ABSTRACT
PURPOSE: Complex stereotactic radiotherapy treatment plans require prior verification. A gel dosimetry system was developed and tested to serve as a high-resolution 3D dosimeter for Quality Assurance (QA) purposes. MATERIALS AND METHODS: A modified version of a polyacrylamide polymer gel dosimeter based on chemical response inhibition was employed. Different sample geometries (cuvettes and phantoms) were manufactured for calibration and QA acquisitions. Irradiations were performed with a Varian Trilogy linac, and analyses of irradiated gel dosimeters were performed via MRI with a 1.5 T Philips Achieva at 1 mm3 or 2 mm3 isotropic spatial resolution. To assess reliability of polymer gel data, 54 stereotactic clinical treatment plans were delivered both on dosimetric gel phantoms and on the Delta4 dosimeter. Results from the two devices were evaluated through a global gamma index over a range of acceptance criteria and compared with each other. RESULTS: A quantitative and tunable control of dosimetric gel response sensitivity was achieved through chemical inhibition. An optimized MRI analysis protocol allowed to acquire high resolution phantom dose data in timeframes of ≈ 1 h. Conversion of gel dosimeter data into absorbed dose was achieved through internal calibration. Polymer gel dosimeters (2 mm3 resolution) and Delta4 presented an agreement within 4.8 % and 2.7 % at the 3 %/1 mm and 2 %/2 mm gamma criteria, respectively. CONCLUSIONS: Gel dosimeters appear as promising tools for high resolution 3D QA. Added complexity of the gel dosimetry protocol may be justifiable in case of small target volumes and steep dose gradients.
Subject(s)
Radiometry , Radiotherapy Planning, Computer-Assisted , Radiotherapy Dosage , Reproducibility of Results , Radiotherapy Planning, Computer-Assisted/methods , Phantoms, Imaging , PolymersABSTRACT
La educación médica continua se define como el conjunto de acciones y recursos dirigidos a cambiar las conductas de los profesionales para mejorar los resultados de su actividad asistencial diaria frente a los pacientes. O bien, toda acción que realiza un médico para seguir aprendiendo y permanecer actualizado, una vez finalizada su formación universitaria. Las estrategias para conseguir tal fin, son la realización de cursos, la ra congresos y/o jornadas, las actividades hospitalarias (recorridas de sala, supervisión y ateneos), la lectura y discusión de artículos biomédicos en internet o en publicaciones en papel en el denominado ateneo bibliográfico, el intercambio con colegas, la consulta con otros profesionales y los cursos a distancia. En el presente artículo, se plantea el ejercicio del ateneo como una de las principales fuentes de aprendizaje al proponer una verdadera reflexión sobre la práctica profesional (AU)
Continuing medical education is defined as the set of actions and resources aimed at changing the behavior of professionals to improve the results of their daily care activity in front of patients. Or, any action that a doctor performs to continue learning and remain updated, once his university education is completed. The strategies to achieve this goal are the completion of courses, the attendance at conferences and/or conferences, hospital activities (visits to the ward, supervision and athenaeums), the reading and disicussion of biomedical articles on the internet or in publications on paper. The so-called bibliographic athenacum, the exchange with colleagues, the consultations with other professionals and the distance courses. In the present article, the exercise of the athenaemum is considered as one of the main sources of learning by proposing a true reflection on professional practice (AU)
Subject(s)
Humans , Education, Medical, Continuing , Teaching Rounds , Access to Essential Medicines and Health TechnologiesABSTRACT
La trombosis auricular masiva impide el pasaje de la sangre a través del orificio mitral Un paciente de 39 años de edad, HIV positivo, con diagnóstico previo de criptococosis meníngea cumplía tratamiento antifúngico con fluconazol por vía oral, consulta por mialgias y dolor cervical. Fallece repentinamente 24 horas después de su internación. La necropsia determinó la presencia de una trombosis biauricular masiva. La criptococosis meníngea es una infección oportunista que se presenta en pacientes HIV positivos con inmunodeficiencia avanzada. Clínicamente se manifiesta por un síndrome meníngeo, por lo general incompleto, o sólo con persistencia de fiebre y cefalea, sin signos meníngeos. La letalidad de la criptococosis meníngea es elevada. La causa del fallecimiento obedece a una enfermedad no relacionada con el sida
