[Interferon gamma as an immunological strategy for the treatment of human leishmaniasis]. / El interferon gamma com estrategia immunológica para el tratamiento de la leishmaniasis humana.

T lymphocytes from patients with visceral leishmaniasis treated in vitro with leishmania antigens are unable to proliferate and to produce gamma interferon. These patients have negative specific skin tests. Opposite results are obtained in patients with another clinical form of the disease named mucocutaneous leishmaniasis, in which both tests are positive. Nevertheless, patients with visceral leishmaniasis or mucocutaneous leishmaniasis, refractory to chemotherapy (antimonium complex), were cured when treated with antimonium in combination with gamma interferon, in spite of different immunological profiles. Different interpretative hypotheses of the reversion of chemoresistance induced by gamma interferon are discussed.

Clinical healing of antimony-resistant cutaneous or mucocutaneous leishmaniasis following the combined administration of interferon-gamma and pentavalent antimonial compounds.

In an open trial, longer courses of pentavalent antimonials (Sbv) at sub-optimal doses (10 mg/kg body weight), in association with recombinant human interferon-gamma (IFN-gamma) (100 micrograms/m2 of body surface area) were administered, by daily intramuscular injections, to 13 patients with diagnoses of cutaneous or mucocutaneous leishmaniasis unresponsive to Sbv. Four patients presented with large skin ulcers, and 9 had mucosal involvement as the main manifestation, the latter affecting the nose (3 cases), nose and septum (2 cases), nose and oral cavity (1 case), and nose, pharynx and larynx (3 cases). Except for one case with severe involvement of the upper respiratory tract, the lesions were fully resolved by the end of therapy (mean duration 40 +/- 12 [SD] d, range 30-60 d) in the 11 patients who completed therapy. The main side effects were headache and fever (7 cases), together with leucopenia and eosinophilia (4 cases). It is concluded that combined administration of low doses of Sbv plus IFN-gamma may provide a novel therapeutic approach for the treatment of antimony-resistant cutaneous or mucocutaneous leishmaniasis. The possible mechanisms by which IFN-gamma contributes to resolution of the disease are discussed.

El interferon gamma como estrategia inmunologica para el tratamiento de la leishmaniasis humana / The interferon gamma as an immunological strategy for the human leishmaniasis treatment

Los enfermos afectados de leishmaniasis visceral poseen tests cutáneos específicos negativos. Los linfocitos T de esos enfermos no proliferan ni sintetizan interferon gamma cuando son tratados in vitro por los antígenos de leishmanias. Se observa lo inverso en las leishmaniasis cutáneo-mucosas donde los tests son positivos. Sin embargo, los enfermos refractarios al tratamiento por antimonio, presentando una u otra de estas dos formas de leishmaniiasis, curan cuando son tratados por antimonio combinado al interferon gamma. Numerosas interpretaciones de la inversión de la resistencia a la quimioterapia inducida por interferon gamma pueden ser considaeradas: acción sobre el sistema de tipo MDR (multidrug resistance), modulación de las sub-poblaciones linfocitarias o acción sobre las poblaciones linfocitarias o acción sobre las poblaciones celulares de las lesiones de la leishmaniasis (AU)

El interferon gamma com estrategia immunológica para el tratamiento de la leishmaniasis humana. / [Interferon gamma as an immunological strategy for the treatment of human leishmaniasis]

T lymphocytes from patients with visceral leishmaniasis treated in vitro with leishmania antigens are unable to proliferate and to produce gamma interferon. These patients have negative specific skin tests. Opposite results are obtained in patients with another clinical form of the disease named mucocutaneous leishmaniasis, in which both tests are positive. Nevertheless, patients with visceral leishmaniasis or mucocutaneous leishmaniasis, refractory to chemotherapy (antimonium complex), were cured when treated with antimonium in combination with gamma interferon, in spite of different immunological profiles. Different interpretative hypotheses of the reversion of chemoresistance induced by gamma interferon are discussed.

