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1.
bioRxiv ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-36778461

RESUMO

Radical cure of Plasmodium vivax malaria must include elimination of quiescent 'hypnozoite' forms in the liver; however, the only FDA-approved treatments are contraindicated in many vulnerable populations. To identify new drugs and drug targets for hypnozoites, we screened the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library and a collection of epigenetic inhibitors against P. vivax liver stages. From both libraries, we identified inhibitors targeting epigenetics pathways as selectively active against P. vivax and P. cynomolgi hypnozoites. These include DNA methyltransferase (DNMT) inhibitors as well as several inhibitors targeting histone post-translational modifications. Immunofluorescence staining of Plasmodium liver forms showed strong nuclear 5-methylcystosine signal, indicating liver stage parasite DNA is methylated. Using bisulfite sequencing, we mapped genomic DNA methylation in sporozoites, revealing DNA methylation signals in most coding genes. We also demonstrated that methylation level in proximal promoter regions as well as in the first exon of the genes may affect, at least partially, gene expression in P. vivax. The importance of selective inhibitors targeting epigenetic features on hypnozoites was validated using MMV019721, an acetyl-CoA synthetase inhibitor that affects histone acetylation and was previously reported as active against P. falciparum blood stages. In summary, our data indicate that several epigenetic mechanisms are likely modulating hypnozoite formation or persistence and provide an avenue for the discovery and development of improved radical cure antimalarials.

2.
Rev Clin Esp (Barc) ; 222(5): 293-298, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35512908

RESUMO

This observational retrospective study aimed to investigate the usefulness of Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), National Early Warning Score (NEWS), and quick NEWS in predicting respiratory failure and death among patients with COVID-19 hospitalized outside of intensive care units (ICU). We included 237 adults hospitalized with COVID-19 who were followed-up on for one month or until death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤200mmHg or the need for mechanical ventilation. Respiratory failure occurred in 77 patients (32.5%), 29 patients (12%) were admitted to the ICU, and 49 patients (20.7%) died. Discrimination of respiratory failure was slightly higher in NEWS, followed by SOFA. Regarding mortality, SOFA was more accurate than the other scores. In conclusion, sepsis scores are useful for predicting respiratory failure and mortality in COVID-19 patients. A NEWS score ≥4 was found to be the best cutoff point for predicting respiratory failure.


Assuntos
COVID-19 , Insuficiência Respiratória , Sepse , Adulto , COVID-19/complicações , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Escores de Disfunção Orgânica , Prognóstico , Curva ROC , Estudos Retrospectivos
3.
Rev. clín. esp. (Ed. impr.) ; 222(5): 293-298, Mayo 2022. tab
Artigo em Espanhol | IBECS | ID: ibc-204740

RESUMO

El presente estudio retrospectivo observacional tiene como objetivo analizar la utilidad de las escalas SOFA (Sequential Organ Failure Assessment), qSOFA (Quick SOFA), NEWS (National Early Warning Score ) y Quick NEWS para predecir el fallo respiratorio y la muerte en pacientes con COVID-19 atendidos fuera de la Unidad de Cuidados Intensivos (UCI). Se incluyeron 237 adultos con COVID-19 hospitalizados seguidos durante un mes o hasta su fallecimiento. El fallo respiratorio se definió como un cociente PaO2/FiO2 ≤ 200 mmHg o la necesidad de ventilación mecánica. Setenta y siete pacientes (32,5%) desarrollaron fallo ventilatorio; 29 (12%) precisaron ingreso en UCI, y 49 fallecieron (20,7%). La discriminación del fallo ventilatorio fue algo mayor con la puntuación NEWS, seguida de la SOFA. En cuanto a la mortalidad, la puntuación SOFA fue más exacta que las otras escalas. En conclusión, las escalas de sepsis son útiles para predecir el fallo respiratorio y la muerte en COVID-19. Una puntuación ≥ 4 en la escala NEWS sería el mejor punto de corte para predecir fallo respiratorio (AU)


