Ultrasound biomicroscopy of the eye in cystinosis.

OBJECTIVE: To describe the ocular ultrasound biomicroscopy (UBM) findings in patients with cystinosis. METHODS: Six patients with infantile nephropathic cystinosis, aged 16 to 25 years, and 6 controls (matched for age and spherical refractive error) were examined clinically and with UBM. Scleral reflectivity, corneal and iris thickness, central anterior chamber depth, angle width, trabecular meshwork to ciliary process distance, and ciliary sulcus width were measured. RESULTS: No patient had glaucoma or posterior synechiae, but all had crystals in the trabecular meshwork apparent with gonioscopy. Using UBM, the cornea and iris appeared similar in both groups, but the scleral reflectivity was increased in patients (P =.003). The angle was narrower in patients (mean +/- SD, 20 degrees +/- 7 degrees ) than controls (31 degrees +/- 5 degrees, P<. 001). The anterior chamber was shallower in patients (2556 +/- 197 microm) than controls (2968 +/- 284 microm, P<.001). The ciliary sulcus was closed or narrow in all patients (83 +/- 112 microm) compared with controls (339 +/- 135 microm, P<.001), with a reduction in the trabecular meshwork to ciliary process distance. CONCLUSIONS: This report of ocular UBM findings in cystinosis demonstrated narrowing of the angle and a ciliary body configuration similar to that reported for plateau iris syndrome. Gonioscopy demonstrated crystals in the trabecular meshwork. These findings may explain the predisposition of these patients to glaucoma.

Diagnosis and management of stenotic aorto-arteriopathy in childhood.

Stenotic aorto-arteriopathy is an uncommon vascular lesion characterized by segmental arterial stenoses. We reviewed the experience with several management algorithms to define the most effective management course. The clinical records of 14 pediatric patients with acquired SAA who presented over a 16-year period were reviewed. Most patients presented with a mid-thoracoabdominal coarctation and were diagnosed with Takayasu arteritis. Differentiating between Takayasu arteritis and fibromuscular dysplasia was difficult on clinical grounds or by angiography. Medical management of the end-organ disease and renovascular hypertension was only palliative. Selective percutaneous transluminal balloon angioplasty of the stenotic renal arteries had only transient benefits; renal autotransplantation had slightly better success. Dilation of stenosed aortic segments with balloon-expandable endovascular stents and subsequent renal autotransplantation proved useful. Distinguishing SAA resulting from fibromuscular dysplasia caused by Takayasu arteritis in the chronic vaso-occlusive phase may be unnecessary for effective treatment. Therapy should focus on interventions to minimize the end-organ damage caused by the vaso-occlusive manifestations of the disorders.

Pediatric pheochromocytoma. A 36-year review.

Fourteen children (10 boys and 4 girls, aged 8 to 17 years) had 20 pheochromocytomas treated over a 36-year period from 1959 to 1995 inclusive. Nine patients had 11 tumors before 1980; 5 children had 9 tumors up to 1987. There were no new children with pheochromocytomas at our hospital from 1988 to 1995. Hypertension, sweating, headache, and visual blurring were the most common symptoms and signs (average 5 months). The most reliable biochemical investigations were the urinary catecholamines and norepinephrine. Before 1980, intravenous pyelography and angiography were most successful in localizing the tumor, but since then ultrasonography and computerized tomography have been the radiological investigations of choice. Early involvement of the anesthesiologist in the preoperative control of the hypertension is essential; blood pressure (BP) control was achieved with phenoxybenzamine. The main anesthetic drugs used were: sodium thiopental, fentanyl, methoxyflurane, isoflurane, nitrous oxide, and metocurine. Sixteen tumors were adrenal and 4 were extra-adrenal (1 intrathoracic and 1 extradural). All except 2 tumors were completely resected; they ranged in size from 1.3 to 14 cm. Ligation of the tumor's venous drainage was usually associated with a sudden, temporary fall in systemic BP. There were 2 children with malignant tumors. Four patients had five recurrences (second pheochromocytoma) within 6 years, and all were heralded by a return of their original symptoms and signs. One girl was left with no adrenal tissue. The only complication was in a boy with a large, partly-resected malignant right adrenal tumor who had a subphrenic abscess drained and was left with a temporary bile fistula, cirrhosis, and chronic pain. All children were normotensive when discharged from hospital and remain alive and well with a follow-up of 7 to 36 years. There were no deaths. Long-term follow-up is essential. Key word Pheochromocytoma

Penoscrotal transposition: a case report and review.

