RESUMEN
Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive enzyme defect of purine metabolism that usually manifests as 2,8-dihydroxyadenine (2,8-DHA) nephrolithiasis and more rarely chronic kidney disease. The disease is most often misdiagnosed and can recur in the renal allograft. We analyzed nine patients with recurrent 2,8-DHA crystalline nephropathy, in all of whom the diagnosis had been missed prior to renal transplantation. The diagnosis was established at a median of 5 (range 1.5-312) weeks following the transplant procedure. Patients had delayed graft function (n=2), acute-on-chronic (n=5) or acute (n=1) allograft dysfunction, whereas one patient had normal graft function at the time of diagnosis. Analysis of allograft biopsies showed birefringent 2,8-DHA crystals in renal tubular lumens, within tubular epithelial cells and interstitium. Fourier transformed infrared microscopy confirmed the diagnosis in all cases, which was further supported by 2,8-DHA crystalluria, undetectable erythrocyte APRT enzyme activity, and genetic testing. With allopurinol therapy, the allograft function improved (n=7), remained stable (n=1) or worsened (n=1). At last follow-up, two patients had experienced allograft loss and five had persistent chronic allograft dysfunction. 2,8-DHA nephropathy is a rare but underdiagnosed and preventable disorder that can recur in the renal allograft and may lead to allograft loss.
Asunto(s)
Adenina Fosforribosiltransferasa/deficiencia , Rechazo de Injerto , Trasplante de Riñón , Errores Innatos del Metabolismo/etiología , Urolitiasis/etiología , Adulto , Anciano , Femenino , Humanos , Masculino , Errores Innatos del Metabolismo/fisiopatología , Persona de Mediana Edad , Recurrencia , Urolitiasis/fisiopatologíaRESUMEN
Peroxisome proliferator activated receptors (PPARs) are nuclear receptors regulating the expression of genes involved in lipid and glucose metabolism. Three different PPARs; alpha (PPARA), gamma (PPARG) and delta (PPARD) have been characterized and they are distinguished from each other by tissue distribution and cell activation. In this study, the structure and detailed chromosomal localization of the human PPARD gene was determined. Three genomic clones containing the PPARD gene was isolated from a human P1 library. The gene spans approximately 85 kb of DNA and consists of 9 exons and 8 introns with exons ranging in size from 84 bp to 2.3 kb and introns ranging from 180 bp to 50 kb. All splice acceptor and donor sites conform to the consensus sequences including the AG-GT motif. Although PPARD lacks a TATA box, the gene is transcribed from a unique start site located 380 bp upstream of the ATG initiation codon. The 5' and 3' ends were mapped by rapid amplification of cDNA ends and the mRNA size of PPARD based upon the structure of the gene is 3803 bp. In addition, the chromosomal sublocalization of PPARD was determined by radiation hybrid mapping. The PPARD gene is located at 14 cR from the colipase gene and 15 cR from the serine kinase gene at chromosomal region 6p21.2.
Asunto(s)
Receptores Citoplasmáticos y Nucleares/genética , Factores de Transcripción/genética , Adulto , Autorradiografía , Secuencia de Bases , Northern Blotting , Cromosomas Humanos Par 6 , Exones , Humanos , Intrones , Datos de Secuencia Molecular , Especificidad de Órganos , Mapeo Físico de Cromosoma , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas , ARN Mensajero/análisis , Receptores Citoplasmáticos y Nucleares/metabolismo , Análisis de Secuencia de ADN , Factores de Transcripción/metabolismoRESUMEN
Rowell's syndrome is believed to be a distinct and rare clinical entity originally described as lupus erythematosus associated with erythema multiforme-like lesions with immunological findings of speckled antinuclear antibodies, anti-La antibodies and a positive test for rheumatoid factor. We report two additional patients with Rowell's syndrome and review all the diagnostic criteria found in the literature. In view of the inconsistent findings of some of the diagnostic features, we propose that major and minor criteria be used to diagnose Rowell's syndrome.
