RESUMEN
Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross-validated by QPCR in the NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q-PCR analysis of a five gene-set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training-set (n = 47) and validated on independent test-set (n = 198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non-AR phenotypes with 91% sensitivity and 90% specificity. The 5-gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool.
Asunto(s)
Rechazo de Injerto/diagnóstico , Trasplante de Riñón , Enfermedad Aguda , Rechazo de Injerto/sangre , Humanos , Reacción en Cadena de la Polimerasa , Sensibilidad y EspecificidadRESUMEN
To determine whether steroid avoidance in pediatric kidney transplantation is safe and efficacious, a randomized, multicenter trial was performed in 12 pediatric kidney transplant centers. One hundred thirty children receiving primary kidney transplants were randomized to steroid-free (SF) or steroid-based (SB) immunosuppression, with concomitant tacrolimus, mycophenolate and standard dose daclizumab (SB group) or extended dose daclizumab (SF group). Follow-up was 3 years posttransplant. Standardized height Z-score change after 3 years follow-up was -0.99 ± 2.20 in SF versus -0.93 ± 1.11 in SB; p = 0.825. In subgroup analysis, recipients under 5 years of age showed improved linear growth with SF compared to SB treatment (change in standardized height Z-score at 3 years -0.43 ± 1.15 vs. -1.07 ± 1.14; p = 0.019). There were no differences in the rates of biopsy-proven acute rejection at 3 years after transplantation (16.7% in SF vs. 17.1% in SB; p = 0.94). Patient survival was 100% in both arms; graft survival was 95% in the SF and 90% in the SB arms (p = 0.30) at 3 years follow-up. Over the 3 year follow-up period, the SF group showed lower systolic BP (p = 0.017) and lower cholesterol levels (p = 0.034). In conclusion, complete steroid avoidance is safe and effective in unsensitized children receiving primary kidney transplants.
Asunto(s)
Inmunosupresores/administración & dosificación , Trasplante de Riñón , Esteroides/administración & dosificación , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Adulto JovenAsunto(s)
Síndrome Nefrótico/tratamiento farmacológico , Alquilantes/administración & dosificación , Alquilantes/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Niño , Ciclosporina/administración & dosificación , Ciclosporina/uso terapéutico , Diuréticos/administración & dosificación , Diuréticos/uso terapéutico , Resistencia a Medicamentos , Quimioterapia Combinada , Humanos , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/administración & dosificación , Hipolipemiantes/uso terapéutico , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Síndrome Nefrótico/diagnóstico , Síndrome Nefrótico/genética , Síndrome Nefrótico/fisiopatología , Esteroides/farmacología , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: While the use of continuous renal replacement therapies in the management of children with acute renal failure (ARF) has increased, the role of peritoneal dialysis (PD) in the treatment of pediatric ARF has received less attention. DESIGN: Retrospective database review of children requiring PD for ARF over a 10-year period. SETTING: Pediatric intensive care unit at a tertiary-care referral center. PATIENTS: Sixty-three children without previously known underlying renal disease who required PD for treatment of ARF. RESULTS: Causes of ARF were congestive heart failure (27), hemolytic-uremic syndrome (13), sepsis (10), nonrenal organ transplant (7), malignancy (3), and other (3). Mean duration of PD was 11 +/- 13 days. Children with ARF were younger (30 +/- 48 months vs 88 +/- 68 months old, p < 0.0001) and smaller (11.9 +/- 15.9 kg vs 28 +/- 22 kg, p < 0.0001) than children with known underlying renal disease who began PD during the same time period. Percutaneously placed PD catheters were used in 62% of children with ARF, compared to 4% of children with known renal disease (p < 0.0001). Hypotension was common in patients with ARF (46%), which correlated with a high frequency of vasopressor use (78%) at the time of initiation of PD. Complications of PD occurred in 25% of patients, the most common being catheter malfunction. Recovery of renal function occurred in 38% of patients; patient survival was 51%. CONCLUSIONS: Peritoneal dialysis remains an appropriate therapy for pediatric ARF from many causes, even in severely ill children requiring vasopressor support. Such children can be cared for without the use of more expensive and technology-dependent forms of renal replacement therapies.