Massive atrial thrombosis prevents passage of blood through the mitral orifice. A 39-year-old HIV-positive patient with previous diagnosis of meningeal cryptococcosis and receiving antifungal treatment with oral fluconazole, consults for myalgias and neck pain and dies suddenly 24 hours after admission. Necropsy determined the presence of massive biauricular thrombosis. Meningeal cryptococcosis is an opportunistic infection that occurs in HIV-positive patients with severe immunodeficiency. Clinically it is manifested by an incomplete meningeal syndrome, or only with persistence of fever and headache, without meningeal signs. The lethality of meningeal cryptococcosis is high. The cause of the death is due to a disease not related to AIDS
Subject(s)
Humans , Male , Adult , Autopsy , Thrombosis/complications , Acquired Immunodeficiency Syndrome/immunology , Meningitis, Cryptococcal/complications , Meningitis, Cryptococcal/mortality , AIDS-Related Opportunistic Infections/complicationsABSTRACT
La criptococosis es una micosis sistémica oportunista con distribución universal causada por una levadura capsulada, el Cryptococcus neoformans (C neoformans). El C neoformans infecta al hombre y a animales susceptibles por vía inhalatoria, provocando en huéspedes inmunocompetentes una primoinfección asintomática. Crece preferentemente en ambientes ricos con componentes nitrogenados, principalmente a partir de las excretas desecadas de las palomas que son ricas en nitrógeno y creatinina, con alto contenido en sales y pH alcalino, cualidades que facilitan la supervivencia del hongo. La diseminación hematógena del agente causal provoca múltiples localizaciones, las cuales se hacen clínicamente evidentes en pacientes con deterioro de la inmunidad mediada por células. A partir de la eclosión del SIDA se produjo un aumento significativo del número de casos, transformándose esta última condición en la causa predisponente más importante de esta micosis. La mayoría de los pacientes con SIDA y criptococosis del SNC presentan signos y síntomas de meningitis o meningoencefalitis subagudas como cefalea, fiebre, parálisis de nervios craneales, letargo, coma o amnesia de varias semanas de evolución. La anfotericina B es el pilar terapéutico del tratamiento. En nuestro estudio analizamos las características demográficas, epidemiológicas, clínicas, el líquido cefalorraquídeo, el diagnóstico micológico y el tratamiento empleado en los pacientes hospitalizados en Sala 11 con diagnóstico de criptococosis meníngea. En la criptococosis meníngea asociada al SIDA el diagnóstico puede realizarse por el análisis de distintos tipos de especímenes biológicos, siendo los principales el examen microscópico directo del LCR con tinción de tinta china y el cultivo.(AU)
Cryptococcosis is a fungal opportunistic infection systemic who has universal distribution, caused by capsulated yeast, Cryptococcus neoformans. C neoformans infects humans and susceptible animals by inhalation, causing an asymptomatic primary infection in immunocompetent hosts. It grows preferentially in rich environments with nitrogen components, mainly from dried excreta of pigeons that are rich in nitrogen and creatinine, with a high salt content and alkaline pH, qualities which facilitate the survival of the fungus. Haematogenous dissemination of the causative agent leads to multiple locations, which are clinically evident in patients with impairment of cell-mediated immunity. Since the emergence of AIDS, it was a significant increase in the number of cases, who becomes in the most important predisposing cause of this mycosis. Most patients with AIDS and CNS cryptococcosis have signs and symptoms of subacute meningitis or meningoencephalitis as headache, fever, cranial nerve palsy, lethargy, coma or amnesia of several weeks of evolution. Amphotericin B therapy is the mainstay of treatment. We analyzed the demographic, epidemiological, clinical, cerebrospinal fluid, mycological diagnosis and treatment used for hospitalized patients in the unit 11 of the Infectious Disease Hospital Muñiz with the diagnosis of meningeal cryptococcosis. In meningeal cryptococcosis associated with AIDS, the diagnosis can be performed by the analysis of different types of biological specimens, mainly direct microscopic examination of CSF with India ink staining and culture.(AU)
Subject(s)
Humans , Male , Young Adult , Adult , Middle Aged , Acquired Immunodeficiency Syndrome/complications , Meningitis, Cryptococcal/cerebrospinal fluid , Meningitis, Cryptococcal/diagnosis , Meningitis, Cryptococcal/etiology , AIDS-Related Opportunistic Infections , Cerebrospinal Fluid Proteins/analysis , Fever , Headache , Hospitals, MunicipalABSTRACT