Asunto(s)
Eritema Multiforme/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico , Eritema Multiforme/patología , Femenino , Humanos , Lupus Eritematoso Sistémico/patología , Persona de Mediana Edad , SíndromeRESUMEN
BACKGROUND: Calciphylaxis is a rare condition occurring most frequently in patients with end-stage renal disease (ESRD). It is characterized by vascular calcifications with a large variety of skin lesions. Even though this entity was first reported almost 50 years ago, the pathogenesis is still not well understood. OBJECTIVE: Having retrieved seven new cases from a single tertiary care hospital, the disease occurs probably more frequently than reported until now. The potential mechanism of action in this disease is discussed, particularly the hypercoagulability state. We also review potential treatments described in the literature. METHODS: Seven patients with calciphylaxis that occurred at the Hôtel-Dieu hospital between 1992 and 1998 were identified and their case histories reviewed and analyzed. CONCLUSION: Although hyperparathyroidism and imbalance of calcium-phosphorus homeostasis are paramount for calciphylaxis to occur, other mechanisms must be involved because the disease manifests itself in only a minority of ESRD patients. As the majority were under anticoagulation therapy and as we found abnormalities of the coagulation pathway in one patient, we suggest emphasizing these phenomena in the future. Along with evaluation of putative risk factors (abnormalities of the calcium:phosphate axis, diabetes), a detailed evaluation of the coagulation system should be done in every patient with calciphylaxis until more data are available.
Asunto(s)
Calcifilaxia , Adulto , Anciano , Calcifilaxia/complicaciones , Calcifilaxia/diagnóstico , Calcifilaxia/fisiopatología , Resultado Fatal , Femenino , Humanos , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana EdadRESUMEN
Community asthma care centers have been introduced to meet the increasing need for community-based assessment, management, and education of patients with asthma. The Asthma Education Centre at Oakville-Trafalgar Hospital, in Ontario, Canada, has implemented a comprehensive assessment, treatment, and education program with a collection of relevant patient data. The findings presented in this article suggest that these specific education and treatment programs are associated with not only significant reductions in the use of health services, but improvements in health outcomes as well.
Asunto(s)
Asma/terapia , Centros Comunitarios de Salud/organización & administración , Evaluación de Resultado en la Atención de Salud , Educación del Paciente como Asunto/organización & administración , Adolescente , Asma/fisiopatología , Niño , Preescolar , Centros Comunitarios de Salud/estadística & datos numéricos , Manejo de la Enfermedad , Investigación sobre Servicios de Salud , Humanos , Lactante , Ontario , Servicio Ambulatorio en Hospital/organización & administración , Admisión del Paciente/estadística & datos numéricos , Autocuidado , Encuestas y CuestionariosRESUMEN
Lipoprotein lipase (LPL) is crucial in the hydrolysis of triglycerides (TG) in TG-rich lipoproteins in the formation of HDL particles. As both these lipoproteins play an important role in the pathogenesis of atherosclerotic vascular disease, we sought to assess the relationship between post-heparin LPL (PH-LPL) activity and lipids and lipoproteins in a large, well-defined cohort of Dutch males with coronary artery disease (CAD). These subjects were drawn from the REGRESS study, totaled 730 in number and were evaluated against 75 healthy, normolipidemic male controls. Fasting mean PH-LPL activity in the CAD subjects was 108 46 mU/ml, compared to 138 44 mU/ml in controls (P < 0.0001). When these patients were divided into activity quartiles, those in the lowest versus the highest quartile had higher levels of TG (P < 0.001), VLDLc and VLDL-TG (P = 0.001). Conversely, levels of TC, LDL, and HDLc were lower in these patients (P = 0.001, P = 0.02, and P = 0.001, respectively). Also, in this cohort PH-LPL relationships with lipids and lipoproteins were not altered by apoE genotypes. The frequency of common mutations in the LPL gene associated with partial LPL deficiency (N291S and D9N carriers) in the lowest quartile for LPL activity was more than double the frequency in the highest quartile (12.0% vs. 5.0%; P = 0.006). By contrast, the frequency of the S447X LPL variant rose from 11.5% in the lowest to 18.3% (P = 0.006) in the highest quartile. This study, in a large cohort of CAD patients, has shown that PH-LPL activity is decreased (22%; P = 0.001) when compared to controls; that the D9N and N291S, and S447X LPL variants are genetic determinants, respectively, in CAD patients of low and high LPL PH-LPL activities; and that PH-LPL activity is strongly associated with changes in lipids and lipoproteins.
