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1.
Rev Neurol ; 78(4): 93-99, 2024 Feb 16.
Article in Spanish | MEDLINE | ID: mdl-38349317

ABSTRACT

AIM: To determine clinical, electroencephalographic, therapeutic and evolutive characteristics of a series of oncopediatric patients with acute symptomatic seizures. PATIENTS AND METHODS: We performed a retrospective and prospective descriptive analysis of clinical records of oncopediatric children evaluated by neurology at the comprehensive outpatient Center for Hemato-Oncological Patients during 2017-2021. We included children aged one month to 17 years with intracranial and extracranial tumors who presented with acute symptomatic seizure (ASC). We defined acute symptomatic seizure according to the 2010 International League Against Epilepsy. We classified seizures according to 2017 International League Against Epilepsy classification. We excluded any patient with a diagnosis of previous epilepsy and non-epileptic paroxysmal episodes. RESULTS: We analyzed 44 cases with a median of 4 years (range: 1 month-17 years) and mean of 5.75 months (range: 1 month-11 months) and 8.33 years (2-17 years). The main etiologies were neurotoxicity and post-surgical context. Four patients presented dysnatremias and two associated with endocranial hypertension. Forty-one electroencephalograms were performed with intercritical results with abnormalities in the baseline rhythm, but without foci or paroxysms. There were no critical recordings. Focal seizures were 25 (56.8%) and generalized seizures 19 (43.18%). Levetiracetam was the most commonly used drug for acute management. CONCLUSIONS: Our cohort shows that ASC, in this population, do not show considerable differences between focal motor and generalized seizures and occur mostly in neurotoxic and post-surgical contexts. Dysnatremias and endocranial hypertension associated with ASC were also recorded. Postcrisis electroencephalograms were without foci or paroxysms and good seizure evolution.


TITLE: Crisis epilépticas sintomáticas agudas. Descripción clinicoelectroencefalográfica etiológica y pronóstico de una serie oncopediátrica.Objetivo. Determinar las características clínicas, electroencefalográficas, terapéuticas y evolutivas de una serie de pacientes oncopediátricos con convulsiones sintomáticas agudas. Pacientes y métodos. Efectuamos un análisis descriptivo retrospectivo y prospectivo de registros clínicos de niños oncopediátricos evaluados por neurología en el Centro Ambulatorio Integral de Pacientes Hematooncológicos durante 2017-2021. Incluimos a niños de 1 mes a 17 años con tumores intracraneales y extracraneales que presentaron convulsiones sintomáticas agudas (CSA). Definimos convulsión sintomática aguda según la clasificación de la Liga Internacional contra la Epilepsia de 2010. Clasificamos las crisis epilépticas según la clasificación de la Liga Internacional contra la Epilepsia de 2017. Excluimos a todo paciente con diagnóstico de epilepsia previa y de episodios paroxísticos no epilépticos. Resultados. Analizamos 44 casos, con una mediana de 4 años (rango: 1 mes-17 años) y una media de 5,75 meses (rango: 1 mes-11 meses) y 8,33 años (2-17 años). Registramos como principales etiologías la neurotoxicidad y el contexto posquirúrgico, con cuatro pacientes asociados a disnatremias y dos a hipertensión endocraneana. Se realizaron 41 electroencefalogramas, con resultados intercríticos con anormalidades en el ritmo de base, pero sin focos ni paroxismos. No hubo registros críticos. Las convulsiones focales fueron 25 (56,8%), y las generalizadas, 19 (43,18%). El levetiracetam fue el fármaco más utilizado para el tratamiento agudo. Conclusiones. Nuestra cohorte muestra que las CSA, en esta población, no evidencian diferencias considerables entre convulsiones focales motoras y generalizadas, y ocurren mayormente en un contexto neurotóxico y posquirúrgico. También se registraron disnatremias e hipertensión endocraneana asociadas a CSA. Los electroencefalogramas poscrisis fueron sin focos o paroxismos y con evolución de las crisis.