Asunto(s)
Lesión Renal Aguda/terapia , Diálisis Peritoneal , Lesión Renal Aguda/etiología , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Diálisis Peritoneal/efectos adversos , Diálisis Peritoneal/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND: Podocytes are highly differentiated glomerular epithelial cells with limited potential to divide. They are responsible for maintaining and supporting the glomerular basement membrane so as to facilitate efficient filtration. The hypothesis tested was whether the development of glomerulosclerosis in the puromycin aminonucleoside (PAN)-treated rat could be attributed to podocyte depletion. METHODS: PAN was injected in Sprague-Dawley rats once, twice, or three times at 30-day intervals. Podocytes were counted in glomeruli using immunoperoxidase histochemistry and antibodies to both GLEPP1 (PTPRO) and WT-1. Podocytes were assayed in urine using reverse transcription-quantitative polymerase chain reaction (RT-QPCR). Glomerular areas were measured by computerized morphometry. RESULTS: In a preliminary experiment, a single injection of PAN caused a reduction in the glomerular podocyte count by 25%. Additional independent confirmation that podocytes were lost from glomeruli after PAN injection was obtained identifying detached podocytes in Bowman's space, measurement of nephrin and GLEPP1 mRNAs in urine, ultrastructural analysis of glomeruli, and identification of TUNEL-positive apoptotic podocytes in glomeruli. In a second experiment, sequential podocyte depletion by 15, 31, and 53% was achieved by the administration of one, two, or three injections of PAN at 30-day intervals. The region of the glomerulus devoid of podocytes developed glomerulosclerosis, and this area progressively increased as podocytes were progressively depleted. The correlation coefficient (r(2)) value for the relationship between percent podocyte depletion and glomerulosclerotic area was 0.99. The Y intercept of this plot showed that glomerulosclerosis was initiated when only 10 to 20% of podocytes were lost. CONCLUSION: This report supports the growing body of data linking glomerulosclerosis directly to a reduction in relative podocyte number [increased glomerular area per podocyte (GAPP)]. It raises important questions related to the mechanisms of podocyte loss, strategies for prevention of podocyte depletion, and the prevention of progression of glomerular diseases.
Asunto(s)
Glomeruloesclerosis Focal y Segmentaria/fisiopatología , Glomérulos Renales/fisiopatología , Puromicina Aminonucleósido , Animales , Recuento de Células , Células Epiteliales/efectos de los fármacos , Glomeruloesclerosis Focal y Segmentaria/inducido químicamente , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Podocalyxin is a CD34-related sialomucin that is expressed at high levels by podocytes, and also by mesothelial cells, vascular endothelia, platelets, and hematopoietic stem cells. To elucidate the function of podocalyxin, we generated podocalyxin-deficient (podxl(-/)-) mice by homologous recombination. Null mice exhibit profound defects in kidney development and die within 24 hours of birth with anuric renal failure. Although podocytes are present in the glomeruli of the podxl(-/)- mice, they fail to form foot processes and slit diaphragms and instead exhibit cell--cell junctional complexes (tight and adherens junctions). The corresponding reduction in permeable, glomerular filtration surface area presumably leads to the observed block in urine production. In addition, podxl(-/)- mice frequently display herniation of the gut (omphalocele), suggesting that podocalyxin may be required for retraction of the gut from the umbilical cord during development. Hematopoietic and vascular endothelial cells develop normally in the podocalyxin-deficient mice, possibly through functional compensation by other sialomucins (such as CD34). Our results provide the first example of an essential role for a sialomucin in development and suggest that defects in podocalyxin could play a role in podocyte dysfunction in renal failure and omphalocele in humans.
