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BACKGROUND: To compare quality of life (QoL) indices between ureteral stent (DJS) and nephrostomy tube (PCN) inserted in the setting of acute ureteral obstruction. METHODS: Prospective bi-centered study. Over the span of 2 years, 45 DJS and 30 PCN patients were recruited. Quality of life was assessed by 2 questionnaires, EuroQol EQ-5D and 'Tube symptoms' questionnaire, at 2 time points (at discharge after drainage and before definitive treatment). RESULTS: Patients' demographics and pre-drainage data were similar. There were no clinically significant differences in patient's recovery between the groups, including post procedural pain, defeverence, returning to baseline renal function, and septic shock complications. More DJS patients presented to the emergency room with complaints related to their procedure compared to PCN patients. At first, DJS patients complained more of urinary discomfort while PCN patients had worse symptoms relating to mobility and personal hygiene, with both groups achieving similar overall QoL score. At second time point, PCN patients' symptoms ameliorated while symptoms in the DJS group remained similar, translating to higher overall QoL score in the PCN group. CONCLUSIONS: The two techniques had a distinct and significantly different impact on quality of life. Over time, PCN patients' symptoms relieve and their QoL improve, while DJS patients' symptoms persist. Specific tube related symptoms, and their dynamics over time, should be a major determinant in choosing the appropriate drainage method, especially when definitive treatment is not imminent.
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Nefrostomía Percutánea , Calidad de Vida , Stents , Uréter/cirugía , Obstrucción Ureteral/cirugía , Enfermedad Aguda , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: Multicystic dysplastic kidney (MCDK) is the most common type of renal cystic disease. It is associated with urinary tract abnormalities in the contralateral kidney in up to 30% of cases, most commonly vesicoureteral reflux (VUR). OBJECTIVES: The objective of this study was to describe the incidence and selected issues in management and evolution for each VUR grade in the contralateral kidney of patients with unilateral MCDK, in order to strengthen the scientific basis regarding the need for voiding cystourethrography (VCUG) screening. METHODS: A comprehensive search of standard and gray literature was performed. Full-text screening, data abstraction, and quality appraisal were conducted in duplicates. Included studies reported a primary diagnosis of unilateral MCDK with contralateral VUR determined by VCUG. Articles had to include a distribution of VUR grade to meet the eligibility criteria. RESULTS: From 698 retrieved articles, 37 studies enrolling 2057 patients were analyzed. Of the patients, 80% were male; 50% had left unilateral MCDK; and 87% were diagnosed prenatally. A total of 1800 patients had VCUG, of whom 303 had VUR (weighted proportion: 17%; 95% confidence interval [CI]: 14-20%). Weighted proportions of VUR were 9%, 7%, and 17% for grades I-II, III-V, and I-V, respectively. Of the patients, 99% (95% CI: 97-100%) were on continuous antibiotic prophylaxis (CAP) and 18% (95% CI: 8-37%) had urinary tract infections (UTIs), with a higher rate of UTIs (23% vs 10%) in patients with dilating (grades III-V) VUR, over a mean follow-up of 40 months. In patients with dilating VUR, reflux resolved or downgraded to grade I in 52% (95% CI: 37-67%) of patients, and 32% (95% CI: 19-49%) had surgical correction of VUR. CONCLUSIONS: Among patients with unilateral MCDK, 17% have VUR in the contralateral kidney, 41% of which is dilating VUR. Of the cases with dilating VUR, half will resolve or downgrade to grade I during follow-up; 23% will develop a UTI despite CAP; and one-third will undergo ureteral re-implantation. While many physicians may thus choose to forego routine VCUG screening of the single functional kidney, shared decision-making with the patient's caregivers is currently recommended, where the risks and benefits of the different approaches can be discussed. The data from this analysis can help inform the discussions.