Subject(s)
Epilepsy , Hypertension , Neurotoxicity Syndromes , Child , Humans , Retrospective Studies , Epilepsy/etiology , Prognosis , Seizures/etiology , Electroencephalography
2.
Cancer Treat Res Commun ; 16: 13-17, 2018.
Article in English | MEDLINE | ID: mdl-31298997

ABSTRACT

INTRODUCTION: Circulating tumor cell (CTC) count and cytokeratin 19 (CK19) mRNA expression have a prognostic value for patients with metastatic breast cancer (MBC), but their clinical utility remains controversial. We studied CTC count and CK19 mRNA expression in the peripheral blood samples from heavily pretreated patients with MBC and their correlations with prognosis and response to the subsequent line of therapy. METHODS: This prospective observational study included 67 consecutive patients with MBC who were on progression to systemic therapy, and criteria for a new line of systemic treatment were proposed outside a clinical trial. CTC counts and CK19 mRNA expression were measured by the CellSearch® and RT-PCR methods, respectively, before and after the first cycle of treatment. Progression-free survival (PFS) was defined as the time elapsed between the initiation of the treatment and either the date of clinical or radiological tumor progression or death from any cause or the last follow-up. Cox proportional hazards regression model was used to assess the univariate prognostic value of CTC and CK19 mRNA expression on PFS and Kaplan-Meier estimates. A multivariate Cox model was also used to additionally account for phenotype and visceral disease. RESULTS: The mean age was 60 (range 35-86) years, and the average number of previous treatments was 3 (range 1-10); 42 patients (62.6%) were ER+ and 38 patients (56.7%) had visceral disease. The median PFS rate was 8 months (95% CI: 3.7-8.2). Univariate analyses showed a significant effect of the initial value of CK19 mRNA expression (HR = 2.00; 95% CI: 1.05-3.8; p = 0.03) and for the second value of CTC (HR = 2.18; 95% CI: 1.22-3.9; p = 0.009) but did not reach statistical significance for the initial value of CTC and the second value of CK19 mRNA expression. The estimated PFS rates at 6 and 12 months were 75% and 31% for patients with a low initial value of CK19 mRNA expression and 36% and 10% for those with a high initial value of CK19 mRNA expression, respectively (p: 0.022). Further, the estimated PFS rates at 6 and 12 months were 86% and 65% for patients with a low second value of CTC and 76% and 47% for those with a high second value of CTC, respectively (p: 0.004). In the multivariate analysis adjusted for phenotype, visceral disease, and the last treatment performed, only the effect of the second value of CTC remained significant (HR = 2.7, p = 0.004). CONCLUSIONS: CK19 mRNA expression and CTC count appeared clinically meaningful in pretreated patients with MBC, even when adjusted for phenotype and visceral disease involvement. These results support the use of CK19 and CTC as relevant biomarkers for predicting clinical response in MBC.

3.
Am J Transplant ; 15(11): 2825-36, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26139432

ABSTRACT

CD40-CD154 pathway blockade prolongs renal allograft survival in nonhuman primates (NHPs). However, antibodies targeting CD154 were associated with an increased incidence of thromboembolic complications. Antibodies targeting CD40 prolong renal allograft survival in NHPs without thromboembolic events but with accompanying B cell depletion, raising the question of the relative contribution of B cell depletion to the efficacy of anti-CD40 blockade. Here, we investigated whether fully silencing Fc effector functions of an anti-CD40 antibody can still promote graft survival. The parent anti-CD40 monoclonal antibody HCD122 prolonged allograft survival in MHC-mismatched cynomolgus monkey renal allograft transplantation (52, 22, and 24 days) with accompanying B cell depletion. Fc-silencing yielded CFZ533, an antibody incapable of B cell depletion but still able to potently inhibit CD40 pathway activation. CFZ533 prolonged allograft survival and function up to a defined protocol endpoint of 98-100 days (100, 100, 100, 98, and 76 days) in the absence of B cell depletion and preservation of good histological graft morphology. CFZ533 was well-tolerated, with no evidence of thromboembolic events or CD40 pathway activation and suppressed a gene signature associated with acute rejection. Thus, use of the Fc-silent anti-CD40 antibody CFZ533 appears to be an attractive approach for preventing solid organ transplant rejection.


