RESUMEN
We have created a human chromosomal map of the location of known and candidate genes involved in primary lymphedema (PLE). This should facilitate further discovery and provide a basis for understanding microdeletions which cause lymphedema.
Asunto(s)
Linfangiogénesis , Linfedema , Cromosomas Humanos , Humanos , Linfangiogénesis/genética , Linfedema/genéticaRESUMEN
PURPOSE: Neonatal lupus erythematosus is caused by the transplacental passage of maternal autoantibodies. The aim of this study was to determine the risk of connective tissue disorders in mothers of children with cutaneous neonatal lupus erythematosus, as compared with the risk in mothers of children with congenital heart block, which is also often caused by maternal autoantibodies. SUBJECTS AND METHODS: We prospectively studied all mothers of children with cutaneous neonatal lupus erythematosus during a 14-year period at the Hospital for Sick Children, Toronto, Ontario, Canada. We identified 28 mothers, of whom 24 were eligible for study. The health and antibody status of the mothers were determined at the birth of the child and at followup. RESULTS: All mothers had anti-Ro antibodies at the time of birth. Initially 10 mothers were healthy and 14 mothers had either a defined (n = 9) or an undifferentiated (n = 5) autoimmune disorder. At a mean follow-up of 7 years, 13 (1 of whom had died) had a defined connective tissue disease, and 5 had an undifferentiated autoimmune disorder. Only 6 (25%) remained asymptomatic. By comparison, 36 (56%) of 64 mothers of children with congenital heart block were asymptomatic at follow-up (P <0.005). CONCLUSIONS: The majority of mothers of children with cutaneous neonatal lupus erythematosus had a defined or undifferentiated autoimmune disorder at the time of the child's birth, and others developed these conditions during follow-up. The health of these mothers appears to differ from that of mothers of children with congenital heart block.
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Autoanticuerpos/sangre , Enfermedades Autoinmunes/inmunología , Bloqueo Cardíaco/congénito , Bloqueo Cardíaco/inmunología , Lupus Eritematoso Cutáneo/congénito , Lupus Eritematoso Cutáneo/inmunología , Madres , Adulto , Enfermedades del Tejido Conjuntivo/inmunología , Femenino , Estudios de Seguimiento , Estado de Salud , Humanos , Recién Nacido , Lupus Eritematoso Sistémico/inmunología , Masculino , Síndrome de Sjögren/inmunologíaRESUMEN
We conducted an observational study to evaluate the effectiveness of an endoscopic technique for harvesting the greater saphenous vein for aortocoronary bypass grafting. We hypothesized that the endoscopic technique would minimize the risk of postoperative wound complications. From May 1997 to July 1998, we used an endoscopic technique to harvest the greater saphenous vein in 50 patients who underwent aortocoronary artery bypass grafting. Twenty-five of the patients had an increased risk for wound complications due to preexisting diabetes, obesity, peripheral vascular disease, or lymphedema. The average duration of the procedure was 39 minutes (range, 11 to 70 minutes). The average length of the harvested vein was 58 cm (range, 25 to 85 cm). We made an average of 2.5 incisions per patient (range, 1 to 5 incisions), and the average incision length was 7 cm (range, 3 to 10 cm). Two patients (4%) required conversion to an open technique using 5 small incisions. Postoperative complications included 1 wound infection (2%) and 1 small hematoma (2%). Two patients (4%) had minor erythema at the incision site, and 5 patients (10%) had postoperative lymphedema. The most common problem, ecchymosis, was seen in 6 patients (12%). None required repeat hospitalization or reoperation for wound complications. In our study, the endoscopic approach yielded superior cosmetic results, and reduced wound complications and discomfort, compared with traditional methods of vein harvesting. After gaining expertise with this minimally invasive method of vein harvesting, a surgeon can safely remove the saphenous vein in 20 to 30 minutes.
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Puente de Arteria Coronaria , Enfermedad Coronaria/cirugía , Disección/métodos , Endoscopía , Vena Safena/trasplante , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Enfermedad Coronaria/epidemiología , Diabetes Mellitus/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Enfermedades Vasculares Periféricas/epidemiología , Complicaciones Posoperatorias , Factores de RiesgoRESUMEN
To examine the possibility for drug metabolism polymorphism, adult human flavin-containing monooxygenases (form 3) (EC 1.14.13.8) that differ at one amino acid were expressed in Escherichia coli as maltose binding protein fusions. The cDNA that was first reported during the cloning of adult human flavin-containing monooxygenase was designated the wild type lys158 enzyme. A second cDNA has been identified as a common polymorphism in some human populations and was designated the glu158 enzyme. The cDNA that encodes both enzymes was subcloned into a high yield protein fusion expression system, expressed, and the protein was partially purified by affinity chromatography and characterized for enzyme activity with selective functional substrate probes. N- and S-oxygenation activity of both enzymes was determined with 10-(N,N-dimethylaminopentyl)-2-(trifluoromethyl)phenothiazine and methyl p-tolyl sulfide, respectively. It was found that expression of both lys158 and glu158 enzymes of the human flavin-containing monooxygenase form 3 as fusions with the maltose binding protein resulted in an enzyme that was soluble and greatly stabilized and had a reduced requirement for detergent during enzyme purification and during the assay for activity. Expression of the fusion proteins has allowed the preparation of stable and highly active enzyme at greater purity than was readily possible in the past. With the exception of the stability and solubility characteristics, the physical and chemical properties of lys158 and glu158 maltose binding fusion proteins of human flavin-containing monooxygenase form 3 variants resembled that of flavin-containing monooxygenase enzyme activity associated with human liver microsomes and enzyme isolated from a previous Escherichia coli expression system that lacked the protein fusion. Comparison of the catalytic activity of the two fusion proteins showed that while both forms were active, there were differences in their substrate specificities. Expression of the adult human flavin-containing monooxygenase form 3 as a maltose binding protein has allowed considerable advances over the previously reported cDNA-expressed enzyme systems and may provide the basis for examining the role of the flavin-containing monooxygenase in human xenobiotic or drug metabolism.