Asunto(s)
Enfermedad Coronaria/enzimología , Lípidos/sangre , Lipoproteína Lipasa/sangre , Lipoproteínas/sangre , Adulto , Apolipoproteínas E/genética , Colesterol/sangre , Estudios de Cohortes , Método Doble Ciego , Ayuno , Humanos , Lipoproteína Lipasa/deficiencia , Lipoproteína Lipasa/genética , Masculino , Persona de Mediana Edad , Mutación , Placebos , Valores de Referencia , Triglicéridos/sangreRESUMEN
Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by mental retardation, seizures, and central nervous system and visceral hamartomas. Pulmonary involvement manifesting as lymphangioleiomyomatosis (LAM) occurs in 1% of patients (all women) with TSC. Micronodular pneumocyte hyperplasia also has been described as a rare pulmonary manifestation of TSC. We report 14 patients with micronodular pneumocyte hyperplasia (MNPH). The patients ranged in age from 23 to 57 years (mean 37.5). There were 12 women and 2 men. Nine of the patients (one man and eight women) had documented clinical manifestations of TSC: seven with LAM, two without LAM (including one man). Of the five patients who did not have TSC, three had LAM and two did not (including one man). Histologically, all 14 cases demonstrated multiple well-demarcated nodules usually measuring up to 8 mm in size, but most were 1-3 mm. The nodules were produced by a proliferation of enlarged cytologically benign type II pneumocytes, with an associated increase in alveolar macrophages and interstitial reticulin. Immunoperoxidase studies showed the type II pneumocytes within lesions to be reactive with antibodies to cytokeratin (four of four), epithelial membrane antigen (EMA) (five of five), and surfactant apoprotein B (8 of 10). HMB-45 was negative in the MNPH lesions in all nine cases studied. Follow-up was available in 9 of 10 living patients and ranged from 1 to 14 years (mean 6 years). Nine patients are alive; six are clinically stable and three have repeated pneumothoraces related to LAM. Four patients have died. None of the deaths were attributable to MNPH. MNPH appears to be a hamartomatous proliferation occurring most frequently in patients with tuberous sclerosis, is separable from and not a manifestation of LAM, has been observed to occur in men, and, like other hamartomas of tuberous sclerosis, does not appear to possess malignant potential.
Asunto(s)
Hiperplasia/patología , Pulmón/patología , Adulto , Biomarcadores/análisis , Femenino , Humanos , Hiperplasia/complicaciones , Hiperplasia/diagnóstico por imagen , Inmunohistoquímica , Hibridación in Situ , Queratinas/análisis , Pulmón/química , Pulmón/diagnóstico por imagen , Pulmón/metabolismo , Linfangioleiomiomatosis/complicaciones , Linfangioleiomiomatosis/diagnóstico por imagen , Masculino , Persona de Mediana Edad , ARN Mensajero/análisis , Proteínas Represoras/metabolismo , Tomografía Computarizada por Rayos X , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/diagnóstico por imagen , Esclerosis Tuberosa/metabolismo , Proteína 2 del Complejo de la Esclerosis Tuberosa , Proteínas Supresoras de TumorRESUMEN
BACKGROUND: Lipoprotein lipase (LPL) is the rate-limiting enzyme in the lipolysis of triglyceride-rich lipoproteins, and the gene coding for LPL is therefore a candidate gene in atherogenesis. We previously demonstrated that two amino acid substitutions in LPL, the Asn291-Ser and the Asp9-Asn, are associated with elevated triglycerides and lower HDL cholesterol and are present with greater frequency in coronary artery disease (CAD) patients than in normolipidemic control subjects. Conversely, a third frequent mutation in this gene, the Ser447-Stop, is reported by some investigators to underlie higher HDL cholesterol