This observational retrospective study aimed to investigate the usefulness of Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), National Early Warning Score (NEWS), and quick NEWS in predicting respiratory failure and death among patients with COVID-19 hospitalized outside of intensive care units (ICU). We included 237 adults hospitalized with COVID-19 who were followed-up on for one month or until death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤ 200 mmHg or the need for mechanical ventilation. Respiratory failure occurred in 77 patients (32.5%), 29 patients (12%) were admitted to the ICU, and 49 patients (20.7%) died. Discrimination of respiratory failure was slightly higher in NEWS, followed by SOFA. Regarding mortality, SOFA was more accurate than the other scores. In conclusion, sepsis scores are useful for predicting respiratory failure and mortality in COVID-19 patients. A NEWS score ≥ 4 was found to be the best cutoff point for predicting respiratory failure (AU)


Assuntos
Humanos , Sepse/diagnóstico , Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Insuficiência Respiratória , Estudos Retrospectivos , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Curva ROC
4.
Rev Clin Esp ; 222(5): 293-298, 2022 May.
Artigo em Espanhol | MEDLINE | ID: mdl-33191944

RESUMO

This observational retrospective study aimed to investigate the usefulness of Sequential Organ Failure Assessment (SOFA), Quick SOFA (qSOFA), National Early Warning Score (NEWS), and quick NEWS in predicting respiratory failure and death among patients with COVID-19 hospitalized outside of intensive care units (ICU). We included 237 adults hospitalized with COVID-19 who were followed-up on for one month or until death. Respiratory failure was defined as a PaO2/FiO2 ratio ≤ 200 mmHg or the need for mechanical ventilation. Respiratory failure occurred in 77 patients (32.5%), 29 patients (12%) were admitted to the ICU, and 49 patients (20.7%) died. Discrimination of respiratory failure was slightly higher in NEWS, followed by SOFA. Regarding mortality, SOFA was more accurate than the other scores. In conclusion, sepsis scores are useful for predicting respiratory failure and mortality in COVID-19 patients. A NEWS score ≥ 4 was found to be the best cutoff point for predicting respiratory failure.

5.
Radiología (Madr., Ed. impr.) ; 62(4): 252-265, jul.-ago. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-194243

RESUMO

En mujeres con alto riesgo de padecer cáncer de mama, la detección precoz tiene un importante papel. Debido a la alta incidencia de cáncer mamario y a edades más tempranas que en la población general, se recomienda que el cribado comience en edad más joven, y existe amplia evidencia de que la resonancia magnética es la herramienta diagnóstica más sensible: las principales guías americanas y europeas coinciden en la recomendación de realizar resonancia magnética anual (con mamografía anual suplementaria) como modalidad óptima de cribado. No obstante, no hay un total consenso actual entre las guías sobre algunos subgrupos de pacientes a incluir en la recomendación de cribado con resonancia magnética. El objetivo de esta primera parte de nuestro trabajo es, mediante una revisión de la bibliografía, explicar y valorar las ventajas que este tipo de cribado con resonancia magnética proporciona respecto al cribado solo con mamografía, como son: mayor detección de cánceres de menor tamaño y con menor afectación ganglionar asociada y una reducción de los cánceres de intervalo, lo que puede tener repercusión en supervivencia y mortalidad, con efectos comparables a otras medidas de prevención. Pero, a su vez, también queremos reflejar los inconvenientes que el cribado con resonancia magnética conlleva, y que dificultan su aplicabilidad


Screening plays an important role in women with a high risk of breast cancer. Given this population's high incidence of breast cancer and younger age of onset compared to the general population, it is recommended that screening starts earlier. There is ample evidence that magnetic resonance imaging (MRI) is the most sensitive diagnostic tool, and American and the European guidelines both recommend annual MRI screening (with supplementary annual mammography) as the optimum screening modality. Nevertheless, the current guidelines do not totally agree about the recommendations for MRI screening in some subgroups of patients. The first part of this article on screening in women with increased risk of breast cancer reviews the literature to explain and evaluate the advantages of MRI screening compared to screening with mammography alone: increased detection of smaller cancers with less associated lymph node involvement and a reduction in the rate of interval cancers, which can have an impact on survival and mortality (with comparable effects to other preventative measures). At the same time, however, we would like to reflect on the drawbacks of MRI screening that affect its applicability