Asunto(s)
Anuria/genética , Muerte Fetal/genética , Hernia Umbilical/genética , Sialoglicoproteínas/genética , Animales , Antígenos CD34/metabolismo , Vasos Sanguíneos/embriología , Vasos Sanguíneos/metabolismo , Diafragma/anomalías , Edema/genética , Femenino , Regulación del Desarrollo de la Expresión Génica , Sistema Hematopoyético/embriología , Sistema Hematopoyético/metabolismo , Riñón/anomalías , Riñón/patología , Masculino , Ratones , Ratones Mutantes , Insuficiencia Renal/genética , Sialoglicoproteínas/metabolismoRESUMEN
OBJECTIVE: To examine the effect of intravenous nicardipine in the treatment of children with severe hypertension. METHODS: The medical records of 29 children (mean age 94 months) treated with intravenous nicardipine were retrospectively reviewed. The mean duration of severe hypertension before nicardipine use was 12.5 hours. Most (74%) patients were receiving other antihypertensive agents before nicardipine. RESULTS: The initial nicardipine dose was 0.8 +/- 0.3 microg/kg/min (mean +/- SD). The mean effective dose was 1.8 +/- 1.0 microg/kg/min (range, 0.3 to 4.0). Blood pressure control was achieved within 2.7 +/- 2.1 hours after nicardipine was started. Nicardipine treatment produced a 16% reduction in systolic blood pressure, a 23% reduction in diastolic blood pressure, and a 7% increase in heart rate. Nicardipine was effective as a single agent on 26 (84%) of 31 occasions. Adverse effects included tachycardia, flushing, palpitations, and hypotension. CONCLUSIONS: When administered in the intensive care unit setting with close patient monitoring, intravenous nicardipine effectively lowered blood pressure in children with severe hypertension. Larger prospective studies should be conducted to confirm these findings.
Asunto(s)
Antihipertensivos/administración & dosificación , Hipertensión/tratamiento farmacológico , Nicardipino/administración & dosificación , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Lactante , Infusiones Intravenosas , Unidades de Cuidado Intensivo Pediátrico , Masculino , Nicardipino/uso terapéutico , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: Henoch-Schönlein Purpura (HSP) is a common childhood vasculitis with manifestations in numerous organ systems, including glomerulonephritis. Patients with more severe HSP-associated glomerulonephritis may develop chronic renal failure. Currently, no widely accepted treatment protocols exist for patients with significant renal involvement. METHODS: We retrospectively reviewed the clinical courses of 12 children (mean age 9 years) with HSP glomerulonephritis treated with high-dose corticosteroids plus oral cyclophosphamide. All patients had nephrotic-range proteinuria, and all had significant histopathologic changes on biopsy, including crescentic nephritis in 10 patients. Treatment consisted of either intravenous pulse methylprednisolone or oral prednisone followed by oral cyclophosphamide (2 mg/kg/day) for 12 weeks, along with either daily or alternate-day oral prednisone. Prednisone was tapered following completion of cyclophsophamide. RESULTS: Serum albumin rose significantly after treatment from 2.8 +/- (SD) 0.5 to 3.7 +/- 0.4 g/dl (p < 0.001), and there was a concurrent reduction in proteinuria, as reflected by decreasing serial protein-to-creatinine ratios: from 6.3 +/- 4.4 to 0.8 +/- 0.8 (p = 0.002). Renal function remained normal in all patients. Hypertension developed during treatment in 10 patients, all but 1 of whom were normotensive at last follow-up, 35 +/- 17 months following biopsy. CONCLUSIONS: We conclude that treatment of children with HSP nephritis with high-dose corticosteroids plus oral cyclophosphamide is safe and, as in nephrotic syndrome, appears to significantly reduce proteinuria which is a known risk factor for the development of renal insufficiency in HSP. Further studies with larger numbers of patients should be conducted to confirm this finding.
