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OBJECTIVES: Many youth sex trafficking victims visit health care facilities while being trafficked. Little is known regarding whether frontline medical professionals recognize risk factors or are aware of effective interviewing approaches to identify and intervene for youth victims. The aim of the present study was to assess frontline medical professionals' knowledge of youth sex trafficking, adolescent development, and forensically informed interviewing to provide guidance for professional training. METHODS: Two hundred seventy-seven frontline medical professionals [first responders and emergency department (ED)/clinical professionals] in Southern California completed an online survey about their background, training, perceptions of likely youth sex trafficking scenarios, knowledge of adolescent development, sex trafficking, and forensically informed interviewing. RESULTS: Nearly all professionals recognized risk and the need to collect additional information, yet few (1% first responders and 12% ED) recognized that risk as sex trafficking. Forty-six percent of first responders also indicated that responding to nonmedical needs was outside of their job responsibilities. A mixed model analysis of covariance revealed significant interactions of gender by domain ( P = 0.01) and domain by training ( P = 0.045). Women evidenced better knowledge (78% accuracy) about sex trafficking and interviewing (73%) than adolescent development (64%), whereas men were more accurate with sex trafficking (64%) than adolescent development (61%) and interviewing (62%). For domain by training, tests of within subjects' contrasts showed a quadratic relation ( P = 0.02) was the best fit model, where training was most strongly associated with accuracy in sex trafficking knowledge. CONCLUSIONS: Frontline medical professionals are lacking in their knowledge of youth sex trafficking, interviewing, and especially adolescent development. An area in which interventions can be targeted is with training (because it emerged in a significant interaction). Training could combat unrepresentative depictions of victims, improve understanding of common victim characteristics, and highlight how forensically informed interviewing can improve medical professionals' ability to gather crucial history about victims' experiences and needs.
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Trata de Personas , Masculino , Humanos , Adolescente , Femenino , Trata de Personas/prevención & control , Encuestas y CuestionariosRESUMEN
RATIONALE & OBJECTIVE: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population. STUDY DESIGN: Multicenter, retrospective cohort study. SETTING & PARTICIPANTS: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). PREDICTORS: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score. OUTCOME: Time to kidney failure. ANALYTICAL APPROACH: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines. RESULTS: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure. LIMITATIONS: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding. CONCLUSIONS: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure.
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Complemento C3/inmunología , Glomerulonefritis Membranoproliferativa/patología , Túbulos Renales/patología , Insuficiencia Renal/patología , Adolescente , Adulto , Atrofia , Niño , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Fibrosis , Tasa de Filtración Glomerular , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/inmunología , Glomerulonefritis/metabolismo , Glomerulonefritis/patología , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Glomerulonefritis Membranoproliferativa/inmunología , Glomerulonefritis Membranoproliferativa/metabolismo , Humanos , Inmunosupresores/uso terapéutico , Riñón/patología , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Proteinuria , Insuficiencia Renal/inmunología , Insuficiencia Renal/metabolismo , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto JovenRESUMEN
aHUS is a rare disease characterized by episodes of TMA that frequently progresses to CKD and often recurs after KT. The most frequent cause of aHUS is defective regulation of complement activation because of genetic anomalies. Eculizumab interrupts the process of TMA and improves renal function. We describe one female patient with aHUS who debuted in 2005 at 3-mo-old with extrarenal manifestations and progressed to end-stage kidney disease (ESKD) within a year. Her family history included several affected members with similar bad outcomes. Our patient carries a strong aHUS genetic predisposition consisting in a pathogenic gain-of-function mutation in complement factor B concurrent with the MCP aHUS risk haplotype MCPggaac. She received a kidney transplant in 2011 without eculizumab prophylaxis. The graft, which was negative for the MCPggaac risk haplotype, had an unexpected excellent evolution without aHUS recurrence. Different retrospective studies have shown that the risk of aHUS recurrence after KT correlates well with the genetic load of aHUS risk factors. Knowing important contribution of the MCPggaac risk haplotype to the risk of developing aHUS in Factor B mutations carriers, we speculate whether the absence of this polymorphism in the graft that our patient received may have decreased the risk of aHUS recurrence after KT.
