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Biomedical subjects

R H Levey

Publications and source records attributed to R H Levey.

At least 19 recordsLinked to original sources

Outcome of renal transplantation in children less than two years of age.

Twenty-two renal transplants were performed in 21 children less than two years of age at Children's Hospital. Fourteen were from living related donors and eight were from cadaveric donors. The five year patient and graft survivals of these recipients were compared to all other pediatric recipients between two and 18 years of age who received renal transplants over the same time period. Five year graft survival for recipients less than two years of age was 86% following living-related donor transplantation and 38% following cadaver donor transplantation. Older pediatric recipients aged between two and 18 years had a five year graft survival of 73% following living-related donor renal transplantation, which was similar to that for recipients less than two years of age. Although older cadaveric recipients had a comparable five year graft survival to younger recipients, at 42%, the patterns of graft loss were different. Graft failures in young recipients occurred within the first seven months post-transplant, whereas the older recipient's grafts failed more gradually. Actuarial five-year patient survival in recipients less than two years of age was 86% following living-related donor renal transplantation and 70% following cadaver-donor renal transplantation. Recipients less than two years of age had a poorer patient survival than older recipients following both living-related donor renal transplantation (P = 0.06) and cadaver-donor renal transplantation (P less than 0.05). These findings suggest that the graft survival of living-related donor renal transplantation in recipients less than two years of age is better than that of cadaver-donor renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The medical and surgical management of typhlitis in children with acute nonlymphocytic (myelogenous) leukemia.

The treatment of acute leukemia in childhood has been increasingly successful. Infectious complications are the major cause of morbidity and mortality among these patients receiving aggressive chemotherapy. In particular, neutropenic enterocolitis or typhlitis has had a reported mortality of 50% to 100%. The authors reviewed a series of 77 previously untreated patients with acute myelogenous leukemia begun on treatment from March 1976 to June 1984 to better define the characteristics of typhlitis and its optimum management. Twenty-five patients had episodes of typhlitis, characterized by fever, abdominal pain, and tenderness, occurring during periods of neutropenia. Ten of these patients had watery diarrhea as a major additional symptom, and nine patients had a significant episode of gastrointestinal bleeding. In seven instances, blood culture results were positive, all for intestinal flora. The episodes of typhlitis occurred most frequently during the induction therapy (19 patients). Five patients experienced typhlitis during maintenance therapy, and one patient had acute appendicitis. Two patients had typhlitis during their reinduction therapy, and of note, one had had abdominal symptoms during her initial induction. All patients were treated initially with broad-spectrum antibiotics and bowel rest. Four criteria have been used for surgical intervention: (1) persistent gastrointestinal bleeding after resolution of neutropenia and thrombocytopenia and correction of clotting abnormalities; (2) evidence of free intraperitoneal perforation; (3) clinical deterioration requiring support with vasopressors, or large volumes of fluid, suggesting uncontrolled sepsis; and (4) development of symptoms of an intra-abdominal process, in the absence of neutropenia, which would normally require surgery. Using these criteria, five patients required surgical intervention for typhlitis or its sequelae and one for acute appendicitis. There was one perioperative death resulting from miliary tuberculosis. Among the 21 patients managed medically, there was 1 death resulting from typhlitis in a patient in whom surgery was deferred because of her multiple failures to enter remission.

Adolescent↗

Maintenance of vascular access patency in pediatrics.

The patency of vascular access shunts and fistulae has been prolonged by a combined surgical and radiological approach that includes percutaneous transluminal angioplasty (PTA), surgical revision, thrombectomy, and thrombolysis. Over the last 3 years, 35 vascular accesses in 27 patients were found to have angiographic abnormality. PTA was performed 32 times on 19 accesses and 7 PTAs resulted in patent accesses by the end of the study. Surgical revision was performed 9 times on 8 accesses and 2 of the surgical revisions resulted in a patent access by the end of the study. Concerning Thomas femoral shunts, PTA prolonged the patency by 2.2 months and surgical revision by 3.8 months per procedure. Concerning arteriovenous (AV) fistulae, PTA prolonged the patency by 4.3 months and surgical revision by 3.5 months per procedure. A combination of procedures effectively doubles the duration of patency of Thomas femoral shunts and almost triples the duration of patency of AV fistulae in children. Forty-one percent of these accesses remain open 1 year following the initiation of these procedures.

Adolescent↗

Progressive tubulointerstitial renal disease in infancy with associated hepatic abnormalities.