Asunto(s)
Ciclofosfamida/administración & dosificación , Glomerulonefritis/tratamiento farmacológico , Vasculitis por IgA/tratamiento farmacológico , Metilprednisolona/administración & dosificación , Prednisona/administración & dosificación , Administración Oral , Adolescente , Niño , Preescolar , Esquema de Medicación , Quimioterapia Combinada , Femenino , Glomerulonefritis/etiología , Humanos , Vasculitis por IgA/complicaciones , Inyecciones Intravenosas , Masculino , Estudios Retrospectivos , Albúmina Sérica/análisisRESUMEN
Hemodialysis is the usual recommended treatment for severe lithium intoxication; however, rebound of lithium levels may require repeated hemodialysis treatments. We proposed that the addition of continuous hemofiltration after hemodialysis would prevent rebound by providing ongoing clearance of lithium. We report two pediatric patients with lithium intoxication treated by hemodialysis followed by continuous venovenous hemofiltration with dialysis (CVVHD). Both patients were symptomatic at presentation and had initial lithium levels more than three times the usual therapeutic range. Hemodialysis followed by CVVHD resulted in rapid resolution of symptoms, followed by continuous clearance of lithium without requiring repeated hemodialysis sessions. Both patients had return of normal mental status during CVVHD treatment, and neither patient experienced complications of hemodialysis or CVVHD. Total duration of treatment with hemodialysis followed by CVVHD was 34.5 hours for the first patient and 26 hours for the second patient. We conclude that hemodialysis followed by CVVHD is a safe and effective approach to the management of lithium intoxication in children.
Asunto(s)
Antimaníacos/envenenamiento , Hemodiafiltración/métodos , Litio/envenenamiento , Adolescente , Antimaníacos/sangre , Femenino , Humanos , Litio/sangre , Masculino , Intoxicación/terapiaRESUMEN
Glomerular epithelial protein 1 (GLEPP1) is a receptor tyrosine phosphatase present on the apical cell surface of the glomerular podocyte. The GLEPP1 gene (PTPRO:) was disrupted at an exon coding for the NH(2)-terminal region by gene targeting in embryonic stem cells. Heterozygote mating produced the expected genotypic ratio of 1:2:1, indicating that the Ptpro(-/-) genotype does not lead to embryonic or neonatal lethality. Kidney and glomerular structure was normal at the gross and light microscopic levels. Scanning and transmission electron microscopy showed that Ptpro(-/-) mice had an amoeboid rather than the typical octopoid structure seen in the wild-type mouse podocyte and that there were blunting and widening of the minor (foot) processes in association with altered distribution of the podocyte intermediate cytoskeletal protein vimentin. Reduced filtration surface area in association with these structural changes was confirmed by finding reduced glomerular nephrin content and reduced glomerular filtration rate in Ptpro(-/-) mice. There was no detectable increase in the urine albumin excretion of Ptpro(-/-) mice. After removal of one or more kidneys, Ptpro(-/-) mice had higher blood pressure than did their wild-type littermates. These data support the conclusion that the GLEPP1 (Ptpro) receptor plays a role in regulating the glomerular pressure/filtration rate relationship through an effect on podocyte structure and function.
Asunto(s)
Hipertensión/fisiopatología , Glomérulos Renales/fisiopatología , Proteínas de la Membrana/fisiología , Proteínas Tirosina Fosfatasas/fisiología , Albúminas/metabolismo , Animales , Células Epiteliales/ultraestructura , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Predisposición Genética a la Enfermedad , Genotipo , Tasa de Filtración Glomerular , Humanos , Hipertensión/genética , Hipertensión/metabolismo , Glomérulos Renales/citología , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Masculino , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fenotipo , Proteínas Tirosina Fosfatasas/genética , Proteínas/metabolismo , Ratas , Proteínas Tirosina Fosfatasas Clase 3 Similares a Receptores , Recombinación Genética , Sialoglicoproteínas/metabolismo , Vimentina/metabolismoRESUMEN
Achieving immunity to childhood viral infections before renal transplantation is crucial. However, children with chronic renal failure (CRF) may respond poorly to vaccination, making it difficult to achieve immunity before transplantation, particularly if they will require transplantation at a young age. To address this problem, we developed a protocol of early measles-mumps-rubella (MMR) vaccination in infants with CRF. Nine infants received MMR vaccine at a mean age of 11.6 +/- 2.5 months. When vaccinated, 6 of the children (67%) were on peritoneal dialysis, and 3 (33%) had CRF [glomerular filtration rate (GFR) < 30 mL/min/1.73 m2]. Eight patients were later transplanted at a mean age of 16.8 +/- 4.8 months. Titers were measured before transplantation in all patients. Response to vaccination was excellent, with 89% developing immunity to measles, 88% developing immunity to mumps, 100% developing immunity to rubella, and 88% developing immunity to all three components of the vaccine. These response rates were equivalent to, or slightly better than, those previously reported by Schulman for older children (19 +/- 6 months) on dialysis: 80% for measles, 50% for mumps, 100% for rubella, and 30% for all three components. We conclude that early MMR vaccination induces immunity in most infants with CRF, even those on peritoneal dialysis. Response rates are similar to those previously reported in older children. This approach may help to facilitate transplantation in young infants by achieving immunity earlier than traditional vaccination schedules.