Assuntos
Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Programas de Triagem Diagnóstica , Espectroscopia de Ressonância Magnética/métodos , Neoplasias da Mama/epidemiologia , Diagnóstico Precoce , Espectroscopia de Ressonância Magnética/efeitos adversos , Mamografia/métodos , Mamografia/tendências , Fatores de Risco , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/prevenção & controle
6.
Radiologia (Engl Ed) ; 62(5): 417-433, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32527577

RESUMO

For women with a high risk of breast cancer, early detection plays an important role. Due to the high incidence of breast cancer, and at a younger age than in the general population, screening begins earlier, and there is considerable evidence that magnetic resonance is the most sensitive diagnostic tool, and the principal American and European guidelines agree on the recommendation to perform annual magnetic resonance (with supplemental annual mammography) as an optimal mode of screening. In addition to the absence of current consensus on which patients should be included in the recommendation for magnetic resonance screening (widely discussed in the introduction of part 1 of this work), there are other aspects that are different between guidelines, that are not specified, or that are susceptible to change based on the evidence of several years of experience, that we have called «controversies¼, such as the age to begin screening, the possible advisability of using a different strategy in different subgroups, performing alternate versus synchronous magnetic resonance and mammography, the age at which to terminate the two techniques, or how to follow up after risk reduction surgery.The aim of the second part of the paper is, by reviewing the literature, to provide an update in relation to some of the main «controversies¼ in high risk screening with magnetic resonance. And finally, based on all this, to propose a possible model of optimal and updated screening protocol.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Detecção Precoce de Câncer/métodos , Imageamento por Ressonância Magnética , Feminino , Humanos , Medição de Risco
7.
Radiologia (Engl Ed) ; 62(4): 252-265, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32241593

RESUMO

Screening plays an important role in women with a high risk of breast cancer. Given this population's high incidence of breast cancer and younger age of onset compared to the general population, it is recommended that screening starts earlier. There is ample evidence that magnetic resonance imaging (MRI) is the most sensitive diagnostic tool, and American and the European guidelines both recommend annual MRI screening (with supplementary annual mammography) as the optimum screening modality. Nevertheless, the current guidelines do not totally agree about the recommendations for MRI screening in some subgroups of patients. The first part of this article on screening in women with increased risk of breast cancer reviews the literature to explain and evaluate the advantages of MRI screening compared to screening with mammography alone: increased detection of smaller cancers with less associated lymph node involvement and a reduction in the rate of interval cancers, which can have an impact on survival and mortality (with comparable effects to other preventative measures). At the same time, however, we would like to reflect on the drawbacks of MRI screening that affect its applicability.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/epidemiologia , Detecção Precoce de Câncer/métodos , Imageamento por Ressonância Magnética , Mamografia , Feminino , Humanos , Medição de Risco
8.
Rev. esp. cir. ortop. traumatol. (Ed. impr.) ; 62(5): 380-386, sept.-oct. 2018. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-177660

RESUMO

Objetivo: Cuantificar el riesgo de lesión de la inervación dorsal al realizar portales directos de la articulación metacarpofalángica del segundo al quinto dedo. Material y método: Se realizó un estudio anatómico de 11 extremidades superiores de cadáveres frescos. Tras colocarlos en torre de tracción, se realizaron los portales metacarpofalángicos a ambos lados del tendón extensor. Se disecaron las ramas sensitivas dorsales y se midieron las distancias entre el portal y el nervio más cercano mediante un calibrador digital. Se compararon de forma global los portales de todos los dedos para valorar el dedo más seguro y se compararon dos a dos los portales radial y ulnar en cada uno de los dedos, para valorar el portal más seguro dentro de cada dedo. Resultados: La comparación global de todos los portales y dedos mostró que el tercer dedo es el más seguro en cualquiera de sus portales, mientras que el lado ulnar del segundo y radial del cuarto son los que tienen riesgo más alto de lesión nerviosa (p=8,96·10-5). La comparación dos a dos de los portales radial y ulnar en cada uno de los dedos mostró que el portal ulnar en más seguro que el radial en el cuarto dedo (p=0,042), mientras que el radial es más seguro que el ulnar en el quinto dedo (p=0,003). Conclusiones: El tercer dedo fue el más seguro para la realización de los portales metacarpofalángicos, mientras que el lado ulnar del segundo dedo y el lado radial del cuarto son los de más alto riesgo de lesión nerviosa