El interferon gamma como estrategia inmunologica para el tratamiento de la leishmaniasis humana / The interferon gamma as an immunological strategy for the human leishmaniasis treatment

Los enfermos afectados de leishmaniasis visceral poseen tests cutáneos específicos negativos. Los linfocitos T de esos enfermos no proliferan ni sintetizan interferon gamma cuando son tratados in vitro por los antígenos de leishmanias. Se observa lo inverso en las leishmaniasis cutáneo-mucosas donde los tests son positivos. Sin embargo, los enfermos refractarios al tratamiento por antimonio, presentando una u otra de estas dos formas de leishmaniiasis, curan cuando son tratados por antimonio combinado al interferon gamma. Numerosas interpretaciones de la inversión de la resistencia a la quimioterapia inducida por interferon gamma pueden ser considaeradas: acción sobre el sistema de tipo MDR (multidrug resistance), modulación de las sub-poblaciones linfocitarias o acción sobre las poblaciones linfocitarias o acción sobre las poblaciones celulares de las lesiones de la leishmaniasis

[Audit of clinical trials in Argentina. Assessment of standardized operational procedures in 12 centers]. / Auditoría de ensayos clínicos en Argentina. Evaluación de procedimientos operacionales normatizados en 12 centros.

The purpose of these audits was to ensure the quality, integrity and validity of investigational data. Audits were performed by control of compliance to standard operational procedures (SOPs) for Good Clinical Practice (GCP). Guidelines were proposed and established by the Food and Drug Administration (FDA) in 1977-1979 and adopted by several countries of the European Community in 1987-1989 and 1990. In Argentina, 12 on site audits of clinical trials performed between 1987 and 1990, were carried out. Basic data of GCP, audited in 58 out of 153 patients included in 12 different centers, were: protection of individual rights, compliance to standard operational procedures, adverse event reports, access to original investigational data and source document archives. The analysis of all audited data showed that patient case reports form recorded findings are credible and reliable and that researchers and monitors had conducted the study with an acceptable level in accordance to SOPs of good clinical practice. Otherwise, several in need of change to obtain better clinical data were identified: ethical committees, written informed consent, protocol adherence, data record, drug accountability, document source archives and the necessity of a thorough theorical and practical training on SOPs for GCP for researchers and monitors of clinical trials.

Auditoría de ensayos clínicos en Argentina. Evaluación de procedimientos operacionales normatizados en 12 centros. / [Audit of clinical trials in Argentina. Assessment of standardized operational procedures in 12 centers]

The purpose of these audits was to ensure the quality, integrity and validity of investigational data. Audits were performed by control of compliance to standard operational procedures (SOPs) for Good Clinical Practice (GCP). Guidelines were proposed and established by the Food and Drug Administration (FDA) in 1977-1979 and adopted by several countries of the European Community in 1987-1989 and 1990. In Argentina, 12 on site audits of clinical trials performed between 1987 and 1990, were carried out. Basic data of GCP, audited in 58 out of 153 patients included in 12 different centers, were: protection of individual rights, compliance to standard operational procedures, adverse event reports, access to original investigational data and source document archives. The analysis of all audited data showed that patient case reports form recorded findings are credible and reliable and that researchers and monitors had conducted the study with an acceptable level in accordance to SOPs of good clinical practice. Otherwise, several in need of change to obtain better clinical data were identified: ethical committees, written informed consent, protocol adherence, data record, drug accountability, document source archives and the necessity of a thorough theorical and practical training on SOPs for GCP for researchers and monitors of clinical trials.

Auditoría de ensayos clínicos en Argentina. Evaluación de procedimientos operacionales normatizados en 12 centros. / [Audit of clinical trials in Argentina. Assessment of standardized operational procedures in 12 centers]

The purpose of these audits was to ensure the quality, integrity and validity of investigational data. Audits were performed by control of compliance to standard operational procedures (SOPs) for Good Clinical Practice (GCP). Guidelines were proposed and established by the Food and Drug Administration (FDA) in 1977-1979 and adopted by several countries of the European Community in 1987-1989 and 1990. In Argentina, 12 on site audits of clinical trials performed between 1987 and 1990, were carried out. Basic data of GCP, audited in 58 out of 153 patients included in 12 different centers, were: protection of individual rights, compliance to standard operational procedures, adverse event reports, access to original investigational data and source document archives. The analysis of all audited data showed that patient case reports form recorded findings are credible and reliable and that researchers and monitors had conducted the study with an acceptable level in accordance to SOPs of good clinical practice. Otherwise, several in need of change to obtain better clinical data were identified: ethical committees, written informed consent, protocol adherence, data record, drug accountability, document source archives and the necessity of a thorough theorical and practical training on SOPs for GCP for researchers and monitors of clinical trials.