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Riñón Displástico Multiquístico/complicaciones , Reflujo Vesicoureteral/epidemiología , Reflujo Vesicoureteral/etiología , Niño , Femenino , Humanos , Incidencia , Masculino , Reflujo Vesicoureteral/patologíaRESUMEN
BACKGROUND: Recently, we have shown that mast cell mitochondrial STAT3 could serve as a new target for the regulation of the allergic response as it plays an essential role in immunologically mediated degranulation of mast cells. In the present work, we explored how two recently developed mitochondrial STAT3 inhibitors (Mitocur-1 and Mitocur-3) modulate the allergic response. METHODS: Experiments were performed both in vitro in cultured human/mouse mast cells and with rat basophilic leukemia (RBL) cells and also in vivo in mice. The effect of mitochondrial STAT3 inhibition on mast cell function was determined via checking degranulation and several cytokines secretion levels. RESULTS: Here, we show that treatment of rodent and human cultured mast cells with low concentrations of mitochondrial STAT3 inhibitors had no effect on STAT3 target gene expression. However, these inhibitors caused a significant reduction in mast cell exocytosis and cytokine release, due to a decrease in OXPHOS activity and STAT3 serine 727 phosphorylation. It was also observed in an OVA mouse model of allergic asthma that one of the inhibitors used significantly reduced eosinophilia and neutrophilia compared to the control mice group. Furthermore, it was observed that treatment with this inhibitor resulted in a significant reduction in blood histamine levels in mice after IgE-Ag challenge. CONCLUSION: The present data strongly suggest that the development of mitochondrial STAT3 inhibitors could serve as a potential treatment for allergy-associated diseases.
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Antialérgicos/farmacología , Hipersensibilidad/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Adenosina Trifosfato/metabolismo , Animales , Antígenos/inmunología , Asma/tratamiento farmacológico , Asma/genética , Asma/inmunología , Asma/metabolismo , Biomarcadores , Caspasa 3 , Línea Celular , Femenino , Histamina/sangre , Humanos , Hipersensibilidad/tratamiento farmacológico , Hipersensibilidad/genética , Hipersensibilidad/inmunología , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Mastocitos/metabolismo , Ratones , Consumo de OxígenoRESUMEN
Microphthalmia transcription factor (MITF) is a basic helix-loop-helix leucine zipper (bHLH-Zip) DNA-binding protein. This transcription factor plays a crucial role in the physiological and pathological functions of distinct cell types. MITF transcriptional activity is inhibited by the histidine triad nucleotide-binding protein 1 (HINT1) through direct binding. We previously reported that this association is disrupted by the binding of the second messenger Ap4A to HINT1. Ap4A is mainly produced in the mammalian cells by S207-phosphorylated Lysyl-tRNA synthetase. In this study, we found first that HINT1 was subjected to K21 acetylation and Y109 phosphorylation in activated mast cells, together with the Ap4A-triggered HINT1 dissociation from MITF. Mutational analysis confirmed that these modifications promote MITF transcriptional and oncogenic activity in melanoma cell lines, derived from human melanoma patients. Thus, we provided here an example that manipulation of the LysRS-Ap4A-HINT1-MITF signalling pathway in melanoma through post-translational modifications of HINT1 can affect the activity of the melanoma oncogene MITF.
