Adolescent health-related quality of life following liver and kidney transplantation.

UNLABELLED: Health perceptions of adolescent transplant patients should be considered in providing appropriate healthcare. OBJECTIVES: (i) quantify health-related quality of life (HRQOL) in adolescent liver and kidney transplant patients, (ii) compare caregiver ratings of their children's HRQOL to adolescent self-reports and (iii) examine the relationship between HRQOL and disease-specific disability (DSD). Adolescent liver (n = 51) and kidney (n = 26) transplant recipients and caregivers were surveyed using the CHQ-CF87 and CHQ-PF50. DSD scores were calculated for each patient. The response rate was >70%. Adolescent's psychological and physical health was similar to a healthy population, but general health poorer (p = 0.0006). Caretakers reported lower physical functioning and general health (p = 0.0001) but similar psychological health to a normative population. All caregivers expressed negative emotional impact of their child's health on themselves and family activities (p = 0.0001). Positive correlations were found between liver transplant recipients and caregivers: perceptions of behavior (ICC = 0.55, p < 0.001), mental health (ICC = 0.56, p < 0.001), self-esteem (ICC = 0.68, p

Comparison of Tc-99 measurement of glomerular filtration rate vs. calculated creatinine clearance to assess renal function pretransplant in pediatric patients undergoing hematopoietic stem cell transplantation.

We compared the results of Tc-99 evaluation of glomerular filtration rate (GFR) vs. the calculation of the creatinine clearance (CCrC) as a predictor for the development of renal insufficiency in pediatric patients following hematopoietic stem cell transplantation (HSCT). We reviewed 95 consecutive patients receiving autologous (n = 37) or allogeneic (n = 58) HSCT at Children's Memorial Hospital between January, 1995 and February, 1998. Diagnoses included leukemia (n = 43), solid tumor (n = 27), bone marrow failure syndrome (n = 12), non-malignant disease (n = 8), CNS tumors (n = 5) and immunodeficiency (n = 3). Tc-99 GFR was compared with a calculated creatinine clearance derived from the Schwartz formula (CCrC) prior to HSCT. These measures of renal function were compared with the patient's subsequent clinical course to determine if patients who developed renal insufficiency of sufficient magnitude as to require continuous veno-venous hemofiltration (CVVH) or dialysis, could have been identified. Overall comparison of the two methods of evaluation of renal function showed low correlation with values obtained by CCrC, which were consistently higher in most patients (r-value 0.01 in the regression analysis and a p = 0.08 95% CI -24.15 to 1.48). When stratified for age, correlation between the two methods was excellent only in children younger than 5 yr of age p = 0.02 95%, CI 0.032-0.49). Eleven patients required therapy with CVVH or dialysis but neither CCrC nor Tc-99 GFR prior to transplant predicted this event. Patients who received TBI were statistically more prone to develop renal insufficiency than those without TBI (p < 0.0001, 95% CI 0.25-0.008). Neither the Tc-99 GFR nor the CCrC was predictive of the development of renal insufficiency in HSCT patients as the majority of patients who required dialysis had normal Tc-99 GFR prior to transplant. The characteristics found in the patients who developed renal insufficiency and required dialysis include: the use of total body irradiation as part of the transplant-conditioning regimen (p < 0.0001) and the use of continuous infusion CSA (p = 0.04).

Cognitive functioning in children on dialysis and post-transplantation.

We studied 124 children, 62 patient-subjects who had end-stage renal disease (ESRD) and 62 sibling-controls who closely matched the patient-subjects in terms of their ethnicity and their socioeconomic status, to discern whether children with ESRD would perform less well than their siblings on standardized achievement and intelligence quotient (IQ) tests, and to determine whether ethnicity would influence such results. The subjects were recruited from nine pediatric transplant and dialysis centers across the United States. Thirty-one subjects were white (Euro-American), 17 were African-American, and 14 were categorized as 'other'. The average age of the patient-subjects was 13.7 +/- 0.44 yr; and of the sibling-controls 13.7 +/- 0.38 yr. Most patients (61%) and siblings (84%) were in regular school classes, and most (87% and 92%, respectively) attended school full-time. The average IQ percentile rank for the patients was significantly lower than their siblings (31 +/- 4 vs. 44 +/- 5, respectively, with normal = 50). Patients tended to score lower on achievement tests compared with their siblings (spelling: 88.7 +/- 4 vs. 94.6 +/- 2; arithmetic: 88.5 +/- 2 vs. 94.0 +/- 2; reading: 91.9 +/- 2 vs. 100 +/- 3, respectively). Patients scores on achievement tests were influenced by age at diagnosis and by the mother/caregiver's lower achievement. Also, increased time on dialysis predicted lower scores on achievement tests. Neither dialysis/transplant status nor ethnicity significantly affected outcome. Our data suggest that ESRD, but not ethnicity or dialysis/transplant status, is a risk factor for lower IQ and academic achievement, especially in younger children, in children who spend more time living with ESRD, and in children whose mother's/caregiver's have lower educational levels.