Aim: To quantify the risk of dorsal innervation injury when performing direct metacarpophalangeal joint portals of the second to fifth fingers. Material and method: An anatomical study of 11 upper limbs of fresh corpses was carried out. After placing them in a traction tower, the metacarpophalangeal portals were developed on both sides of the extensor tendon. The dorsal sensory branches were dissected and the distances between the portal and the nearest nerve were measured by a digital caliper. The portals of all the fingers were compared globally to assess the safest finger and two to two radial and ulnar portals were compared in each of the fingers to assess the safest portal within each finger. Results: The overall comparison of all portals and fingers showed that the third finger is the safest in any of its portals, while the ulnar side of the second and radial of the fourth are the portals with the highest risk of nerve injury (P=8.96·10-5). Comparing two to two of the radial and ulnar portals in each of the fingers showed that the ulnar portal is safer than the radial on the fourth finger (P=.042), while the radial is safer than the ulnar on the fifth finger (P=.003). Conclusions: The third finger was the safest to perform metacarpophalangeal portals, while the ulnar side of the second finger and radial side of the fourth had the highest risk of nerve injury


Assuntos
Humanos , Masculino , Feminino , Articulação Metacarpofalângica/inervação , Erros Médicos/prevenção & controle , Extremidade Superior/anatomia & histologia , Articulação Metacarpofalângica/cirurgia , Cadáver , Doença Iatrogênica/prevenção & controle
9.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29198935

RESUMO

AIM: To quantify the risk of dorsal innervation injury when performing direct metacarpophalangeal joint portals of the second to fifth fingers. MATERIAL AND METHOD: An anatomical study of 11 upper limbs of fresh corpses was carried out. After placing them in a traction tower, the metacarpophalangeal portals were developed on both sides of the extensor tendon. The dorsal sensory branches were dissected and the distances between the portal and the nearest nerve were measured by a digital caliper. The portals of all the fingers were compared globally to assess the safest finger and two to two radial and ulnar portals were compared in each of the fingers to assess the safest portal within each finger. RESULTS: The overall comparison of all portals and fingers showed that the third finger is the safest in any of its portals, while the ulnar side of the second and radial of the fourth are the portals with the highest risk of nerve injury (P=8.96·10-5). Comparing two to two of the radial and ulnar portals in each of the fingers showed that the ulnar portal is safer than the radial on the fourth finger (P=.042), while the radial is safer than the ulnar on the fifth finger (P=.003). CONCLUSIONS: The third finger was the safest to perform metacarpophalangeal portals, while the ulnar side of the second finger and radial side of the fourth had the highest risk of nerve injury.


Assuntos
Articulação Metacarpofalângica/inervação , Idoso , Idoso de 80 Anos ou mais , Artroscopia/efeitos adversos , Feminino , Humanos , Complicações Intraoperatórias/prevenção & controle , Masculino , Articulação Metacarpofalângica/cirurgia , Pessoa de Meia-Idade , Segurança do Paciente , Traumatismos dos Nervos Periféricos/prevenção & controle
11.
Prostate Cancer Prostatic Dis ; 9(3): 266-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16683010

RESUMO

Radiofrequency interstitial tumor ablation (RITA) is a thermal ablation method that uses needles and low radiofrequency (RF) energy. The aim of our study was to evaluate the histopathology of thermal lesions induced by RF energy delivered interstitially in prostate cancer patients who subsequently underwent prostatectomy, and to determine the feasibility, effectiveness and safety of this new method in a pilot study.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Terapia por Radiofrequência , Adenocarcinoma/cirurgia , Idoso , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia
12.
Curr Drug Targets ; 7(5): 629-37, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16719772