Clinical, pathologic, and biochemical data are reported in two male infants who had rapidly progressive renal failure, enlarged kidneys, hepatosplenomegaly, and fat malabsorption. One infant, studied prior to the onset of significant renal insufficiency, manifested renal Fanconi syndrome, hyperparathyroidism, and marked hypocalcemia. After a brief period of dialysis, both received renal transplants. Neither has clinical evidence of reoccurrence of the renal disorder in the transplant, but both still have hepatic abnormalities. Morphologic features present in both patients include a renal lesion characterized by tubulointerstitial injury with a tubulocystic component and hepatic abnormalities with bile duct proliferation, portal fibrosis, and inflammation. These cases do not readily conform to any single published diagnostic category, including nephronophthisis-congenital hepatic fibrosis or infantile polycystic kidney disease, and appear to be unique.

Biopsy↗

The surgical management of fungal pulmonary infections in children with acute myelogenous leukemia.

Infections are the primary cause of complications and death in patients with acute myelogenous leukemia. Current aggressive treatment protocols have improved patient survival but produce extended periods of profound neutropenia during which the patients are particularly susceptible to opportunistic infections. Candida and Aspergillus species are the most common of the fungi causing invasive infections in these patients. In a group of 77 previously untreated children with acute myelogenous leukemia begun on treatment from March 1976 to June 1984, four patients developed localized fungal infections of the lung. These initially appeared as pulmonary infiltrates on chest roentgenograms during periods of severe neutropenia (three during remission induction and one after intensive consolidation therapy). Endobronchial cultures failed to identify the infectious organism in all cases. Computerized axial tomography best defined the cavitary nature of the lesions in 2 patients. All four patients underwent surgical resection, both to establish a diagnosis (three patients) and as part of therapy. There was no operative morbidity. The organisms involved were Aspergillus (2), Torulopsis (1), and Penicillium (1). Three patients were cured of their fungal infections. The fourth patient failed to enter remission and died of a cerebral fungal abscess that developed shortly after thoracotomy. We report these cases to encourage early surgical intervention in leukemics with a localized pulmonary process consistent with a fungal infection. Resection of the primary focus obviates the risk of life threatening pulmonary hemorrhage or dissemination of the fungus and allows for early reinstitution of chemotherapy which is vital to these patients' survival.

Adolescent↗

Heterochromia iridis and Horner's syndrome due to paravertebral neurilemmoma.

A case of heterochromia iridis and Horner's syndrome is reported in a 7-year old girl with paravertebral neurilemmoma. These clinical findings can be useful in the early diagnosis of mediastinal tumors in the paravertebral axis. While typically associated with neuroblastoma, these findings can be due to tumors which are inately benign--in this case neurilemmoma. The mechanism for heterochromia is briefly discussed.

Child↗

Comparison of cell-mediated lympholysis and mixed lymphocyte culture in the immunologic evaluation for renal transplantation.

We investigated the relationship between both pre-transplant cell-mediated lympholysis assay (CML) and mixed lymphocyte culture (MLC) and transplant outcome (graft function and survival) in 33 living, related donor renal transplants performed during the past 5 yr. Both assays were excellent predictors of transplant outcome. A positive CML assay was correlated with the occurrence of early acute rejection episodes (p less than 0.005), shortened time to graft dysfunction (serum creatinine greater than 1.5 mg/dl) (p less than 0.001), and poor long-term graft survival (p = 0.07). Similarly, a positive MLC was correlated with acute rejection episodes (p less than 0.005), graft dysfunction (p = 0.001), and poor graft survival (p less than 0.01). To determine the relative prognostic significance of the CML and MLC assays, we compared the correlation of each of them with the occurrence of acute rejection episodes. Under a logistic model of probability, the CML and MLC assays were equally predictive of an early acute rejection episode (p less than 0.01); however, the combination of CML and MLC together improved the accuracy of the prediction of an acute rejection episode by 50%. These results indicate that the CML and MLC assays are independent predictors of transplant outcome and that both tests should be an integral part of the immunologic evaluation of prospective living, related donors for renal transplantation.

Adolescent↗

Acquisition of immune competence by a subset of human cortical thymocytes expressing mature T cell antigens.

