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1.
Indian J Urol ; 40(1): 25-30, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38314074

RESUMEN

Introduction: Patient education is an essential element of the treatment pathway. Augmented reality (AR), with disease simulations and three-dimensional visuals, offers a developing approach to patient education. We aim to determine whether this tool can increase patient understanding of their disease and post-visit satisfaction in comparison to current standard of care (SOC) educational practices in a randomized control study. Methods: Our single-site study consisted of 100 patients with initial diagnoses of kidney masses or stones randomly enrolled in the AR or SOC arm. In the AR arm, a physician used AR software on a tablet to educate the patient. SOC patients were educated through traditional discussion, imaging, and hand-drawn illustrations. Participants completed pre- and post-physician encounter surveys adapted from the Press Ganey® patient questionnaire to assess understanding and satisfaction. Their responses were evaluated in the Readability Studio® and analyzed to quantify rates of improvement in self-reported understanding and satisfaction scores. Results: There was no significant difference in participant education level (P = 0.828) or visit length (27.6 vs. 25.0 min, P = 0.065) between cohorts. Our data indicate that the rate of change in pre- to post-visit self-reported understanding was similar in each arm (P ≥ 0.106 for all responses). The AR arm, however, had significantly higher patient satisfaction scores concerning the educational effectiveness and understanding of images used during the consultation (P < 0.05). Conclusions: While AR did not significantly increase self-reported patient understanding of their disease compared to SOC, this study suggests AR as a potential avenue to increase patient satisfaction with educational tools used during consultations.

2.
Indian J Urol ; 39(2): 142-147, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37304981

RESUMEN

Introduction: The American Cancer Society estimates 79,000 individuals will be diagnosed with kidney cancer in 2022, most of which are initially found as small renal masses (SRMs). Proper management of SRM patients includes careful evaluation of risk factors such as medical comorbidities and renal function. To investigate the importance of these risk factors, we examined their effect on crossover to delayed intervention (DI) and overall survival (OS) in patients undergoing active surveillance (AS) for SRMs. Methods: This is an Institutional Review Board-approved retrospective analysis of AS patients presented at kidney tumor conferences with SRMs between 2007 and 2017. Univariable and multivariable logistic regression analyses were performed to determine how factors including estimated glomerular filtration rate (eGFR), diabetes, and chronic kidney disease are associated with DI and OS. Results: A total of 111 cases were reviewed. In general, AS patients were elderly and had significant comorbidities. On univariate analysis, intervention was more likely to occur in patients with a younger age (P = 0.01), better kidney function (P = 0.01), and higher tumor growth rates (GRs) (P = 0.02). Higher eGFR was associated with better survival (P = 0.03), while higher tumor GRs (P = 0.014), greater Charlson Comorbidity Index (P = 0.01), and larger tumors (P = 0.01) were associated with worse OS. Of the comorbidities, diabetes was found to be an independent predictor of worse OS (P = 0.01). Conclusions: Patient-level factors - such as diabetes and eGFR - are associated with the rate of DI and OS among SRM patients. Consideration of these factors may facilitate better AS protocols and improve patient outcomes for those with SRMs.

3.
J Am Soc Nephrol ; 28(7): 2081-2092, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28122967

RESUMEN

Highly aerobic organs like the kidney are innately susceptible to ischemia-reperfusion (I/R) injury, which can originate from sources including myocardial infarction, renal trauma, and transplant. Therapy is mainly supportive and depends on the cause(s) of damage. In the absence of hypervolemia, intravenous fluid delivery is frequently the first course of treatment but does not reverse established AKI. Evidence suggests that disrupting leukocyte adhesion may prevent the impairment of renal microvascular perfusion and the heightened inflammatory response that exacerbate ischemic renal injury. We investigated the therapeutic potential of hydrodynamic isotonic fluid delivery (HIFD) to the left renal vein 24 hours after inducing moderate-to-severe unilateral IRI in rats. HIFD significantly increased hydrostatic pressure within the renal vein. When conducted after established AKI, 24 hours after I/R injury, HIFD produced substantial and statistically significant decreases in serum creatinine levels compared with levels in animals given an equivalent volume of saline via peripheral infusion (P<0.05). Intravital confocal microscopy performed immediately after HIFD showed improved microvascular perfusion. Notably, HIFD also resulted in immediate enhancement of parenchymal labeling with the fluorescent dye Hoechst 33342. HIFD also associated with a significant reduction in the accumulation of renal leukocytes, including proinflammatory T cells. Additionally, HIFD significantly reduced peritubular capillary erythrocyte congestion and improved histologic scores of tubular injury 4 days after IRI. Taken together, these results indicate that HIFD performed after establishment of AKI rapidly restores microvascular perfusion and small molecule accessibility, with improvement in overall renal function.