La criptococosis es una micosis sistémica oportunista con distribución universal causada por una levadura capsulada. El Cryptococcus neoformans (C. neoformans). C. neoformans infecta al hombre y a animales susceptibles por vía inhalatoria, provocando en huéspedes inmunocompetentes una primoinfección asintomática. Crece preferentemente en ambientes ricos con componentes nitrogenados, principalmente a partir de las excretas desecadas de las palomas que son ricas en nitrógeno y creatinina, con alto contenido en sales y pH alcalino, cualidades que facilitan la supervivencia del hongo. La diseminación hematógena del agente causal provoca múltiples localizaciones, las cuales se hacen clínicamente evidentes en pacientes con deterioro de la inmunidad mediada por células. A partir de la eclosión del SIDA se produjo un aumento significativo del número de casos, transformándose esta última condición en la causa predisponente más importante de esta micosis. La mayoría de los pacientes con SIDA y criptococosis del SNC presentan signos y síntomas de meningitis o meningoencefalitis subagudas como cefalea, fiebre, parálisis de nervios craneales, letargo, coma o amnesia de varias semanas de evolución. La anfotericina B es el pilar terapéutico del tratamiento. En nuestro estudio analizamos las características demográficas, epidemiológicas, clínicas, el líquido cefalorraquídeo, el diagnóstico micológico y el tratamiento empleado en los pacientes hospitalizados en Sala 11 con diagnóstico de criptococosis meníngea. En la criptococosis meníngea asociada al SIDA, el diagnóstico puede realizarse por el análisis de distintos tipos de especímenes biológicos, siendo los principales el examen microscópico directo del LCR con tinción de tinta china y el cultivo. (AU)
Cryptococcosis is a fungal opportunistic infection systemic who has universal distribution, caused by capsulated yeast, Cryptococcus neoformans. C. neoformans infects humans and susceptible animals by inhalation, causing an asymptomatic primary infection in immunocompetent hosts. It grows preterentially in rich environments with nitrogen components, mainly from dried excreta of pigeons that are rich in nitrogen and creatinine, with a high salt content and alkaline pH, qualities which facilitate the survival of the fungus. Haematogenous dissemination of the causative agent leads to multiple locations, which are clinically evident in patients with impairment of cell-mediated immunity. Since the emergence of AIDS, it was a significant in crease in the number of cases, who becomes in the most important predisposing cause of this mycosis. Most patients with AIDS and CNS cryptococcosis have signs and symptoms of subacute meningitis or meningoencephalitis as headache, fever, cranial nerve palsy, lethargy, coma or amnesia of several weeks of evolution. Amphotericin B therapy is the mainstay of treatment. We analyzed the demographic, epidemiological, clinical, cerebrospinal fluid, mycological diagnosis and treatment used for hospitalized patients in the unit 11 of the Infectious Disease Hospital Muñiz with the diagnosis of meningeal cryptococcosis. In meningeal cryptococcosis associated with AIDS, the diagnosis can be performed by the analysis of different types of biological specimens, mainly direct microscopic examination of CSF with India ink staining and culture. (AU)
Subject(s)
Humans , Male , Meningitis, Cryptococcal/cerebrospinal fluid , Meningitis, Cryptococcal/epidemiology , Meningitis, Cryptococcal/etiology , Meningitis, Cryptococcal/pathology , Meningitis, Cryptococcal/therapy , Acquired Immunodeficiency Syndrome/complications , Hospitals, Municipal , AIDS-Related Opportunistic Infections , Cryptococcus neoformans/pathogenicity , Central Nervous System Diseases , Amphotericin B/administration & dosage , Amphotericin B/therapeutic use , Azoles/therapeutic useABSTRACT
La criptococosis es una micosis sistémica oportunista con distribución universal causada por una levadura capsulada. El Cryptococcus neoformans (C. neoformans). C. neoformans infecta al hombre y a animales susceptibles por vía inhalatoria, provocando en huéspedes inmunocompetentes una primoinfección asintomática. Crece preferentemente en ambientes ricos con componentes nitrogenados, principalmente a partir de las excretas desecadas de las palomas que son ricas en nitrógeno y creatinina, con alto contenido en sales y pH alcalino, cualidades que facilitan la supervivencia del hongo. La diseminación hematógena del agente causal provoca múltiples localizaciones, las cuales se hacen clínicamente evidentes en pacientes con deterioro de la inmunidad mediada por células. A partir de la eclosión del SIDA se produjo un aumento significativo del número de casos, transformándose esta última condición en la causa predisponente más importante de esta micosis. La mayoría de los pacientes con SIDA y criptococosis del SNC presentan signos y síntomas de meningitis o meningoencefalitis subagudas como cefalea, fiebre, parálisis de nervios craneales, letargo, coma o amnesia de varias semanas de evolución. La anfotericina B es el pilar terapéutico del tratamiento. En nuestro estudio analizamos las características demográficas, epidemiológicas, clínicas, el líquido cefalorraquídeo, el diagnóstico micológico y el tratamiento empleado en los pacientes hospitalizados en Sala 11 con diagnóstico de criptococosis meníngea. En la criptococosis meníngea asociada al SIDA, el diagnóstico puede realizarse por el análisis de distintos tipos de especímenes biológicos, siendo los principales el examen microscópico directo del LCR con tinción de tinta china y el cultivo.
