RESUMEN
X-linked recessive nephrolithiasis (XRN) was described in a large kindred in which nephrolithiasis; proximal tubular dysfunction, proteinuria, nephrocalcinosis, and renal failure occur only in males. Carrier females are asymptomatic, but formal studies of them have not been done. The gene for XRN has been mapped to the pericentromeric region of the X chromosome, close to the loci for several eye disease genes. We studied six affected males, 13 carrier females, and 25 normal members of this family including 7 females whose genetic haplotype predicted them to be carriers. Studies were done in the Clinical Research Unit on a diet containing 400 mg of calcium and 2 g of sodium, and by an additional outpatient urine collection was obtained on a 1-g calcium intake. Hypercalciuria occurred in five of six affected males, 4 of 12 carrier females, and three of seven predicted carriers. Significant proteinuria was present in all affected males and in no other subjects. Low-molecular-weight proteinuria was present in all affected males: the excretion of alpha 1-microglobulin exceeded normal by 3- to 14-fold, of beta 2-microglobulin exceeded normal by 100- to 400-fold, and of retinol-binding protein exceeded normal by 1,000- to 3,000-fold. The excretion of these proteins was less strikingly elevated in carrier females, but the excretion of alpha 1-microglobulin was abnormal in 9 of 15 carriers, beta 2-microglobulin was abnormal in 12 of 15, and retinolbinding protein in was abnormal 12 of 13, and this pattern was similar in predicted carriers. The urinary concentrating ability was abnormal in four affected males with renal insufficiency but normal in all other subjects. Urinary wasting of potassium, phosphorous, and glucose occurred infrequently, and no subject was hypouricemic. Formal ophthalmologic studies were normal in five affected males. Thus, the most consistent urinary abnormalities in XRN are hypercalciuria and low-molecular-weight proteinuria, the latter of which appears to be a marker for the carrier state.
Asunto(s)
Portador Sano , Genes Recesivos , Ligamiento Genético , Cálculos Renales/genética , Cromosoma X , Adolescente , Adulto , Anciano , Calcio/orina , Niño , Preescolar , Creatinina/metabolismo , Ojo/fisiopatología , Femenino , Humanos , Cálculos Renales/fisiopatología , Cálculos Renales/orina , Túbulos Renales/fisiopatología , Masculino , Persona de Mediana Edad , Fenotipo , Proteinuria/orinaRESUMEN
X-linked recessive nephrolithiasis is associated with kidney stones and renal tubular dysfunction in childhood progressing to renal failure in adulthood. The primary defect causing this renal tubular disorder is unknown and determining the chromosomal location of the mutant gene would represent an important step toward defining the biochemical basis. We have performed linkage studies in 102 members (10 affected males, 47 unaffected males, 15 obligate heterozygote females, and 30 unaffected females) from five generations of one family. As genetic markers we used 10 cloned human X chromosome fragments identifying restriction fragment length polymorphisms and seven pairs of oligonucleotide primers identifying microsatellite polymorphisms. Linkage with the locus DXS255 was established with a peak LOD score = 5.91 at 3.6% recombination, thereby localizing the X-linked recessive nephrolithiasis gene to the pericentromeric region of the short arm of the X chromosome (Xp11.22). Multilocus analysis indicated that the mutant gene was distal to DXS255 but proximal to the Duchenne muscular dystrophy locus on Xp. Thus, the gene that causes X-linked recessive nephrolithiasis maps to the pericentromeric region of the short arm of the X chromosome (Xp11.22), and further characterization of this gene will help to elucidate the factors controlling renal tubular function and mineral homeostasis.