Asunto(s)
Fallo Renal Crónico/inmunología , Vacuna Antisarampión/inmunología , Vacuna contra la Parotiditis/inmunología , Diálisis Peritoneal , Vacuna contra la Rubéola/inmunología , Adolescente , Niño , Femenino , Humanos , Fallo Renal Crónico/terapia , Trasplante de Riñón , Masculino , Sarampión/inmunología , Vacuna contra el Sarampión-Parotiditis-Rubéola , Paperas/inmunología , Rubéola (Sarampión Alemán)/inmunología , Vacunación , Vacunas Combinadas/inmunologíaRESUMEN
OBJECTIVE: The validity of supplementing the three-item recall portion of the Mini-Mental State Examination (MMSE) with a cued recall procedure to help specify the nature of patients' memory problems was examined. METHOD: Subjects were 247 individuals representing three diagnostic groups: Alzheimer's disease (AD), subcortical vascular ischemic dementia (SVaD), and normal controls. Individuals were administered a battery of neuropsychological tests, including the MMSE, as part of a comprehensive evaluation for the presence of dementia or other neurologic disorder. RESULTS: MMSE performance differed among groups. The three-item free recall performance also differed among groups, with post hoc analyses revealing the AD and SVaD groups were more impaired than controls but did not differ significantly from each other. Following a cued recall procedure of the MMSE three-items, groups differed, with post hoc analyses showing that AD patients failed to benefit from cues, whereas SVaD patients performed significantly better and comparable to control subjects. Significant correlations between the MMSE three-item cued recall performance and other memory measures demonstrated concurrent validity. CONCLUSIONS: Consistent with previous research indicating that SVaD is associated with memory encoding and retrieval deficits, whereas AD is associated with consolidation and storage problems, the present study supported the validity of the cued recall procedure of the three items on the MMSE in helping to distinguish between patients with AD and those with a vascular dementia with primarily subcortical pathology; however, despite these findings, a more extensive battery of neuropsychological measures is still recommended to consistently assess subtle diagnostic differences in these memory processes.
Asunto(s)
Enfermedad de Alzheimer/psicología , Demencia Vascular/psicología , Recuerdo Mental , Escala del Estado Mental/normas , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/diagnóstico , Demencia Vascular/clasificación , Demencia Vascular/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
A reverse transcriptase-polymerase chain reaction (RT-PCR) and microplate-reverse hybridization method were developed to detect and type dengue viruses in patients plasma specimens. A silica method was used to isolate RNA; and 3'-noncoding region universal primers were used to amplify dengue virus RNA. Using RT-PCR and ethidium bromide staining we could detect dengue virus in serum spiked with serially diluted dengue virus with a level of sensitivity similar to that of a quantitative fluorescent focus assay of dengue viruses in cell culture, i.e. 1.4 fluorescent focus units per reaction. Applying this assay to 14 dengue-positive plasma samples and 13 dengue-negative samples, dengue viremia was detectable by RT-PCR with a sensitivity comparable to mosquito inoculation. To determine the serotypes, digoxigenin-labeled PCR products from plasma samples and six laboratory adapted dengue viruses were hybridized in stringent conditions to serotype-specific DNA probes immobilized on microplates, and the hybridized product was detected with a colorimetric assay. Serotypes of dengue viruses, in cell culture and in patient plasma specimens, were identified using this method.