RESUMO

Protease-activated receptors (PARs) are characterised by a unique mechanism of activation, which enables them to act as cellular sensors for protease activity. PARs are expressed throughout the cardiovascular, gastrointestinal and pulmonary systems, where they are potential drug targets for the treatment of disease. However, there are currently very few selective PAR antagonists or potent PAR agonists available as effective research tools, and moreover, there is considerable evidence to suggest that PARs can promote both pro-inflammatory and anti-inflammatory responses in a wide range of disease models. These confounding issues have, to date, prevented us from developing a clear understanding of the role of PARs in disease. Nevertheless, this review provides an overview of the distribution and function of PARs in the cardiovascular, gastrointestinal and pulmonary systems, and attempts to evaluate whether PAR agonists or antagonists have a place in future drug therapy.


Assuntos
Receptores Ativados por Proteinase/fisiologia , Animais , Asma/tratamento farmacológico , Asma/etiologia , Coagulação Sanguínea , Plaquetas/fisiologia , Pressão Sanguínea , Brônquios/fisiologia , Humanos , Inflamação/etiologia , Inflamação/prevenção & controle , Músculo Liso Vascular/fisiologia , Receptores Ativados por Proteinase/agonistas , Receptores Ativados por Proteinase/antagonistas & inibidores , Traqueia/fisiologia
13.
Pathol Res Pract ; 199(10): 659-65, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14666968

RESUMO

The histological patterns of anti-androgen-treated prostate adenocarcinoma mimic high grade tumors classified according to the widely used Gleason scoring system. However, the biological characteristics of anti-androgen treated carcinoma are largely unknown. E-cadherin, alpha-catenin, and beta-catenin adhesion molecules are down-regulated in pharmacologically untreated high grade prostate carcinoma. In this study, we used immunohistochemical techniques to investigate their expression in twenty acinar adenocarcinomas after anti-androgen therapy in prostatectomy specimens. After adrogen ablation therapy, expression of all these adhesion molecules was higher than that of pretreatment biopsies of the same patient group and high grade matched untreated controls. These results emphasize the inaccuracy of the Gleason score for anti-androgen-treated prostate adenocarcinoma and the more differentiated phenotype of prostate adenocarcinoma after anti-hormonal therapy.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antagonistas de Androgênios/uso terapêutico , Anilidas/toxicidade , Antineoplásicos/uso terapêutico , Caderinas/metabolismo , Proteínas do Citoesqueleto/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Transativadores/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Humanos , Técnicas Imunoenzimáticas , Masculino , Invasividade Neoplásica/patologia , Nitrilas , Prostatectomia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Compostos de Tosil , Resultado do Tratamento , alfa Catenina , beta Catenina
14.
Prog. obstet. ginecol. (Ed. impr.) ; 45(7): 305-308, jul. 2002.
Artigo em Es | IBECS | ID: ibc-16475

RESUMO

La alfafetoproteína y la acetilcolinesterasa son dos marcadores en líquido amniótico de defectos abiertos del tubo neural (DTN) fetal, pero por su conocida capacidad de difusión a través de la membrana amniótica, aunque no de esperar en la acetilcolinesterasa por su elevado peso molecular, en gestaciones gemelares en la que un feto presente DTN, la ecografía constituiría una técnica complementaria útil en la valoración del gemelo aparentemente normal, aunque sin la fiabilidad diagnóstica suficiente para descartar con seguridad la existencia de un DTN en este gemelo, como se describe en un caso de estas características acontecido en nuestro hospital (AU)


Assuntos
Adulto , Feminino , Humanos , Diagnóstico Pré-Natal/métodos , Gravidez Múltipla/fisiologia , alfa-Fetoproteínas/análise , Líquido Amniótico/microbiologia , Acetilcolinesterase/análise , Acetilcolinesterase , Defeitos do Tubo Neural/diagnóstico , Defeitos do Tubo Neural , Amniocentese/métodos , Ultrassonografia/métodos , Cesárea/métodos , Mortalidade Infantil , Biomarcadores/análise , Eletroforese em Gel de Poliacrilamida/classificação , Eletroforese em Gel de Poliacrilamida/métodos , Eletroforese em Gel de Poliacrilamida
15.
Int J Cancer ; 94(3): 383-9, 2001 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11745418