Asunto(s)
Aberraciones Cromosómicas , Cálculos Renales/genética , Cromosoma X , Adolescente , Anciano , Animales , Secuencia de Bases , Niño , Preescolar , Mapeo Cromosómico , ADN Satélite/genética , Femenino , Genes Recesivos/genética , Ligamiento Genético , Marcadores Genéticos , Humanos , Células Híbridas , Masculino , Datos de Secuencia Molecular , New York , Hibridación de Ácido Nucleico , Linaje , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Roedores , Caracteres SexualesRESUMEN
BACKGROUND AND METHODS: Nephrolithiasis may occur as a consequence of a number of hereditary disorders. We describe a large kindred from northern New York with hereditary nephrolithiasis accompanied by urinary concentrating defects, nephrocalcinosis, renal insufficiency, and renal wasting of potassium, phosphate, calcium, and uric acid. The pattern of inheritance was established by examining the patients and their records and interviewing family members. Selected members of the family were evaluated in detail, with measurements of erythrocyte cation fluxes and carbonic anhydrase (carbonate dehydratase) activity. RESULTS: The kindred consisted of 162 family members from six generations. All nine affected persons were male and appeared to have inherited the disease from their mothers. No affected man transmitted the gene to a son, but the daughters of affected men were carriers. The patients presented in childhood with calcium nephrolithiasis and proteinuria, with progression to nephrocalcinosis, urinary concentrating defects, and renal insufficiency. Renal biopsies revealed tubular atrophy, interstitial fibrosis, and glomerulosclerosis; the characteristic features of other forms of hereditary nephritis were absent. Abnormalities in the renal excretion of calcium, phosphate, potassium, and uric acid were found only in the adult members of the kindred, although renal biopsies were abnormal even in younger members. In one patient who has had a renal transplant for seven years, the disease has not recurred. CONCLUSIONS: This kindred manifested an X-linked recessive nephrolithiasis with renal failure, a new form of hereditary renal disease. Most of the identifiable physiologic abnormalities occurred after the development of nephrolithiasis and renal insufficiency and may not be of pathogenetic importance.
Asunto(s)
Genes Recesivos , Cálculos Renales/genética , Fallo Renal Crónico/genética , Cromosoma X , Adulto , Anhidrasas Carbónicas/metabolismo , Niño , Eritrocitos/metabolismo , Femenino , Humanos , Riñón/patología , Cálculos Renales/complicaciones , Cálculos Renales/patología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/patología , Masculino , Persona de Mediana Edad , LinajeRESUMEN
Forty-eight adult patients without clinical evidence of inguinal or abdominal wall hernias underwent peritoneal scintigraphy shortly after beginning continuous ambulatory peritoneal dialysis (CAPD). Scintigraphically detectable subclinical structural defects involving the inguinal canal or abdominal wall were present in 14 patients. Within 5 months, four of these defects progressed to clinically significant CAPD-related structural complications. These patients could not be distinguished by clinical or scintigraphic criteria from the 10 patients with nonprogressive structural defects. No scintigraphic structural defects were detected in 34 patients, 30 of whom remained free of CAPD-related structural complications. Five patients developed symptomatic structural complications during follow-up in areas that had been scintigraphically normal at the onset of CAPD. We conclude that some CAPD-related structural complications arise de novo, while others represent progression of subclinical pre-existent structural abnormalities that can be detected by peritoneal scintigraphy. However, most asymptomatic scintigraphic defects do not progress to a symptomatic stage, limiting the usefulness of prospective peritoneal scintigraphy as a guide to recommend prophylactic repair of all asymptomatic structural defects in patients beginning CAPD.