Asunto(s)
Virus del Dengue/clasificación , Virus del Dengue/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Dengue/virología , Etidio , Humanos , ARN Viral/sangre , Sensibilidad y Especificidad , Serotipificación , Coloración y EtiquetadoRESUMEN
Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell (VGEC) foot processes. Double label immunofluorescence, immunoelectron microscopy, and peroxidase immunohistochemistry were used to map the GLEPP1 distribution in the developing glomerulus and in minimal-change nephropathy (MCN), congenital nephrotic syndrome of the Finnish type, and focal-segmental glomerulosclerosis (FSGS). In MCN GLEPP1 was shifted away from the glomerular basement membrane on the apical cell membrane of effaced foot processes. These data are compatible with the previously suggested concept that MCN can be considered a form of dedifferentiation of the podocyte phenotype. Similarly, changes seen in congenital nephrotic syndrome of the Finnish type can be considered a consequence of failure to complete normal podocyte development. In FSGS glomeruli GLEPP1 was frequently absent from VGECs, even when no sclerosis was detectable in that glomerulus. Therefore, in FSGS, VGECs may lose GLEPP1, and this loss appears to occur in the absence of scarring and may, therefore, precede the scarring process. We speculate that a changed VGEC phenotype that does not express GLEPP1 might have properties similar to the early undifferentiated VGEC developmental phenotype. GLEPP1 distribution pattern and absence from glomeruli of individuals with nephrotic syndrome may, therefore, represent a useful phenotypic marker.
Asunto(s)
Glomeruloesclerosis Focal y Segmentaria/patología , Glomérulos Renales/química , Glomérulos Renales/embriología , Proteínas de la Membrana/análisis , Síndrome Nefrótico/patología , Proteínas Tirosina Fosfatasas/análisis , Animales , Animales Recién Nacidos , Anticuerpos Monoclonales , Biomarcadores , Técnica del Anticuerpo Fluorescente , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Humanos , Técnicas para Inmunoenzimas , Inmunofenotipificación , Glomérulos Renales/ultraestructura , Proteínas de la Membrana/genética , Proteínas de la Membrana/inmunología , Ratones , Microscopía Inmunoelectrónica , Nefrosis Lipoidea/metabolismo , Nefrosis Lipoidea/patología , Síndrome Nefrótico/metabolismo , Fenotipo , Proteínas Tirosina Fosfatasas/genética , Proteínas Tirosina Fosfatasas/inmunología , Conejos , Proteínas Tirosina Fosfatasas Clase 3 Similares a ReceptoresRESUMEN
The leukocyte adhesion molecule, L-selectin, mediates the recruitment of lymphocytes to secondary lymphoid organs via interactions with specific ligands presented on high endothelial venules (HEV). Although the HEV-derived ligands for L-selectin are still incompletely defined, they share a common sialomucin-like structure which is thought to present clustered oligosaccharides to the lectin domain of L-selectin. Podocalyxin-like protein (PCLP) is a transmembrane sialomucin that is similar in structure to the well-characterized L-selectin ligand CD34. PCLP has been shown previously to be expressed on the foot processes of podocytes in the kidney glomerulus as well as on vascular endothelium at some sites. We have determined that PCLP is present on HEV, where it binds to both recombinant L-selectin and the HEV-specific monoclonal antibody MECA-79. Furthermore, purified HEV-derived PCLP is able to support the tethering and rolling of lymphocytes under physiological flow conditions in vitro. These results suggest a novel function for PCLP as an adhesion molecule and allow the definition of conserved structural features in PCLP and CD34, which may be important for L-selectin ligand function.