Subject(s)
Antibodies, Monoclonal/therapeutic use , CD40 Antigens/immunology , Graft Survival/drug effects , Graft Survival/immunology , Kidney Transplantation/methods , Animals , CD40 Ligand/immunology , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Female , Kidney Transplantation/adverse effects , Macaca fascicularis , Male , Random Allocation , Time Factors , Transplantation Immunology/physiology , Transplantation, Homologous
5.
Emergencias (St. Vicenç dels Horts) ; 25(6): 467-471, dic. 2013. tab
Article in Spanish | IBECS | ID: ibc-118111

ABSTRACT

Los registros de mortalidad son un instrumento para la planificación de las actuaciones en el ámbito de la salud pública. A pesar de ello, los datos sobre fallecimientos por intoxicación aguda en España son escasos. Se presenta un estudio descriptivo, de encuesta transversal, de pacientes fallecidos en el año 2012 como consecuencia de una intoxicación aguda en 8 hospitales públicos españoles, incluidos en el registro EXITOX. Se registraron 14 casos, con una edad media de 59,1 años, 71% varones y de causa suicida en el 50%. Los cáusticos fueron el principal grupo de tóxicos implicado(35,7%), seguido de los fármacos (21,4%) y las drogas de abuso (21,4%). La tasa de mortalidad por intoxicación fue de 0,5 casos/100.000 habitantes. Se utilizaron medidas terapéuticas toxicológicas específicas en el 28,6%. Se consideró como indudable la relación entre intoxicación y fallecimiento en el 71%. Aún con las limitaciones existentes, el registro EXITOX parece ser una herramienta adecuada para conocer la mortalidad por intoxicación aguda en España (AU)


Death registers are a tool for planning public health care interventions, but data on deaths due to acute poisoning are scarce in Spain. We report a descriptive study based on a cross-section of patients who died from acute poisoning in2012 in 8 Spanish public hospitals and whose deaths were recorded in the EXITOX register. Of the 14 registered cases, 7(50%) were suicides; 71% were men, and the mean age was 59.1 years. Caustic substances comprised the largest category (35.7%) of toxic agents, followed by medications (21.4%), and street drugs (21.4%). The mortality rate was0.5 deaths/100 000 inhabitants. Specific antidotes were used in 28.6% of the cases. In 71%, there was a clear relationship between death and acute poisoning. The EXITOX register, even with its limitations, seems to provide an appropriate tool for understanding mortality due to acute intoxication in Spain (AU)


Subject(s)
Humans , Drug Overdose , Poisoning/mortality , Substance-Related Disorders/mortality , Hospital Mortality/trends , Hospital Records/statistics & numerical data
6.
Mol Plant Microbe Interact ; 26(4): 451-60, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23216086

ABSTRACT

The nodulation (nod) genes of Rhizobium tropici CIAT899 can be induced by very low concentrations (micromolar to nanomolar range) of several flavonoid molecules secreted by the roots of leguminous plants under a number of different conditions. Some of these conditions have been investigated and appear to have a great influence on the concentration and the number of different Nod factors, which can induce root nodule primordia and pseudonodules in several leguminous plant roots. In one such condition, we added up to 300 mM NaCl to the induction medium of R. tropici CIAT899 containing the nod gene inducer apigenin. At the higher concentrations of NaCl, larger amounts and more different Nod factors were produced than in the absence of extra NaCl. To our surprise, under control conditions (300 mM NaCl without apigenin), some Nod-factor-like spots were also observed on the thin-layer plates used to detect incorporation of radiolabeled glucosamine into newly synthesized Nod factors. This phenomenon was further investigated with thin-layer plates, fusions of nod genes to the lacZ gene, high-performance liquid chromatography, mass spectrometry, and the formation of pseudonodules on bean roots. Here, we report that, in the absence of flavonoid inducers, high concentrations of NaCl induced nod genes and the production of Nod factors.