levels and would represent a beneficial genetic variant in lipoprotein metabolism. We therefore sought conclusive evidence for these allegations by investigating the effects of the LPL Ser447-Stop mutation on LPL and hepatic lipase (HL) activity, HDL cholesterol, and triglycerides in a large group of CAD patients (n = 820) with normal to mildly elevated total and LDL cholesterol levels. METHODS AND RESULTS: Carriers of the Ser447-Stop allele (heterozygotes and homozygotes) had significantly higher postheparin LPL activity (P = .034), normal postheparin HL activity (P = .453), higher HDL cholesterol levels (P = .013), and lower triglyceride levels (P = .044) than noncarriers. The influence of the Ser447-Stop allele on LPL activity was pronounced in patients using beta-blockers (P = .042) and not significant in those not using them (P = .881), suggesting a gene-environment interaction between the Ser447-Stop mutation and beta-blockers. CONCLUSIONS: We conclude that the LPL Ser447-Stop mutation has a significant positive effect on LPL activity and HDL cholesterol and triglyceride levels and that certain subgroups of CAD patients carrying the Ser447-Stop mutation will have less adverse metabolic effects when placed on beta-blockers. The LPL Ser447-Stop mutation therefore should have a protective effect against the development of atherosclerosis and subsequent CAD.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , HDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Variación Genética , Lipoproteína Lipasa/sangre , Lipoproteína Lipasa/genética , Triglicéridos/sangre , Alelos , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Inhibidores Enzimáticos/uso terapéutico , Frecuencia de los Genes , Genotipo , Humanos , Hidroximetilglutaril-CoA Reductasas , Masculino , Persona de Mediana Edad , Mutación , Pravastatina/uso terapéuticoRESUMEN
BACKGROUND: Many patients suffering from premature coronary artery disease report a family history for such events. A mutation in a particular gene, which confers susceptibility for atherosclerosis, will be found more frequently in individuals suffering from coronary atherosclerosis than in the general population. We have recently reported the identification of an Asp9 Asn substitution in the lipoprotein lipase (LPL) enzyme. We analyzed the impact of this mutation on the progression of coronary atherosclerosis and the effect of pravastatin in both carriers and noncarriers. METHODS AND RESULTS: All patients were enrolled in the quantitative coronary angiographic clinical trial REGRESS, which studied the impact of pravastatin therapy on coronary atherosclerosis. The Asp9 Asn mutation was identified in 38 of 819 (4.8%) patients. Carriers of the mutation more often had a positive family history of cardiovascular disease and lower HDL cholesterol levels than noncarriers. In the placebo group, carriers showed more progression of coronary atherosclerosis than noncarriers: mean reduction of the minimum obstruction diameter of -0.25 mm versus -0.12 mm (P = .029) and increase of percentage diameter stenosis of 6.4% versus 1.4% (P = .004). Moreover, the adjusted relative risk for a clinical event for carriers was calculated at 2.16 (95% CI, 1.09 to 4.29; P = .027). Although the lipid-lowering effect of pravastatin was attenuated in carriers, it appeared that these patients showed a response similar to noncarriers in terms of less progression of atherosclerosis and event-free survival. CONCLUSIONS: This study shows that heterozygosity for a mutation in the LPL gene, which causes only subtle changes in fasting plasma lipids, may promote the progression of coronary atherosclerosis and diminish clinical event-free survival.