Cryptococcosis is a fungal opportunistic infection systemic who has universal distribution, caused by capsulated yeast, Cryptococcus neoformans. C. neoformans infects humans and susceptible animals by inhalation, causing an asymptomatic primary infection in immunocompetent hosts. It grows preterentially in rich environments with nitrogen components, mainly from dried excreta of pigeons that are rich in nitrogen and creatinine, with a high salt content and alkaline pH, qualities which facilitate the survival of the fungus. Haematogenous dissemination of the causative agent leads to multiple locations, which are clinically evident in patients with impairment of cell-mediated immunity. Since the emergence of AIDS, it was a significant in crease in the number of cases, who becomes in the most important predisposing cause of this mycosis. Most patients with AIDS and CNS cryptococcosis have signs and symptoms of subacute meningitis or meningoencephalitis as headache, fever, cranial nerve palsy, lethargy, coma or amnesia of several weeks of evolution. Amphotericin B therapy is the mainstay of treatment. We analyzed the demographic, epidemiological, clinical, cerebrospinal fluid, mycological diagnosis and treatment used for hospitalized patients in the unit 11 of the Infectious Disease Hospital Muñiz with the diagnosis of meningeal cryptococcosis. In meningeal cryptococcosis associated with AIDS, the diagnosis can be performed by the analysis of different types of biological specimens, mainly direct microscopic examination of CSF with India ink staining and culture.
Subject(s)
Humans , Male , Meningitis, Cryptococcal/epidemiology , Meningitis, Cryptococcal/etiology , Meningitis, Cryptococcal/cerebrospinal fluid , Meningitis, Cryptococcal/pathology , Meningitis, Cryptococcal/therapy , Acquired Immunodeficiency Syndrome/complications , Amphotericin B/administration & dosage , Amphotericin B/therapeutic use , Azoles/therapeutic use , Cryptococcus neoformans/pathogenicity , Central Nervous System Diseases , Hospitals, Municipal , AIDS-Related Opportunistic InfectionsABSTRACT
Mancozeb, manganese ethylene-bis-dithiocarbamate with zinc salts, is one of the most commonly used fungicides in the United States. Epidemiological and experimental data showed that mancozeb causes detrimental effects on various organ systems including the reproductive, endocrine, immune, and central nervous system. Increasing evidence has shown a strong association between pesticides and neurodegenerative diseases. In this study, we examined the neurotoxic potential of mancozeb in rat hippocampal astrocytes. The cytotoxicity of mancozeb was found to be dose dependent and recovery studies showed that cells exposed to mancozeb for 1 h did not recover from mancozeb-induced insult. Atomic absorption data showed a significant accumulation of manganese in astrocytes after 1 h of treatment. This study further investigated whether various chelators and antioxidants could prevent mancozeb-induced cytotoxicity. Our data reported that butylated hydroxytoluene (BHT) was the most effective agent in protecting against mancozeb insult. BHT also increased total cellular antioxidants of astrocytes after 1-h mancozeb exposure. In summary, this study reported for the first time that the manganese portion of mancozeb might be, at least in part, responsible for the toxicity. Mancozeb-induced cytotoxicity in astroyctes can be protected by BHT and that this antioxidant increased the total cellular antioxidant capacity.
Subject(s)
Antioxidants/pharmacology , Astrocytes/drug effects , Chelating Agents/pharmacology , Fungicides, Industrial/toxicity , Hippocampus/cytology , Maneb/toxicity , Zineb/toxicity , Animals , Animals, Newborn , Astrocytes/metabolism , Butylated Hydroxytoluene/pharmacology , Cations, Divalent , Cell Survival , Dose-Response Relationship, Drug , In Vitro Techniques , Male , Manganese/metabolism , Rats , Rats, Sprague-Dawley , Zinc/metabolismABSTRACT
Tributyltin oxide (TBTO) is the main constituent of tin-based antifouling marine paint used on the hulls of ships to prevent the growth of fouling organisms. TBTO was shown to be hazardous to nontarget organisms. The stingray, Urolophus jamaicensis, may represent the ideal study organism for the adverse effects of TBTO to elasmobranches. This study investigated the toxicity and accumulation of tin in the gill tissue of the stingray U. jamaicensis after acute exposure to TBTO. This work demonstrates the alterations in the morphological architecture of the gill using electron and light microscopy, the induction of stress proteins, and peroxidative damage in response to tributyltin (TBT) exposure. A captured population of U. jamaicencis was housed in isolated, static tank systems. After a minimum 30-d acclimation period, the animals were exposed to one of 5 experimental doses of TBTO (4 microg/L, 2 microg/L, 1 microg/L, 0.5 microg/L, or 0.05 microg/L). A sixth group served as a control population. At 3h following treatment, animals were sacrificed and gill tissue was extracted, processed, and stored for analysis. Results indicate that U. jamaicensis is hypersensitive to TBT exposure. The elasmobranch gill showed a distorted, swollen epithelium with exfoliation following acute exposure to as little as 0.05 microg/L TBTO for 3 h. Graphite furnace atomic absorption spectroscopy (GFAAS) results indicate that tissues of treated animals contained a significantly increased tin concentration as compared to controls. Western blot analysis demonstrated the induction of the stress proteins Hsp 70 and HO1. 4-Hydroxynonenol (4HNE) adduct formation determined by Western blot analysis provides further evidence that observed membrane degradation is a result of lipid peroxidation.