Asunto(s)
Fluidoterapia/métodos , Hidrodinámica , Soluciones Isotónicas/administración & dosificación , Riñón/irrigación sanguínea , Daño por Reperfusión/terapia , Animales , Masculino , Ratas , Ratas Sprague-Dawley , Índice de Severidad de la Enfermedad
4.
J Infect Dis ; 211(4): 518-28, 2015 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-25165165

RESUMEN

BACKGROUND: Defining mucosal immune responses and inflammation to candidate human immunodeficiency virus type 1 (HIV-1) vaccines represents a current research priority for the HIV-1 vaccine field. In particular, it is unclear whether intramuscular immunization can elicit immune responses at mucosal surfaces in humans. METHODS: In this double-blind, randomized, placebo-controlled clinical trial, we evaluated systemic and mucosal immune responses to a candidate adenovirus serotype 26 (Ad26) vectored HIV-1 envelop (Env) vaccine in baseline Ad26-seronegative and Ad26-seropositive healthy volunteers. Systematic mucosal sampling with rectal Weck-Cel sponges and rectal biopsies were performed. RESULTS: Intramuscular immunization elicited both systemic and mucosal Env-specific humoral and cellular immune responses in the majority of subjects. Individuals with preexisting Ad26-specific neutralizing antibodies had vaccine-elicited immune responses comparable to those of subjects who were Ad26 seronegative. We also observed no increase in activated total or vector-specific mucosal CD4+ T lymphocytes following vaccination by either histopathology or flow cytometry. CONCLUSIONS: These data demonstrate that a single intramuscular administration of this Ad26-vectored HIV-1 Env vaccine elicited both systemic and mucosal immune responses in humans. Induction of antigen-specific humoral and cellular mucosal immunity was not accompanied by a detectable increase in mucosal inflammation. CLINICAL TRIALS REGISTRATION: NCT01103687.


Asunto(s)
Vacunas contra el SIDA/inmunología , Adenovirus Humanos/inmunología , VIH-1/inmunología , Inmunidad Mucosa/inmunología , Vacunas contra el SIDA/administración & dosificación , Vacunas contra el SIDA/efectos adversos , Adulto , Linfocitos T CD4-Positivos/inmunología , Colon/inmunología , Colon/patología , Citocinas/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Anticuerpos Anti-VIH/sangre , Anticuerpos Anti-VIH/inmunología , Infecciones por VIH/prevención & control , Humanos , Inyecciones Intramusculares , Mucosa Intestinal/inmunología , Mucosa Intestinal/patología , Masculino , Persona de Mediana Edad , Adulto Joven , Productos del Gen env del Virus de la Inmunodeficiencia Humana/inmunología
6.
Proc Natl Acad Sci U S A ; 109(30): 12111-6, 2012 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-22773820

RESUMEN

HIV-1 envelope glycoprotein is the primary target for HIV-1-specific antibodies. The native HIV-1 envelope spike on the virion surface is a trimer, but trimeric gp140 and monomeric gp120 currently are believed to induce comparable immune responses. Indeed, most studies on the immunogenicity of HIV-1 envelope oligomers have revealed only marginal improvement over monomers. We report here that suitably prepared envelope trimers have nearly all the antigenic properties expected for native viral spikes. These stable, rigorously homogenous trimers have antigenic properties markedly different from those of monomeric gp120s derived from the same sequences, and they induce potent neutralizing antibody responses for a cross-clade set of tier 1 and tier 2 viruses with titers substantially higher than those elicited by the corresponding gp120 monomers. These results, which demonstrate that there are relevant immunologic differences between monomers and high-quality envelope trimers, have important implications for HIV-1 vaccine development.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Anti-VIH/inmunología , Proteína gp120 de Envoltorio del VIH/inmunología , VIH-1/inmunología , Multimerización de Proteína/inmunología , Productos del Gen env del Virus de la Inmunodeficiencia Humana/inmunología , Animales , Cromatografía en Gel , Ensayo de Inmunoadsorción Enzimática , Cobayas , Humanos , Pruebas de Neutralización , Resonancia por Plasmón de Superficie , Ultracentrifugación
7.
Nat Genet ; 38(2): 191-6, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16415887