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Síndrome Hemolítico Urémico Atípico/genética , Trasplante de Riñón , Proteína Cofactora de Membrana/genética , Polimorfismo Genético , Femenino , Humanos , Lactante , Linaje , Medición de RiesgoRESUMEN
This study assessed the intra-individual reliability of oxygen saturation in intercostal muscles (SmO2-m.intercostales) during an incremental maximal treadmill exercise by using portable NIRS devices in a test-retest study. Fifteen marathon runners (age, 24.9 ± 2.0 years; body mass index, 21.6 ± 2.3 kg·m-2; VÌO2-peak, 63.7 ± 5.9 mL·kg-1·min-1) were tested on two separate days, with a 7-day interval between the two measurements. Oxygen consumption (VÌO2) was assessed using the breath-by-breath method during the VÌO2-test, while SmO2 was determined using a portable commercial device, based in the near-infrared spectroscopy (NIRS) principle. The minute ventilation (VE), respiratory rate (RR), and tidal volume (Vt) were also monitored during the cardiopulmonary exercise test. For the SmO2-m.intercostales, the intraclass correlation coefficient (ICC) at rest, first (VT1) and second ventilatory (VT2) thresholds, and maximal stages were 0.90, 0.84, 0.92, and 0.93, respectively; the confidence intervals ranged from -10.8% - +9.5% to -15.3% - +12.5%. The reliability was good at low intensity (rest and VT1) and excellent at high intensity (VT2 and max). The Spearman correlation test revealed (p ≤ 0.001) an inverse association of SmO2-m.intercostales with VÌO2 (ρ = -0.64), VE (ρ = -0.73), RR (ρ = -0.70), and Vt (ρ = -0.63). The relationship with the ventilatory variables showed that increased breathing effort during exercise could be registered adequately using a NIRS portable device.
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Ejercicio Físico/fisiología , Músculos Intercostales/fisiología , Consumo de Oxígeno/fisiología , Espectroscopía Infrarroja Corta/instrumentación , Trabajo Respiratorio/fisiología , Adulto , Rendimiento Atlético/fisiología , Prueba de Esfuerzo/métodos , Humanos , Masculino , Reproducibilidad de los Resultados , Frecuencia Respiratoria/fisiología , Carrera/fisiología , Volumen de Ventilación Pulmonar/fisiología , Adulto JovenRESUMEN
Malignant hypertension is listed among the causes of secondary thrombotic microangiopathy, but pathogenic mutations in complement genes have been reported in patients with hypertension-induced thrombotic microangiopathy. Here we investigated the frequency and severity of hypertension in 55 patients with primary atypical hemolytic uremic syndrome (aHUS). A genetic analysis was performed in all patients, and funduscopic examination was performed in all the patients with Grades 2 and 3 hypertension. A cohort of 110 patients with malignant hypertension caused by diseases other than aHUS served as control. Thirty-six patients with aHUS presented Grade 2 or Grade 3 hypertension and funduscopic examination showed malignant hypertension in 19. Genetic abnormalities in complement were found in 19 patients (37% among patients with malignant hypertension). Plasmapheresis was performed in 46 patients and 26 received eculizumab. Renal and hematological responses were significantly lower after plasmapheresis (24%) than after eculizumab (81%). Renal survival was significantly higher in patients treated with eculizumab (85% at one, three and five years) compared to patients who did not receive this treatment (54%, 46% and 41%), respectively. Response to eculizumab was independent of hypertension severity and the presence of complement genetic abnormalities. Among patients with malignant hypertension caused by other diseases the prevalence of thrombotic microangiopathy was very low (5%). Thus, severe and malignant hypertension are common among patients with aHUS and eculizumab treatment leads to a higher renal survival when compared to plasmapheresis. However, thrombotic microangiopathy is uncommon among patients presenting with malignant hypertension caused by diseases other than aHUS.