Previous studies indicated that the human thymus is composed of several discrete compartments. Cortical thymocytes are reactive with a monoclonal antibody, anti-T6 (TL-like) and coexpress antigens defined by antibodies anti-T4 and anti-T8. In contrast, most medullary thymocytes are unreactive with anti-T6, express either T4 or T8 antigens, and more importantly, brightly stain with anti-T3 and anti-T1, which define mature T cell antigens. Only a minor population of cortical thymocytes strongly express T1 and T3 antigens (T1+T3+). In the present study, we characterized this latter subpopulation of brightly staining T1+ cortical thymocytes. Because murine and human cortical thymocytes alone bear receptors for peanut agglutinin (PNA), cortical PNA+ thymocytes were separated from medullary PNA- thymocytes by fluorescence-activated cell sorting and were subsequently fractionated into PNA+T1+ (strongly anti-T1-reactive) and PNA+T1- (unreactive or weakly anti-T1-reactive) populations. The PNA+T1+ cells represented only 10 to 20% of thymic cortical lymphocytes. Whereas the PNA+T1- subset was unresponsive to PHA or alloantigen even in the presence of IL 2, the PNA+T1+ subset gave a brisk response to both stimuli on addition of IL 2. This latter response was similar to that of the PNA-T1+ medullary thymocytes. These results suggest that acquisition of mature T cell antigens is associated with immunocompetence despite a cortical localization.

Antigens, Surface↗

Antihelper T cell autoantibody in acquired agammaglobulinemia.

A patient with acquired agammaglobulinemia had an antihelper T cell factor that was identified as an immunoglobulin of the IgG class. The factor specifically bound to the TH2- T cell subset and, in the presence of complement, abolished the helper effect of normal T cells. The antihelper T cell antibody preceded by several years the appearance of suppressor TH2+Ia+ T cells, at which time the clinical course rapidly deteriorated. Plasmapheresis resulted in lymphocytosis and reappearance of a functionally intact helper T cell population. It did not affect the suppressor cells. Conversely, total thymectomy resulted in a temporary disappearance of the TH2+Ia+ suppressor cells, but did not decrease the levels of the autoantibody to helper T cells. Neither of these treatments reversed the state of agammaglobulinemia.

Adolescent↗

Renal growth after transplantation: infant kidney received by adolescent.

Renal growth and function were studied in a sixteen year old recipient of a renal transplant from a 16 month old cadaveric donor. Within one month, as measured by sequential inulin and creatinine clearances, glomerular filtration rate was 40 ml/min, which was more than 6 times the estimated pretransplant clearance. Ultrasound of the transplanted kidney revealed longitudinal growth from 7 cm at transplant to 11.5 cm by 8 weeks post-transplant. Radionuclide renal scintiphotography confirmed rapid functional and dimensional growth. There was no evidence of rejection, obstruction, or other complications during the time the allograft rapidly increased in size. Thus this case demonstrates a remarkable capacity of the human kidney to hypertrophy rapidly.

Adolescent↗

Mortality of chronic hemodialysis and renal transplantation in pediatric end-stage renal disease.

The long-term mortality of chronic hemodialysis and renal transplantation was analyzed in all children treated for end-stage renal disease at Children's Hospital Medical Center over the pase 8 1/2 years. A total of 216 transplantation or dialysis courses in 120 patients were studied. No patients were excluded from treatment or analysis. Overall actuarial survival was 92% at six months, 90% at 12 months, and 89% at five years. When actuarial survival for each form of treatment was examined, patient survival was 100% at six months and 95% at five years for chronic hemodialysis; 92% at six months and five years for living related transplantation; and 88% at six months and 85% at five years for cadaveric transplantation. We conclude that most children with end-stage renal disease can be kept alive with current treatment programs, and that the mortality of chronic hemodialysis in children is comparable to that of renal transplantation.

Adolescent↗

Post-transplant hypertension in the absence of rejection or recurrent disease.

Post-transplant hypertension was reviewed in 86 consecutive renal transplant recipients and occurred in 86 percent. In order to eliminate concomitant causes, those 16 of 86 patients in whom there had never been any rejection episode nor any recurrent diseases were further evaluated for the presence of hypertension. Follow-up period was 1-5 years. All 16 patients were hypertensive in the first postoperative weeks. Nine patients, all with various nephritides, had pre-transplant hypertension, leading to pre-transplant nephrectomies in 5. Post-transplant, all 9 were hypertensive in the first 6 months. By one year post-transplant, blood pressure had normalized in 2 and was controlled on medication in 5 others. In contrast, none of the 7 other patients (all with structural lesions) had pre-transplant hypertension though three had pre-transplant nephrectomies. Only 2 of these 7 patients had post-transplant hypertension, mild in both. The experience demonstrates that prior hypertension correlates positively with post-transplant hypertension, irrespective of native kidney nephrectomies. Patients with previous nephritides carry the greatest risk of becoming hypertensive. Furthermore, the majority of young renal allograft recipients appears to develop hypertension, even in the absence of rejection or recurrent disease.