Subject(s)
Disinfectants/toxicity , Environmental Monitoring , Gills/drug effects , Skates, Fish , Trialkyltin Compounds/toxicity , Animals , Disinfectants/pharmacokinetics , Gills/chemistry , Gills/pathology , HSP70 Heat-Shock Proteins/analysis , Heme Oxygenase-1/analysis , Lipid Peroxidation/drug effects , Microscopy , Oxidative Stress/drug effects , Paint/adverse effects , Ships , Tissue Distribution , Trialkyltin Compounds/pharmacokinetics , Water Pollutants, Chemical/pharmacokinetics , Water Pollutants, Chemical/toxicityABSTRACT
La corioretinitis toxoplamósica es una zoonosis producida por el Toxoplasma gondii, que provoca una retinitis necrotizante, con frecuentes recaídas y que puede evolucionar a la amaurosis. El diagnóstico se realiza por un exhaustivo examen oftalmológico, siendo el estudio serológico específico un dato complementario. Presentamos el caso clínico de un paciente de 22 años de edad, con toxoplasmosis ocular recidivante
Subject(s)
Male , Adult , Humans , Toxoplasmosis, Ocular/diagnosis , Chorioretinitis , Serology , Patient Care TeamABSTRACT
La corioretinitis toxoplamósica es una zoonosis producida por el Toxoplasma gondii, que provoca una retinitis necrotizante, con frecuentes recaídas y que puede evolucionar a la amaurosis. El diagnóstico se realiza por un exhaustivo examen oftalmológico, siendo el estudio serológico específico un dato complementario. Presentamos el caso clínico de un paciente de 22 años de edad, con toxoplasmosis ocular recidivante
Subject(s)
Male , Adult , Humans , Chorioretinitis , Serology , Toxoplasmosis, Ocular , Patient Care TeamABSTRACT
Se evaluaron retrospectivamente aspectos epidemiológicos, clínicos y micológicos de 15 pacientes con histoplasmosis asociada al SIDA internados en la Sala 11 del Hospital Muñiz, durante un período de 5 años. La mayor parte de los pacientes habitaban al momento de la internación o habían nacido dentro del área endémica de la histoplasmosis, en localidades del Gran Buenos Aires o en la ciudad de Buenos Aires. Fiebre, disminución del peso corporal, tos con expectoración y lesiones mucocutáneas fueron los hallazgos clínicos más frecuentes, seguidos por adenomegalias, sudoración, diarrea, dolor abdominal, cefalea y disnea. La radiografía de tórax reveló infiltrados pulmonares, en su mayoría con distribución bilateral y la ecografía abdominal evidenció la presencia de hepato y esplenomegalia. La microscopía del material obtenido por escarificación de las lesiones cutáneomucosas y los hemocultivos por el método de lisis-centrifugación permitieron el diagnóstico micológico de la casi totalidad de los casos
Subject(s)
Humans , Male , Histoplasmosis , HIV , CD4 Lymphocyte CountABSTRACT
Se evaluaron retrospectivamente aspectos epidemiológicos, clínicos y micológicos de 15 pacientes con histoplasmosis asociada al SIDA internados en la Sala 11 del Hospital Muñiz, durante un período de 5 años. La mayor parte de los pacientes habitaban al momento de la internación o habían nacido dentro del área endémica de la histoplasmosis, en localidades del Gran Buenos Aires o en la ciudad de Buenos Aires. Fiebre, disminución del peso corporal, tos con expectoración y lesiones mucocutáneas fueron los hallazgos clínicos más frecuentes, seguidos por adenomegalias, sudoración, diarrea, dolor abdominal, cefalea y disnea. La radiografía de tórax reveló infiltrados pulmonares, en su mayoría con distribución bilateral y la ecografía abdominal evidenció la presencia de hepato y esplenomegalia. La microscopía del material obtenido por escarificación de las lesiones cutáneomucosas y los hemocultivos por el método de lisis-centrifugación permitieron el diagnóstico micológico de la casi totalidad de los casos