RESUMEN

Meckel-Gruber syndrome is a severe autosomal, recessively inherited disorder characterized by bilateral renal cystic dysplasia, developmental defects of the central nervous system (most commonly occipital encephalocele), hepatic ductal dysplasia and cysts and polydactyly. MKS is genetically heterogeneous, with three loci mapped: MKS1, 17q21-24 (ref. 4); MKS2, 11q13 (ref. 5) and MKS3 (ref. 6). We have refined MKS3 mapping to a 12.67-Mb interval (8q21.13-q22.1) that is syntenic to the Wpk locus in rat, which is a model with polycystic kidney disease, agenesis of the corpus callosum and hydrocephalus. Positional cloning of the Wpk gene suggested a MKS3 candidate gene, TMEM67, for which we identified pathogenic mutations for five MKS3-linked consanguineous families. MKS3 is a previously uncharacterized, evolutionarily conserved gene that is expressed at moderate levels in fetal brain, liver and kidney but has widespread, low levels of expression. It encodes a 995-amino acid seven-transmembrane receptor protein of unknown function that we have called meckelin.


Asunto(s)
Anomalías Múltiples/genética , Mutación/genética , Proteínas/genética , Ratas Mutantes/genética , Animales , Secuencia de Bases , Análisis Mutacional de ADN , Modelos Animales de Enfermedad , Exones/genética , Femenino , Marcadores Genéticos , Haplotipos , Humanos , Intrones/genética , Masculino , Proteínas de la Membrana , Datos de Secuencia Molecular , Defectos del Tubo Neural/genética , Linaje , Mapeo Físico de Cromosoma , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Síndrome
8.
J Am Soc Nephrol ; 24(3): 385-92, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23274427

RESUMEN

Hypoxia is associated with tissue injury and fibrosis but its functional role in fibroblast activation and tissue repair/regeneration is unknown. Using kidney injury as a model system, we demonstrate that injured epithelial cells produce an increased number of exosomes with defined genetic information to activate fibroblasts. Exosomes released by injured epithelial cells promote proliferation, α-smooth muscle actin expression, F-actin expression, and type I collagen production in fibroblasts. Fibroblast activation is dependent on exosomes delivering TGF-ß1 mRNA among other yet to be identified moieties. This study suggests that TGF-ß1 mRNA transported by exosomes constitutes a rapid response to initiate tissue repair/regenerative responses and activation of fibroblasts when resident parenchyma is injured. The results also inform potential utility of exosome-targeted therapies to control tissue fibrosis.


Asunto(s)
Riñón/lesiones , Riñón/fisiopatología , Regeneración/fisiología , Factor de Crecimiento Transformador beta1/fisiología , Animales , Hipoxia de la Célula/fisiología , Células Cultivadas , Células Epiteliales/fisiología , Exosomas/fisiología , Fibroblastos/fisiología , Fibrosis , Humanos , Riñón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Biológicos , Células 3T3 NIH , ARN Mensajero/genética , ARN Mensajero/metabolismo , Regeneración/genética , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Factor de Crecimiento Transformador beta1/genética
9.
J Virol ; 86(13): 7052-9, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22532675