We report on a boy born with complete penoscrotal transposition, normal scrotum, twisted penile shaft with hypoplastic penile urethra, meatal stenosis, normal bladder, and bilateral cystic dysplastic kidneys. The patient died of renal failure at 2.5 months. This is the 13th reported case of complete penoscrotal transposition with normal scrotum. The possible pathogenesis is discussed and the literature is reviewed.

Peritoneal dialysis in the prune belly syndrome.

OBJECTIVES: To describe our experience with chronic ambulatory peritoneal dialysis in children with the prune belly syndrome (PBS). DESIGN: From our peritoneal dialysis (PD) program we were able to review the medical records of 6 boys with PBS. Data were collected on potential complications such as infections, hernias, growth, and problems encountered with PD catheter insertion. RESULTS: The ages of the 6 boys ranged from 10 months-17 years. The dialysis duration was from 9-22 months, with a total of 76 patient-months on PD. There was one death, possibly as a complication of an exit-site infection. Five received a renal transplant, and 4 have functioning grafts. Peritonitis occurred once in every 10.8 patient-months, and exit-site or tunnel infection was diagnosed every 7.6 patient-months. Four patients required PD catheter replacement because of tunnel infection in 2, persistent exit-site infection in 1, and fluid leakage in 1. Of a total of nine catheters, three were inserted using a laparoscopic technique. There were no leaks in these three; however, there was one exit-site infection. Two patients had inguinal hernias that required surgery. CONCLUSION: Deficiency of abdominal musculature in PBS poses potential problems for the use of PD, in particular, catheter anchorage, exit-site healing, and leakage. In our patients the most serious complications were infections of the exit site or catheter tunnel. Our experience suggests that a laparoscopic technique may provide improved catheter placement. PD offers a potentially successful form of dialysis for patients with PBS.

Inherited WT1 mutation in Denys-Drash syndrome.

Patients with the Denys-Drash syndrome (Wilms' tumor, genital anomalies, and nephropathy) have been demonstrated to carry de novo constitutional mutations in WT1, the Wilms' tumor gene at chromosome 11p13. We report three new cases, two carrying a previously described WT1 exon 9 mutation and one with a novel WT1 exon 8 mutation. However, unlike patients in previous reports, one of our three patients inherited the affected allele from his phenotypically unaffected father. This observation indicates that the WT1 exon 9 mutation affecting 394Arg demonstrated in over one-half of the patients with the Denys-Drash syndrome may exhibit incomplete penetrance. Consequently, familial studies in patients affected by this syndrome are recommended.

Renal osteodystrophy in children on CAPD: a prospective trial of 1-alpha-hydroxycholecalciferol therapy.

The efficacy of 1 alpha-hydroxycholecalciferol in the prevention of renal osteodystrophy in children commencing continuous ambulatory peritoneal dialysis was studied in 12 patients, 0.8-17 years of age, who were randomly assigned to either group I receiving standard therapy or to group II receiving in addition 10-20 ng/kg body weight/day of 1 alpha-hydroxycholecalciferol. Calcium carbonate compounds were used to control hyperphosphataemia. Mean plasma calcium (total and ionised) and phosphate levels were not significantly different between the two groups. All group I patients continued to have elevated plasma immunoreactive parathyroid hormone levels at 6 months compared to only 1 patient in group II (p less than 0.05). Four patients in group I developed subperiosteal erosions on radiography compared to the healing of mild lesions in 2 patients in group II. Bone histomorphometry on iliac crest needle biopsy specimens revealed a significant reduction in osteoid index and seam width in group II. Serum aluminum levels decreased during the course of continuous ambulatory peritoneal dialysis, and the significant staining for bone aluminum in 6 patients at the beginning of the study was no longer present in 5 patients at 6 months. Our data demonstrate that 1 alpha-hydroxycholecalciferol is beneficial in the prevention and treatment of bone disease in children on continuous ambulatory peritoneal dialysis.

Interstitial foam cells in renal biopsies: an aid in differentiating idiopathic membranoproliferative glomerulonephritis (type I) and membranoproliferative glomerulonephritis associated with systemic lupus erythematosus.