Adolescent↗

Growth acceleration following renal transplantation in children less than 7 years of age.

Of 110 consecutive renal allografts performed at Children's Hospital Medical Center 12 were in 11 patients aged 3 to 7 years. Patient and graft survival and linear growth were evaluated in these 11 children. All 11 are surviving, seven (64%) with functioning allografts 12 to 92 months after transplant. Six of these seven have normal renal function (on alternate day prednisone dose less than 0.7 mg/kg every two days plus daily azathioprine) and all seven have shown catch-up growth, reaching and maintaining normal height for age. An eighth patient, now returned to dialysis, grew from below the third percentile at age 3 years to the 25th percentile at age 8 years, after which renal function deteriorated. Three patients rapidly rejected allografts and have had decreased growth velocity for age. In contrast, although many of the remaining 76 patients who received 98 transplants after age 7 years are growing, none showed accelerated linear growth sufficient to catch up if below the third percentile for age or to cross centile lines if above. Neither the degree of pretransplant bone age retardation nor steroid dose per kilogram accounted for lack of growth acceleration of those more than 7 years of age. Despite small sample size, the growth of renal transplant recipients less than 7 years of age suggests that they are good, and in some ways, favored transplant candidates.

Adolescent↗

Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage.

A series of monoclonal antibodies was used to define three discrete stages of human intrathymic T-cell differentiation. The earliest stage was confined to <10% of thymocytes, which were.reactive with both OKT9 and OKT10. Subsequently, approximately 70% of human thymocytes acquired a thymocyte-restricted antigen, OKT6, lost OKT9 antigen, and expressed reactivity with OKT4 and OKT5. These last two monoclonal antibodies were previously shown to define inducer (helper) and cytotoxic/suppressor populations, respectively, in peripheral blood. The OKT4(+), OKT5(+), OKT6(+) "common" thymocyte population represents the majority of thymocytes and accounts for more than 70% of thymocytes. With further maturation, thymocytes lose OKT6 reactivity, segregate into OKT4(+) and OKT5(+) subsets, and acquire reactivity with OKT3 (and OKT1). This latter stage corresponds to the more functionally mature subset. The possible relationship of acute lymphoblastic leukemia of T-cell lineage to these proposed stages of intrathymic differentiation was determined. Analysis of 25 tumor populations showed that 21 could be related to one or another differentiative stage. The majority (15/21) were derived from an early thymocyte or prothymocyte subpopulation, 5/25 were derived from a common thymocyte subpopulation, and 1/25 was derived from a mature (OKT3(+)) subpopulation. These data suggest that is it now possible to define stages of T-cell differentiation that can be related to T-cell malignancies in humans.

Antibodies, Neoplasm↗

Aplastic anemia: lack of inhibitory effect of bone marrow lymphocytes on in vitro granulopoiesis.

Prompted by previous reports that in certain patients with aplastic anemia, cell-mediated autoimmune suppression of myeloid stem cell proliferation may be demonstrable in vitro, we studied the effects of bone marrow lymphocytes from 18 patients with myeloid aplasia on the proliferation of committed granulocytic-monocytic progenitor cells (CFU-C). When assayed in soft agar cultures, marrow suspensions from 10 patients with aplastic anemia contained significantly fewer viable CFU-C than similar cell preparations from control subjects. To deplete marrow cell suspensions of lymphocytes, we employed rabbit anti-human thymocyte serum (ATS), which after multiple adsorptions exhibited marked cytotoxicity for human B and T lymphocytes but had negligible effect on normal CFU-C proliferation. Preincubation of marrow samples from 12 patients with ATS and complement resulted in no inhibition or enhancement of CFU-C growth. In further experiments, marrow cells from 8 patients were incubated with marrow from control subjects prior to CFU-C culture. No suppression of donor CFU-C proliferation was observed in any of these studies, and in 4 cocultures, mixture of the 2 marrow suspensions resulted in stimulation of CFU-C growth. Using these assays, we detected no evidence of cell-mediated inhibition of CFU-C proliferation in any of the 18 patients that we evaluated. Our data support the conclusion that in the majority of patients with aplastic anemia, an absolute deficiency of hemopoietic stem cells is present within the marrow that does not appear to be effected or sustained by suppressor lymphocytes. Whether the reduction of viable stem cells is the cause or the consequence of the process that leads to marrow failure remains unknown.

Anemia, Aplastic↗