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Proteínas Portadoras/metabolismo , Proteínas de Unión al ADN/metabolismo , Melanoma/metabolismo , Factor de Transcripción Asociado a Microftalmía/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Procesamiento Proteico-Postraduccional , Neoplasias Cutáneas/metabolismo , Activación Transcripcional , Acetilación , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Línea Celular Tumoral , Quinasa 2 Dependiente de la Ciclina/genética , Quinasa 2 Dependiente de la Ciclina/metabolismo , Análisis Mutacional de ADN , Humanos , Mastocitos/metabolismo , Melanoma/genética , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Factor de Transcripción Asociado a Microftalmía/genética , Proteínas del Tejido Nervioso/genética , Fosforilación , Unión Proteica , Transducción de Señal , Neoplasias Cutáneas/genéticaRESUMEN
OBJECTIVES: To evaluate the current incidence, risk factors, management, and long-term follow-up of urinary leakage following partial nephrectomy, in order to propose an algorithm for diagnosis and evaluation of postoperative urinary leakage. MATERIALS AND METHODS: The study included 752 patients who underwent elective partial nephrectomies for renal masses between the years 1988 and 2013. Patients' demographics, clinico-pathologic variables, and operative details were collected retrospectively. The associations between urinary leakage and patients' variables were assessed by univariate and multivariate analyses. RESULTS: Of the 752 patients, 21 (2.8%) experienced urinary leakage; 4 of the 21 patients with urinary leakage had spontaneous resolution, 1 patient underwent nephrectomy, and 16 patients were treated by retrograde ureteral stents insertion. One of them necessitated insertion of an additional percutaneous nephrostomy and another one deserved concomitant percutaneous drainage of a perirenal urinoma. The average period of time that elapsed from the operation until the insertion of stent was 8.5 ± 4.5 days. Stents were removed 68 ± 20.5 days postoperatively. None of the patients had either persistent or repeated leakage. On univariate analysis, hilar renal masses (p < 0.04) and higher preoperative creatinine levels (p < 0.01) were found to be associated with higher rates of urinary leakage. None of these variables was significant on a multivariate analysis. Review of the urinary leakage rate over time revealed it has been constantly decreasing over time, from 4% in early cases to 1.3% among the most recent ones. CONCLUSION: None of the preoperative variables that were examined in this study was significantly associated with increased risk of urinary leakage. However, cumulative surgical experience was associated with lower rates of urinary leakage, suggesting that the decrease in its incidence is related to the improved surgical skills, rather than to differences in tumors' or patients' characteristics.
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Neoplasias Renales/cirugía , Nefrectomía/efectos adversos , Stents , Incontinencia Urinaria/etiología , Incontinencia Urinaria/terapia , Adulto , Anciano , Algoritmos , Tratamiento Conservador/métodos , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nefrectomía/métodos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/terapia , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Ultrasonografía Doppler/métodos , Incontinencia Urinaria/diagnóstico por imagen , Incontinencia Urinaria/epidemiología , Procedimientos Quirúrgicos Urológicos/métodosRESUMEN
BACKGROUND: While combat casualty care shares many key concepts with civilian trauma systems, its unique features mandate certain practices that are distinct from the civilian ones. METHODS: This is a review of the most current literature on combat casualty care, based on computer database searches for studies on combat casualty care and military medicine. Studies were selected for inclusion in this review based on their relevance and contribution. RESULTS: Over the last decade, meticulous, international data collection and research efforts have led to significant improvements in military trauma care. Combat medicine has focused on the causes of preventable deaths and targeted on bleeding control and resuscitation strategies, as well as improved evacuation. En route care and forward surgical interventions have resulted in unprecedented low fatality rates and the saving of more lives. CONCLUSION: This overview of the developments in combat casualty care in recent years emphasizes medical practices that are characteristic of combat medicine, yet with the potential to save lives in other scenarios, as well.