Asunto(s)
Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/fisiopatología , Genes , Lipoproteína Lipasa/genética , Mutación , Secuencia de Aminoácidos , Angioplastia Coronaria con Balón , Estudios de Cohortes , Angiografía Coronaria , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria/terapia , Progresión de la Enfermedad , Método Doble Ciego , Heterocigoto , Humanos , Lípidos/sangre , Lipoproteínas/sangre , Persona de Mediana Edad , Pravastatina/uso terapéuticoRESUMEN
Uniparental disomy (UPD)-the inheritance of two homologous chromosomes from a single parent-may be unmasked in humans by the unexpected appearance of developmental abnormalities, genetic disorders resulting from genomic imprinting, or recessive traits. Here we report a female patient with familial chylomicronemia resulting from complete lipoprotein-lipase (LPL) deficiency due to homozygosity for a frameshift mutation in exon 2 of the LPL gene. She was the normal term product of an unremarkable pregnancy and had shown normal development until her current age of 5.5 years. The father (age 33 years) and the mother (age 24 years) were unrelated and healthy, with no family history of stillbirths or malformations. The father was a heterozygous carrier of the mutation, whereas no mutation in the LPL gene was detected in the mother. Southern blotting did not reveal any LPL gene rearrangement in the proband or her parents. The proband was homozygous for 17 informative markers spanning both arms of chromosome 8 and specifically for the haplotype containing the paternally derived LPL gene. This shows that homozygosity for the defective mutation in the LPL gene resulted from a complete paternal isodisomy for chromosome 8. This is the first report of UPD for chromosome 8 unmasked by LPL deficiency and suggests that normal development can occur with two paternally derived copies of human chromosome 8.
Asunto(s)
Cromosomas Humanos Par 8/genética , Lipoproteína Lipasa/deficiencia , Lipoproteína Lipasa/genética , Mutación , Adulto , Secuencia de Bases , Femenino , Homocigoto , Humanos , Lípidos/sangre , Masculino , Datos de Secuencia MolecularRESUMEN
Familial combined hyperlipoproteinemia (FCH) is a common familial lipoprotein disorder characterized by elevated plasma cholesterol and triglyceride levels with segregation in first-degree relatives. Most affected subjects with FCH have elevated plasma levels of apolipoprotein (apo) B. The disorder results from oversecretion of hepatic apoB-containing lipoprotein particles. The genetic defect(s) are unknown. Previous work has suggested that genetic polymorphisms of the apoA-I gene and functional abnormalities of the lipoprotein lipase (LPL) gene are associated with FCH. We investigated the XmnI and SstI restriction fragment length polymorphisms (RFLP) of the apoA-I gene in FCH subjects of French Canadian descent. We also investigated three common functional mutations of the lipoprotein lipase (LPL) gene (LPLGly188Glu, LPLPro207Leu, and LPLAsp250Asn) in French Canadians that account for approximately 97% of cases of complete LPL deficiency in the province of Québec, Canada. We identified and characterized 54 FCH probands in lipid clinics and examined at least one first-degree relative. There were 37 men and 17 women (mean age 48 +/- 9 and 58 +/- 8 years, respectively). None of the probands had diabetes mellitus; mean plasma glucose was 5.5 mmol/L. High blood pressure was diagnosed in 32% of men and 29% of women. The body mass index (weight (kg)/height(m2)) was elevated in probands (27 +/- 4 for men and 26 +/- 4 for women). Mean plasma levels of cholesterol (C) was 7.6 +/- 1.5 mmol/L, triglycerides 3.5 +/- 1.6 mmol/L, LDL-C 4.9 +/- 1.2 mmol/L, HDL-C 1.0 +/- 0.3 mmol/L, and apoB 1.83 +/- 0.67 g/L in the probands. Allele frequency of the rare alleles of the XmnI and SstI RFLP was not significantly different from a healthy reference group. In several families studied, the XmnI and SstI RFLP did not unequivocally segregate with the FCH phenotype. There was no significant effect of the presence or absence of the XmnI or SstI RFLP's on plasma lipids, lipoprotein cholesterol or apoB levels. Only one FCH proband was found to have a mutation of the LPL gene (Gly188Glu), and this did not segregate with the FCH phenotype in the family. We conclude that in our highly selected group of FCH subjects of French Canadian descent, the XmnI and SstI RFLPs of the apoA-I gene and common functional mutations of the LPL gene resulting in complete LPL deficiency are not associated with FCH.
