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1.
J Med Entomol ; 52(5): 925-31, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26336242

RESUMEN

The understanding of the transmission dynamics of Leishmania spp. Ross as well as the epidemiology and spread of leishmaniasis is related to parasite-vector-host interactions. These interactions can be studied using specimens of a sand fly population reared in the laboratory, exposing individuals to experimental infection for the investigation of vector competence and parameters of the vectorial capacity of the species. The present study sought to describe an alternative method for the implantation of a Lutzomyia (Lutzomyia) cruzi colony with wild specimens captured in the municipality of Corumbá, Brazil. With Method 1, engorged females were individualized for oviposition. The eggs were transferred to an acrylic petri dish with a layer of plaster on the bottom, on which food was placed after hatching of the first larvae. With Method 2, females were kept in groups for oviposition in containers, in which soil and food were placed on their bottom for the larvae. In addition, the exposure time of the larvae to light was reduced in comparison with Method 1. With Method 2, a significantly greater number of specimens of Lu. cruzi was obtained. The ratio between the number of emerged adults and the females followed for oviposition was 0.42 with Method 1 and 2.75 with Method 2. The optimization of the rearing conditions for Lu. cruzi will enable the establishment of a colony providing a sufficient number of specimens to develop experimental infection by Leishmania as well as vectorial competence and some parameters of the vectorial capacity of this sand fly.


Asunto(s)
Crianza de Animales Domésticos/métodos , Entomología/métodos , Psychodidae/crecimiento & desarrollo , Animales , Femenino , Larva/crecimiento & desarrollo , Masculino , Pupa/crecimiento & desarrollo
2.
Braz J Med Biol Res ; 55: e12376, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36629525

RESUMEN

The aim of our study was to validate the use of the standardized Radiological Society of North America (RSNA) reporting system in individuals with known lung cancer who presented to the emergency department with suspected COVID-19. We included patients aged 18 years or older from the Cancer Institute of the State of São Paulo (ICESP) with a confirmed diagnosis of lung cancer, admitted to the emergency department and undergoing chest computed tomography (CT) for suspicion of COVID-19. Comparison between SARS-CoV2 RT-PCR across RSNA categories was performed in all patients and further stratified by diagnosis of lung cancer progression. Among 58 individuals included in the analysis (65±9 years, 43% men), 20 had positive RT-PCR. Less than a half (43%) had no new lung findings in the CT. Positive RT-PCR was present in 75% of those with typical findings according to RSNA and in only 9% when these findings were classified as atypical or negative (P<0.001). Diagnostic accuracy was even higher when stratified by the presence or absence of progressive disease (PD). Extent of pulmonary inflammatory changes was strongly associated with higher mortality, reaching a lethality of 83% in patients with >25% of lung involvement and 100% when there was >50% of lung involvement. The lung involvement score was also highly predictive of prognosis in this population as was reported for non-lung cancer individuals. Collectively, our results demonstrated that diagnostic and prognostic values of chest CT findings in COVID-19 are robust to the presence of lung abnormalities related to lung cancer.


Asunto(s)
COVID-19 , Neoplasias Pulmonares , Masculino , Humanos , Femenino , COVID-19/diagnóstico por imagen , SARS-CoV-2 , ARN Viral , Brasil , Tomografía Computarizada por Rayos X/métodos , Neoplasias Pulmonares/diagnóstico por imagen , América del Norte/epidemiología , Estudios Retrospectivos
3.
Parasitology ; 139(4): 516-21, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22309735

RESUMEN

Genetic diversity of Trypanosoma cruzi may play a role in pathogenesis of Chagas disease forms. Natural populations are classified into 6 Discrete Typing Units (DTUs) Tc I-VI with taxonomical status. This study aimed to identify T. cruzi DTUs in bloodstream and tissue samples of Argentinean patients with Chagas disease. PCR-based strategies allowed DTU identification in 256 clinical samples from 239 Argentinean patients. Tc V prevailed in blood from both asymptomatic and symptomatic cases and Tc I was more frequent in bloodstream, cardiac tissues and chagoma samples from immunosuppressed patients. Tc II and VI were identified in a minority of cases, while Tc III and Tc IV were not detected in the studied population. Interestingly, Tc I and Tc II/VI sequences were amplified from the same skin biopsy slice from a kidney transplant patient suffering Chagas disease reactivation. Further data also revealed the occurrence of mixed DTU populations in the human chronic infection. In conclusion, our findings provide evidence of the complexity of the dynamics of T. cruzi diversity in the natural history of human Chagas disease and allege the pathogenic role of DTUs I, II, V and VI in the studied population.