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Síndrome Hemolítico Urémico Atípico/complicaciones , Proteínas del Sistema Complemento/genética , Hipertensión Maligna/epidemiología , Índice de Severidad de la Enfermedad , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome Hemolítico Urémico Atípico/genética , Síndrome Hemolítico Urémico Atípico/terapia , Inactivadores del Complemento/uso terapéutico , Femenino , Humanos , Hipertensión Maligna/diagnóstico , Hipertensión Maligna/genética , Hipertensión Maligna/terapia , Incidencia , Masculino , Persona de Mediana Edad , Plasmaféresis , Estudios Retrospectivos , Adulto JovenRESUMEN
After opening, the Shaker voltage-gated potassium (KV) channel rapidly inactivates when one of its four N-termini enters and occludes the channel pore. Although it is known that the tip of the N-terminus reaches deep into the central cavity, the conformation adopted by this domain during inactivation and the nature of its interactions with the rest of the channel remain unclear. Here, we use molecular dynamics simulations coupled with electrophysiology experiments to reveal the atomic-scale mechanisms of inactivation. We find that the first six amino acids of the N-terminus spontaneously enter the central cavity in an extended conformation, establishing hydrophobic contacts with residues lining the pore. A second portion of the N-terminus, consisting of a long 24 amino acid α-helix, forms numerous polar contacts with residues in the intracellular entryway of the T1 domain. Double mutant cycle analysis revealed a strong relationship between predicted interatomic distances and empirically observed thermodynamic coupling, establishing a plausible model of the transition of KV channels to the inactivated state.
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Activación del Canal Iónico , Modelos Moleculares , Canales de Potasio con Entrada de Voltaje/metabolismo , Aminoácidos/química , Células HEK293 , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Simulación de Dinámica Molecular , Canales de Potasio con Entrada de Voltaje/química , Pliegue de Proteína , Estructura Secundaria de Proteína , Reproducibilidad de los Resultados , TermodinámicaRESUMEN
Fast uncaging of low affinity competitive receptor antagonists can in principle measure the timing and concentration dependence of transmitter action at receptors during synaptic transmission. Here, we describe the development, synthesis and characterization of MNI-caged γ-D-glutamyl-glycine (γ-DGG), which combines the fast photolysis and hydrolytic stability of nitroindoline cages with the well-characterized fast-equilibrating competitive glutamate receptor antagonist γ-DGG. At climbing fiber-Purkinje cell (CF-PC) synapses MNI-caged-γ-DGG was applied at concentrations up to 5 mM without affecting CF-PC transmission, permitting release of up to 1.5 mM γ-DGG in 1 ms in wide-field flashlamp photolysis. In steady-state conditions, photoreleased γ-DGG at 0.55-1.7 mM inhibited the CF first and second paired EPSCs by on average 30% and 60%, respectively, similar to reported values for bath applied γ-DGG. Photolysis of the L-isomer MNI-caged γ-L-glutamyl-glycine was ineffective. The time-course of receptor activation by synaptically released glutamate was investigated by timed photolysis of MNI-caged-γ-DGG at defined intervals following CF stimulation in the second EPSCs. Photorelease of γ-DGG prior to the stimulus and up to 3 ms after showed strong inhibition similar to steady-state inhibition; in contrast γ-DGG applied by a flash at 3-4 ms post-stimulus produced weaker and variable block, suggesting transmitter-receptor interaction occurs mainly in this time window. The data also show a small and lasting component of inhibition when γ-DGG was released at 4-7 ms post stimulus, near the peak of the CF-PC EPSC, or at 10-11 ms. This indicates that competition for binding and activation of AMPA receptors occurs also during the late phase of the EPSC, due to either delayed transmitter release or persistence of glutamate in the synaptic region. The results presented here first show that MNI-caged-γ-DGG has properties suitable for use as a synaptic probe at high concentration and that its photolysis can resolve timing and extent of transmitter activation of receptors in glutamatergic transmission.