Auditoría de ensayos clínicos en Argentina. Evaluación de procedimientos operacionales normatizados en 12 centros / [Audit of clinical trials in Argentina. Assessment of standardized operational procedures in 12 centers]

The purpose of these audits was to ensure the quality, integrity and validity of investigational data. Audits were performed by control of compliance to standard operational procedures (SOPs) for Good Clinical Practice (GCP). Guidelines were proposed and established by the Food and Drug Administration (FDA) in 1977-1979 and adopted by several countries of the European Community in 1987-1989 and 1990. In Argentina, 12 on site audits of clinical trials performed between 1987 and 1990, were carried out. Basic data of GCP, audited in 58 out of 153 patients included in 12 different centers, were: protection of individual rights, compliance to standard operational procedures, adverse event reports, access to original investigational data and source document archives. The analysis of all audited data showed that patient case reports form recorded findings are credible and reliable and that researchers and monitors had conducted the study with an acceptable level in accordance to SOPs of good clinical practice. Otherwise, several in need of change to obtain better clinical data were identified: ethical committees, written informed consent, protocol adherence, data record, drug accountability, document source archives and the necessity of a thorough theorical and practical training on SOPs for GCP for researchers and monitors of clinical trials.

[Comparison of empirical treatment with antibiotics in community acquired lung diseases]. / Comparación de tratamientos empíricos con antibióticos en neumopatías extrahospitalarias.

From December 1984 to June 1986, a prospective clinical trial was carried out in 48 patients with acute community-acquired pneumonia, comparing 2 possible therapeutic schemes: one, using only one antibiotic (roxithromycin: RXT) presumptively active on most of the germs usually involved. In a second group, the identification of the germs involved was attempted on the basis of clinical, epidemiological and radiological data, followed by treatment with the antibiotic/s (ATB) known to be more active against the suspected organisms. The dosage of RXT was 300 mg/day, orally during an average of 9 days. The mean duration of treatment in ATB group was 12 days. In both groups, the following microorganisms were identified: RXT group: St. pneumoniae (13 cases), H. influenzae (1), B. catarrhalis (1); mixed infections: St. pneumoniae + H. influenzae (2); Mycoplasma pneumoniae (3) and 4 patients with unidentified germ; in ATB group: St. aureus (3), St. pneumoniae (5), H. influenzae (2), B. catarrhalis (1); mixed infections: St. aureus + Enterobacter + E. coli (1); Mycoplasma pneumoniae (2) and 10 patients with unidentified germ. The therapeutic results were satisfactory (curation rate: 92%) and similar for both groups of treatment, concluding that both schemes are comparable. Therefore, the choice for one or the other scheme should be based on other reasons, such as easy administration and cost of the treatment.

Comparación de tratamientos empíricos con antibióticos en neumopatías extrahospitalarias. / [Comparison of empirical treatment with antibiotics in community acquired lung diseases]

From December 1984 to June 1986, a prospective clinical trial was carried out in 48 patients with acute community-acquired pneumonia, comparing 2 possible therapeutic schemes: one, using only one antibiotic (roxithromycin: RXT) presumptively active on most of the germs usually involved. In a second group, the identification of the germs involved was attempted on the basis of clinical, epidemiological and radiological data, followed by treatment with the antibiotic/s (ATB) known to be more active against the suspected organisms. The dosage of RXT was 300 mg/day, orally during an average of 9 days. The mean duration of treatment in ATB group was 12 days. In both groups, the following microorganisms were identified: RXT group: St. pneumoniae (13 cases), H. influenzae (1), B. catarrhalis (1); mixed infections: St. pneumoniae + H. influenzae (2); Mycoplasma pneumoniae (3) and 4 patients with unidentified germ; in ATB group: St. aureus (3), St. pneumoniae (5), H. influenzae (2), B. catarrhalis (1); mixed infections: St. aureus + Enterobacter + E. coli (1); Mycoplasma pneumoniae (2) and 10 patients with unidentified germ. The therapeutic results were satisfactory (curation rate: 92

) and similar for both groups of treatment, concluding that both schemes are comparable. Therefore, the choice for one or the other scheme should be based on other reasons, such as easy administration and cost of the treatment.