RESUMO

Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been shown to be mechanisms for tumor-suppressor gene inactivation in human oncogenesis. In our study, we examined LOH and MSI using 16 polymorphic markers of DNA for chromosomes 1, 3, 7, 8, 10 and 11. Microdissected tumor samples were isolated from 32 patients, representing 11 foci of incidentally discovered prostate cancer of the transitional zone (TZ), 12 prostate cancer of the peripheral zone (PZ) and 10 of high-grade PIN. We found loss of heterozygosity in the TZ group in 91% of informative cases (10/11) with al least 1 marker compared to 58% of cases (7/12) in PZ group and 70% of cases (7/10) in the HGPIN group. Chromosome 7 showed the highest rate of allelic loss in all 3 categories, with loss of 43% of loci in PIN, 37% in TZ tumors and 31% in PZ tumors. At chromosome 11, LOH was detected in 26% of loci in the TZ group, in 7% of loci in the PZ group and in 13% of loci in the PIN group. On chromosome 8, the PZ and HGPIN group showed allelic loss in 22% and 21% of loci, respectively, compared to 10% detected in the TZ group. The TZ group showed a significant higher rate of allelic instability compared to that observed in tumor samples from the peripheral zone: 73% of cases (8/11) showed genetic alterations (RER+ phenotype) in at least 4 loci analyzed compared to 8% and 10% in the PZ and HGPIN groups, respectively (p = 0.0006). These data suggest that transitional zone carcinoma and peripheral zone carcinoma display distinct and specific genetic alterations in different chromosomes. This diversity may help explain biologic and clinical differences between carcinomas arising in these distinct zones of the prostate. Also our results strongly suggest that the RER+ mutator phenotype could be linked to early development of transitional zone prostate carcinoma.


Assuntos
Adenocarcinoma/genética , Perda de Heterozigosidade , Neoplasias da Próstata/genética , Expansão das Repetições de Trinucleotídeos/genética , Alelos , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 7 , Marcadores Genéticos , Humanos , Imuno-Histoquímica , Masculino , Mutação , Fenótipo , Polimorfismo Genético
16.
J Clin Pathol ; 54(3): 236-7, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11253138

RESUMO

Whole mount sections of the prostate are widely used in many laboratories. Macrocryosections of the gland; that is, whole mount frozen sections of the prostate from radical prostatectomies represent a useful new research protocol. The technique is very simple and does not require expensive equipment.


Assuntos
Crioultramicrotomia/métodos , Próstata/patologia , Crioultramicrotomia/instrumentação , Humanos , Masculino , Prostatectomia , Coloração e Rotulagem
17.
Mol Pharmacol ; 58(1): 18-26, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10860923