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Few studies are focused on the antioxidant status and its changes in anorexia nervosa (AN). Based on the hypothesis that renutrition improves that status, the aim was to determine the plasma antioxidant status and the antioxidant enzymes activity at the beginning of a personalized nutritional program (T0) and after recovering normal body mass index (BMI) (T1). The relationship between changes in BMI and biochemical parameters was determined. Nutritional intake, body composition, anthropometric, hematological and biochemical parameters were studied in 25 women with AN (19.20 ± 6.07 years). Plasma antioxidant capacity and antioxidant enzymes activity were measured. Mean time to recover normal weight was 4.1 ± 2.44 months. Energy, macronutrients and micronutrients intake improved. Catalase activity was significantly modified after dietary intake improvement and weight recovery (T0 = 25.04 ± 1.97 vs. T1 = 35.54 ± 2.60 µmol/min/mL; p < 0.01). Total antioxidant capacity increased significantly after gaining weight (T0 = 1033.03 ± 34.38 vs. T1 = 1504.61 ± 99.73 µmol/L; p < 0.01). Superoxide dismutase activity decreased (p < 0.05) and glutathione peroxidase did not change. Our results support an association between nutrition improvement and weight gain in patients with AN, followed by an enhancement of antioxidant capacity and catalase antioxidant system.
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Anorexia Nerviosa/dietoterapia , Antioxidantes/metabolismo , Estado Nutricional , Aumento de Peso , Adolescente , Adulto , Anorexia Nerviosa/sangre , Composición Corporal , Índice de Masa Corporal , Catalasa/sangre , Carbohidratos de la Dieta/administración & dosificación , Grasas de la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Ingestión de Energía , Femenino , Glutatión Peroxidasa/sangre , Humanos , Micronutrientes/administración & dosificación , Micronutrientes/sangre , Superóxido Dismutasa/sangre , Adulto JovenRESUMEN
The association between interstitial lung disease and polymyositis/dermatomyositis is well known. It severely affects patients' quality of life, worsens prognosis and represents a major risk factor for premature death. Current treatment is unclear and therapeutic options are based on case series. We report the case of a 15-year old female diagnosed with end-stage lung disease associated to polymyositis who received a double lung transplant after 20 days of extracorporeal membrane oxygenation. She died 9 months later and microscopic post-mortem findings revealed recurrence of interstitial lung disease. This is the first time that recurrence of polymyositis-associated lung disease following lung transplantation is described in the literature.
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Enfermedades Pulmonares Intersticiales/cirugía , Trasplante de Pulmón/efectos adversos , Polimiositis/cirugía , Adolescente , Resultado Fatal , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/etiología , Polimiositis/complicaciones , Polimiositis/diagnóstico , Recurrencia , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Dense-deposit disease (DDD) is a rare glomerulopathy characterized by electron-dense deposits in the glomerular basement membrane. About 50 % of patients with DDD progress to end-stage kidney disease and require dialysis within 10 years of diagnosis, and the disease often recurs after renal transplantation. CASE-DIAGNOSIS/TREATMENT: We describe a 14-year-old girl with recurrent DDD in her transplanted kidney. Clinical onset was at 8 years of age, when steroid-resistant nephrotic syndrome was diagnosed with microhematuria, severe hypocomplementemia and normal kidney function. Although remission was initially observed after several plasma exchanges, nephrotic proteinuria returned and kidney function further declined 1 year later. The patient received a living-related kidney transplant. Initial allograft function was good, but proteinuria reappeared 3 months after transplantation, accompanied by a slight deterioration in kidney function. After histological confirmation of DDD recurrence and subsequent management with plasmapheresis, the patient was treated for 30 months with eculizumab, a humanized monoclonal antibody that binds to C5 complement protein. This intervention proved effective and resulted in complement inhibition, sustained remission of proteinuria and preservation of renal function. A graft biopsy 6 months later showed no progression of the renal lesions. CONCLUSIONS: Early clinical and histological recurrence of DDD in the transplanted kidney in this 14-year-old patient was treated for 30 months with eculizumab. The patient remains asymptomatic, has no proteinuria and her kidney function is intact.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Trasplante de Riñón , Adolescente , Femenino , Humanos , RecurrenciaRESUMEN
The systematic SAR study of a "caging" group showed a strong influence of the position of the donor dimethylamino group on the efficiency of photolysis of the DMAQ (2-hydroxymethylene-(N,N-dimethylamino)quinoline) caged acetate under one-photon near-UV or two-photon near-IR excitation. Photorelease of l-glutamate by the most efficient 8-DMAQ derivative strongly and efficiently activated glutamate receptors, generating large, fast rising responses similar to those elicited by glutamate photoreleased from the widely used MNI-caged glutamate.