Asunto(s)
Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/parasitología , Enfermedades Endémicas , Trypanosoma cruzi/clasificación , Trypanosoma cruzi/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Argentina/epidemiología , Cardiomiopatía Chagásica/epidemiología , Cardiomiopatía Chagásica/parasitología , Cardiomiopatía Chagásica/fisiopatología , Enfermedad de Chagas/fisiopatología , Niño , Preescolar , ADN Protozoario/análisis , ADN Protozoario/genética , Femenino , Variación Genética , Genotipo , Corazón/parasitología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Filogenia , Reacción en Cadena de la Polimerasa , Trypanosoma cruzi/aislamiento & purificación , Adulto Joven
4.
Nat Med ; 3(12): 1354-61, 1997 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9396605

RESUMEN

Intratumoral implantation of murine cells modified to produce retroviral vectors containing the herpes simplex virus-thymidine kinase (HSV-TK) gene induces regression of experimental brain tumors in rodents after ganciclovir (GCV) administration. We evaluated this approach in 15 patients with progressive growth of recurrent malignant brain tumors. Antitumor activity was detected in five of the smaller tumors (1.4 +/- 0.5 ml). In situ hybridization for HSV-TK demonstrated survival of vector-producing cells (VPCs) at 7 days but indicated limited gene transfer to tumors, suggesting that indirect, "bystander," mechanisms provide local antitumor activity in human tumors. However, the response of only very small tumors in which a high density of vector-producing cells had been placed suggests that techniques to improve delivery and distribution of the therapeutic gene will need to be developed if clinical utility is to be achieved with this approach.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/terapia , Ganciclovir/uso terapéutico , Terapia Genética , Vectores Genéticos , Retroviridae/genética , Timidina Quinasa/genética , Adulto , Animales , Trasplante de Células , Femenino , Técnicas de Transferencia de Gen , Herpesvirus Humano 1/enzimología , Herpesvirus Humano 1/genética , Humanos , Masculino , Ratones , Persona de Mediana Edad , Timidina Quinasa/biosíntesis , Trasplante Heterólogo
5.
Infection ; 38(4): 261-7, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20508967

RESUMEN

BACKGROUND: Detailed reports on the treatment of visceral leishmaniasis (VL) are scarce, particularly with regard to the utilization of antimoniate of N-methylglucamine. The aim of this study was to analyze the treatment of children admitted to a reference hospital, focusing in particular on the use of antimoniate of N-methylglucamine and on the supportive measures adopted. MATERIALS AND METHODS: Medical records of children treated for VL from January 1998 to February 2005 in the Hospital of the University of Mato Grosso do Sul, Central-West Region of Brazil, were reviewed retrospectively. RESULTS: A total of 116 children were treated, and 111 received antimoniate as the first therapeutic choice. The drug was highly efficient (96.9%) in patients with no signs of gravity on admission, in cases presenting warning signs of potential evolution to gravity, and even in some severely ill children. The most common adverse effects were increases in transaminase (22.5%) and amylase (17.5%) levels, and generally reversible electrocardiogram changes (18%). Some problems were detected during the treatment, such as inadequate prescription (causing an under- or overdose) or inappropriate change to a second-line scheme. Of the 116 children, 80% were given antibiotics, 71.5% needed a transfusion of red blood cells, 10.3% required a transfusion of platelets, fresh frozen plasma was given to 4.3%, albumin was administered in 3.4, and 8.6% needed intensive care support. The mortality rate was about 2.6%. CONCLUSION: Antimoniate of N-methylglucamine remains highly efficient and well tolerated in pediatric patients, which allows its utilization as a first-line therapy in Brazilian children until a better drug for widespread use becomes available; however, it should be used with caution, and special attention is required during its prescription and for the management of adverse effects. The low mortality rate obtained confirms that, in addition, successful treatment demands the correction of serious anemia and thrombocytopenia, the vigorous use of antibiotics to fight intercurrent bacterial infections, and sometimes the availability of intensive care units to treat more severe patients.


Asunto(s)
Antiprotozoarios/uso terapéutico , Leishmaniasis Visceral/tratamiento farmacológico , Meglumina/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Adolescente , Antiprotozoarios/efectos adversos , Brasil/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , Leishmaniasis Visceral/diagnóstico , Leishmaniasis Visceral/epidemiología , Masculino , Meglumina/efectos adversos , Antimoniato de Meglumina , Compuestos Organometálicos/efectos adversos , Estudios Retrospectivos , Encuestas y Cuestionarios , Resultado del Tratamiento
6.
Exp Parasitol ; 124(3): 253-7, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19854175