Asunto(s)
Fallo Renal Crónico/terapia , Cavidad Peritoneal/diagnóstico por imagen , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Adulto , Anciano , Femenino , Humanos , Fallo Renal Crónico/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Cintigrafía , Azufre Coloidal Tecnecio Tc 99mRESUMEN
The current role of nuclear medicine in clinical diagnosis was surveyed in a retrospective review of medical records by two internists. About one radiologic imaging study in 20 was a radionuclide procedure, and a somewhat larger fraction was performed in outpatients. The internists found that diagnostic screening procedures in nuclear medicine influenced patient management in 63% of hospital inpatients, and quantitative/monitoring types of tests influenced management in 56%. Of the projected health care costs in the United States of $490 billion, all imaging procedures will account for only $12 billion, and nuclear medicine procedures will account for about $1 billion. Nuclear medicine research continues to blossom. The National Institutes of Health budget for diagnostic imaging research in fiscal year 1988 totaled $86.6 million; nuclear medicine projects represented 43% of this total, all other projects in radiology represented 30%, and projects outside radiology represented 30%. Research with positron emitters and positron emission tomography totaled $20.5 million, and research with radiolabeled monoclonal antibodies totaled $6.2 million. Two major problems may hinder the future practice of nuclear medicine in the United States compared with that in other developed countries: (a) the serious time lag in the approval process for new radiopharmaceuticals by the U.S. Food and Drug Administration and other agencies and (b) the lack of a facility dedicated to the continuous production of radionuclides for biomedical research. Now, there is sporadic production permitted only during high-energy physics experiments. The recent developments which will probably induce the greatest changes in clinical nuclear medicine in the near future are the improvements in design and utilization of single photon emission computed tomographic devices and prolific generation of new radiopharmaceuticals, especially technetium-99m agents for cerebral and myocardial imaging and tumor agents.
Asunto(s)
Técnicas de Diagnóstico por Radioisótopo/tendencias , Departamentos de Hospitales/estadística & datos numéricos , Servicio de Medicina Nuclear en Hospital/estadística & datos numéricos , Medicina Nuclear/tendencias , Costos y Análisis de Costo , Diagnóstico por Imagen/tendencias , Humanos , Medicina , National Institutes of Health (U.S.) , Medicina Nuclear/estadística & datos numéricos , Apoyo a la Investigación como Asunto/tendencias , Especialización , Estados Unidos , Recursos HumanosRESUMEN
These experiments examined the effects of genes outside of the H-2 region on disease susceptibility and pathogenesis. Four strains of mice with the susceptible H-2 type, H-2d, but different non-H-2 genes were studied. B10, D2, Balb/c, NZB, and DBA/2J mice were injected with 4 mg of apoferritin i.p. q.d. for 28 days. B10, D2 and Balb/c mice developed proliferative and crescentic glomerulonephritis. NZB mice developed proliferative and crescentic glomerulonephritis with wire loop lesions suggestive of lupus. DBA/2J mice developed only minimal mesangial proliferation without crescents or necrosis. Electron microscopy showed subepithelial and mesangial deposits in B10, D2, moderate subepithelial and mesangial deposits in Balb/c, and marked mesangial, subendothelial and subepithelial deposits in NZB. Immunofluorescence demonstrated the presence of IgG, IgM, C3 and apoferritin in these deposits. The DBA/2J mice had only minimal mesangial deposits by immunofluorescence and electron microscopy. These experiments demonstrate that non-H-2 genes alter the H-2d determined disease susceptibility seen in H-2 congenic mice. NZB genes can alter the disease so that lupus-like lesions develop and DBA/2J genes can substantially ameliorate the disease.
Asunto(s)
Genes MHC Clase I/inmunología , Genes/inmunología , Glomerulonefritis/genética , Enfermedades del Complejo Inmune/genética , Animales , Apoferritinas/inmunología , Técnica del Anticuerpo Fluorescente , Predisposición Genética a la Enfermedad , Glomerulonefritis/inmunología , Enfermedades del Complejo Inmune/inmunología , Glomérulos Renales/patología , Masculino , Ratones , Ratones Endogámicos , Microscopía ElectrónicaRESUMEN
The role of the major histocompatibility complex in the development of apoferritin induced immune complex glomerulonephritis was studied in H-2 congenic B10 mice. The glomerular lesions varied strikingly among the three different strains studied. The B10 (H-2b) mice had minimal mesangial expansion or no lesions at all. The B10.BR (H-2k) mice had mesangial expansion and proliferative glomerulonephritis without crescents or interstitial mononuclear cell infiltration. In contrast, the B10.D2 (H-2d) mice had necrotizing glomerulonephritis with crescents and an interstitial mononuclear cell infiltrate. Immunofluorescence and electron microscopy demonstrated only minimal mesangial deposits in B10 (H-2b) mice, predominantly mesangial deposition in the B10.BR (H-2k) mice, and mesangial and subepithelial immune complex deposits in B10.D2 (H-2d) mice. These morphologic differences correlated with functional abnormalities. Only the B10.D2 (H-2d) mice developed proteinuria, hematuria, and elevated blood urea nitrogen. They also had the most elevated antiapoferritin IgG levels. These experiments demonstrate that differences in the pathologic lesions and susceptibility to immune complex glomerulonephritis can be seen in animals that differ only at the H-2 locus. This model will lend itself to the study of the mechanisms by which the major histocompatibility complex influences the development of immune complex glomerulonephritis.