Asunto(s)
Endotelio Linfático/metabolismo , Selectina L/metabolismo , Sistema Linfático/metabolismo , Glicoproteínas de Membrana/metabolismo , Secuencia de Aminoácidos , Antígenos de Superficie/inmunología , Antígenos de Superficie/metabolismo , Apéndice/química , Apéndice/metabolismo , Endotelio Linfático/química , Epítopos , Humanos , Células Jurkat , Ligandos , Sistema Linfático/química , Glicoproteínas de Membrana/inmunología , Glicoproteínas de Membrana/aislamiento & purificación , Proteínas de la Membrana , Datos de Secuencia Molecular , Tonsila Palatina/química , Tonsila Palatina/metabolismo , Unión Proteica , Receptores Mensajeros de Linfocitos/metabolismo , Homología de Secuencia de Aminoácido , SialoglicoproteínasRESUMEN
Neoral was instituted in pediatric renal transplant patients with the hypothesis it would have more predictable kinetics than Sandimmun. However, significant questions have arisen concerning potential toxicity and dosing interval related to its rapid absorption with subsequent high initial peak. This is compounded by the fact that children appear to metabolize cyclosporine at a greater rate than adults. This combination of a rapid peak and rapid absorption may then result in lower trough levels at 12 h. We compared the trough cyclosporine levels of nine children who received Neoral with nine who received Sandimmun at the time of initial transplantation. More frequent dosing (every 8 h) was required in the Neoral population compared with the Sandimmun population for the 1st month in order to obtain comparable trough levels. Beyond the initial 4-6 weeks, trough levels were similar for Neoral and Sandimmun. Whereas 1-month creatinine levels and blood pressures were similar, the number of blood pressure medications was significantly higher in the Neoral group. At 5.5 +/- 1.1 months' followup, a single patient in the current Neoral group and in the retrospective Sandimmun group each experienced a single OKT3 allograft-treated rejection. We suggest that the area under the curve is different in Neoral than Sandimmun, and the initial dosing frequency may need to be adjusted accordingly.
Asunto(s)
Ciclosporina/uso terapéutico , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Riñón/inmunología , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Niño , Ciclosporina/efectos adversos , Ciclosporina/farmacocinética , Femenino , Rechazo de Injerto/patología , Rechazo de Injerto/fisiopatología , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/farmacocinética , MasculinoRESUMEN
Vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCA) can be accompanied by a focal and necrotizing glomerulonephritis that carries a high morbidity. As many as 60% of reported children with ANCA-associated glomerulonephritis progress to end-stage renal disease. Seven children (13.0+/-0.89 years, mean age +/- SEM) with both a focal and necrotizing glomerulonephritis and a positive ANCA titer are described. Presenting symptoms were constitutional (100%) and sinopulmonary (71%); additional renal features included microscopic hematuria (100%), proteinuria (71%), and renal insufficiency (71%). Acute therapy (0 to 2 weeks from diagnosis) included intravenous corticosteroids and intravenous cyclophosphamide for all patients. Induction therapy (2 weeks to 6 months from diagnosis) consisted of cyclophosphamide (100%) and daily corticosteroids (86%) for a minimum of 6 months. Maintenance therapy that followed 6 months of induction therapy consisted of alternate day steroids (100%) combined with either oral azathioprine (50%) or oral cyclophosphamide (50%). Long-term follow-up for 48+/-12 months in all seven patients revealed that only one (14%) patient had end-stage renal disease, whereas the remaining patients had microscopic hematuria (100%), proteinuria (50%), and renal insufficiency (33%). These findings suggest that early recognition and aggressive treatment of children with ANCA-associated glomerulonephritis and vasculitis may result in an improved renal outcome compared with previous reports.