Asunto(s)
Apolipoproteína A-I/genética , Apolipoproteínas A/genética , Apolipoproteínas C/genética , Hiperlipidemia Familiar Combinada/genética , Lipoproteína Lipasa/genética , Polimorfismo de Longitud del Fragmento de Restricción , Adulto , Anciano , Apolipoproteína C-III , Secuencia de Bases , Desoxirribonucleasas de Localización Especificada Tipo II , Femenino , Francia/etnología , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación , Linaje , QuebecRESUMEN
We performed denaturing gradient gel electrophoresis (DGGE) of exons 4, 5, 6 and their exon-intron boundaries of the LPL-gene in 169 unrelated male patients suffering from familial combined hyperlipidemia (FCH). Twenty patients were found to carry a nucleotide substitution in exon 6. Sequence and PCR/digestion analysis revealed one common mutation (Asn291Ser) in all these cases. This mutation was talso present in 215 male controls, albeit at a lower frequency than in FCH patients (10/215 = 4.6% vs. 20/169 = 11.8%; p < 0.02). Analysis of lipid, lipoprotein and apolipoprotein levels demonstrated an association between the presence of this Asn291Ser substitution and decreased HDL-cholesterol (0.94 +/- 0.31 vs. 1.12 +/- 0.26 mmol/l; p < 0.04) in our controls. FCH patients carrying this mutation showed decreased HDL-cholesterol (0.75 +/- 0.16 vs. 0.95 +/- 0.36 mmol/l; p = 0.05) and increased triglyceride levels (5.96 +/- 4.12 vs. 3.48 +/- 1.78 mmol/l; p < 0.005) compared to non-carriers. The high triglyceride and low HDL-cholesterol phenotype in carriers of this substitution was most obvious when BMI exceeded 27 kg/m2. Our study of male FCH patients revealed the presence of a common mutation in the LPL-gene that is associated with lipoprotein abnormalities, indicating that defective LPL is at least one of the factors contributing to the FCH-phenotype.
Asunto(s)
Asparagina/genética , Hiperlipidemia Familiar Combinada/genética , Lipoproteína Lipasa/genética , Mutación Puntual , Serina/genética , Secuencia de Bases , Cartilla de ADN , Electroforesis en Gel de Poliacrilamida/métodos , Humanos , Lípidos/sangre , Lipoproteínas/sangre , Masculino , Datos de Secuencia MolecularRESUMEN
A reduction of high density lipoprotein cholesterol (HDC) is recognized as an important risk factor for coronary artery disease (CAD). We now show in approximately 1 in 20 males with proven atherosclerosis that an Asn291Ser mutation in the human lipoprotein lipase (LPL) gene is associated with significantly reduced HDL levels (P = 0.001) and results in a significant decrease in LPL catalytic activity (P < 0.0009). The relative frequency of this mutation increases in those patients with lower HDL cholesterol levels. In vitro mutagenesis and expression studies confirm that this change is associated with a significant reduction in LPL activity. Our data support the relationship between LPL activity and HDL-C levels, and suggest that a specific LPL mutation may be a factor in the development of atherosclerosis.
Asunto(s)
Arteriosclerosis/etiología , HDL-Colesterol/metabolismo , Lipoproteína Lipasa/genética , Mutación , Adulto , Anciano , Alelos , Animales , Arteriosclerosis/genética , Arteriosclerosis/metabolismo , Secuencia de Bases , Línea Celular , Colesterol/metabolismo , Enfermedad Coronaria/etiología , Frecuencia de los Genes , Humanos , Lipoproteína Lipasa/fisiología , Lipoproteínas LDL/metabolismo , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Factores de Riesgo , Transfección , Triglicéridos/metabolismoRESUMEN
Dialysis amyloidosis is one of the most incapacitating complications of long-term dialysis treatment. Quantitative assessment of amyloid deposition using radiolabelled tracers has been recently proposed but convincing evidence of its validity in uraemic patients remains to be provided. We studied the plasma kinetics of i.v. administered 125I-labelled serum amyloid P component (125I-SAP) in 20 chronic haemodialysis patients compared with those of nine healthy volunteers and three non-dialysed patients with systemic amyloidosis. Plasma clearance of the tracer was abnormal in 17 of 20 dialysis patients in whom plasma radioactivity declined in a bi-exponential mode, in contrast to the single-exponential slope observed in all healthy controls. 125I-SAP plasma half-life of the second component, probably reflecting metabolic clearance, was significantly prolonged in these dialysis patients compared with the healthy controls (35.3 versus 24.6 h, P < 0.001). Among the long-term haemodialysis patients the calculated extravascular distribution of 125I-SAP was significantly greater in those with severe arthropathy than in asymptomatic patients. These findings demonstrate for the first time that SAP clearance is disturbed in haemodialysis patients due to both failing renal elimination and retention in extravascular sites. The extravascular diffusion is greatly enhanced in patients with clinical evidence of amyloidosis. Therefore the study of plasma 125I-SAP kinetics promises to be a valuable tool to quantitate the extent of amyloidosis.