Asunto(s)
Apoferritinas/inmunología , Ferritinas/análogos & derivados , Glomerulonefritis/genética , Complejo Mayor de Histocompatibilidad , Animales , Apoferritinas/análisis , Glomerulonefritis/etiología , Glomerulonefritis/patología , Antígenos H-2/genética , Inmunoglobulina G/análisis , Glomérulos Renales/patología , Masculino , Ratones , Proteinuria/etiologíaRESUMEN
Recovery of organisms from continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis presents special problems to the laboratory. The Isolator (Dupont Co, Wilmington, DE), based on lysis and centrifugation, is generally used for the recovery of blood isolates. This study determined the efficacy of the Isolator relative to the Bactec System (Johnston Laboratories, Inc, Towson, MD) for the culture of dialysates from CAPD patients with peritonitis. On the basis of clinical criteria, 31 episodes of peritonitis were included for our study. Dialysate was inoculated into an Isolator and Bactec 6B and 7D bottles. A causative agent was isolated by the Isolator in 29 of 31 episodes, by the Bactec in 29 of 31, and by one or both techniques in 30 of 31 episodes (overall sensitivity 97%). The Isolator failed to detect a Pseudomonas luteola and the Bactec failed to detect a coagulase-negative staphylococcus. Coagulase-positive and negative staphylococci represented 58.1% of the isolates. The Isolator detected 21.4% (six of 28) of the isolates 24 to 72 hours earlier than the Bactec; the Bactec was faster in this regard in 3.6% (one of 28). Time to positivity for the remaining 21 cultures was the same in both systems. Isolate identification and antimicrobial sensitivity was available 24 hours earlier using the Isolator in 96.4% (27 of 28). The Isolator was more rapid and as sensitive as the Bactec system in detecting causative organisms of peritonitis in CAPD patients.
Asunto(s)
Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Peritonitis/microbiología , Técnicas Bacteriológicas/instrumentación , Centrifugación/instrumentación , Estudios de Evaluación como Asunto , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Humanos , Peritonitis/etiología , Factores de TiempoRESUMEN
Eighteen patients with complications secondary to continuous ambulatory peritoneal dialysis underwent peritoneal scintigraphy utilizing Technetium-99m sulfur colloid. Patients were divided into three groups. Group 1 patients (11) had dialysate leaks leading to abdominal-wall edema, genital edema, or exit-site drainage. Scintigrams were abnormal in nine patients in this group and frequently provided localizing information that aided in the management of leaks. Group 2 patients (five) had recurrent peritonitis. Two of these patients had abnormal scintigrams. In one instance, scintigraphy detected multiple abdominal-wall hernias that may have been responsible for recurrent peritonitis, which resolved following corrective surgery. Group 3 patients (two) had inadequate ultrafiltration but no clinical evidence of a dialysate leak. Scintigrams were negative in this group, eliminating consideration of an underlying structural defect in the peritoneum. Scintigraphic imaging is possible for several hours following instillation of labeled dialysate. This capability is important, since scintigrams that were initially negative frequently became positive after several hours of ambulation. Postdrainage images were also helpful in confirming extraperitoneal leakage. This study demonstrates that peritoneal scintigraphy is a useful diagnostic tool in the management of complications of continuous ambulatory peritoneal dialysis.