RESUMEN

In the New World, visceral leishmaniasis (VL), which is a progressive disease and frequently fatal, is caused by Leishmania (Leishmania) infantum/chagasi. It is endemic in many regions of Brazil and occasionally occurs in non-endemic regions when dogs from an endemic area are introduced. The aim of the present study is to compare different skin infection patterns of dogs from two leishmaniasis endemic areas. A histological analysis of dogs from Campo Grande, Mato Grosso do Sul state, a region where epidemic episodes are currently taking place, showed dermic inflammatory infiltrates, composed of numerous vacuolated parasitized macrophages, few lymphocytes, plasma cells and many degranulated mast cells. In the other region of the study, São Luís, Maranhão state, the skin of dogs presented a remarkable inflammatory reaction composed mainly of plasma cells, lymphocytes and very few parasites. We concluded that there is a difference in the skin lesion patterns of dogs with leishmaniasis that is directly related to the endemic area where the animals live.


Asunto(s)
Enfermedades de los Perros/patología , Enfermedades Endémicas/veterinaria , Leishmania infantum/aislamiento & purificación , Leishmaniasis Visceral/veterinaria , Piel/patología , Animales , Brasil , Tejido Conectivo/parasitología , Reservorios de Enfermedades , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/parasitología , Perros , Femenino , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/patología , Linfocitos/parasitología , Linfocitos/patología , Macrófagos/parasitología , Masculino , Mastocitos/patología , Células Plasmáticas/parasitología , Células Plasmáticas/patología , Piel/parasitología
7.
Cytogenet Genome Res ; 125(1): 19-25, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19617692

RESUMEN

Xist non-coding RNA (ncRNA) is essential for X chromosome inactivation (XCI). Some genes can escape from XCI, but how this occurs is unknown. We developed a modified RNA tagging and recovery of associated proteins (TRAP) method to study the association between Xist RNA and its target genes. In mouse cells, Xist RNA was detected on the Uba1 gene, but not on Jarid1c and Utx genes, which escape from XCI. Using this technique we were able to show that the Xist RNA molecule is not present on active genes that escape from XCI, but is present on genes inactivated by XCI, suggesting that this method is a powerful tool for functional analysis of ncRNA.


Asunto(s)
Cromatina/genética , Cromatina/metabolismo , ARN no Traducido/genética , ARN no Traducido/metabolismo , Inactivación del Cromosoma X/genética , Cromosoma X/genética , Cromosoma X/metabolismo , Animales , Línea Celular , Inmunoprecipitación de Cromatina , ADN/genética , ADN/metabolismo , Femenino , Expresión Génica , Hibridación in Situ , Hibridación Fluorescente in Situ , Masculino , Ratones , ARN Largo no Codificante , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
8.
J Med Entomol ; 54(1): 114-124, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-28082638

RESUMEN

Recording the nycthemeral rhythm of sand flies allows the evaluation of the daily activity in different ecotypes, the period of greatest activity, and their degree of anthropophily. We investigated the fauna and the rhythm of sand fly activity in an ecotourism region in Mato Grosso do Sul (MS) state, Brazil. Sand flies were captured monthly, using a Shannon trap for 24 h periods between July 2012 and June 2014. We collected 1,815 sand flies, in which Lutzomyia whitmani (=Nyssomyia whitmani, sensu Galati) and Lutzomyia longipalpis were the most abundant species during the dry season, with activity from 5 p.m.-7 a.m. and 6 p.m.-5 a.m., respectively. Both species require particular attention as vectors of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum in several regions of Brazil, including MS. However, Lutzomyia dispar was more anthropophilic, and was most active between January and March, from 5 p.m. to 5 a.m. Lutzomyia misionensis (=Pintomyia misionensis, sensu Galati) was present throughout both years, active from 4 p.m. to 5 a.m. Other species were active from 5 p.m. to 6 a.m. Due to intense tourism in the months that coincide with a high number of vectors for leishmaniases in Piraputanga, it is essential to determine vector-monitoring strategies in the area by investigating sand fly rhythm while not neglecting other periods of the year when the insects are present.


Asunto(s)
Ritmo Circadiano , Psychodidae/fisiología , Animales , Conducta Animal , Biodiversidad , Brasil , Conducta Alimentaria , Femenino , Masculino , Psychodidae/clasificación , Estaciones del Año , Especificidad de la Especie
9.
Braz. j. med. biol. res ; 55: e12376, 2022. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1420744