RESUMEN

A major goal of AIDS vaccine development is to design vaccination strategies that can elicit broad and potent protective antibodies. The initial viral targets of neutralizing antibodies (NAbs) early after human or simian immunodeficiency virus (HIV/SIV) infection are not known. The identification of early NAb epitopes that induce protective immunity or retard the progression of disease is important for AIDS vaccine development. The aim of this study was to determine the Env residues targeted by early SIV NAbs and to assess the influence of prior vaccination on neutralizing antibody kinetics and specificity during early infection. We previously described stereotypic env sequence variations in SIVmac251-infected rhesus monkeys that resulted in viral escape from NAbs. Here, we defined the early viral targets of neutralization and determined whether the ability of serum antibody from infected monkeys to neutralize SIV was altered in the setting of prior vaccination. To localize the viral determinants recognized by early NAbs, a panel of mutant pseudoviruses was assessed in a TZM-bl reporter gene neutralization assay to define the precise changes that eliminate recognition by SIV Env-specific NAbs in 16 rhesus monkeys. Changing R420 to G or R424 to Q in V4 of Env resulted in the loss of recognition by NAbs in vaccinated monkeys. In contrast, mutations in the V1 region of Env did not alter the NAb profile. These findings indicate that early NAbs are directed toward SIVmac251 Env V4 but not the V1 region, and that this env vaccination regimen did not alter the kinetics or the breadth of NAbs during early infection.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Epítopos de Linfocito B/inmunología , Productos del Gen env/inmunología , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Virus de la Inmunodeficiencia de los Simios/inmunología , Animales , Epítopos de Linfocito B/genética , Productos del Gen env/genética , Macaca mulatta , Masculino , Proteínas Mutantes/genética , Proteínas Mutantes/inmunología , Pruebas de Neutralización , Virus de la Inmunodeficiencia de los Simios/genética
10.
Nat Commun ; 14(1): 1703, 2023 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-36973273

RESUMEN

Ca2+ overload-induced mitochondrial dysfunction is considered as a major contributing factor in the pathogenesis of alcohol-associated liver disease (ALD). However, the initiating factors that drive mitochondrial Ca2+ accumulation in ALD remain elusive. Here, we demonstrate that an aberrant increase in hepatic GRP75-mediated mitochondria-associated ER membrane (MAM) Ca2+-channeling (MCC) complex formation promotes mitochondrial dysfunction in vitro and in male mouse model of ALD. Unbiased transcriptomic analysis reveals PDK4 as a prominently inducible MAM kinase in ALD. Analysis of human ALD cohorts further corroborate these findings. Additional mass spectrometry analysis unveils GRP75 as a downstream phosphorylation target of PDK4. Conversely, non-phosphorylatable GRP75 mutation or genetic ablation of PDK4 prevents alcohol-induced MCC complex formation and subsequent mitochondrial Ca2+ accumulation and dysfunction. Finally, ectopic induction of MAM formation reverses the protective effect of PDK4 deficiency in alcohol-induced liver injury. Together, our study defines a mediatory role of PDK4 in promoting mitochondrial dysfunction in ALD.


Asunto(s)
Retículo Endoplásmico , Hepatopatías , Ratones , Animales , Masculino , Humanos , Retículo Endoplásmico/metabolismo , Mitocondrias , Hepatopatías/metabolismo
11.
Artículo en Inglés | MEDLINE | ID: mdl-35732498

RESUMEN

Liquid biopsy is considered an alternative to standard next-generation sequencing (NGS) of solid tumor samples when biopsy tissue is inadequate for testing or when testing of a peripheral blood sample is preferred. A common assumption of liquid biopsies is that the NGS data obtained on circulating cell-free DNA is a high-fidelity reflection of what would be found by solid tumor testing. Here, we describe a case that challenges this widely held assumption. A patient diagnosed with lung carcinoma showed pathogenic IDH1 and TP53 mutations by liquid biopsy NGS at an outside laboratory. Subsequent in-house NGS of a metastatic lymph node fine-needle aspiration (FNA) sample revealed two pathogenic EGFR mutations. Morphologic and immunophenotypic assessment of the patient's blood sample identified acute myeloid leukemia, with in-house NGS confirming and identifying pathogenic IDH1, TP53, and BCOR mutations, respectively. This case, together with a few similar reports, demonstrates that caution is needed when interpreting liquid biopsy NGS results, especially if they are inconsistent with the presumptive diagnosis. Our case suggests that routine parallel sequencing of peripheral white blood cells would substantially increase the fidelity of the obtained liquid biopsy results.


Asunto(s)
Leucemia Mieloide Aguda , Neoplasias Pulmonares , Biopsia con Aguja Fina/métodos , Análisis Mutacional de ADN/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Hallazgos Incidentales , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Biopsia Líquida/métodos , Pulmón/patología , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación
12.
J Biol Chem ; 285(53): 41874-85, 2010 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-20847057

RESUMEN

The network organization of type IV collagen consisting of α3, α4, and α5 chains in the glomerular basement membrane (GBM) is speculated to involve interactions of the triple helical and NC1 domain of individual α-chains, but in vivo evidence is lacking. To specifically address the contribution of the NC1 domain in the GBM collagen network organization, we generated a mouse with specific loss of α3NC1 domain while keeping the triple helical α3 chain intact by connecting it to the human α5NC1 domain. The absence of α3NC1 domain leads to the complete loss of the α4 chain. The α3 collagenous domain is incapable of incorporating the α5 chain, resulting in the impaired organization of the α3α4α5 chain-containing network. Although the α5 chain can assemble with the α1, α2, and α6 chains, such assembly is incapable of functionally replacing the α3α4α5 protomer. This novel approach to explore the assembly type IV collagen in vivo offers novel insights in the specific role of the NC1 domain in the assembly and function of GBM during health and disease.