Reversal of severe late left ventricular failure after pediatric heart transplantation and possible role of plasmapheresis.

Late acute cardiac graft failure carries a high mortality in adults. Vascular mediators and factors other than classic T-cell-mediated rejection may play a role in this process, and aggressive multimodality therapy may improve survival. We report experience with plasmapheresis in treating late severe acute left ventricular dysfunction in a group of pediatric heart transplant recipients. We retrospectively reviewed clinical records, echocardiograms, hemodynamics, coronary angiograms, biopsy specimens, and treatment regimens for 5 patients with 7 episodes of late-onset severe graft failure who recovered. Plasmapheresis was applied in all cases, in addition to methylprednisolone, cyclophosphamide, lympholytic agents, and aggressive supportive care including mechanical ventilation and hemofiltration. All patients presented with acute severe left ventricular dysfunction 1.4 to 7.9 years (mean 3.6) after orthotopic heart transplantation. Mean shortening fraction at presentation was 13 to 23% (mean 16), initial endomyocardial biopsy specimens were grade 0 to 3B, and immunofluorescence studies were negative. Treatment included plasmapheresis, cyclophosphamide, mechanical ventilation, hemofiltration, and inotropes. Clinical recovery was slow, with 4 to 8 weeks until left ventricular function normalized, and 2.2 to 9.4 (mean 4.6) weeks to hospital discharge. At follow-up (50 to 38 months, mean 24), all are alive. Two patients are well, whereas coronary vasculopathy developed in 3. Thus, survival may improve in patients with late graft failure with low biopsy score and plasmapheresis combined with multimodality therapy.

Elevated bladder urine concentration of transforming growth factor-beta1 correlates with upper urinary tract obstruction in children.

PURPOSE: We evaluated urinary transforming growth factor-beta1 (TGF-beta1) concentration in children with upper urinary tract obstruction as a potential tool for supporting the diagnosis of clinically significant obstruction. MATERIALS AND METHODS: Renal pelvic and bladder urine samples were obtained for analysis from 30 patients a median of 5 months old who underwent surgery for obstruction at the ureteropelvic (29) and ureterovesical (1)junctions. Urinary TGF-beta1 concentration was measured using a quantitative sandwich enzyme-linked immunoassay technique. Bladder urine TGF-beta1 in patients with obstruction was compared with that in controls. In addition, we compared renal pelvic and bladder urine TGF-beta1 in patients with obstruction. RESULTS: Mean bladder urine TGF-beta1 plus or minus standard error of mean was 4-fold higher in patients with upper tract obstruction than in controls (195 +/- 29 versus 47 +/- 7 pg./mg. creatinine, p <0.001). In the obstructed group mean TGF-beta1 in the renal pelvic urine was 378 +/-86 pg./mg. creatinine, or twice that of the bladder urine (p = 0.02). CONCLUSIONS: Bladder urine TGF-beta1 in patients with upper urinary tract obstruction is significantly elevated compared with that in controls. To our knowledge our study is the first to identify a bladder urinary marker that correlates with upper urinary tract obstruction with greater than 90% sensitivity. Measuring TGF-beta1 in a voided bladder urine sample may provide an objective and noninvasive test for assisting in the diagnosis of upper urinary tract obstruction.

Plasma calcium oxalate supersaturation in children with primary hyperoxaluria and end-stage renal failure.