RESUMEN

The aim of our study was to validate the use of the standardized Radiological Society of North America (RSNA) reporting system in individuals with known lung cancer who presented to the emergency department with suspected COVID-19. We included patients aged 18 years or older from the Cancer Institute of the State of São Paulo (ICESP) with a confirmed diagnosis of lung cancer, admitted to the emergency department and undergoing chest computed tomography (CT) for suspicion of COVID-19. Comparison between SARS-CoV2 RT-PCR across RSNA categories was performed in all patients and further stratified by diagnosis of lung cancer progression. Among 58 individuals included in the analysis (65±9 years, 43% men), 20 had positive RT-PCR. Less than a half (43%) had no new lung findings in the CT. Positive RT-PCR was present in 75% of those with typical findings according to RSNA and in only 9% when these findings were classified as atypical or negative (P<0.001). Diagnostic accuracy was even higher when stratified by the presence or absence of progressive disease (PD). Extent of pulmonary inflammatory changes was strongly associated with higher mortality, reaching a lethality of 83% in patients with >25% of lung involvement and 100% when there was >50% of lung involvement. The lung involvement score was also highly predictive of prognosis in this population as was reported for non-lung cancer individuals. Collectively, our results demonstrated that diagnostic and prognostic values of chest CT findings in COVID-19 are robust to the presence of lung abnormalities related to lung cancer.

10.
Cancer Res ; 54(8): 2141-5, 1994 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-8174120

RESUMEN

In meningeal carcinomatosis, retroviral vector-producer cells can be introduced into the thecal sac and circulate in the cerebrospinal fluid to reach malignant tumor cells in the leptomeninges, release vector particles, and selectively infect and transfer a gene of interest to these cells. Gene transfer experiments with the lacZ gene and in vitro retroviral titer measurements showed that retroviral vectors can survive in the cerebrospinal fluid, retain their infectivity, and successfully transduce tumor cells. To examine the potential of intrathecal gene therapy, we evaluated the antitumor efficacy of in situ transduction with the herpes simplex-thymidine kinase gene followed by ganciclovir therapy in a rat model of leptomeningeal neoplasia. Fischer rats were inoculated via a subarachnoid catheter implanted at the upper thoracic level, and thymidine kinase vector-producer cells were injected into the subarachnoid space the day of tumor inoculation. Seven days later, rats received ganciclovir for 14 days by daily i.p. injections (30 mg/kg/ml) or intrathecal injections (25 micrograms/kg or 600 micrograms/kg) for 14 days. To evaluate possible enhancement of tumor eradication by the ability of helper virus to package the vector in the cells and further extend gene transfer, additional rats received thymidine kinase vector-producer cells that had been previously coinfected with a replication-competent retrovirus (4070A). In all groups, control rats received i.p. or intrathecal saline injections. Ganciclovir administration i.p. resulted in significant prolongation of survival in rats given injections of thymidine kinase vector-producer cells. Injection of producer cells coinfected with the 4070A retrovirus did not improve antitumor efficacy. Intrathecal administration of ganciclovir (low and high doses) did not extend survival; histological examination of the spinal cords showed elimination of the infiltrative tumor in the leptomeninges, but residual tumor mass was present at the inoculation site, consistent with limited penetration of topical ganciclovir into the tumor. These results support the potential application of gene therapy using the thymidine kinase/ganciclovir approach for treatment of meningeal carcinomatosis.


Asunto(s)
Ganciclovir/uso terapéutico , Técnicas de Transferencia de Gen , Terapia Genética/métodos , Neoplasias Meníngeas/terapia , Simplexvirus/enzimología , Timidina Quinasa/biosíntesis , Células 3T3 , Animales , Células Clonales , Vectores Genéticos , Inyecciones Espinales , Neoplasias Meníngeas/patología , Ratones , Ratas , Ratas Endogámicas F344 , Simplexvirus/genética , Médula Espinal/patología , Timidina Quinasa/genética , beta-Galactosidasa/biosíntesis , beta-Galactosidasa/genética
11.
Cancer Res ; 54(11): 2923-7, 1994 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-8187079

RESUMEN

Phenylacetate is a naturally occurring plasma component that suppresses the growth of tumor cells and induces differentiation in vitro. To evaluate the in vivo potential and preventive and therapeutic antitumor efficacy of sodium phenylacetate against malignant brain tumors, Fischer 344 rats (n = 50) bearing cerebral 9L gliosarcomas received phenylacetate by continuous s.c. release starting on the day of tumor inoculation (n = 10) using s.c. osmotic minipumps (550 mg/kg/day for 28 days). Rats with established brain tumors (n = 12) received continuous s.c. phenylacetate supplemented with additional daily i.p. dose (300 mg/kg). Control rats (n = 25) were treated in a similar way with saline. Rats were sacrificed during treatment for electron microscopic studies of their tumors, in vivo proliferation assays, and measurement of phenylacetate levels in the serum and cerebrospinal fluid. Treatment with phenylacetate extended survival when started on the day of tumor inoculation (P < 0.01) or 7 days after inoculation (P < 0.03) without any associated adverse effects. In the latter group, phenylacetate levels in pooled serum and cerebrospinal fluid samples after 7 days of treatment were in the therapeutic range as determined in vitro (2.45 mM in serum and 3.1 mM in cerebrospinal fluid). Electron microscopy of treated tumors demonstrated marked hypertrophy and organization of the rough endoplasmic reticulum, indicating cell differentiation, in contrast to the scant and randomly distributed endoplasmic reticulum in tumors from untreated animals. In addition, in vitro studies demonstrated dose-dependent inhibition of the rate of tumor proliferation and restoration of anchorage dependency, a marker of phenotypic reversion. Phenylacetate, used at clinically achievable concentrations, prolongs survival of rats with malignant brain tumors through induction of tumor differentiation. Its role in the treatment of brain tumors and other cancers should be explored further.