Asunto(s)
Colágeno Tipo IV/química , Colágeno/química , Albúminas/metabolismo , Secuencia de Aminoácidos , Animales , Creatina/orina , Modelos Animales de Enfermedad , Matriz Extracelular/metabolismo , Genotipo , Humanos , Riñón/metabolismo , Ratones , Ratones Transgénicos , Datos de Secuencia Molecular , Nefritis Hereditaria/genética , Regiones Promotoras Genéticas , Estructura Terciaria de Proteína , Homología de Secuencia de Aminoácido
13.
Hum Mol Genet ; 18(17): 3311-23, 2009 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-19515853

RESUMEN

Meckel syndrome (MKS) is a lethal disorder characterized by renal cystic dysplasia, encephalocele, polydactyly and biliary dysgenesis. It is highly genetically heterogeneous with nine different genes implicated in this disorder. MKS is thought to be a ciliopathy because of the range of phenotypes and localization of some of the implicated proteins. However, limited data are available about the phenotypes associated with MKS1 and MKS3, and the published ciliary data are conflicting. Analysis of the wpk rat model of MKS3 revealed functional defects of the connecting cilium in the eye that resulted in lack of formation of the outer segment, whereas infertile wpk males developed spermatids with very short flagella that did not extend beyond the cell body. In wpk renal collecting duct cysts, cilia were generally longer than normal, with additional evidence of cells with multiple primary cilia and centrosome over-duplication. Kidney tissue and cells from MKS1 and MKS3 patients showed defects in centrosome and cilia number, including multi-ciliated respiratory-like epithelia, and longer cilia. Stable shRNA knockdown of Mks1 and Mks3 in IMCD3 cells induced multi-ciliated and multi-centrosomal phenotypes. These studies demonstrate that MKS1 and MKS3 are ciliopathies, with new cilia-related eye and sperm phenotypes defined. MKS1 and MKS3 functions are required for ciliary structure and function, including a role in regulating length and appropriate number through modulating centrosome duplication.


Asunto(s)
Anomalías Múltiples/genética , Centrosoma/metabolismo , Cilios/metabolismo , Proteínas de la Membrana/metabolismo , Mutación , Proteínas/metabolismo , Anomalías Múltiples/metabolismo , Anomalías Múltiples/patología , Animales , Cilios/genética , Femenino , Humanos , Proteínas de la Membrana/genética , Proteínas/genética , Ratas , Ratas Wistar
14.
Spinal Cord Ser Cases ; 7(1): 16, 2021 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-33674552

RESUMEN

STUDY DESIGN: Online survey distributed to healthcare professionals (HCPs) involved in care of spinal cord injury (SCI) patients with neurogenic lower urinary tract dysfunction (NLUTD). OBJECTIVES: Identify and bring awareness to the variation of neurogenic bladder management in around the world. SETTING: International online questionnaire. METHODS: A 32-question survey was drafted and circulated among a global network of SCI experts for review. The survey was disseminated to healthcare professionals involved in the care of NLUTD in SCI patients via social media, grassroots methods, and international societies. The survey was available for 6 weeks and respondents answered questions regarding SCI population demographics, access to care, common neurogenic bladder management, diagnostic and imaging methods, complications, and follow up. RESULTS: A total of 296 healthcare professionals, 132 from North America, 87 from Europe, 27 from Asia, 24 from Australia, 14 from South America, and 6 from Africa, responded to the survey. Global concurrence was noted among management method for patients without adequate hand function, first-line treatment for neurogenic detrusor overactivity, and common complications. Continents highly differed in responses regarding management method for patients with adequate hand function, frequency of patients reusing catheters, timing of urodynamics, and duration of antibiotic therapy for urinary tract infections. CONCLUSIONS: The results of this international survey demonstrate the variability and uniqueness in neurogenic bladder management in SCI patients around the world. Increased international discourse and education will improve global communication and transparency with the efforts of reducing discrepancies in care.