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Glutamatos/química , Fotones , Quinolinas/química , Estructura Molecular , Fotólisis , Relación Estructura-ActividadRESUMEN
Photolysis is widely used in experimental neuroscience to isolate post-synaptic receptor activation from presynaptic processes, to determine receptor mechanisms in situ, for pharmacological dissection of signaling pathways, or for photostimulation/inhibition in neural networks. We have evaluated new caged neuroactive amino acids that use 4-methoxy-7-nitroindolinyl- (MNI) or 1-(2-nitrophenyl)ethoxycarbonyl (NPEC) photoprotecting groups to make caged ligands specific for glutamate receptor sub-types. Each was tested for interference with synaptic transmission and excitability and for receptor-specific actions in slice preparations. No adverse effects were found at glutamate receptors. At high concentration, MNI-caged, but not NPEC-caged ligands, interfered with GABA-ergic transmission. MNI-caged amino acids have sub-microsecond release times suitable for investigating mechanisms at fast synaptic receptors in situ. MNI-NMDA and MNI-kainate were synthesized and tested. MNI-NMDA showed stoichiometric release of chirally pure NMDA. Wide-field photolysis in cerebellar interneurons produced a fast-rising sustained activation of NMDA receptors, and localized laser photolysis gave a fast, transient response. Photolysis of MNI-kainate to release up to 4 µM kainate generated large inward currents at resting membrane potential in Purkinje neurons. Application of GYKI 53655 indicated that 40% of the current was due to AMPA receptor activation by kainate. Signaling via metabotropic glutamate receptors (mGluR) does not require fast release rates. NPEC cages are simpler to prepare but have slower photorelease. Photolysis of NPEC-ACPD or NPEC-DHPG in Purkinje neurons generated slow inward currents blocked by the mGluR type 1 antagonist CPCCOEt similar to the slow sEPSC seen with parallel fiber burst stimulation. NPEC-AMPA was also tested in Purkinje neurons and showed large sustained inward currents selective for AMPA receptors with little activation of kainate receptors. MNI-caged l-glutamate, NMDA and kainate inhibit GABA-A receptors with IC50 concentrations close to the maximum concentrations useful in receptor signaling experiments.
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Agonistas de Aminoácidos Excitadores/farmacología , Ácido Kaínico/análogos & derivados , N-Metilaspartato/análogos & derivados , Proteínas del Tejido Nervioso/agonistas , Receptores Ionotrópicos de Glutamato/agonistas , Animales , Cerebelo/efectos de los fármacos , Cerebelo/metabolismo , Potenciales Evocados/efectos de los fármacos , Agonistas de Aminoácidos Excitadores/efectos adversos , Agonistas de Aminoácidos Excitadores/efectos de la radiación , Antagonistas de Aminoácidos Excitadores/farmacología , Técnicas In Vitro , Indoles/química , Interneuronas/efectos de los fármacos , Interneuronas/metabolismo , Ácido Kaínico/efectos adversos , Ácido Kaínico/farmacología , Ácido Kaínico/efectos de la radiación , Ligandos , N-Metilaspartato/efectos adversos , N-Metilaspartato/farmacología , N-Metilaspartato/efectos de la radiación , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Proteínas del Tejido Nervioso/metabolismo , Nitrocompuestos/química , Fotólisis , Isoformas de Proteínas/agonistas , Isoformas de Proteínas/metabolismo , Células de Purkinje/efectos de los fármacos , Células de Purkinje/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Ionotrópicos de Glutamato/antagonistas & inhibidores , Receptores Ionotrópicos de Glutamato/metabolismo , Transmisión Sináptica/efectos de los fármacos , Rayos UltravioletaRESUMEN
Although it has been described in adults that renal grafts in the context of CLKT have a lower number of AR episodes and improved renal allograft survival, this has never been examined in pediatrics. We performed a single center retrospective case-control study examining 10 patients aged 10+/-6 yr with a CLKT that survived the post-surgery period of six months, and compared outcomes to a group of 20 KO transplants matched for age, era, and immunosuppression. We observed a significant reduction in the incidence of AR episodes in the CLKT group. To evaluate whether or not this experience was reproducible nationally, we performed an analysis of the 1995-2005 UNOS database. As of March 2007, 111 CLKT and 3798 KO transplants were identified from the OPTN/UNOS data. There was a significant improvement in the late kidney graft survival at five yr post-transplant in the CLKT group. These findings support the concept that liver transplantation is immunologically protective of the kidney allograft in CLKT.