Asunto(s)
Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/prevención & control , Gliosarcoma/mortalidad , Gliosarcoma/prevención & control , Fenilacetatos/uso terapéutico , Animales , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/ultraestructura , División Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Gliosarcoma/metabolismo , Gliosarcoma/patología , Gliosarcoma/ultraestructura , Microscopía Electrónica , Trasplante de Neoplasias , Fenilacetatos/sangre , Fenilacetatos/líquido cefalorraquídeo , Ratas , Ratas Endogámicas F344 , Ensayo de Tumor de Célula Madre
12.
Cancer Res ; 55(6): 1306-9, 1995 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-7882327

RESUMEN

Cyclopentenylcytosine (CPEC; NSC 375575) is a pyrimidine nucleoside analogue that has potent antitumor effects when tested in vitro and also when tested in experimental tumors outside the central nervous system. CPEC exerts its antiproliferative effect through inhibition of CTP synthetase and consequent depletion of CTP and dCTP pools required for cell replication. Due to its poor penetration of the bloodbrain barrier, CPEC has failed to demonstrate therapeutic efficacy in experimental brain tumors after systemic administration. We therefore examined the in vivo activation, distribution, and antitumor effect of CPEC after long-term regional infusion of the drug directly into experimental brain tumors in rats. HPLC analysis of CPEC incubated with homogenized human brain and brain tumor tissue showed minimal degradation of the drug over 24 h. Analysis of rat cerebral 9L gliosarcoma infused with tritium-labeled CPEC demonstrated intratumoral accumulation of the active metabolite CPEC-triphosphate and concomitant depletion of CTP to a much greater extent in tumor tissue than in the adjacent brain. Tumor tissue UTP also decreased, but no significant effects on other ribonucleoside triphosphates were detected. Only trace amounts (< 1%) of CPEC and its metabolites reached peripheral sites, including the liver and kidneys, after intratumoral infusion. Rats treated with continuous intratumoral infusion of CPEC for 4 weeks using s.c. implanted osmotic pumps survived significantly longer than control rats receiving intratumoral saline or i.p. CPEC (P < 0.0001). Long-term intratumoral infusion of CPEC was not associated with any detectable toxicity. Our results support the feasibility of using intratumoral administration of CPEC as a regional therapy for malignant brain tumors.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Citidina/análogos & derivados , Gliosarcoma/tratamiento farmacológico , Animales , Biotransformación , Neoplasias Encefálicas/metabolismo , Citidina/administración & dosificación , Citidina/farmacocinética , Citidina/uso terapéutico , Citidina Trifosfato/metabolismo , Estabilidad de Medicamentos , Gliosarcoma/metabolismo , Ratas , Ratas Endogámicas F344 , Distribución Tisular
13.
Cancer Gene Ther ; 2(2): 87-95, 1995 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7621261