Asunto(s)
Traumatismos de la Médula Espinal , Vejiga Urinaria Neurogénica , Infecciones Urinarias , Humanos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/epidemiología , Traumatismos de la Médula Espinal/terapia , Encuestas y Cuestionarios , Vejiga Urinaria Neurogénica/epidemiología , Vejiga Urinaria Neurogénica/etiología , Vejiga Urinaria Neurogénica/terapia , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/epidemiología
15.
Urology ; 153: 93-100, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33524433

RESUMEN

OBJECTIVE: To determine the influence of socioeconomic parameters on urinary stone surgeries. METHODS: A retrospective cohort study analyzed patients undergoing urolithiasis surgery in our community network hospital in North Carolina from 2005-2018. RESULTS: Of 7731 patients, 2160 (28%), 5,174 (67%), and 397 (5%) underwent SWL, URS, and PCNL, respectively. A higher proportion of Whites underwent URS (67%) and SWL (74%) than PCNL (56%); whereas a larger percentage of Blacks underwent PCNL (24%) than URS (20%) and SWL (15%) groups (P <.001). Private insurance payers were greater in the SWL (95%) group than URS (80%) and PCNL (81%) (P <.001). The distribution of median income was significantly different amongst the 3 surgeries with higher income classes overutilizing SWL and underutilizing PCNL compared to lower income classes (P <.001). In linear regression modeling, the proportion of SWL in a postal code was positively associated with median income (R2=0.55, P <.001); URS and PCNL were negatively associated with median income (R2=0.40, P <.001 and R2=0.41, P <.001, respectively). On multivariate logistic regression modeling, Blacks were significantly more likely to undergo PCNL than Whites (aOR 1.32, 95% CI 1.01-1.74 P <.050). Private insurance payers were more likely to undergo SWL (aOR 11.0, 95% CI 7.26-16.8, P <.0001) than public insurance payers. Patients in higher median income brackets are significantly less likely to undergo PCNL than those in the <$40,000 income bracket (P <.0001). CONCLUSION: Our study suggests that socioeconomic status impacts urolithiasis surgical management, underscoring disparity recognition importance in endourologic care and ensuring appropriate surgical care regardless of socioeconomic status.


Asunto(s)
Litotricia , Aceptación de la Atención de Salud , Manejo de Atención al Paciente , Salud Urbana , Urolitiasis , Procedimientos Quirúrgicos Urológicos , Demografía , Femenino , Necesidades y Demandas de Servicios de Salud , Disparidades en Atención de Salud/normas , Humanos , Revisión de Utilización de Seguros/estadística & datos numéricos , Litotricia/métodos , Litotricia/estadística & datos numéricos , Masculino , Persona de Mediana Edad , North Carolina/epidemiología , Aceptación de la Atención de Salud/etnología , Aceptación de la Atención de Salud/estadística & datos numéricos , Manejo de Atención al Paciente/métodos , Manejo de Atención al Paciente/estadística & datos numéricos , Determinantes Sociales de la Salud , Factores Socioeconómicos , Salud Urbana/etnología , Salud Urbana/normas , Salud Urbana/estadística & datos numéricos , Urolitiasis/epidemiología , Urolitiasis/cirugía , Procedimientos Quirúrgicos Urológicos/métodos , Procedimientos Quirúrgicos Urológicos/estadística & datos numéricos
16.
J Am Soc Nephrol ; 20(11): 2359-70, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19833902

RESUMEN

Patients with Alport syndrome progressively lose renal function as a result of defective type IV collagen in their glomerular basement membrane. In mice lacking the alpha3 chain of type IV collagen (Col4A3 knockout mice), a model for Alport syndrome, transplantation of wild-type bone marrow repairs the renal disease. It is unknown whether cell-based therapies that do not require transplantation have similar potential. Here, infusion of wild-type bone marrow-derived cells into unconditioned, nonirradiated Col4A3 knockout mice during the late stage of disease significantly improved renal histology and function. Furthermore, transfusion of unfractionated wild-type blood into unconditioned, nonirradiated Col4A3 knockout mice improved the renal phenotype and significantly improved survival. Injection of mouse and human embryonic stem cells into Col4A3 knockout mice produced similar results. Regardless of treatment modality, the improvement in the architecture of the glomerular basement membrane is associated with de novo expression of the alpha3(IV) chain. These data provide further support for testing cell-based therapies for Alport syndrome.