Subject(s)
Humans , Male , Histoplasmosis/epidemiology , Histoplasmosis/microbiology , HIV , CD4 Lymphocyte CountABSTRACT
alpha-Synuclein is the major component of Lewy bodies. Its aggregation can be accelerated by copper, iron, or beta-amyloid (Abeta) and has been thought to provide a nucleation center during the formation of amyloid plaques. The main structural component of amyloid plaque is Abeta, which is derived from a larger protein, amyloid precursor protein (APP). Xenobiotics have been implicated in the etiology of the neurodegenerative disease. Mechanisms of diethyldithiocarbamate (DDC) neurotoxicity involve copper chelation and interactions with SH groups resulting in oxidative stress. In this study, rat hippocampal astrocytes were treated with DDC (75 microM), CuCl(2) (0.2 microM), or DDC (75 microM) plus CuCl(2) (0.2 microM) for 1h. Cells were allowed to recover with or without 10 mM GSH. Results showed an increase of APP and alpha-synuclein production occurring in a time-dependent manner. At 4 h post-treatment, cells contained small positively stained material deposited throughout the cytosol for APP and by 8 h post-treatment increases were seen in both APP and alpha-synuclein. Immunoblots supported immunocytochemical results. Glutathione (GSH) decreased the accumulation of these proteins at 8 h post-treatment.
Subject(s)
Amyloid beta-Protein Precursor/biosynthesis , Astrocytes/drug effects , Copper/toxicity , Ditiocarb/toxicity , Glutathione/pharmacology , Hippocampus/drug effects , Nerve Tissue Proteins/biosynthesis , Amyloid beta-Protein Precursor/analysis , Animals , Astrocytes/metabolism , Blotting, Western , Cells, Cultured , Cytoskeleton/physiology , Hippocampus/metabolism , Immunohistochemistry , Nerve Tissue Proteins/analysis , Rats , Rats, Sprague-Dawley , Synucleins , alpha-SynucleinABSTRACT
Ebselen is a seleno-organic compound with documented cytoprotective properties. Little work has been done, however, demonstrating ebselen's cytoprotective properties in neural cell lines. In order to examine the effects of this compound and its mechanism of action, astrocytes were exposed to two known neurotoxicants, cisplatin and diethyldithiocarbamate (DDC). Cells were pretreated with 30 microM ebselen and subsequently treated with either 150 microM DDC for 1 h or 250 and 500 microM cisplatin for 24 h. Results indicate significant increases in viability in cells pretreated with ebselen and exposed to cisplatin. Ebselen pretreatment did not significantly increase viability in cells exposed to DDC. Light and scanning electron microscopy studies confirm the viability studies. Gross morphological damage was seen in cells treated with cisplatin, however, cells pretreated with ebselen and then exposed to cisplatin, appeared similar to controls. No differences were noted in cells pretreated with ebselen and then exposed to DDC or cells treated with DDC alone. In order to examine the mechanism of protection of this compound, glutathione status was examined. Results show that ebselen does not significantly increase reduced or oxidized glutathione (GSH, GSSG). All cell groups treated with cisplatin showed an increase in GSH levels. Ebselen showed protection in glutathione depleted cells at the 250 microM cisplatin dose. DDC treatment showed no significant increase in either reduced or oxidized glutathione. We conclude that ebselen significantly protects against cisplatin, but not DDC toxicity. We further conclude that this protection is not related to changes in glutathione status in the rat hippocampal cell line as has been reported in other cell types.