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Transportadoras de Casetes de Unión a ATP , Proteínas Portadoras/genética , Proteínas de Escherichia coli , Proteínas de Transporte de Monosacáridos , Oxigenasas/metabolismo , Clonación Molecular , ADN Complementario , Escherichia coli/genética , Humanos , Cinética , Proteínas de Unión a Maltosa , Oxigenasas/genética , Oxigenasas/aislamiento & purificación , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/aislamiento & purificación , Proteínas Recombinantes de Fusión/metabolismoRESUMEN
OBJECTIVES: To determine the health of mothers of offspring with complete congenital heart block (CHB) both at the time of delivery of the affected child and in the long-term, and the percentage of mothers and children with CHB who had anti-SSA/Ro and/or SSB/La antibodies. PATIENTS AND METHODS: Sixty-four mothers of 64 children with CHB (seen between 1964 and 1993) were identified through the Cardiology database of The Hospital for Sick Children, Toronto, Canada. Medical information from these of children with CHB was evaluated. Data were obtained from the mothers by mailed questionnaire, telephone interview, and/or from the attending physicians. The presence of anti-Ro antibodies and anti-La antibodies were evaluated by ELISA assay. RESULTS: The mean age at the time of delivery of the first child with CHB was 28 +/- 6 years. At the time of delivery 42 (66%) mothers were healthy, 2 (3%) had systemic lupus erythematosus (SLE), 2 (3%) had linear scleroderma, 2 (3%) had rheumatoid arthritis; 3 (5%) had a history of rheumatic fever (but were otherwise well), 1 (2%) had Sjogren's syndrome (SS), and 12 (19%) had an undifferentiated autoimmune syndrome (UAS) (arthralgia, myalgia, photosensitivity, skin vasculitis, Raynaud's phenomenon). The mean time to follow-up from deliver to study was 121 +/- 88 months. The mean maternal age at study was 38 +/- 9 years. Three of 12 mothers who initially had a UAS progressed to SLE (average follow-up time of 80 months, median 96), and 2 developed SS (with average follow-up time 140 months, median 132) and 1 went into remission. The mean follow-up time for the other mothers who did not develop an autoimmune disease was 150 +/- 102 months. Thirty-six of the 42 initially healthy mothers remained well. One mother developed SLE; 1 developed hyperthyroidism; 1 developed anky-losing spondylitis; and 3 developed an UAS. The mean follow-up time of the 36 mothers who remained healthy was similar (123 +/- 97 months) to the 6 initial healthy mothers who developed an autoimmune disease (121 +/- 36 months). Anti-Ro and/or anti-La antibodies were positive in 32 of 53 (60%) mothers tested. Fourteen of the 53 mothers were symptomatic at the time of delivery and 39 were asymptomatic. Anti-Ro and/or anti-La antibodies were positive in 12 of 13 mothers tested at the time of delivery. CONCLUSIONS: The long-term maternal outcome in our cohort was very good as most of the initially healthy mothers remained well at follow-up. Twenty-five percent of the mothers with a UAS and only 2% of the initially healthy mothers developed SLE. The development of an autoimmune disease in an asymptomatic mother identified by the birth of a child with CHB was less common in our study than in previous studies. However, close follow-up of mothers with UAS is warranted.
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Autoanticuerpos/sangre , Enfermedades Autoinmunes/sangre , Estado de Salud , Bloqueo Cardíaco/congénito , Madres , Complicaciones del Embarazo/sangre , Adulto , Anciano , Anticuerpos Antinucleares/sangre , Enfermedades Autoinmunes/inmunología , Niño , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Embarazo , Complicaciones del Embarazo/inmunología , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , SíndromeAsunto(s)
Enfermedades Cardiovasculares/epidemiología , Espondilitis Anquilosante/complicaciones , Adolescente , Anticuerpos Antinucleares/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Niño , Femenino , Antígeno HLA-B27/sangre , Humanos , Masculino , Ontario/epidemiología , Prevalencia , Estudios Prospectivos , Factor Reumatoide/sangre , Espondilitis Anquilosante/diagnósticoRESUMEN
OBJECTIVE: Physical disability is perhaps the most important outcome of juvenile dermatomyositis (JDM). No functional assessment tool has been validated for inflammatory myopathies either in children or adults. We studied the measurement properties of the Childhood Health Assessment Questionnaire (CHAQ) in children with JDM. METHODS: We studied 37 patients followed at the JDM clinic and compared the results obtained by the CHAQ to a global disease severity score and quantitative muscle strength testing measured by sphygmomanometry (construct validity). We also measured the reliability of the CHAQ and its responsiveness to clinical change. RESULTS: For the initial measurement of each subject, the correlation between disease severity and CHAQ was high [Spearman's correlation, (rs = 0.71, p < 0.002)]. Disability as measured by the CHAQ was inversely correlated with proximal muscle strength (hip abduction rs = -0.57, p < 0.002; shoulder abduction rs = -0.51, p < 0.01) but, as expected, less so with more distal muscle strength (knee extension rs = -0.40, p = 0.05; grip strength rs = -0.079, p > 0.20). The CHAQ was reliable in subjects who showed no clinical change in muscle strength (intraclass correlation coefficient = 0.87) and responsive to treatment induced clinical change (responsiveness coefficient = 0.90). CONCLUSION: The CHAQ can serve as a valid and sensitive tool in the evaluation of functional outcomes in JDM.