Asunto(s)
Glomerulonefritis/terapia , Vasculitis/terapia , Adolescente , Anticuerpos Anticitoplasma de Neutrófilos , Niño , Ciclofosfamida/uso terapéutico , Femenino , Glomerulonefritis/complicaciones , Glomerulonefritis/inmunología , Glomerulonefritis/fisiopatología , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Pruebas de Función Renal , Masculino , Metilprednisolona/uso terapéutico , Estudios Retrospectivos , Vasculitis/complicaciones , Vasculitis/inmunología , Vasculitis/fisiopatologíaRESUMEN
To respond to the difficulties that community-based providers face in keeping abreast of the rapid changes in HIV-related care, an intensive pediatric HIV mentoring program (Pediatric HIV Miniresidency [MR]) was developed, linking a regional AIDS Education and Training Center (AETC) with an urban children's hospital HIV outpatient care site. The purpose of this study was to evaluate HIV-related knowledge and perceived skills, abilities, and willingness of community-based primary care pediatric providers and providers completing the MR. A convenience sample of community-based primary pediatric practitioners and those participants in the MR program completed a three-part mailed survey. The survey assessed practice characteristics, knowledge of pediatric HIV clinical care, and perceived skills, ability, and willingness (PSAW) to provide HIV-related care. The main outcome measures were overall knowledge and PSAW scores. One hundred nineteen community-based practitioners (NMRs), 20% of those surveyed, completed the instrument, as did 19 of 20 MR participants. NMRs exhibited low knowledge scores in key areas relating to the identification and evaluation of HIV-exposed children. Fewer than half of these respondents correctly answered questions related to HIV antibody incidence in HIV-exposed newborns and recommended diagnostic testing of such infants. Providers completing the MR scored significantly higher on the knowledge survey (15.2 vs. 8.8, p < 0.001), and had higher PSAW scores (45.8 vs. 33.9, p < 0.001). Although the generalizability of our study is limited by the low response rate, community-based physicians completing the survey demonstrated a lack of knowledge we believe necessary to provide pediatric HIV-related care (as defined by Public Health Service practice guidelines). Physicians completing the MR program had substantial HIV-related knowledge and expressed a willingness to provide care to HIV-exposed/infected children. An effective MR program provides a mechanism for developing a network of dedicated community-based physicians who are willing and capable of providing care to HIV-infected or exposed infants and children.
Asunto(s)
Competencia Clínica/estadística & datos numéricos , Educación Médica Continua , Infecciones por VIH/terapia , Conocimientos, Actitudes y Práctica en Salud , Pediatría/educación , Atención Primaria de Salud/métodos , Síndrome de Inmunodeficiencia Adquirida/terapia , Adulto , Niño , Preescolar , Recolección de Datos , Femenino , Humanos , Lactante , Masculino , Evaluación de Resultado en la Atención de Salud , Pediatría/métodos , PennsylvaniaRESUMEN
Estimating a person's premorbid cognitive abilities is common practice as part of a dementia assessment. Vocabulary has traditionally served as a "hold" measure because of its relative resilience to neurologic impairment and aging and its high correlation with overall intellectual functioning. Normative data for the Vocabulary subtest of the Shipley Institute of Living Scale (SILS) only go to age 64. This study describes the relations among age, gender, education, and SILS Vocabulary subtest performance. Normative data and Wechsler Adult Intelligence Scale-Revised equivalent Full-Scale IQ scores are reported for SILS Vocabulary subtest performance for a sample of 383 nonimpaired community-dwelling older adults, ranging in age from 60 to 94. Results expand the utility of the Vocabulary subtest of the SILS in providing an estimated level of premorbid cognitive ability.
RESUMEN
Use of intraperitoneal insulin in diabetic end-stage renal disease (ESRD) patients receiving continuous ambulatory peritoneal dialysis (CAPD) is known to result in improved glycemic control. This route of insulin administration, although standard in adult diabetic CAPD patients, has not previously been reported in children. A 12-year old boy with ESRD from renal dysplasia who also had insulin-dependent diabetes mellitus (IDDM) was treated with CAPD and intraperitoneal insulin prior to renal transplantation. Diabetes and renal dysplasia were both diagnosed at 11 weeks of age. When he reached end-stage he was initially started on hemodialysis via a central line but was switched to CAPD because of recurrent line sepsis. His IDDM had been poorly controlled up to that time. CAPD was performed using 4 exchanges per day of 1.5% dialysate with a fixed dose of insulin added to each bag and with adjustments made based on blood glucose. His glycemic control markedly improved, with a fall in his glycosylated hemoglobin from 13.6% to 6%. CAPD was continued for 7 months until a living-related renal transplant was performed. Two episodes of peritonitis occurred while the patient received CAPD (1 episode/3.5 patient-months). We conclude that the use of intraperitoneal insulin in children with IDDM and ESRD leads to improved glycemic control. The rate of peritonitis, however, may be increased in these children.