Subject(s)
Antineoplastic Agents/antagonists & inhibitors , Antineoplastic Agents/toxicity , Astrocytes/pathology , Azoles/pharmacology , Chelating Agents/toxicity , Cisplatin/antagonists & inhibitors , Cisplatin/toxicity , Ditiocarb/toxicity , Hippocampus/pathology , Neuroprotective Agents/pharmacology , Organoselenium Compounds/pharmacology , Animals , Astrocytes/drug effects , Cell Line , Cell Survival/drug effects , Glutathione/metabolism , Hippocampus/drug effects , Isoindoles , Microscopy, Electron, Scanning , Nerve Tissue Proteins/metabolism , Rats , Rats, Sprague-Dawley , Tetrazolium Salts , ThiazolesABSTRACT
PURPOSE: Giant condyloma acuminatum (Buschke-Loewenstein tumor) of the anorectum is a rare disease with a potentially fatal course. Controversy exists as to the epidemiology, pathologic nature, and management of the tumor. METHODS: We present a 42-year-old male with a 12-cm x 10-cm exophytic mass of the anal verge. Treatment included wide local excision and partial closure with rotation flaps. Pathology revealed a giant condyloma acuminatum with foci of well-differentiated squamous-cell carcinoma. We identified 51 reported cases of giant condyloma acuminatum in the English literature, and to our knowledge this is the largest review to date. RESULTS: Giant condyloma acuminatum presents with a 2.7:1 male-to-female ratio. For patients younger than 50 years of age, this ratio is increased to 3.5:1. The mean age at presentation is 43.9 years, 42.9 in males and 46.6 in females (P = 0.44). There seems to be a recent trend toward a younger presentation. The most common presenting symptoms are perianal mass (47 percent), pain (32 percent), abscess or fistula (32 percent), and bleeding (18 percent). Giant condyloma acuminatum has been linked to human papilloma virus and has distinct histologic features. Foci of invasive carcinoma are noted in 50 percent of the reports, "carcinoma in situ" in 8 percent, and no invasion in 42 percent. Historically, treatment strategies have included topical chemotherapy, wide local excision, abdominopelvic resection, and the frequent addition of adjuvant and neoadjuvant systemic chemotherapy and radiation therapy. Recurrence is common. CONCLUSION: There seems to be a trend toward younger age at presentation and male predominance of giant condyloma acuminatum of the anorectum. Foci of invasive cancer within giant condyloma specimens are of uncertain significance and do not seem to correlate with recurrence or prognosis. Local invasion and local recurrence are the major source of morbidity in this disease. Complete excision is the preferred initial therapy when feasible. Wide local excision, fecal diversion, or abdominoperineal resection have been used. Chemotherapy with 5-fluorouracil and focused radiation therapy may be used in certain cases of recurrence or extensive pelvic disease, with unpredictable response. Controlled, prospective, multi-institutional studies are necessary to further define the nature and treatment of this rare disease.
Subject(s)
Anus Diseases/surgery , Condylomata Acuminata/surgery , Rectal Diseases/surgery , Adult , Anus Diseases/complications , Anus Diseases/epidemiology , Anus Neoplasms/complications , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/surgery , Condylomata Acuminata/complications , Condylomata Acuminata/epidemiology , Humans , Male , Rectal Diseases/complications , Rectal Diseases/epidemiology , Rectal Neoplasms/complicationsABSTRACT
The time and dose-dependent effects of kainic acid (KA) induced excitotoxicity on the oxidative defense system and the relationship to the induction of stress proteins were investigated in the rat hippocampus. Male Long-Evans rats were injected subcutaneously with 5.0, 7.5, or 10 mg KA/kg. Rats were sacrificed and the hippocampus removed and processed for biochemical and electrophoretic analysis. The activity of glutathione peroxidase (GPx) increased significantly at the 5 mg KA/kg dose, while malondialdehyde (MDA) levels significantly increased at 7.5 mg KA/kg when measured at 24 h. A dose of 10 mg KA/kg depleted significantly hippocampal glutathione (GSH) levels at 8, 16 and 24 h post-treatment while GPx activity was increased significantly at 2, 4, 8 and 16 hr post-treatment. The 10 mg KA/kg increased significantly hippocampal MDA levels at 2 h post-treatment and decreased significantly thereafter. The induction of stress proteins increased in a dose and time dependent manner. The expression of Hp72 and Hsp32 increased significantly at 16 h with a maximum induction observed at 24 h post-treatment. The data suggests that KA toxicity is mediated through the formation of reactive oxygen species resulting in alterations in the oxidative defense system. The expression of stress proteins following KA administration may reflect a concomitant but alternate response to excitotoxic events.
