66 years and exhibiting various clinical forms of the disease were studied. Twenty-five came from endemic areas in north east Argentina (Chaco, Formosa, Misiones, Corrientes and northern Santa Fe) and the remaining three from Paraguay. Twenty patients were engaged in agricultural work or at woodmills. single or multiple lesions were observed in 24 cases. Thirteen were suffering from infection of the larynx and in two of them a tracheotomy was necessary. Twenty-three showed pulmonary lesions on X-rays. Twelve had ganglionic lesions, eight had cutaneous lesions and one patient had osteoarthritis of the knee. One patient had hepatomegaly which was unrelated to chronic alcoholism. Fourteen patients had received previous treatments such as sulphonamides and amphotericin B (7 cases); sulphonamides (3), sulphonamides and the combination sulfamethoxazole + trimethoprim (3), and one patient had received all three medications. All patients had relapsed before starting miconazole therapy. Diagnosis was established by the presence of P. brasiliensis in all cases, recovered either from cutaneous or mucosal biopsy samples or from the sputum. Complement fixation tests were positive in all patients at the onset of the treatment and the immunodiffusion reactions showed precipitation bands in 27/28 patients. Skin tests with P. brasiliensis antigens proved to be positive in 18 cases and negative in 10. The erythrocyte sedimentation rate was markedly accelerated in 22 patients (greater than 20 mm in the first hour).(ABSTRACT TRUNCATED AT 250 WORDS)

A new, nontoxic material extracted from Aspergillus fumigatus, is described with complement-depletion capacity both in vivo and in vitro. Extracts of the mycelium of A. fumigatus were found to haemolyse sheep red blood cells, to be lethal for mice and to convert C3 into its faster electrophoretic form when incubated with normal human serum. Conversion did not take place when purified C3 was used, suggesting that serum factors were required in the reaction. Adsorption of the extracts with activated carbon or heating at 100 degrees C for 30 min yielded detoxified materials devoid of both toxic and haemolytic properties but still capable of converting serum C3. In guinea pigs, administration of detoxified extracts was followed by complement depletion lasting not less than 48 h. Heating (100 degrees C for 30 min) extracts which had been previously detoxified by carbon adsorption resulted in a partial loss (40%) of their complement-inhibitory capacity indicating that part of the anticomplementarity of AFE was due to a heat-stable substance.

Some of the biological properties of saline extracts of the mycelia of several species of the Aspergillus genus, namely, A. fumigatus, A. flavus, A. niger, A. nidulans, A. parasitucus and A. glaucus, were studied. Only the extract prepared from A. fumigatus was found to be hemolytic for sheep red blood cells. In contrast, all the extracts with the only exception of that of A. glaucus, had cytotoxic effects on Vero cells. Both, the hemolytic and cytotoxic constituents of the extracts were removable by adsorption with activated carbon. Heating of the extracts at 100 degrees C for 30 minutes also resulted in detoxification. In vivo studies, performed only with detoxified extracts of A. fumigatus, showed these were capable of depleting complement levels in guinea pigs. Complement inactivation was also found to occur in vitro and was cuased by all the extracts tested. Also triggered by the extracts was the conversion of serum C3 but not of purified C3, indicating that other serum factors are essential in the process. Despite the similarity in this respect with cobra venom factor, differences in activity after heating-negative in cobra venom factor-indicate that the complement inactivating substance/s present in the Aspergillus extracts differ from those of the snake product.

One hundred and twenty-one patients with tinea (pityriasis) versicolor, confirmed by pretherapeutic clinical and mycological examination, were treated with a single daily application of bifonazole (BAY h 4502) 1% gel for 2 weeks. Weekly clinical controls were performed during the treatment period and at least two clinical and mycological post-therapeutic controls were given. Overall results were very good in 98 patients, good in 15, moderate in 7 and failure in 1 patient. Local tolerance was very good; only 1 patient presented with slight erythema and pruritus during the treatment.

Ketoconazole was administered orally in daily doses of 200 mg to 70 patients with onychomycosis. Complete recovery was attained by 48 patients, improvement of > 50% by 10 patients, and for three patients therapy failed. For the remaining nine patients the results could not be evaluated. The average duration of treatment was 7.5 months for disease due to Trichophyton species and 6.5 months for disease due to Candida species. There were no adverse effects or signs of toxicity attributable to the administration of ketoconazole. It is concluded that ketoconazole is a positive development in the effort to control the difficult problems presented by onychomycosis.

Sixty four patients suffering a chronic disseminated histoplasmosis were studied with the aim of fingind if they had predisposing factors. Thirty cases (46.8%) presented the following predisposing conditions: long treatment with low doses of corticosteroids in 7, ethilic hepatopathy in 7, diabetes in 4, lymphoma in 3, epitheliomas in 3, epitheliomas and diabetes in 1, renal insufficiency in 1, toxic hepatitis in 1, radiations in 1, long treatment with psychotropics in 1 and primary combined immunodeficiency in 1. Only slight differences were detected between these two groups of patients; those who exhibited predisposing factors presented an increased number of clinical localizations, altered cell mediated immunological tests were more frequent as well as the number of patients with multiple relapses and deaths. Histoplasmosis was not the cause of death in any case. It is possible that if a more frequent aggressive exploration, as hepatic biopsy, would be done a higher number of patients with predisposing factors would have been demonstrated.