RESUMO

The effects of 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBHQ), a synthetic phenolic antioxidant and a blocker of the sarco-endoplasmic ATPase, were evaluated on low and high voltage-activated Ca(2+) currents (ICas) with rodent dorsal root ganglion, hippocampal, and motor neurons. In all cell types tested, tBHQ (IC(50) = 35 microM) blocked ICa at concentrations used to inhibit sarco-endoplasmic ATPase. This effect was specific to tBHQ because the other sarco-endoplasmic reticulum calcium ATPase pump inhibitors (thapsigargin and cyclopiazonic acid) had no effect. Selective blockade of the N-type current with omega-conotoxin GVIA and of P- (motoneuron) or Q-type currents (hippocampal neuron) with omega-agatoxin IVA indicated that tBHQ inhibited N, P, and Q types of ICa. tBHQ had no effect on nitrendipine-sensitive (L-type) and residual drug-resistant (R-type) ICa, nor on the low voltage-activated T-type ICa. Contrary to neuronal cells, the L-type ICa was inhibited by tBHQ in a differentiated mouse neuroblastoma and rat glioma hybrid cell line. Injection of cDNAs encoding the alpha1A, alpha1B, alpha1C, and alpha1E subunits into oocytes showed that tBHQ blocked ICas at the level of the pore-forming protein. This effect of tBHQ on ICa should be considered when interpreting results obtained with tBHQ used on neuronal preparations. It also may be useful for developing new strategies for the generation of more potent intracellular calcium transient inhibitors.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/metabolismo , ATPases Transportadoras de Cálcio/antagonistas & inibidores , Hidroquinonas/farmacologia , Neurônios Motores/efeitos dos fármacos , Animais , Cálcio/metabolismo , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo N/efeitos dos fármacos , Canais de Cálcio Tipo N/metabolismo , Canais de Cálcio Tipo P/efeitos dos fármacos , Canais de Cálcio Tipo P/metabolismo , Canais de Cálcio Tipo Q/efeitos dos fármacos , Canais de Cálcio Tipo Q/metabolismo , Canais de Cálcio Tipo R/metabolismo , Canais de Cálcio Tipo T/metabolismo , Células Cultivadas , DNA Complementar/genética , DNA Complementar/metabolismo , Retículo Endoplasmático/enzimologia , Inibidores Enzimáticos/farmacologia , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Glioma/patologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Células Híbridas/efeitos dos fármacos , Células Híbridas/metabolismo , Camundongos , Neurônios Motores/metabolismo , Neuroblastoma/patologia , Ratos , Ratos Sprague-Dawley , Tapsigargina/farmacologia
18.
Eur Urol ; 37(1): 50-5, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10671785

RESUMO

OBJECTIVES: The aim of this study was to assess the longterm mechanical reliability of AMS (American Medical Systems) three-piece inflatable implants and their impact on patient-partner satisfaction in 200 consecutive patients with erectile dysfunction who underwent surgery in five different institutions. METHODS: Patient charts included in the study were collected and extensively assessed to record pre- and intraoperative data and postoperative complications. All patients and 120 partners were then seen often in the office at a mean follow-up of 59 months (range 6-130) and they were extensively questioned about function of the device and its impact on the couple's sexual life. RESULTS: At the long-term follow-up, 185 patients (92.5%) were still engaging in sexual intercourse with a mean frequency of 1.7/week. Patients and partners reported prosthetic erections as excellent, satisfactory or poor in 96 (48%), 100 (50%) and 4 (2%) cases, and in 20 (17%), 80 (66%) and 20 (17%) cases, respectively. Postoperative sexual activity was considered excellent, satisfactory or poor by 140 (70%), 44 (22%) and 16 (8%) patients and by 34 (28%), 81 (68%) and 5 (4%) partners, respectively. Reasons for patients' complaints included postoperative penile shortening in 60 (30%) cases and poor glandular engorgement in 40 (20%) cases. Partners' main complaint was unnaturalness of the prosthetic erection, a factor reported by 30 (25%) subjects. Complications requiring surgical exploration included infection in 12 patients (6%) and mechanical failure in 8 patients (4%). Kaplan-Meier estimates demonstrated significantly decreased mechanical survival for the Ultrex type of cylinders compared to the CX type of cylinders. CONCLUSIONS: AMS three-piece inflatable implants provide an overall patient and partner satisfaction rate of 92 and 96%, respectively. However, postoperative penile shortening and poor glandular engorgement were the causes of some complaints among the patient population as well as the unnaturalness of prosthetic erection among female partners. In the long-term, mechanically speaking, CX cylinders seem to be more reliable than the Ultrex ones.