Asunto(s)
Nefritis Hereditaria/cirugía , Trasplante de Células Madre , Animales , Autoantígenos/genética , Células de la Médula Ósea , Colágeno Tipo IV/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados
17.
Lab Invest ; 88(3): 284-92, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18180701

RESUMEN

One current theory for the emergence of glomerular nephritis implicates Th1-type cellular responses associated with delayed-type hypersensitivity, involving T cells and macrophages. Using a mouse model for progressive glomerulonephritis, we investigate the role of B and T cells in the pathogenesis of glomerular inflammation. Deletion of alpha3 chain of type IV collagen in mice (alpha3(IV) collagen null mice) results in GBM defects, glomerulonephritis and tubulointerstitial inflammation, fibrosis and significant immune infiltration including activated B- and T-lymphocytes. To evaluate the contribution of lymphocytes to the pathogenesis of glomerulonephritis and renal fibrosis, we generated mice that are deficient in both the alpha3(IV) collagen and Rag-1 (alpha3/Rag-1 DKO). Lymphocyte deficiency significantly reduces fibrosis in the renal interstitium, but ultrastructural GBM defects persist. Interestingly, glomerulonephritis in the double null mice persists at a similar level with comparable proteinuria. Here we demonstrate that despite the presence of B-cell and T-cells in the inflamed glomeruli, their deletion does not impede the emergence of glomerulonephritis but has a negative impact on the progression of renal interstitial fibrosis.


Asunto(s)
Linfocitos/fisiología , Nefritis Hereditaria/genética , Nefritis Hereditaria/fisiopatología , Albuminuria/etiología , Albuminuria/fisiopatología , Animales , Linfocitos B/fisiología , Colágeno Tipo IV/genética , Creatina/análisis , Creatina/sangre , Creatina/orina , Cruzamientos Genéticos , Ensayo de Inmunoadsorción Enzimática , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Fibrosis/etiología , Fibrosis/patología , Eliminación de Gen , Membrana Basal Glomerular/patología , Membrana Basal Glomerular/ultraestructura , Glomerulonefritis/etiología , Proteínas de Homeodominio/genética , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Nefritis Hereditaria/ultraestructura , Proteinuria/etiología , Proteinuria/fisiopatología , Estadística como Asunto , Linfocitos T/fisiología , Factores de Tiempo
18.
Arch Phys Med Rehabil ; 89(6): 1162-8, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18503815

RESUMEN

OBJECTIVE: To investigate whether the lag signs were valid tools in diagnosing full-thickness tears of the rotator cuff. DESIGN: A same-subject, correlation, double-blinded design was used. The results of the external rotation lag sign, drop sign, and internal rotation lag sign were compared with the criterion standard of diagnostic ultrasound to establish their accuracy. SETTING: A regional orthopedic hospital. PARTICIPANTS: Consecutive subjects (N=37), 21 women and 16 men, with shoulder pain referred to a consultant orthopedic surgeon specializing in shoulder conditions were recruited for this investigation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative likelihood ratios of the lag signs when using ultrasound as the reference test. RESULTS: The specificities of the drop sign and internal rotation lag sign were 77% and 84%, respectively, which, together with low positive likelihood ratios 3.2 (95% confidence interval [CI], 1.5-6.7) and 6.2 (95% CI, 1.9-12.0), indicate that a positive result was poor at recognizing the presence of full-thickness tears. The drop sign had a sensitivity of 73% with a negative likelihood ratio of .34 (95% CI, 0.2-0.8), suggesting that a negative test was fair at ruling out the presence of full-thickness tears. The sensitivity of the internal rotation lag sign (100%) supported by the negative likelihood ratio of 0 (95% CI, 0.0-2.5) suggests that a negative test will effectively rule out the presence of full-thickness tears of the subscapularis. A positive external rotation lag sign is the clinical test most likely to indicate that full-thickness tears of the supraspinatus and infraspinatus are present (specificity, 94%). However, the external rotation lag sign did demonstrate a low sensitivity score of 46% and negative likelihood ratio of .57 (95% CI, 0.4-0.9), which means that a negative test will not rule out the presence of full-thickness tears. CONCLUSIONS: The findings of this investigation suggest that a clinical diagnosis of a full-thickness tear of the rotator cuff cannot be conclusively reached using one or more of the lag signs.