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The present study was conducted in order to evaluate whether physiological strain is alleviated by a new personal cooling system (CS) consisting of a layered vest and integrated blower that generate a flow of air. Twelve male volunteers were exposed to climatic conditions of 40 degrees C, 40%RH (40/40), and 35 degrees C, 60%RH (35/60) during a 115 min exercise routine, followed by 70 min resting recovery, while wearing a battle dress uniform (BDU) and a ballistic vest, with (COOL) or without (NOCOOL) CS. The CS was able to attenuate the physiological strain levels during exercise, when compared to identical exposures without the CS. Temperature elevation, (DeltaT (re)) after 100 min of exercise, was lower by 0.26 +/- 0.20 and 0.34 +/- 0.21 degrees C in 40/40 and 35/60, respectively, (p < 0.05). Mean skin temperature (T(sk)) was lower by 0.9 +/- 0.4 and 0.6 +/- 0.5 degrees C for 40/40 and 35/60, respectively. Heart rate (HR) was not significantly different for COOL versus NOCOOL for 40/40. At 35/60, HR was lower by 10 beats per min (bpm) (p < 0.05). Physiological strain index (PSI) was 9 and 21% lower for the 40/40 and 35/60, respectively, for COOL versus NOCOOL (p < 0.05). Heat storage (S) rates were 19 and 24% lower and sweat rates were 21 and 25% lower for the 40/40 and 35/60, respectively, for COOL versus NOCOOL (p < 0.05). However, the CS was not effective in alleviating physiological strain during resting recovery with no difference in T (re) cooling rate, S, or HR drop rate between groups over resting recovery periods. The CS tested in this study was found to be an effective tool for lowering physiological strain while exercising but not during resting recovery. Therefore, the CS should be further developed in order to achieve greater attenuation of the thermal strain during exercise and improve effectiveness during rest. Overall, it has the potential to be useful for both military and sports personnel.
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Trastornos de Estrés por Calor/fisiopatología , Ropa de Protección/efectos adversos , Ventilación/instrumentación , Aclimatación/fisiología , Adulto , Temperatura Corporal/fisiología , Regulación de la Temperatura Corporal/fisiología , Ejercicio Físico/fisiología , Frecuencia Cardíaca/fisiología , Calor , Humanos , Masculino , Personal Militar , Temperatura Cutánea/fisiología , Sudoración/fisiologíaRESUMEN
Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive syndrome associated with chromosomal instability, hypersensitivity to DNA crosslinking agents, and predisposition to malignancy. The gene for FA complementation group A (FAA) recently has been cloned. The cDNA is predicted to encode a polypeptide of 1,455 amino acids, with no homologies to any known protein that might suggest a function for FAA. We have used single-strand conformational polymorphism analysis to screen genomic DNA from a panel of 97 racially and ethnically diverse FA patients from the International Fanconi Anemia Registry for mutations in the FAA gene. A total of 85 variant bands were detected. Forty-five of the variants are probably benign polymorphisms, of which nine are common and can be used for various applications, including mapping studies for other genes in this region of chromosome 16q. Amplification refractory mutation system assays were developed to simplify their detection. Forty variants are likely to be pathogenic mutations. Seventeen of these are microdeletions/microinsertions associated with short direct repeats or homonucleotide tracts, a type of mutation thought to be generated by a mechanism of slipped-strand mispairing during DNA replication. A screening of 350 FA probands from the International Fanconi Anemia Registry for two of these deletions (1115-1118del and 3788-3790del) revealed that they are carried on about 2% and 5% of the FA alleles, respectively. 3788-3790del appears in a variety of ethnic groups and is found on at least two different haplotypes. We suggest that FAA is hypermutable, and that slipped-strand mispairing, a mutational mechanism recognized as important for the generation of germ-line and somatic mutations in a variety of cancer-related genes, including p53, APC, RB1, WT1, and BRCA1, may be a major mechanism for FAA mutagenesis.
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Proteínas de Ciclo Celular , Proteínas de Unión al ADN , Anemia de Fanconi/genética , Proteínas Nucleares , Proteínas/genética , Secuencia de Consenso , Proteínas del Grupo de Complementación de la Anemia de Fanconi , Humanos , Mutación , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Eliminación de SecuenciaRESUMEN
An oxidative pathway of glucose-6-phosphate was found in the microsomal fraction of two extra-hepatic tissues: human placenta and pig kidney cortex. Oxidation activity in microsomes, measured by the formation of 14CO2 from [1-14C] glucose-6-phosphate, was observed only after Triton X-100 treatment and in the presence of methylene blue and NADP. Hexose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were present in a latent form and required treatment with detergent for full activation. Our results suggest that these enzymes are located in the luminal space of placental and kidney microsomes, and that, as in the liver, they generate NADPH on the inner side of the endoplasmic reticulum when G6P and NADP are available.