BACKGROUND: Children with primary hyperoxaluria type 1 (PH 1) are at great risk to develop systemic oxalosis in end-stage renal disease (ESRD), as endogenous oxalate production exceeds oxalate removal by dialytic therapy. As oxalate accumulates, calcium oxalate (CaOx) tissue deposition occurs. Children with other causes of ESRD, however, are not prone to CaOx deposition despite elevated plasma oxalate (POx) levels. METHODS: Our study objective was to examine the potential mechanisms for these observations. We measured POx, sulfate, citrate, and calculated CaOx saturation (betaCaOx) in 7 children with ESRD caused by PH 1 and in 33 children with non-PH-related ESRD. Maintenance hemodialysis (HD) was performed in 6 PH 1 and 22 non-PH patients: Pre- and post-HD levels were analyzed at this point and were repeated twice within 12 months in 5 PH 1 and 14 non-PH patients. Samples were obtained only once in 12 patients (one PH 1) on peritoneal dialysis (PD). After liver-kidney or kidney transplantation, plasma levels were measured repetitively. RESULTS: The mean POx was higher in PH 1 (125.7 +/- 17.9 micromol/liter) than in non-PH patients (44.2 +/- 3.3 micromol/liter, P < 10(-4)). All other determined anions did not differ between the two groups. betaCaOx was higher in PH 1 (4.71 +/- 0.69 relative units) compared with non-PH children (1.56 +/- 0.12 units, P < 10(-4)). POx and betaCaOx were correlated in both the PH 1 (r = 0.98, P < 2 x 10(-4)) and the non-PH group (r = 0.98, P < 10(-4)). POx and betaCaOx remained stable over time in the non-PH children, whereas an insignificant decline was observed in PH 1 patients after six months of more aggressive dialysis. betaCaOx was supersaturated (more than 1) in all PH 1 and in 25 out of 33 non-PH patients. Post-HD betaCaOx remained more than 1 in all PH 1, but in only 2 out of 22 non-PH patients. In non-PH children, POx and betaCaOx decreased to normal within three weeks after successful kidney transplantation, whereas the levels still remained elevated seven months after combined liver-kidney transplantation in two PH 1 patients. CONCLUSION: Systemic oxalosis in PH 1 children with ESRD is due to higher POx and betaCaOx levels. As betaCaOx remained supersaturated in PH 1 even after aggressive HD, oxalate accumulation increases, and CaOx tissue deposition occurs. Therefore, sufficient reduction of POx and betaCaOx is crucial in PH 1 and might only be achieved by early, preemptive, combined liver-kidney transplantation or liver transplantation alone.

Endoscopic photocoagulation of the ciliary body for treatment of refractory glaucomas.

PURPOSE: To evaluate the safety and efficacy of endoscopic cyclophotocoagulation in the treatment of refractory glaucomas. METHODS: The preoperative and postoperative courses of 68 eyes of 68 patients who underwent endoscopic cyclophotocoagulation at our institution were retrospectively reviewed. Study patients had diverse forms of glaucoma, and most had failed maximal medical therapy as well as failed filtration or transscleral cyclodestructive procedures, or both. Endoscopic cyclophotocoagulation treatment encompassed 180 to 360 degrees of the ciliary body circumference and was performed through a limbal incision (56 eyes, 12 of which underwent concurrent cataract extraction) or pars plana incision (12 eyes). A second laser treatment was required in five eyes (7%). RESULTS: During the mean follow-up period of 12.9 months, mean +/- SD intraocular pressure decreased from 27.7 +/- 10.3 mm Hg preoperatively to 17.0 +/- 6.7 mm Hg at the final postoperative visit (P < .0001), for a mean reduction of 10.7 mm Hg and a mean percent decrease of 34%. Sixty-one eyes (90%) achieved an intraocular pressure < or = 21 mm Hg. Using this definition of success, Kaplan-Meier analysis predicted a successful outcome in 94% of patients after 1 year and 82% after 2 years. The mean number of glaucoma medications used by each patient was reduced from 3.0 +/- 1.3 preoperatively to 2.0 +/- 1.3 postoperatively (P < .0001). Best-corrected visual acuity was stable or improved in 64 eyes (94%), with four (6%) losing 2 or more lines of Snellen acuity. No case of hypotony (intraocular pressure < 5 mm Hg) or phthisis was observed. CONCLUSION: These early results suggest that endoscopic cyclophotocoagulation is a safe and effective therapeutic modality for refractory glaucomas.

Propionibacterium endophthalmitis following Molteno tube repositioning.

PURPOSE: We describe an aphakic patient who developed recurrent Propionibacterium acnes endophthalmitis after Molteno tube revision. PATIENT AND METHOD: The patient presented with a red painful right eye, decreased vision, and a hypopyon. A moderate anterior chamber reaction and mild vitritis were present. Two weeks earlier, the patient had undergone Molteno tube repositioning. A diagnosis of P. acnes endophthalmitis was made after positive culture of anterior chamber needle aspirate. RESULTS: Initially the patient was treated with repeated intraocular vancomycin injections, to which the eye "responded poorly." Temporary clearance of the infection was achieved after placement of the tube in the subconjunctival space. The patient required explantation of the implant to achieve complete resolution of the infection. CONCLUSION: Tube reinsertion into the anterior chamber resulted in recurrence of the infection. The evaluation of alternative therapies of aqueous tube shunt-related endophthalmitis would require a large case-controlled series of patients.