Asunto(s)
Examen Físico/métodos , Lesiones del Manguito de los Rotadores , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Humanos , Funciones de Verosimilitud , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Rotación , Manguito de los Rotadores/diagnóstico por imagen , Sensibilidad y Especificidad , Ultrasonografía
19.
Bone ; 113: 68-76, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29738853

RESUMEN

Osteocytic perilacunar/canalicular turnover in hemodialysis patients has not yet been reported. Osteocyte lacunae in lamellar bone and woven bone were classified as eroded surface-, osteoid surface-, and quiescent surface-predominant osteocyte lacunae (ES-Lc, OS-Lc, QS-Lc, respectively) in 55 hemodialysis patients with either high- (n = 45) or low- (n = 10) parathyroid hormone levels, and 19 control subjects without chronic kidney disease. We calculated the area and number of ES-Lc, OS-Lc, and QS-Lc. The mineralized surface on the osteocyte lacunar walls was measured in each group, and compared among the three groups. The shapes of the osteocyte lacunar walls were validated by backscattered electron microscopy. While the number of ES-Lc per bone area (N.ES-Lc/B.Ar) was higher than the number of OS-Lc per bone area (N.OS-Lc/B.Ar) in all groups, N.ES-Lc/B.Ar and N.OS-Lc/B.Ar were greater in high-parathyroid hormone group than in low-parathyroid hormone and control groups. The total volume of ES-Lc per bone area (ES-Lc.Ar/B.Ar) was greater than the total volume of OS-Lc per bone area (OS-Lc.Ar/B.Ar) in both parathyroid hormone groups. However, both lacunar erosion and lacunar formation increased proportionally, suggesting that global coupling between them was maintained. N.ES-Lc/B.Ar was higher in woven bone than in lamellar bone. The rate of OS-Lc stained by tetracycline hydrochloride, the mineralized lacunar surface and the mean area of OS-Lc with Tc obtained from both parathyroid hormone groups were greater than those in the control group. We conclude that osteocytic perilacunar/canalicular turnover is increased in hemodialysis patients with high parathyroid hormone levels. Osteocytic perilacunar/canalicular turnover depends, at least in part, on serum parathyroid hormone level. However, the ideal PTH level for osteocytic perilacunar/canalicular turnover could not be determined but osteocytic osteolysis was predominant in both the high- and low-PTH groups in this study. Thus, attention should be paid to bone loss from the viewpoint of osteocytic perilacunar/canalicular turnover in hemodialysis patients.


Asunto(s)
Remodelación Ósea/fisiología , Osteocitos/patología , Hormona Paratiroidea/sangre , Diálisis Renal , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteocitos/metabolismo , Osteólisis/metabolismo , Osteólisis/patología , Insuficiencia Renal Crónica/terapia
20.
AIDS Res Hum Retroviruses ; 31(11): 1192-201, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26149894

RESUMEN

A number of potent broadly neutralizing antibodies against HIV-1 have recently been identified that target epitopes on the viral envelope that contain N-linked glycans. It remains unknown how frequently glycan-dependent neutralizing antibodies generally arise during the course of natural infection or whether particular glycosylation sites are preferentially targeted. We tested sera with a broad range of neutralization activity from individuals infected with HIV-1 clades B or C against panels of HIV-1 Env pseudoviruses that lacked specific glycans in the outer domain glycan cluster (ODGC) or inner domain glycan cluster (IDGC) to determine the presence of glycan-dependent neutralizing antibodies. Overall, 54% of individuals were observed to have neutralizing antibodies targeting these glycan regions. Glycan-specific neutralizing antibodies were readily detected in sera that were selected for having broad, moderate, or weak neutralization potency and breadth. Our results demonstrate that glycan-specific neutralizing antibodies arise with appreciable frequency in individuals chronically infected with HIV-1 clades B and C. Antibody responses that commonly occur during natural infection may be more feasible to induce by vaccination; thus glycan-specific neutralizing antibodies may be desirable responses to elicit with candidate HIV-1 vaccines.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Genotipo , Anticuerpos Anti-VIH/sangre , Infecciones por VIH/inmunología , VIH-1/química , VIH-1/inmunología , Polisacáridos/inmunología , Infecciones por VIH/virología , VIH-1/clasificación
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