A patient with nephrotic syndrome whose renal biopsy showed membranoproliferative glomerulonephritis (MPGN) is described. Clinical and laboratory findings included an erythematous malar flush, proteinuria, casts in the urine and a positive antinuclear factor. Hence, it was not clear whether the MPGN was idiopathic, secondary to early systemic lupus erythematosus (SLE) or mainly a renal form of SLE. Treatment with prednisone and azathioprine was unsuccessful, and no new clinical or serological features of SLE appeared. A second renal biopsy 19 months later showed MPGN and large numbers of interstitial foam cells. The finding of foam cells prompted a review of other renal biopsies which were diagnosed as MPGN type I and diffuse proliferative lupus nephritis (DPLN), including lupus-associated MPGN. Nine of thirty-eight (24%) MPGN type I but none of 22 DPLN biopsies contained interstitial foam cells. Therefore, finding foam cells in a renal biopsy may help in differentiating MPGN type I from lupus-associated MPGN.

Naproxen-associated renal failure in a child with arthritis and inflammatory bowel disease.

Renal failure occurred in a 14-year-old girl with peripheral arthritis associated with inflammatory bowel disease while she was being treated with naproxen. She had previously received aspirin and tolmetin sodium and had no complications. A renal biopsy showed a severe tubulointerstitial nephritis. Although her renal function improved somewhat with corticosteroid treatment, it worsened when the steroids were discontinued. This case emphasizes that renal failure can develop insidiously in children on nonsteroidal anti-inflammatory drug therapy and that such children must be monitored closely for signs of nephrotoxicity.

Pancreatic endocrine insufficiency in posttransplant cystinosis.

Nephropathic cystinosis causes renal death by approximately age 10 years. With increased life span due to kidney transplantation, ten to 25 years of cystine accumulation has resulted in pancreatic complications in individuals with cystinosis. We noted severe hyperglycemia in five posttransplant patients, three of whom remained insulin-dependent diabetics several years after transplant. The clinical findings were not consistent with steroid-dependent or insulin-resistant diabetes. Pancreatic cystine deposition was detected histologically and biochemically on post-mortem examination of two other patients. We conclude that hyperglycemia may be anticipated in the immediate posttransplant period in cystinotic patients and that some patients will require insulin therapy years later. The use of cystine-depleting agents should be considered in posttransplant cystinosis as an attempt to prevent potential damage to the pancreas and other organs from cystine deposition.

Postoperative hypertension after repair of coarctation of aorta in children: protective effect of propranolol?

The effects of the nonselective beta blocker, propranolol, on coarctectomy-induced hypertension were evaluated relative to changes in cardiac function, sympathetic tone, and plasma renin activity (PRA). A randomized, placebo-controlled, double-blind, age-stratified design was employed. Propranolol (n = 11, mean age 9.4 years) or placebo (n = 12, mean age 10.2 years) was started 2 days before surgery and continued until 6 days after surgery. In patients on placebo, systolic and diastolic blood pressure, heart rate, and cardiac index increased rapidly and peaked within 1 day after surgery. Over the ensuing days these increases gradually abated. Plasma epinephrine and PRA increased markedly within 12 hours after surgery, but returned quickly toward preoperative levels. In contrast, plasma norepinephrine increased more gradually and remained elevated longer. In patients on propranolol, systolic blood pressure, heart rate, cardiac index and PRA showed only negligible increases. However, diastolic blood pressure, increased even faster with propranolol than with placebo but to the same extent. Plasma catecholamines showed similar increases on the two treatments. Only in the placebo group was the code broken in the intensive care unit because of hypertension uncontrolled by sodium nitroprusside; this occurred in 6 of 12 patients. We conclude that nonselective beta blockade ameliorates the hyperdynamic circulation and increase in systolic blood pressure following coarctectomy. The initial increase in diastolic blood pressure following surgery in the propranolol group may have been caused by vascular beta-2-receptor blockade resulting in unopposed alpha-receptor-mediated vasoconstriction.

Exercise in children before and after coarctectomy: hemodynamic, echocardiographic, and biochemical assessment.

After repair of coarctation of the aorta, some patients with normal blood pressure at rest have an exaggerated hypertensive response to activity. Blood pressure response to exercise was studied in 15 children, aged 5 to 15 years, prior to and at periods up to 6 months following coarctectomy. Preoperatively, 11 of 15 children had systolic hypertension at rest and 12 of 15 after exercise. After surgery, only one child had mild systolic hypertension at rest, whereas exercise-induced hypertension persisted in 33% of patients (all older than 10 years). Exercise plasma renin activity was elevated preoperatively but normalized following surgery. No significant difference was seen in resting and exercise plasma catecholamine levels measured before and after surgery. Over the follow-up period of 6 months, echocardiographic evidence of left ventricular hypertrophy regressed in the younger patients but not in the older patients with exercise-induced hypertension. Exercise testing defines a subgroup of patients with exercise-induced hypertension evident soon after surgery. Structural upper segment arterial vessel wall changes in the older patient may explain these observations.