Subject(s)
Flavonoids/pharmacology , Lipopolysaccharides/metabolism , Rhizobium tropici/drug effects , Rhizobium tropici/metabolism , Sodium Chloride/pharmacology , Gene Expression Regulation, Plant/drug effects , Gene Expression Regulation, Plant/genetics , Lipopolysaccharides/genetics
7.
Rev. esp. patol. torac ; 22(3): 195-198, jul.-sept. 2010. ilus
Article in Spanish | IBECS | ID: ibc-97261

ABSTRACT

Mujer de 64 años diagnositicada de asma bronquial en la juventud, catalogada como asma de difícil control y corticode pendiente. En las pruebas complementarias se ha objetivado una eosinofilia mantenida (>7%), IgE total elevada con un pico (..) (AU)


A 64 year-old woman diagnosed with bronchial asthma, proven difficult to control and corticoid-dependent since an early age, was studied. Complementary test performed demonstrated (..) (AU)


Subject(s)
Humans , Female , Middle Aged , Pulmonary Aspergillosis/drug therapy , Asthma/drug therapy , Antibodies, Monoclonal/pharmacokinetics , Immunoglobulin E , Patient Selection , Anti-Inflammatory Agents/pharmacokinetics
8.
Mar Pollut Bull ; 59(4-7): 175-81, 2009.
Article in English | MEDLINE | ID: mdl-19560169

ABSTRACT

The (210)Pb dating method was first introduced by Goldberg (1963), and since then has been applied to study sediment from lakes, estuaries and coastal marine environments. Hundreds of studies around the world have used (210)Pb as a geochronological tool in aquatic ecosystems. However little attention has been paid to the potential of this naturally occurring isotope as an environmental tracer of ecological events. Here we report three instances in which (210)Pb profiles measured on undisturbed sediment cores from lakes, rivers and fjords show us the potential of (210)Pb profile as a tracer of natural and anthropogenic processes. The methodology used here is a suite of techniques combining biogeochemistry (micro-electrodes), paleomagnetism (susceptibility), sediment characteristics (LOI) and visualization (SPI and X-ray) applied to the interpretation of (210)Pb profiles. We measured (210)Pb profiles on sediments from a river, Cruces River (Chile), which recorded a clear shift in the water chemistry caused by a pulp mill effluent to the river. Here metal mobilization and remobilization of the tracer may be the cause of the observed profile. We also measured (210)Pb profiles in sediment from two fjords of Southern Chile (Pillan and Reñihue), the sudden deposition change of fresh (210)Pb with depth observed could very well be the result of bioturbation but it occurred in a seafloor area deprived of bioturbators. In this case, (210)Pb recorded the onset of aquaculture activities (fish farming) that took place two decades ago. Finally, (210)Pb profiles measured in two lakes in the "pampa Argentina": Epecuen and Venado showed a particular shape with depth. These profiles apparently registered a sudden depositional event with recent (210)Pb material, probably related to strong shifts in precipitation and drought cycles in that part of the world. These three examples show that (210)Pb profiles provide valuable information not only on geochronology, but also related to natural and anthropogenic short term processes, as shown here, but these are not always reported and well understood.


Subject(s)
Ecosystem , Environmental Monitoring , Geologic Sediments/chemistry , Lead Radioisotopes/analysis , Rivers/chemistry , Water Pollutants, Chemical/analysis
11.
Chemosphere ; 73(1 Suppl): S137-42, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18499220

ABSTRACT

Results of a preliminary survey of particulate and dioxin emissions in combustion gases from hospital waste incinerators in Antioquia-Colombia are presented. Base line data of total suspended particulate (TSP) and polychlorinated dibenzodioxin and dibenzofuran (PCDD/PCDF) emissions in incinerators from health care institutions in Antioquia-Colombia will be used to improve the management of medical waste in the local context. All monitored incinerators are batch operated. TSP exceeds 80 mg Nm(-3) in 8 out of 12 incinerators. Dioxin emissions are in the range from about 7 to 700 I-TEQ (ng Nm(-3)). Such a significant amount of dioxin emissions did correlate with entrained particulate matter, mainly as a consequence of poor control of operation parameters. Several suggestions are made to improve medical waste management practices in Colombia.