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Rechazo de Injerto/inmunología , Trasplante de Riñón/inmunología , Trasplante de Hígado/inmunología , Adolescente , Factores de Edad , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Rechazo de Injerto/mortalidad , Supervivencia de Injerto , Humanos , Incidencia , Lactante , Trasplante de Riñón/mortalidad , Trasplante de Hígado/mortalidad , Los Angeles/epidemiología , Masculino , Sistema de Registros , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Mutations in the TRPC6 gene have been reported in six families with adult-onset (17-57 years) autosomal dominant focal segmental glomerulosclerosis (FSGS). Electrophysiology studies confirmed augmented calcium influx only in three of these six TRPC6 mutations. To date, the role of TRPC6 in childhood and adulthood non-familial forms is unknown. METHODS: TRPC6 mutation analysis was performed by direct sequencing in 130 Spanish patients from 115 unrelated families with FSGS. An in silico scoring matrix was developed to evaluate the pathogenicity of amino acid substitutions, by using the bio-physical and bio-chemical differences between wild-type and mutant amino acid, the evolutionary conservation of the amino acid residue in orthologues, homologues and defined domains, with the addition of contextual information. RESULTS: Three new missense substitutions were identified in two clinically non-familial cases and in one familial case. The analysis by means of this scoring system allowed us to classify these variants as likely pathogenic mutations. One of them was detected in a female patient with unusual clinical features: mesangial proliferative FSGS in childhood (7 years) and partial response to immunosupressive therapy (CsA + MMF). Asymptomatic carriers of this likely mutation were found within her family. CONCLUSIONS: We describe for the first time TRPC6 mutations in children and adults with non-familial FSGS. It seems that TRPC6 is a gene with a very variable penetrance that may contribute to glomerular diseases in a multi-hit setting.
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Glomeruloesclerosis Focal y Segmentaria/genética , Canales Catiónicos TRPC/genética , Adolescente , Adulto , Niño , Preescolar , Análisis Mutacional de ADN , Femenino , Humanos , Lactante , Persona de Mediana Edad , Canal Catiónico TRPC6 , Adulto JovenRESUMEN
STUDY OBJECTIVE: To evaluate the incidence and impact on clinical outcome of complications observed during high-frequency jet ventilation (HFJV) at interventional bronchoscopy and to identify the perioperative factors that may be associated to an increased incidence of such complications. DESIGN: Observational retrospective, study with an observational prospective validation of the statistically significant associations. SETTING: University hospital. PATIENTS: The retrospective study involved 276 patients who underwent an interventional rigid bronchoscopy during general anesthesia and HFJV. Forty consecutive patients were accrued for the prospective validation group. INTERVENTIONS/MEASUREMENTS: Information recorded included patient medical history and perioperative complications observed at HFJV-managed bronchoscopic procedures and their impact on clinical outcome until hospital discharge. MAIN RESULTS: At least one complication was detected in 38% of retrospective patients and 55% of prospective patients. Most frequent complications were hypercapnia, hypoxemia, and hemodynamic instability, but just one case of barotrauma in the retrospective group. Despite the high incidence, these complications were transient and did not increase hospital stay, whereas technical failure to widen airway lumen was associated with an adverse prognosis. Several clinical parameters showed a significant association with complications in the univariate analysis. However, the multivariate analysis only evidenced two independent predictive factors: the ASA physical status scale and baseline oxygen saturation. CONCLUSIONS: Classification in ASA physical status IV group and a baseline oxygen saturation of 95% or less independently predicted the development of complications during interventional rigid bronchoscopy with HFJV.