RESUMEN

The use of intrathecal, retroviral-mediated transfer of the herpes simplex thymidine kinase (HStk) gene and subsequent ganciclovir (GCV) administration has recently been shown to improve survival in a rat model of leptomeningeal carcinomatosis. Clinical application of this approach is attractive because access to the cerebrospinal fluid (CSF) space is relatively noninvasive and distribution of producer cells and vectors may be facilitated by circulation of CSF, overcoming distribution problems inherent in solid tumors. However, meningeal inflammation, transduction and injury to normal CNS tissue, proliferation of the xenogeneic producer cells in the subarachnoid space, immune-mediated injury, and development of hydrocephalus are possible complications of intraventricular or intrathecal administration of vector-producer cells. In addition, the dynamics of producer cell and vector distribution in the CSF are unknown. To address these issues, we evaluated the safety of this approach for gene delivery and assessed the dynamics of distribution of producer cells and retroviral vectors in rats and non-human primates. In rats, transduction of normal central nervous system (CNS) structures surrounding the subarachnoid space was evaluated after intrathecal and intraventricular injections of beta-galactosidase and HStk vector-producer cells, with and without GCV. In primates, beta-galactosidase and HStk vector-producer cells were injected intraventricularly and GCV was administered either intrathecally or intravenously. Toxicity was evaluated by neurologic examination, serial gadolinium-enhanced MRI scans of the brain, and blood and CSF profiles. A subgroup of monkeys received repeated intraventricular injection of vector-producer cells and intravenous GCV. The titer of retroviral-vector was measured in cisternal and lumbar CSF samples after repeated producer cell injection.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Células 3T3/trasplante , Ganciclovir/toxicidad , Terapia Genética/métodos , Vectores Genéticos , Proteínas Recombinantes de Fusión/metabolismo , Timidina Quinasa/genética , Proteínas Virales/genética , Animales , Encefalopatías/etiología , Plexo Coroideo/metabolismo , Plexo Coroideo/patología , Plexo Coroideo/virología , Genes Reporteros , Vectores Genéticos/administración & dosificación , Vectores Genéticos/farmacocinética , Vectores Genéticos/toxicidad , Supervivencia de Injerto , Inyecciones Intraventriculares , Inyecciones Espinales , Macaca mulatta/sangre , Macaca mulatta/líquido cefalorraquídeo , Imagen por Resonancia Magnética , Ratones , Virus de la Leucemia Murina de Moloney/genética , Ratas/sangre , Ratas/líquido cefalorraquídeo , Proteínas Recombinantes de Fusión/uso terapéutico , Simplexvirus/enzimología , Simplexvirus/genética , Simplexvirus/inmunología , Espacio Subaracnoideo , Timidina Quinasa/inmunología , Timidina Quinasa/uso terapéutico , Distribución Tisular , Proteínas Virales/inmunología , Proteínas Virales/uso terapéutico , beta-Galactosidasa/biosíntesis
14.
Acta Trop ; 46(4): 213-22, 1989 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-2571248

RESUMEN

Trypanosoma evansi was seen in blood samples taken randomly from both wild and semi-captive capybaras caught in Mato Grosso do Sul State, Brazil and in sick dogs brought into local veterinary clinics. Trypanosome stocks from capybaras and dogs were significantly different in their patterns of growth in mice, while the trypanosomes from dogs were mostly dyskinetoplastic. By isoenzyme electrophoresis all the trypanosomes were of the most common type of T. evansi found elsewhere.


Asunto(s)
Enfermedades de los Perros/parasitología , Isoenzimas/análisis , Enfermedades de los Roedores/parasitología , Trypanosoma/enzimología , Tripanosomiasis/veterinaria , Animales , Animales Salvajes/parasitología , Brasil , Perros , Electroforesis en Acetato de Celulosa , Electroforesis en Gel de Almidón , Femenino , Congelación , Masculino , Ratones , Preservación Biológica , Roedores/parasitología , Trypanosoma/clasificación , Tripanosomiasis/parasitología
15.
Neurosurgery ; 41(1): 140-7; discussion 147-8, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9218306

RESUMEN

OBJECTIVE: Although the Hunt and Hess Scale (HHS) and World Federation of Neurological Surgeons Scale (WFNSS) are the most widely used subarachnoid hemorrhage (SAH) grading systems, neither system has achieved universal acceptance. We propose a simplified grading system based entirely on the Glasgow Coma Scale (GCS), which compresses the 15-point GCS into five grades that are comparable with those of the HHS and WFNSS. We refer to this system as the GCS grading system and present a direct comparison with the HHS and WFNSS for predictive value regarding patient outcome and interrater reliability. METHODS: We reviewed 291 consecutive patients with aneurysms treated at our institution between January 1992 and January 1996 and compared the admission grades from the GCS, WFNSS, and HHS with outcome measures at discharge from hospitalization. The Glasgow Outcome score was used as the major outcome measure to evaluate the predictive value of the three scales. Mortality and length of stay (LOS) were also evaluated as outcome measures. The predictive value of each scale was tested with an ordinal logistic regression model for Glasgow Outcome score, a logistic regression model for mortality data, and a linear regression model for LOS. RESULTS: Using the logistic regression model, the GCS was the best predictor of discharge Glasgow Outcome score, with an odds ratio of 2.585 (P = 0.0001), compared with 2.311 (P = 0.0001) for the WFNSS and 2.262 (P = 0.0001) for the HHS. Using mortality data in the logistic model, the HHS was the best predictor, with an odds ratio of 3.391 (P = 0.0001), compared with 2.859 (P = 0.0001) for the GCS and 2.560 (P = 0.0001) for the WFNSS. Each of the three scales had a high predictive value for LOS, using a linear model. We discuss, however, the problematic nature of LOS as an outcome measure for SAH. Interrater reliability for each scale was evaluated using kappa statistics, based on 15 additional patients evaluated prospectively, and showed that the GCS grade also had the greatest interrater reliability, with a kappa of 0.46 (P = 0.0002), compared with 0.41 (P = 0.0005) for the HHS and 0.27 (P = 0.027) for the WFNSS. CONCLUSION: We conclude that the GCS grade has equal or greater predictive value regarding outcome after SAH than do the currently used grading systems and that it has greater reproducibility across observers. Broader familiarity with the GCS among medical and paramedical personnel may further enhance the usefulness of the GCS grade over the HHS and WFNSS in providing a standardized, universally accepted grading system for SAH.