Comparacion de tratamientos empiricos con antibioticos en neumopatias extrahospitalarias / Comparative empirical treatment with antibiotics in community acquired pneumonia

Desde diciembre de 1984 a junio de 1986 se realizó un ensayo prospectivo sobre 48 pacientes con neumopatías agudas de la comunidad, comparando dos actitudes terapéuticas posibles. Un grupo fue tratado con un solo antibiótico (roxitromicina: RXT), presuntamente activo sobre la mayoría de los gérmenes habitualmente involucrados en las neumonías extrahospitalarias. Mientras que en un segundo grupo se intentó la identificación presuntiva del germen involucrado sobre bases clínicas, epidemiológicas y radiológicas seguida del tratamiento con el o los antibióticos (ATB) que se reconocen más activos frente al germen causal sospechado. La posología de RXT fue de 300 mg/día, vía oral durante un promedio de 9 días. Con otros ATB la duración del tratamiento fue de 12 días. Los microorganismos identificados en ambos grupos fueron los siguientes: Grupo RXT: St, pneumoniae (13 casos), H. influenzae (1), B. catarrhalis (1); infección mixta: St. pneumoniae + H. segundo grupo: St. aureus (3), St. pneumoniae (5), H. influenzaae (2), B. catarrhalis (1); infección mixta: St. aureus ñ Enterobacter ñ E. coli (1) Mycoplasma pneumoniae (2) y 10 pacientes con germen no identificado. Los resultados obtenidos fueron satisfactorios (92%) de curación clínica) y similares para ambos grupos de tratamiento, concluyéndose que ambos esquemas son comparable desde el punto de vista de la actividad terapéutica..

Comparacion de tratamientos empiricos con antibioticos en neumopatias extrahospitalarias / Comparative empirical treatment with antibiotics in community acquired pneumonia

Desde diciembre de 1984 a junio de 1986 se realizó un ensayo prospectivo sobre 48 pacientes con neumopatías agudas de la comunidad, comparando dos actitudes terapéuticas posibles. Un grupo fue tratado con un solo antibiótico (roxitromicina: RXT), presuntamente activo sobre la mayoría de los gérmenes habitualmente involucrados en las neumonías extrahospitalarias. Mientras que en un segundo grupo se intentó la identificación presuntiva del germen involucrado sobre bases clínicas, epidemiológicas y radiológicas seguida del tratamiento con el o los antibióticos (ATB) que se reconocen más activos frente al germen causal sospechado. La posología de RXT fue de 300 mg/día, vía oral durante un promedio de 9 días. Con otros ATB la duración del tratamiento fue de 12 días. Los microorganismos identificados en ambos grupos fueron los siguientes: Grupo RXT: St, pneumoniae (13 casos), H. influenzae (1), B. catarrhalis (1); infección mixta: St. pneumoniae + H. segundo grupo: St. aureus (3), St. pneumoniae (5), H. influenzaae (2), B. catarrhalis (1); infección mixta: St. aureus ñ Enterobacter ñ E. coli (1) Mycoplasma pneumoniae (2) y 10 pacientes con germen no identificado. Los resultados obtenidos fueron satisfactorios (92%) de curación clínica) y similares para ambos grupos de tratamiento, concluyéndose que ambos esquemas son comparable desde el punto de vista de la actividad terapéutica..

Gangrena de pie y oclusión de los grandes vasos de la pierna secundarias a lupus eritematoso sistémico con vasculitis / Post gangrene and occlusion of the great vessels of the leg secondary systemic lupus erythematosus with vasculitis

Se presenta el caso de una paciente de 29 años de edad portadora de un LES con vasculitis de la arteria tibial que ocasiona gangrena del pie. El diagnóstico de LES se efectuó por hallazgos clínicos y de laboratorio; el de vasculitis por la angiografía y los hallazgos histológicos. El pie con gangrena debió ser amputado, el resto de las manifestaciones, incluyendo la vasculitis del otro miembro inferior, fueron controlados con metilprednisona y ciclofosfamida. Se discuten las posibilidades diagnósticas en un paciente lúpico que presenta trastornos isquémicos. A pesar de ser poco frecuente la gangrena en esta enfermedad, el diagnóstico de LES debe ser considerado en pacientes, especialmente jóvenes, que presentan enfermedad arterial obstructiva periférica grave (AU)