Subject(s)
Heat-Shock Proteins/biosynthesis , Hippocampus/drug effects , Kainic Acid/toxicity , Oxidative Stress , Animals , Dose-Response Relationship, Drug , Glutathione/analysis , Glutathione Peroxidase/metabolism , Hippocampus/metabolism , Lipid Peroxidation/drug effects , Male , Rats , Rats, Long-EvansSubject(s)
AIDS-Related Opportunistic Infections/diagnosis , Cryptococcosis/diagnosis , Lung Diseases, Fungal/diagnosis , AIDS-Related Opportunistic Infections/diagnostic imaging , Adult , Cryptococcosis/diagnostic imaging , Cryptococcus neoformans/isolation & purification , Humans , Lung Diseases, Fungal/diagnostic imaging , Male , RadiographyABSTRACT
The neurotoxicity of diethyldithiocarbamate (DDC) has been documented for decades. In particular, cytotoxic effects against rat astrocytes have been noted by a decrease in cell viability and numerous ultrastructural defects. This study indicates an in vitro protective effect by zinc administration prior to DDC insult. Cell groups pre-treated with 50 microM ZnCl2 prior to the addition of 35 microg/ml DDC showed significant protection when compared with cells treated with DDC alone. Zinc reduced the DDC-mediated toxicity to astrocytes as indicated by an increase in cell adherence and viability. Morphological evaluation indicated a significant decrease in ultrastructural alterations. Metallothionein (MT), a metal regulatory protein known to be induced by zinc was studied to determine its role in this mechanism of protection. Immunocytochemistry and immunoblots showed increased presence of MT in all zinc treated groups. This suggests a protective effect against DDC cytotoxicity on rat astrocytes in vitro may be associated with an increase in MT concentration.
Subject(s)
Astrocytes/drug effects , Chelating Agents/toxicity , Ditiocarb/toxicity , Zinc/pharmacology , Animals , Animals, Newborn , Astrocytes/cytology , Astrocytes/ultrastructure , Blotting, Western , Cell Adhesion/drug effects , Cell Division/drug effects , Cell Survival/drug effects , Cells, Cultured , Chlorides/pharmacology , Electrophoresis, Polyacrylamide Gel , Metallothionein/drug effects , Metallothionein/metabolism , Microscopy, Electron , Rats , Rats, Sprague-Dawley , Zinc Compounds/pharmacologyABSTRACT
Scanning electron microscope gave new insights into real morphology of the inner ear and has enhanced basic research. In fact, during the last twenty years, the cellular system that composes the organ of Corti and the vestibular apparatus has been clearly described by many authors. We now have a better understanding of each cell type and that they have a physiological functioning as ear and vestibular system. In addition, new insights into the damage caused by many drugs, such as aminoglucosides, can be investigated by studying the morphological changes and the reparative process following the injury. Animals such as guinea pigs can be used as ideal models to investigate the alterations in the sensory epithelium of the cochlear and vestibular receptors following ototoxic poisoning.
Subject(s)
Anti-Bacterial Agents/adverse effects , Ear, Inner/drug effects , Aminoglycosides , Animals , Cochlea/drug effects , Cochlea/pathology , Cochlea/ultrastructure , Ear, Inner/pathology , Ear, Inner/ultrastructure , Female , Guinea Pigs , Male , Microscopy, Electron , Organ of Corti/drug effects , Organ of Corti/pathology , Organ of Corti/ultrastructureABSTRACT
Se presenta un paciente de 34 años de edad HIV (+), adicto a drogas endovenosas, y con secuelas de poliomielitis en miembros inferiores, que concurrió a la consulta el 20/2/97 encontrándose afebril, con parálisis del nervio motor ocular externo (MOE) derecho, cefalea, sin signos meníngeos ni adenomegalias, hipoacusia, síndrome vertiginoso incompleto, hepatoesplenomegalia y recuento de linfocitos TCD4+ y CD8+ de 58 y 1561 células/ml, respectivamente. La tomografía axial computada no evidenció lesiones parenquimatosas; en tanto la resonancia magnética nuclear mostró una lesión peduncular izquierda. El examen del líquido cefalorraquídeo (LCR) evidenció levaduras capsuladas en la microscopía con tinta china y desarrollo de C. neoformans en los cultivos. Comenzó tratamiento con anfotericina B (dosis total acumulada 1 gr.), continuando luego con fluconazol a dosis de 800 mg/día. Concomitantemente inició terapia antirretroviral con 3 TC-d4T e indinavir. Un mes después, se observó la remisión clínica de la sintomatología neurológica. En abril/97 ante la persistencia de cultivos positivos para C. neoformans en el LCR se suspendió el fluconazol y se reinició la anfotericina B en forma ambulatoria hasta acumular 500 mg (50 mg 3 veces/semana), con buena tolerancia. Un mes después de iniciado el tratamiento antirretroviral se realiza una carga viral (RT-PCR Amplicore) con resultado no detectable (menor a 400 copias/ml). En mayo/97 se realizó nueva punción lumbar, observándose en LCR levaduras capsuladas, deterioradas, con cultivos posteriores negativos. En ese momento, el recuento de CD4 fue de 90 células/mm3. Continuó profilaxis secundaria con fluconazol a dosis de 400 mg/día. En octubre/97, el paciente se encontraba asintomático, con un incremento de 16 kg. en el peso corporal desde el momento del diagnóstico; una nueva carga viral, por el mismo método, resultaba no detectable y el recuento de CD4 era de 80 células/mm3