Nephrotic syndrome accompanying familial hemophagocytic syndrome.

PURPOSE: We describe the first reported case of familial hemophagocytic syndrome (FHS) with concurrent minimal change nephrotic syndrome (MCNS). PATIENTS AND METHODS: This is a case report of a 30-month-old girl who presented to Children's Memorial Hospital with pancytopenia and heavy proteinuria. RESULTS: This patient presented with anemia, neutropenia, thrombocytopenia, hypertriglyceridemia, and proteinuria. A brother died at 2 months of age with similar findings. A bone marrow biopsy demonstrated histiocyte proliferation with marked erythrophagocytosis, consistent with FHS. Treatment was begun with corticosteroids and VP-16. The patient developed worsening peripheral edema and hypoalbuminemia, with heavy proteinuria. After 1 month of therapy with persistence of heavy proteinuria, a renal biopsy was performed, the results of which were consistent with MCNS. CONCLUSION: This is the first reported case of FHS with coincident MCNS.

Verrucous carcinoma of the esophagus: surgical treatment for an often fatal disease.

Verrucous carcinoma of the esophagus is a very rare esophageal cancer, with only 12 cases reported in the literature. Although this cancer is slow growing and rarely metastasizes, it is associated with a significantly high mortality. Because of the disease's insidious onset and its rarity, diagnosis has often been late, after local invasion has produced significant symptoms. We present the thirteenth reported case of verrucous carcinoma of the esophagus and support resection as the best form of treatment for this disease.

Germline intronic and exonic mutations in the Wilms' tumour gene (WT1) affecting urogenital development.

Denys-Drash syndrome is a rare human developmental disorder affecting the urogenital system and leading to renal failure, intersex disorders and Wilms' tumour. In this report, four individuals with this syndrome are described carrying germline point mutations in the Wilms' tumour suppressor gene, WT1. Three of these mutations were in the zinc finger domains of WT1. The fourth occurred within intron 9, preventing splicing at one of the alternatively chosen splice donor sites of exon 9 when assayed in vitro. These results provide genetic evidence for distinct functional roles of the WT1 isoforms in urogenital development.

Favorable experience with pre-emptive renal transplantation in children.

We retrospectively examined our experience with live-related donor kidney transplants in 66 children during the 7-year period 1984-1990. We compared the clinical courses of 26 children who did not receive any dialytic therapy prior to transplantation with 40 children who were dialyzed (27 via peritoneal dialysis and 13 via hemodialysis). We did not find any statistically significant differences in patient or graft survival between these three groups with a follow-up period of 6-87 months. Based on our results, we conclude that pre-emptive transplantation is an acceptable treatment for children who will inevitably require renal replacement therapy.

Favorable outcome of neonatal aortic thrombosis and renovascular hypertension.

Fifteen children with renovascular hypertension as a result of aortic thrombosis were followed for a mean of 26 months (range 5 to 58 months) to determine outcome. As neonates, all patients had hypertension and elevated plasma renin activity. Of 11 patients studied with radionuclide renography and scintigraphy, 10 had abnormal renal blood flow; three had complete absence of unilateral perfusion. On follow-up examination all children were normotensive; five children ages 5 to 24 months required antihypertensive medication. Of 15 children, 14 had normal statural growth; all had normal serum creatinine, plasma renin activity, and calculated glomerular filtration rate values. Patients with complete absence of renal perfusion unilaterally remained functionally anephric; children with less severe perfusion deficits had improved perfusion as shown by radionuclide renography and scintigraphy. We believe that many patients with aortic thrombosis and renovascular hypertension who have had aggressive antihypertensive therapy in the neonatal period will have good renal function and increased perfusion to the affected kidney 2 years later.

Acute renal vein thrombosis: successful treatment with intraarterial urokinase.

When acute renal vein thrombosis is associated with renal failure, aggressive therapy to eliminate the venous obstruction is indicated. There are reports of successful treatment of this condition with thrombolytic agents administered systemically or directly into the renal vein. Renal arterial administration of urokinase was used successfully to treat acute renal vein thrombosis associated with renal failure in a 9 1/2-year-old child.