Subject(s)
Air Pollutants/analysis , Benzofurans/analysis , Incineration , Medical Waste , Particulate Matter/analysis , Polychlorinated Dibenzodioxins/analogs & derivatives , Air Pollutants/chemistry , Benzofurans/chemistry , Colombia , Dibenzofurans, Polychlorinated , Particulate Matter/chemistry , Polychlorinated Dibenzodioxins/analysis , Polychlorinated Dibenzodioxins/chemistry , Suspensions
12.
Med. intensiva (Madr., Ed. impr.) ; 32(2): 71-77, mar. 2008. ilus, tab
Article in Es | IBECS | ID: ibc-63851

ABSTRACT

Objetivo. Demostrar que el consenso interdisciplinar mejora la calidad del trabajo en la Unidad de Cuidados Intensivos (UCI), evitando exploraciones radiológicas rutinarias innecesarias, planteándose una monitorización de los resultados para mantener este bajo porcentaje de peticiones. Diseño. Ciclo de mejora de calidad asistencial. Ámbito. UCI de 18 camas de carácter polivalente. Pacientes. Pacientes ingresados en la UCI en el periodo de un mes, durante el cual se hizo un muestreo aleatorio sistemático. Intervenciones. Establecimiento de un protocolo consensuado de petición de radiografías de tórax portátiles (RTP) rutinarias. Tras comprobar el exceso de RTP siguiendo estos criterios, se acordó con todos los intensivistas su aplicación. Cinco años después se volvió a valorar el grado de incumplimiento y se incluyó un calendario de monitorizaciones para evitar la vuelta al exceso de solicitudes no justificadas. Además se introdujo un sistema de petición consensuado entre dos intensivistas, de manera que todas las RTP programadas para cada día se solicitaban por parte de dos intensivistas, atendiendo a los mencionados criterios. Variable. Peticiones que incumplen el protocolo de RTP programada. Resultados. En 1997, el grado global de incumplimiento era del 16,9%. Tras reducirlo al 6,1%, la falta de control posterior llevó a que en 2003 fuese del 27,6%. Los pacientes estables con cardiopatía isquémica (44,4% y 53,8% de todos los incumplimientos en esos dos años) constituyen el grueso de las indicaciones inadecuadas. El uso de un modelo de solicitud que requiere del consenso de dos intensivistas consiguió una reducción del incumplimiento al 2,5% en 2003. El calendario de monitorización ha permitido seguir en el tiempo el grado de cumplimiento y detectar la relajación en la prescripción. Conclusiones. Las RTP innecesarias pueden reducirse fácilmente incidiendo sobre los pacientes clínicamente estables. La obligación de justificar una petición rutinaria (consenso entre intensivistas) permite disminuir el número de peticiones de RTP. La monitorización periódica es la herramienta final para el éxito del ciclo de mejora


Purpose. To demonstrate that interdisciplinary consensus improves the quality of work in the daily Intensive Care Unit (ICU), thus avoiding unnecessary routine x-ray examinations. We propose to monitor the results to maintain this low percentage of requests for x-rays. Design. Cycle of improvement in care quality. Setting. An 18-bed polyvalent ICU. Patients. A random sample of patients admitted in ICU during one month. Interventions. Establishment of basic agreed on protocol for routine chest portable x-ray (CPR) indications. After assessing the excessive amount of CPR according to those criteria, all intensivists accepted their application. Five years later, a second assessment of the degree of non-compliance was carried out and a monitoring schedule was established in order to avoid making unnecessary CPR again. Furthermore, a consensus between two intensivists was considered obligatory before a CPR request. Accordingly, all non-urgent CPR forms were signed by two intensivists, following the mentioned clinical criteria. Variable. Unsuitable portable chest x-ray indications. Results. In 1997, the overall non-compliance rate (ONCR) was 16.9%. After reducing it to 6.1%, lack of follow-up led to a non-compliance rate of 27.6% in 2003. Stable patients with uncomplicated ischemic heart disease (44.4% in 1997 and 53.8% in 2003) accounted for most of the inadequate ONCR indications. By using the consensus system for requesting routine portable x-rays that required the agreement of two intensivists achieved a reduction of non-compliance to 2.5% in 2003. The monitoring schedule designed has made it possible to follow the time of compliance degree and detect relaxation in the prescriptions. Conclusions. Unnecessary CPR can be easily reduced stressing our control in clinically stable patients. The requirement to justify a routine request (agreement between intensivists) makes it possible to decrease the number of CPRs. Periodic monitoring is the definitive tool for a successful improvement cycle