Correlation of renal histology with outcome in children with lupus nephritis.

We assessed renal histological features in 20 children with diffuse proliferative lupus nephritis (DPLN) to determine whether they were useful in predicting clinical outcome. Renal biopsies were analyzed by assigning scores indicating an activity index (AI) and chronicity index (CI). Clinical assessment of renal function at biopsy and outcome were graded according to urinalysis, serum creatinine, need for dialysis and/or transplantation, and/or death from end-stage renal failure. Renal function at biopsy correlated significantly with AI and CI. Serum complement (C3 and C4) correlated significantly with CI but not with AI. The usefulness of the clinical grading system was confirmed in ten patients who underwent repeat biopsies. Of these, four converted from DPLN to mesangial or membranous lupus and showed improvement in their grade, while only one of the six with DPLN on both biopsies improved. After a mean follow-up of 4.0 years, 14 of the 20 patients showed clinical improvement, four were unchanged, and two were worse. CI predicted clinical outcome (P less than 0.01) but AI did not. Histologic scores of AI and CI obtained from renal biopsies showing DPLN may be useful in predicting therapeutic responses and designing prospective clinical trials to determine optimum management of children with DPLN.

Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis.

A study was conducted to examine renal function in 10 healthy control subjects and eight patients with cystic fibrosis in stable condition. Sequential bolus injections of 99mTc-DTPA and 125I-OIH were administered to assess glomerular filtration rate and effective renal plasma flow, respectively. Blood was subsequently collected for 3 hours, and urine for 24 hours. Renal clearances of both radioisotope markers were virtually identical in patients and controls. Inasmuch as neither glomerular filtration rate nor effective renal plasma flow was enhanced in patients with cystic fibrosis, increased clearance of drugs in these patients is unlikely to be the result of enhanced glomerular filtration or tubular secretion.

Abnormal mitochondria on a renal biopsy from a case of mitochondrial myopathy.

Mitochondrial myopathy (MM) is reported in a 5-year-old girl with short stature, hypotonia, ptosis, retinal pigmentation, and Fanconi's syndrome. A muscle biopsy showed the characteristic features of MM, and a renal biopsy revealed abnormal mitochondria in tubular cells that were similar to those seen in the muscle. This is the first report of such findings in association with MM.

Wilms' tumor and glomerular disease. Occurrence with features of membranoproliferative glomerulonephritis and secondary focal, segmental glomerulosclerosis.

A case of bilateral Wilms' tumor occurred in which a renal biopsy performed for proteinuria showed features of membranoproliferative glomerulonephritis (MPGN) type 1 and focal segmental glomerulosclerosis (FSGS). A review of the literature for similar cases revealed 24 patients with Wilms' tumor associated with glomerular disease; MPGN was present in one of these cases and FSGS in six. In our patient, circulating immune complexes were detected in the serum and likely played a role in the pathogenesis of the MPGN; the FSGS may have resulted from hyperperfusion of the remaining glomeruli in a kidney that was largely replaced by Wilms' tumor.

Cadaveric renal transplants in children under 6 years of age.

Thirty-nine cadaveric renal allografts were performed in 28 children under 6 years of age. Common primary renal diseases were glomerulonephritis, dysplasia/hypoplasia, and reflux/obstructive nephropathy. After a mean follow-up of 40 months of patients with surviving grafts, 19 patients had functioning grafts, 3 had returned to dialysis, and 6 had died. These children required an extraordinary amount of care postoperatively because of anorexia, diarrhea, and ileus. Their psychomotor and physical development was retarded prior to transplant; this reversed dramatically after transplant, but catch-up growth occurred in only 4 patients. Many patients were noticeably more active and distractible for 1 to 2 years post-transplant. Major causes of graft failure were primary nonfunction of 5 donor kidneys (4 from donors under 1 year old) and renal vessel thrombosis in 5 recipients (3 with native kidneys in place who received kidneys from donors over 10 years old). Other causes were recurrence of hemolytic uremic syndrome and Wilms tumor, rejection, and sepsis. Kidneys from donors under 1 year old proved unsatisfactory, and large donor kidneys in small children tended to thrombose, especially when native kidneys with high urine output were left in situ.