Asunto(s)
Aneurisma Roto/clasificación , Escala de Coma de Glasgow , Aneurisma Intracraneal/clasificación , Examen Neurológico/estadística & datos numéricos , Hemorragia Subaracnoidea/clasificación , Aneurisma Roto/diagnóstico , Aneurisma Roto/mortalidad , Aneurisma Roto/cirugía , Intervalos de Confianza , Craneotomía , Humanos , Aneurisma Intracraneal/diagnóstico , Aneurisma Intracraneal/mortalidad , Aneurisma Intracraneal/cirugía , Tiempo de Internación/estadística & datos numéricos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Hemorragia Subaracnoidea/diagnóstico , Hemorragia Subaracnoidea/mortalidad , Hemorragia Subaracnoidea/cirugía , Análisis de Supervivencia , Resultado del Tratamiento
16.
J Neurosurg ; 87(2): 163-9, 1997 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9254077

RESUMEN

In patients with bilateral supratentorial aneurysms, surgical clipping of all aneurysms via a unilateral approach would obviate the need for a second operation. The authors conducted a microsurgical study in human cadaver heads to examine the contralateral exposure for four common aneurysm sites in the anterior circulation: the ophthalmic artery (OA) origin, the posterior communicating artery (PCoA) origin, the internal carotid artery (ICA) termination, and the middle cerebral artery (MCA) bifurcation. Frontotemporal craniotomies were performed in 16 cadavers to evaluate the corridor for exposure of these sites from the contralateral side. Morphometric data, including lengths and diameters of major arterial segments and optic nerves, were documented for anatomical correlation. In this study, the contralateral OA origin was successfully exposed in 62% of specimens, the PCoA origin in 50%, the ICA bifurcation in 100%, and the MCA bifurcation in 62%. Exposure of the OA origin and, in some cases, the PCoA, required incision of the falciform ligament and mobilization of the contralateral optic nerve. Exposure of the MCA bifurcation was dependent on the length of the M1 segment, with successful exposure only when this segment was shorter than 14 mm. Implications for the contralateral approach to aneurysms at these sites are discussed and the microsurgical corridors for exposure are described. For correlation with the anatomical study, a brief clinical review of patients with bilateral supratentorial aneurysms treated at The Johns Hopkins Hospital between 1992 and 1995 is presented. Guidelines for the contralateral approach to aneurysms are discussed with reference to the anatomical study and the clinical review.


Asunto(s)
Arterias Cerebrales/patología , Aneurisma Intracraneal/patología , Microcirugia/métodos , Adulto , Autopsia , Humanos
17.
J Neurosurg ; 82(1): 70-6, 1995 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7815137

RESUMEN

Among the appealing features of adenoviruses as vectors for transfer of genes into the central nervous system (CNS) are that they are not neurotoxic, they can accommodate the insertion of several large genes, they are not associated with the hazards of insertional mutagenesis, and they can be concentrated to a high-titer preparation. The authors evaluated the feasibility of using adenovirally mediated gene transfer into cultured human glioma cells and in rat models of solid brain tumors and meningeal cancer. Replication-deficient adenoviral vector particles carrying a nuclear-localizing lacZ gene were injected into established 9L cerebral gliomas in Fischer rats. In addition, the adenoviral vector was injected into the subarachnoid space, either simultaneously with intrathecal tumor inoculation or after establishing leptomeningeal cancer. The brains and spinal cords were removed at various intervals for histochemical evaluation for beta-galactosidase activity using X-Gal staining. Additional rats received a stereotactic intracerebral injection of the vector into normal brain. No clinical abnormalities were observed in the injected rats. Injection of the adenoviral vector into normal brain resulted in diffuse transduction of astrocytes, microglia, neurons, and endothelial cells at the injection site. Injection of a high-concentration vector preparation into cerebral gliomas resulted in effective tumor transduction. Intrathecal injection of the vector in rats with meningeal cancer resulted in transduction of the infiltrating tumor in the subarachnoid space when injections were given simultaneously with, or 7 days after, tumor inoculation. Transduction rates of both solid and leptomeningeal tumors correlated with the number of injected particles. These results suggest that adenoviral vectors can efficiently transduce solid brain tumors and that the vectors survive in the cerebrospinal fluid for a sufficient period of time to allow leptomeningeal tumor transduction. Adenoviral vector should be evaluated for its potential use in therapeutic gene transfer approaches in malignancies of the CNS.