Subject(s)
Humans , Radiography, Thoracic , Intensive Care Units/organization & administration , 34002 , Cost Savings/trends , Mass Screening , Patient Selection
13.
Med Intensiva ; 32(2): 71-7, 2008 Mar.
Article in Spanish | MEDLINE | ID: mdl-18275754

ABSTRACT

PURPOSE: To demonstrate that interdisciplinary consensus improves the quality of work in the daily Intensive Care Unit (ICU), thus avoiding unnecessary routine x-ray examinations. We propose to monitor the results to maintain this low percentage of requests for x-rays. DESIGN: Cycle of improvement in care quality. SETTING: An 18-bed polyvalent ICU. PATIENTS: A random sample of patients admitted in ICU during one month. INTERVENTIONS: Establishment of basic agreed on protocol for routine chest portable x-ray (CPR) indications. After assessing the excessive amount of CPR according to those criteria, all intensivists accepted their application. Five years later, a second assessment of the degree of non-compliance was carried out and a monitoring schedule was established in order to avoid making unnecessary CPR again. Furthermore, a consensus between two intensivists was considered obligatory before a CPR request. Accordingly, all non-urgent CPR forms were signed by two intensivists, following the mentioned clinical criteria. VARIABLE: Unsuitable portable chest x-ray indications. RESULTS: In 1997, the overall non-compliance rate (ONCR) was 16.9%. After reducing it to 6.1%, lack of follow-up led to a non-compliance rate of 27.6% in 2003. Stable patients with uncomplicated ischemic heart disease (44.4% in 1997 and 53.8% in 2003) accounted for most of the inadequate ONCR indications. By using the consensus system for requesting routine portable x-rays that required the agreement of two intensivists achieved a reduction of non-compliance to 2.5% in 2003. The monitoring schedule designed has made it possible to follow the time of compliance degree and detect relaxation in the prescriptions. CONCLUSIONS: Unnecessary CPR can be easily reduced stressing our control in clinically stable patients. The requirement to justify a routine request (agreement between intensivists) makes it possible to decrease the number of CPRs. Periodic monitoring is the definitive tool for a successful improvement cycle.


Subject(s)
Guideline Adherence/statistics & numerical data , Intensive Care Units/standards , Radiography, Thoracic/statistics & numerical data , Humans , Quality Control
14.
Acta Ortop Mex ; 21(4): 217-23, 2007.
Article in Spanish | MEDLINE | ID: mdl-17970563

ABSTRACT

OBJECTIVE: To repair experimental osteochondral knee lesions in pigs using tissue engineering. MATERIAL AND METHODS: Eight 40-kg pigs underwent surgery. Cartilage and periosteal biopsies of their control knee were taken. Cartilage and periosteal cells were independently isolated, cultured and seeded in biodegradable PGA and PLA polymers that were fixed on the bottom of an osteochondral defect in the pig's experimental knee, with bioabsorbable Mitek implants. Four months later the pigs were sacrificed and the knees were analyzed with nuclear magnetic resonance imaging (NMRI), macroscopic assessment, histology, electron microscopy (EM), scanning electron microscopy (SEM) and SEM element analysis. RESULTS: All the defects were filled with cartilage-like tissue according to the NMRI evaluation and the visual examination. Hyaline-like cartilage was obtained in 3 defects and fibrocartilage in 5. The EM showed chondrocytes in the repair tissue. The SEM showed appropriate integration to the bone and the surrounding tissue. SEM element analysis showed sulphurized matrix attached to the bone with calcium and phosphates as predominant elements. DISCUSSION: Tissue engineering enabled the production of tissues similar to normal ones. The polymer fixation system was effective.