Assuntos
Prótese de Pênis , Adulto , Idoso , Idoso de 80 Anos ou mais , Coito , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Ereção Peniana , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Desenho de Prótese , Falha de Prótese , Estudos Retrospectivos , Fatores de Tempo
19.
Urology ; 51(3): 506-9, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9510365

RESUMO

OBJECTIVES: To evaluate the efficacy of electromotive administration (EMDA) of intravesical mitomycin-C (MMC) in patients with superficial bladder tumors and to evaluate the toxicity of the treatment. METHODS: Thirteen patients with multifocal Stages Ta-T1 and G1-G2 transitional cell carcinoma (TCC) of the bladder, primary or recurrent (group A), received MMC 40 mg (retained in the bladder for 2 hours) once a week for 8 weeks. Fifteen patients with the same characteristics (group B) were treated with EMDA/MMC at a current of 15 mA for 20 minutes once a week for 8 weeks. All lesions in the bladder except one (marker) were resected in each patient. RESULTS: In group A, 5 of 12 patients (41.6%) demonstrated complete macroscopic and histologic disappearance of the marker lesion (complete response [CR]). In group B, 6 of 15 patients (40%) had a similar CR. Recurrence rate in responders was 60% in group A versus 33% in group B after 7.6 and 6 months, respectively. Disease-free interval was 14.5 months in the EMDA/MMC group compared to 10.5 months in the MMC group. Side effects were few. CONCLUSIONS: In intermediate risk patients with TCC of the bladder, EMDA/MMC was not superior to MMC alone with a CR rate of 41% versus 41.6%. In responders, a lower recurrence rate and a longer disease-free interval were observed in the EMDA/MMC group.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Carcinoma de Células de Transição/tratamento farmacológico , Mitomicina/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Idoso , Carcinoma de Células de Transição/patologia , Eletricidade , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias da Bexiga Urinária/patologia
20.
Urology ; 49(6): 847-50, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9187689

RESUMO

OBJECTIVES: This prospective study evaluated the clinical and urodynamic changes in patients with obstruction due to benign prostatic hyperplasia (BPH) treated with transurethral needle ablation (TUNA). METHODS: One hundred twenty patients with obstructive uropathy due to BPH were treated with the TUNA procedure between January 1994 and December 1995. All patients were selected according to the criteria established by the guidelines proposed by the International Consensus Committee (World Health Organization, Paris, 1993). The TUNA procedure was performed in an outpatient setting using topical intraurethral anesthesia (2% lidocaine gel). RESULTS: Patients showed a decrease in irritative symptoms as measured by the international Prostate Symptom Score (IPSS) and postprocedure urodynamic parameters. The mean (+/- SD) pretreatment IPSS was 20.8 +/- 4.5. At 3 months, the IPSS decreased to 9.7 +/- 3.0 (108 patients) (P < 0.001). At 6 months it decreased to 6.8 +/- 3.1 (86 patients) and remained at 6.2 +/- 2.9 (72 patients) and 6.7 +/- 3.8 (42 patients) at 12 and 18 months, respectively (P < 0.001). At 1 year after treatment, the peak flow rate (Qmax) increased from 8.2 +/- 3.4 mL/s to 15.9 +/- 2.1 mL/s and was 14.1 +/- 2.5 mL/s at 18 months of follow-up (P < 0.01). Urodynamic re-evaluation performed in 72 patients 12 months after TUNA demonstrated the absence of obstruction in 30 (41.7%). An additional 30 patients (41.7%) had equivocal results, whereas the remaining 12 (16.6%) still had obstruction, according to the Abrams-Griffith nomogram. Mean detrusor pressure at Qmax decreased from 85.3 +/- 18.5 cm H2O to 63.7 +/- 24.9 cm H2O at 12 months of follow-up. CONCLUSIONS: Our results confirm that the TUNA procedure is safe and effective when performed as an outpatient procedure. In addition, TUNA produced better results in patients presenting with moderate to severe irritative symptoms and minimal obstruction as determined by pressure/flow studies.


Assuntos
Ablação por Cateter , Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Obstrução do Colo da Bexiga Urinária/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/economia , Custos e Análise de Custo , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Prostatectomia/efeitos adversos , Prostatectomia/economia , Hiperplasia Prostática/complicações , Hiperplasia Prostática/fisiopatologia , Obstrução do Colo da Bexiga Urinária/etiologia , Obstrução do Colo da Bexiga Urinária/fisiopatologia , Urodinâmica
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