Asunto(s)
Amiloidosis/metabolismo , Componente Amiloide P Sérico/farmacocinética , Microglobulina beta-2/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Amiloidosis/etiología , Amiloidosis/fisiopatología , Estudios de Casos y Controles , Femenino , Semivida , Humanos , Radioisótopos de Yodo , Masculino , Persona de Mediana Edad , Diálisis Renal/efectos adversos , Uremia/metabolismoRESUMEN
Familial combined hyperlipidemia (FCHL) is a common lipid disorder characterized by an increase in cholesterol and/or triglyceride levels in multiple individuals of the same family. Prior reports document a decreased activity of lipoprotein lipase (LPL) in FCHL, and studies of the role of LPL in the remodeling of nascent lipoproteins suggest that disturbances in LPL function could underlie FCHL. We studied the LPL gene in 31 unrelated individuals with FCHL. A total of 25 DNA changes (13 "silent" substitutions and 12 DNA changes resulting in amino acid substitutions) were detected in 16 patients. Three new exonic polymorphisms as well as a previously described Ser447-->stop and an Asp9-->Asn substitution were seen with similar frequency on control and FCHL chromosomes. Two novel DNA changes resulting in an Asp21-->Val and an His44-->Tyr substitution were seen in only two FCHL individuals. In vitro studies showed no effect of these mutations on LPL catalytic activity. LPL mutations impairing catalytic activity did not represent a significant factor leading to FCHL in this population. Variations in any portion of the coding region of the LPL gene affecting other functions besides catalysis are not a frequent cause of FCHL.
Asunto(s)
ADN/análisis , Hiperlipidemia Familiar Combinada/genética , Lipoproteína Lipasa/genética , Adulto , Anciano , Secuencia de Aminoácidos , Aminoácidos/análisis , Secuencia de Bases , Exones , Humanos , Lipoproteína Lipasa/química , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación , FenotipoRESUMEN
We report a case of adenine phosphoribosyltransferase deficiency in which the initial presentation was chronic renal failure. Diagnosis was made after infrared microscopy analysis of microcrystalline deposits on a kidney allograft biopsy specimen. This type of presentation is rarely seen, the most frequent manifestation of this disease being urolithiasis. This is the first report of recurrence of the microcrystalline nephritis in a kidney transplant with subsequent loss of allograft function.
Asunto(s)
Adenina Fosforribosiltransferasa/deficiencia , Adenina/análogos & derivados , Fallo Renal Crónico/enzimología , Trasplante de Riñón , Adenina/fisiología , Adulto , Humanos , Fallo Renal Crónico/cirugía , Masculino , RecurrenciaRESUMEN
Mid-dermal elastolysis is a well-defined clinical and histopathologic entity manifested by fine wrinkling of the skin and a mid-dermal loss of elastic fibers. Ultrastructural and histologic studies were performed in an attempt to better define the cause of the elastolytic process. Biopsy specimens from the lesions of 3 patients with mid-dermal elastolysis were studied at light and electron microscopic levels. Ultrastructural evidence of normal elastic fiber engulfment by activated macrophages was observed; however, some fields also demonstrated envelopment of abnormally degenerated elastic tissue. Although there are many potential causes of this degeneration, photodistribution of the lesions suggests that ultraviolet damage is a primary inciting factor.