Asunto(s)
Adenoviridae/genética , Neoplasias Encefálicas/terapia , Técnicas de Transferencia de Gen , Glioma/terapia , Neoplasias Meníngeas/terapia , Animales , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Expresión Génica , Glioma/genética , Glioma/patología , Operón Lac , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patología , Ratas , Ratas Endogámicas F344 , Células Tumorales Cultivadas , beta-Galactosidasa
18.
Surg Endosc ; 15(12): 1448-51, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11965463

RESUMEN

BACKGROUND: Although abdominal wall retraction is said to be advantageous in laparoscopic cholecystectomy (LC), many surgeons have found that, when this option is chosen, more time is needed to prepare for and carry out the surgical procedure. Our aim was to determine the time required for surgical preparation and operation in patients undergoing LC with carbon dioxide (CO2) pneumoperitoneum (CO2 PP) vs abdominal wall retraction (AWR). METHODS: We performed a prospective randomized study of a CO2 PP LC group (n = 19) vs an AWR LC group (n = 15). Demographic data were collected preoperatively. LC was performed with either CO2 PP (12 mmHg) or AWR (6-10 kps). Two phases were considered: (a) time employed to create the surgical field (phase 1) and (b) operating time (phase 2). The chi-square test was used to compare the medians of the two groups. RESULTS: The two groups were homogeneous. Phase 1 required 35 min in the CO2 PP group vs 25 min in the AWR group (p = 0.24). Phase 2 required 60 min in both groups (p = 0.76). CONCLUSION: We found no statistically significant difference between the PP CO2 and AWR groups in either time spent to create the surgical field or actual operating time.


Asunto(s)
Dióxido de Carbono/uso terapéutico , Colecistectomía Laparoscópica/métodos , Neumoperitoneo Artificial/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Distribución Aleatoria , Factores de Tiempo
19.
Ann Otol Rhinol Laryngol ; 98(7 Pt 1): 491-5, 1989 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-2751207

RESUMEN

The electrophysiologic response of the guinea pig cochlea was monitored after sequential lesions to Reissner's membrane and the round window (RW). Action potential (AP) responses to click stimuli were recorded from the RW before and after discrete puncture-type lesions were created in the cochlear partition of the second turn. Observed decrements were typically minor, comparable to no greater than 10 dB attenuation of stimulus intensity. The RW membranes then were perforated to create perilymphatic fistulas. Further monitoring demonstrated a rapid (within 5 to 10 minutes), severe decrement in AP amplitude and latency, with complete loss of the AP within 1 hour. Control animals with RW perforations alone did not show these decrements. Correct placement of the second turn lesions was documented by histology. We conclude that discrete lesions in the cochlear duct are not reflected in the AP input-output functions unless there is a fluid leak from the RW, and thus present a possible model for idiopathic sudden hearing loss.


Asunto(s)
Cóclea/fisiopatología , Fístula/complicaciones , Pérdida Auditiva Súbita/etiología , Enfermedades del Laberinto/complicaciones , Líquidos Laberínticos , Perilinfa , Potenciales de Acción , Animales , Conducto Coclear/lesiones , Potenciales Microfónicos de la Cóclea , Cobayas , Ventana Redonda/lesiones , Factores de Tiempo
20.
Int Surg ; 80(3): 223-6, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-8775607

RESUMEN

Contamination by septic materials may represent an important handicap in evaluating the tolerance of reabsorbable prostheses, increasing the possible onset of abdominal fistulae. This is also the case when these materials are used in the treatment of abdominal wall defects. Nevertheless, reabsorbable meshes exist that allow visceroprosthetic contact without risk, thus making it possible to use them in spite of the presence of infection. We have performed this experimental study with the aim of evaluating the behaviour and evolution of polyglycolic acid reabsorbable meshes contaminated by septic materials in the treatment of abdominal wall defects. For this purpose, 40 Wistar rats were operated and distributed into two series of 20 animals each. Massive mesh contamination by fecaloid material did not jeopardise the fact that prostheses were well tolerated in experimental animals throughout the reabsorption process, without increasing the incidence of infection.


Asunto(s)
Músculos Abdominales/cirugía , Ácido Poliglicólico/uso terapéutico , Mallas Quirúrgicas , Músculos Abdominales/patología , Animales , Contaminación de Equipos , Femenino , Masculino , Ratas , Ratas Wistar
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