The results of skin tests with two antigens of the yeast phase of Histoplasma capsulatum are presented. Both antigens were able to fix complement and form precipitating bands in the presence of sera from patients with active histoplasmosis. Their sensitivity was lower than the metabolic antigen usually employed in serology. Results of skin tests obtained with both yeast phase antigens and a standard histoplasmin coincided in animals infected with H. capsulatum. Only one cross reaction was observed in animals inoculated with Paracoccidioides brasiliensis. Skin tests in humans were conducted on patients with and without mycotic disease. The percentages of positive reactions in patients with histoplasmosis were not significantly different between control histoplasmin and whole cell extracts. In the patients with non mycotic diseases the frequency of positive tests varied between 28.8% and 32%, which agrees with previous statistical data for the general population of the area. Equally the positive percentage of 55% and 68% in patients with paracoccidioidomycosis coincided with the results of previous studies. The histological patterns of these skin tests showed that they were produced by cell mediated hypersensitivity. The sensitivity of a whole yeast cell extract was similar to histoplasmin L48, but its preparation was quicker and easier to perform and it had no foreign substances from the culture medium, so we think that it would be easier to standardize it chemically.

Different immunodiffusion techniques with and without the addition of polyetilenglycol 6000 (PEG), were studied to determine its effect on the sensitivity of these reactions. One hundred thirteen sera from patients who suffered or had suffered deep mycoses (paracoccidioidomycosis: 49, histoplasmosis: 25, aspergillosis: 25, candidiasis: 8 and coccidioidomycosis: 6) were examined by the quantitative Ouchterlony's immunodiffusion procedure. Regular medium and media with 2% and 4% PEG were used. Eighty two out of the one hundred thirteen sera were positive for the regular medium and 91 for the medium containing 2% of PEG; furthermore, an increase of 1 or 2 two fold dilutions in the titers was observed in 40% of the sera, for the later media. Twenty one sera from aspergillosis cases were examined by agarose gel immunoelectrophoresis, 80% had more precipitin bands in the medium with 2% of PEG. Thirty four serum samples of patients suffering aspergillosis, paracoccidioidomycosis and histoplasmosis were studied using the agarose electroosmophoresis with the secondary immunodiffusion test. An increase in the number of the anodic bands were observed in 55% while 64% presented more catodic bands, when the PEG medium was used. This results would indicate that the addition of 2% PEG 6000 to the regular medium improves the sensitivity of the immunodiffusion tests for mycoses.

A comparative study between itraconazole, ketoconazole and amphotericin B in the treatment of experimental histoplasmosis in hamsters was carried out. Seventy five animals were inoculated intracardiacally with the yeast-phase of Histoplasma capsulatum. They were divided in 5 groups: 1) treated with itraconazole by gavage (g) at a daily dose of 16 mg/kg; 2) treated with ketoconazole by (g) at a daily dose of 80 mg/kg; 3) treated with amphotericin B intraperitoneally (i.p.) at 6 mg/kg every other day; 4) control animals receiving distilled water i.p. and 5) control animals receiving P.E.G. 200 by (g). All the treatments were started one week after the challenge inoculation and they were given for 21 days. The results were evaluated by autopsy of all the animals one week after the end of the treatments. The following determinations were taken into account: microscopic examinations of spleen, liver and lungs and cultures of the spleen with determination of colony forming units/g. All the antifungal drugs used in this study were able to cause negative microscopic examinations of the liver, spleen and lungs; but only amphotericin B produced culture negative results. Itraconazole and ketoconazole presented 66% and 86% of positive cultures respectively, nevertheless the C.F.U. were lower than those obtained in control groups. In these experimental conditions amphotericin B seems to be more active than the azolic compounds and itraconazole is slightly superior to ketoconazole at a lower dose.

A comparative study of serologic cross-reactions between histoplasmosis and paracoccidioidomycosis was carried out using complement fixation (CF) and agar gel immunodiffusion (ID) tests. Sera from 77 patients with paracoccidioidomycosis, 38 with histoplasmosis and 50 healthy individuals were studied. The Pan American Health Organization microtiter CF test and the Hupper ID technique were employed. The antigens were prepared by the method of Ajello as modified by Negroni. Paracoccidioidin CF test was positive in all patients with paracoccidioidomycosis; 29 of these (37%) presented serologic cross-reaction with histoplasmin. Histoplasmin CF test was positive in all but one of the patients with histoplasmosis and only 4 of them (10%) showed cross-reaction with paracoccidioidin. Positive reactions with the ID test were registered in 74/77 cases of paracoccidiodomycosis, with only one case of cross-reaction (1,3%). The result for the ID test was positive in all but one of the cases of histoplasmosis, with only one cross-reaction with paracoccidiodin (2,7%). The ID test seemed to be much more specific although it could be less sensitive. It was also easier to perform and less expensive than the CF test. Nevertheless the authors urge that the CF test also be carried out whenever posible, since the information obtained is likely to be of more value in follow-up and control of patients.