Asunto(s)
Tejido Elástico/ultraestructura , Enfermedades de la Piel/patología , Piel/ultraestructura , Adulto , Tejido Elástico/patología , Femenino , Humanos , Persona de Mediana Edad , Necrosis/patología , Piel/patologíaAsunto(s)
Enfermedades de la Piel/patología , Adulto , Carcinoma/patología , Preescolar , Dermatofibrosarcoma/patología , Erupciones por Medicamentos , Femenino , Enfermedad Injerto contra Huésped/inducido químicamente , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos adversos , Granuloma/complicaciones , Granuloma/patología , Hidradenitis/inducido químicamente , Histiocitosis Sinusal/complicaciones , Histiocitosis Sinusal/patología , Humanos , Hidroxiquinolinas/efectos adversos , Enfermedades Linfáticas/complicaciones , Enfermedades Linfáticas/patología , Masculino , Persona de Mediana Edad , Mixedema/patología , Nevo/patología , Paraproteinemias/complicaciones , Paraproteinemias/patología , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/complicaciones , Sífilis/patología , Xantomatosis/complicaciones , Xantomatosis/patologíaRESUMEN
The purpose of the present study was to examine the effect of a two day and a five day administration of 22-oxa-calcitriol (OCT) on calcium metabolism in rats with advanced chronic renal failure and severe secondary hyperparathyroidism. A first series of 27 uremic rats received either placebo, OCT or calcitriol (0.3 microgram i.p./rat) 48 and 24 hours before sacrifice. A second series of 18 uremic rats received either placebo, OCT (0.3 microgram i.p./rat) or calcitriol (0.05 microgram i.p./rat) for five days. We found that after 48 hours (series 1) both calcitriol and OCT increased blood ionized calcium (Ca2+) as compared to vehicle (1.23 +/- 0.04 and 1.10 +/- 0.02 mM, P < 0.01 and P < 0.05, respectively vs. control, 1.02 +/- 0.03 mM). Duodenal Ca transport (S/M) using the everted gut sac technique was not stimulated by OCT, even though it increased from 2.8 +/- 0.4 to 7.0 +/- 0.6 (P < 0.01) with calcitriol. In contrast, duodenal calbindin-D9k mRNA expression and protein content increased to a similar extent with OCT and calcitriol. Calcitriol was more potent in reducing plasma iPTH1-34 levels than OCT: 344 +/- 75 pg/ml (calcitriol) versus 632 +/- 46 pg/ml (OCT) compared with 897 +/- 74 pg/ml (control), P < 0.01. In the second series of rats, the injection of OCT (0.3 microgram i.p./rat) over five days was less effective than the lower dose of calcitriol (0.05 microgram i.p./rat) in reducing circulating iPTH: 110 +/- 26 (calcitriol) and 281 +/- 64 (OCT) versus 624 +/- 135 pg/ml (control), P < 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Calcitriol/análogos & derivados , Calcio/metabolismo , Hiperparatiroidismo Secundario/tratamiento farmacológico , Hiperparatiroidismo Secundario/metabolismo , Animales , Calbindinas , Calcitriol/farmacología , Calcio/sangre , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Duodeno/metabolismo , Hiperparatiroidismo Secundario/etiología , Transporte Iónico , Masculino , Hormona Paratiroidea/sangre , Fragmentos de Péptidos/sangre , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Proteína G de Unión al Calcio S100/metabolismo , Teriparatido , Uremia/complicacionesRESUMEN
BACKGROUND: Chordoma, an uncommon tumor originating from remnants of the notochord, with cutaneous involvement has rarely been reported. OBJECTIVE: Our purpose was to document clinical manifestations, histopathologic features, immunohistochemical findings, treatment, and course of chordoma with cutaneous involvement. METHODS: Pathologically proven cases of chordoma were reviewed retrospectively for cutaneous involvement. Detailed clinical data and histopathologic changes were studied. Skin biopsy specimens were stained for immunohistochemical phenotyping. RESULTS: Of 207 cases of chordoma, 19 had skin involvement: as local recurrences or metastasis in 12, as direct extension of primary tumor in 6, and as a result of distant metastasis from sacrococcygeal chordoma in 1. Local recurrences were frequent, but distant metastasis to various organs, including skin, occurred. CONCLUSION: We propose the term chordoma cutis to describe this condition. In seven patients, cutaneous lesions were detected when the diagnosis of primary chordoma was made.