Asunto(s)
Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Enfermedades Peritoneales/diagnóstico por imagen , Peritoneo/diagnóstico por imagen , Adolescente , Adulto , Anciano , Niño , Edema/diagnóstico por imagen , Edema/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Peritoneales/etiología , Peritonitis/diagnóstico por imagen , Peritonitis/etiología , Cintigrafía , Recurrencia , Azufre Coloidal Tecnecio Tc 99mRESUMEN
Recurrent Pseudomonas luteola (CDC group Ve-1) peritonitis occurred in a patient undergoing continuous ambulatory peritoneal dialysis. Catheter removal was required for cure despite therapy based on antibiotic susceptibilities. This is the third report in the English literature of severe P. luteola infection and the first report of peritonitis caused by this organism.
Asunto(s)
Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Peritonitis/etiología , Infecciones por Pseudomonas/etiología , Adulto , Catéteres de Permanencia , Glomerulonefritis/complicaciones , Humanos , Fallo Renal Crónico/complicaciones , Masculino , Pseudomonas/aislamiento & purificación , RecurrenciaRESUMEN
Hemoptysis as a presenting symptom of pheochromocytoma has not received wide recognition. This report describes a patient with a pheochromocytoma complicated by hemoptysis. The hemoptysis occurred during paroxysms of hypertension and was cured by surgical removal of the tumor. Knowledge of this association could lead to more rapid diagnosis.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/complicaciones , Hemoptisis/etiología , Feocromocitoma/complicaciones , Neoplasias de las Glándulas Suprarrenales/fisiopatología , Neoplasias de las Glándulas Suprarrenales/cirugía , Femenino , Humanos , Hipertensión/etiología , Persona de Mediana Edad , Feocromocitoma/fisiopatología , Feocromocitoma/cirugíaRESUMEN
We used technetium Tc 99m medronate (methylene diphosphonate) scanning in the treatment of seven patients with rhabdomyolysis. In three patients the intense, diffuse, symmetric nature of the scans was suggestive of an underlying metabolic muscle disorder. The scans defined the extent of the muscle injury in three patients and demonstrated muscle injury that was not initially suspected in two patients. The scan also demonstrated clinically unsuspected metastatic pulmonary and gastric calcifications in one patient. All scans showed evidence of renal dysfunction. In conclusion, these cases demonstrate that Tc 99m medronate scanning helps to define the extent and location of muscle injury in rhabdomyolysis, and that diffuse muscle uptake of Tc 99m medronate may be associated with metabolic muscle disease.
Asunto(s)
Huesos/diagnóstico por imagen , Rabdomiólisis/diagnóstico por imagen , Medronato de Tecnecio Tc 99m , Lesión Renal Aguda/diagnóstico por imagen , Lesión Renal Aguda/etiología , Adulto , Anciano , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Músculos/diagnóstico por imagen , Músculos/metabolismo , Cintigrafía , Rabdomiólisis/complicacionesRESUMEN
The autologous mixed lymphocyte reaction (AMLR) was studied in 10 patients who were azotemic from renal diseases not considered to be immunologically mediated. These patients were not on chronic dialysis. The AMLR was significantly depressed in patients with azotemia when compared to the AMLR in normals. When the AMLR was performed utilizing lymphocytes from normals, the proliferative response was markedly decreased if azotemic serum was substituted for normal serum. However, when the AMLR was performed utilizing lymphocytes from azotemic patients, the proliferative response did not significantly improve if normal serum was substituted for azotemic serum. In addition, the proliferative responses of T cells to concanavalin A (Con A) and phytohemagglutinin (PHA) were not significantly depressed in azotemic patients when compared to normal controls. These data suggest that the AMLR is abnormal in azotemic patients because of an intrinsic defect in the mononuclear cells, possibly in the stimulating non-T cells, and an inhibitory factor in the serum.