The ELISA has been extensively evaluated as a serodiagnostic method for tuberculosis. However, there is scarce information about its application to cases that cannot be diagnosed by microscopic examination: those with closed lesions or undergoing early stages of the disease. Since a reliable serological test might substantially contribute to their prompt detection, the objective of the present study was to determine the diagnostic value of an ELISA applied to adult smear-negative cases of tuberculosis. Sera from 235 patients with active tuberculosis--176 pulmonary and 59 extrapulmonary cases--and 181 control subjects were tested for IgG antibodies to PPD by ELISA. Eleven cases of non tuberculous mycobacterial (MOTT) disease and 33 cases of mycosis were also included in this group. With the adopted cut-off value, 73.9% (105/142) of smear positive and 52.7% (49/93) of smear negative tuberculosis cases, were correctly classified. Particularly in the latter, the test was positive in 55.2% (32/58) of patients with positive cultures for Mycobacterium tuberculosis and in 48.6% (17/35) of patients diagnosed by clinical, radiological and or histopathological findings. No antibody activity was demonstrated in 92.7% of sera from the control population which included 92 healthy volunteers, 32 non tuberculous diseased subjects and 13 household contacts of smear-positive cases. Among those control subjects who were skin tested, ELISA results were not related to the tuberculin reactivity: 93.7% (30/32) of tuberculin negative and 95.2% (40/42) of tuberculin positive healthy individuals had no detectable antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Eight male tuberculous patients, between 20 and 60 years of age, were given Isoniazid 5 mg/kg and Ketoconazole 200 mg, first one at a time and then associated. Plasma concentrations were measured 0, 2 and 5 hs after taking the drugs. Isoniazid was measured by spectrophotometry and Ketoconazole by the microbiologic method with Candida albicans as test microorganism. When both drugs were given simultaneously Ketoconazole plasma concentration decreased 75% at 2 hs (p less than 0.025) and 85% at 5 hs (p less than 0.05), whereas that of Isoniazid remained unchanged (Table 1). Mean half-life of Isoniazid was 3.9 +/- 1.4 hs in 7 slow acetylators and 1.1 hs in one fast acetylator when given one at a time and 4.4 +/- 1.5 hs when given simultaneously. A similar study was conducted on 11 tuberculous patients who were given Rifampicin 10 mg/kg and Ketoconazole 200 mg, one at a time and concurrently. Rifampicin was measured by high pressure liquid chromatography. When Rifampicin and Ketoconazole were given concurrently plasma concentration of both drugs was reduced: Ketoconazole decreased 85% at 2 hs (p less than 0.025) and 98% at 5 hs (p less than 0.025) whereas Rifampicin decreased 45% at 2 hs (p less than 0.005) and 40% at 5 hs (p less than 0.005) (Table 2). Mean half-life of Rifampicin was 3.5 +/- 0.8 and 4.2 +/- 1.1 hs, respectively, when it was given alone and concurrently. Studies on chemical interactions between Isoniazid and Ketoconazole and between Rifampicin and Ketoconazole yielded negative results.(ABSTRACT TRUNCATED AT 250 WORDS)

Cocidioidomycosis is a systemic mycosis, endemic in arid areas of the American continent. The rat was employed as an experimental host, since it had been shown to reproduce human lesions and present a chronic course of disease with granulomas mainly restricted to lungs. Given the influence of immunosuppressive therapy on the clinical course of human coccidioidomycosis, we studied the effect of cyclophosphamide (CY) in the experimental rat model. Accordingly, animals were inoculated with 400 Coccidioides immitis arthroconidia of the Acosta strain, by intracardiacal route. As single CY doses failed to alter the course of disease, three schedules were used: A) 4 daily doses of 20 mg/kg each, prior to C. immitis inoculation; B) 4 similar daily doses after infection; and C); 6 doses of 20 mg/kg each, given from day +1 to +4 then on days +8 and +9, post infection (pi), taking day 0 as the time of fungal inoculation. The first two schedules inhibited antibody formation up to day 28 pi, without modifying cellular response to coccidioidin as measured by foodpad swelling. Initially, there was greater fungal spread than in controls receiving C. immitis alone, which proved self-limiting in the latter. In contrast, schedule C led to 55% mortality with both humoral and cellular response abrogation, accompanied by extensive C. immitis dissemination. Histology disclosed significant alterations, such as the persistence of primary infection sporangia, corresponding to the acute stage of coccidioidomycosis in the absence of granuloma development. Therefore, the observed depression in cellular immunity seems responsible for the lack of inflammatory reaction capable of restricting sporangia proliferation in tissues which, in turn, enhances pathogen spread and mortality rate.