Subject(s)
Absorbable Implants , Cartilage, Articular/injuries , Knee Injuries/surgery , Lactic Acid/therapeutic use , Polyglycolic Acid/therapeutic use , Polymers/therapeutic use , Tissue Engineering , Animals , Bone Matrix/chemistry , Calcium/analysis , Cartilage, Articular/cytology , Cartilage, Articular/surgery , Cells, Cultured/cytology , Cells, Cultured/transplantation , Chondrocytes/cytology , Chondrocytes/transplantation , Female , Osseointegration , Periosteum/cytology , Phosphates/analysis , Polylactic Acid-Polyglycolic Acid Copolymer , Porosity , Prospective Studies , Sus scrofa , Wound Healing
19.
Exp Dermatol ; 14(6): 429-37, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15885078

ABSTRACT

Photodynamic therapy (PDT) is widely used to treat preneoplastic skin lesions and non-melanoma skin tumours. Studies analyzing the effects of PDT on malignant melanoma have yielded conflicting results. On the one hand, melanoma cell lines in culture as well as cell lines transplanted into experimental animals were sensitive to PDT. On the other hand, spontaneous melanomas of human patients responded poorly to most PDT regimens tested so far. Here, we analyzed effects of 5-aminolaevulinic acid (5-ALA)-based PDT on melanoma cell lines and on experimental melanomas. To mimic the clinical situation as closely as possible, metallothionein-I/ret (MT-ret) mice, a transgenic model of skin melanoma development, were used. Optimal doses of 5-ALA as well as energy doses and power densities were determined in vitro using a cell line (Mel25) established by us from a melanoma of an MT-ret transgenic mouse as well as commercially available human and mouse melanoma cell lines. Treatment with light irradiation alone had no effect. In combination with 5-ALA, however, this illumination readily induced the death of all mouse and human melanoma cell lines examined. Still, 5-ALA PDT caused only minor focal regressive changes including haemorrhages and fibrosis of MT-ret melanomas in vivo and did not significantly delay tumour growth. These results show that, even though MT-ret melanoma cells are vulnerable to 5-ALA PDT in vitro, malignant MT-ret melanomas in vivo are quite resistant to this type of therapy at doses which are highly effective in vitro.


Subject(s)
Aminolevulinic Acid/therapeutic use , Melanoma, Experimental/therapy , Melanoma/therapy , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Skin Neoplasms/therapy , Animals , Cell Line, Tumor , Cell Survival , Disease Models, Animal , Fibrosis , Flow Cytometry , Humans , Light , Melanoma/genetics , Melanoma, Experimental/genetics , Mice , Mice, Transgenic , NIH 3T3 Cells , Neoplasm Metastasis , Neoplasms, Experimental , Skin Neoplasms/genetics , Tetrazolium Salts/pharmacology , Thiazoles/pharmacology , Trypan Blue/pharmacology
20.
Ann Trop Med Parasitol ; 99(2): 125-30, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15814031

ABSTRACT

Although visceral leishmaniasis is often fatal in the developing world, Leishmania-attributable deaths in Europe are relatively rare and nowadays almost always linked to HIV infection. In Spain, however, a HIV-negative man with a history of chronic obstructive pulmonary disease and prednisone treatment was recently hospitalized because of hypotension and asthenia. Although the patient was afebrile, a bone-marrow aspirate, collected after thrombo- and leuco-cytopenia had been observed, was found to contain huge numbers of amastigotes. A course of antileishmanial treatment with meglumine antimoniate was initiated but the patient went into refractory shock and died within 6 h. The significance of this case, in terms of the routine investigation and treatment of immunosuppressed patients who may have leishmaniasis, is discussed.


Subject(s)
Bone Marrow Diseases/immunology , HIV Seronegativity/immunology , Immunocompromised Host , Leishmaniasis, Visceral/immunology , Antiprotozoal Agents/therapeutic use , Bone Marrow/parasitology , Bone Marrow Diseases/drug therapy , Bone Marrow Diseases/parasitology , Fatal Outcome , Glucocorticoids/adverse effects , Humans , Hypotension/complications , Hypotension/drug therapy , Leishmaniasis, Visceral/complications , Leishmaniasis, Visceral/drug therapy , Male , Meglumine/therapeutic use , Meglumine Antimoniate , Middle Aged , Organometallic Compounds/therapeutic use , Prednisone/adverse effects , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy
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