Joseph H. Clark

Purine excretion during tumor lysis in children with acute lymphocytic leukemia receiving allopurinol: Relationship to acute renal failure*

We measured serial urine levels of hypoxanthine, xanthine, and uric acid in 19 children with acute lymphocytic leukemia (ALL) receiving allopurinol therapy during tumor lysis; four of these children developed acute renal failure. The urinary excretion of uric acid rose moderately from 447 +/- 251 micrograms/dl glomerular filtrate before chemotherapy to 778 +/- 463 micrograms/dl glomerular filtrate during tumor lysis (P less than 0.05) whereas the urinary excretion of hypoxanthine (17.9 +/- 15 to 292 +/- 213 micrograms/dl glomerular filtrate) and xanthine (74 +/- 62 to 1091 +/- 1085 micrograms/dl glomerular filtrate) rose dramatically (P less than 0.001). The urinary excretion of uric acid, hypoxanthine, and xanthine per deciliter of filtrate was significantly higher (P less than 0.001) in those who developed acute renal failure than in those who did not, but the highest urine concentration of these purine metabolites did not differ in the two groups. In all 19 children, the highest urine concentration of uric acid and hypoxanthine during tumor lysis did not exceed the solubility limit of each in an alkaline urine specimen. In contrast, the peak urine concentration of xanthine exceeded its solubility limit in an alkaline urine specimen in 16 of 19 children. The urine sediment during the period of tumor lysis was examined by diffuse reflectance infrared spectroscopy; precipitated xanthine was found in sediment from eight of the 19 children, was significantly (P less than 0.001) associated with a urine xanthine level greater than 350 mg/dL, and occurred with equal frequency in those who did or did not develop acute renal failure. We conclude that urinary excretion of hypoxanthine and xanthine increases dramatically whereas uric acid excretion rises moderately in children undergoing tumor lysis while receiving allopurinol, that acute renal failure occurs in children with a higher purine load per deciliter of glomerular filtrate, but that factors other than tubular precipitation of purine metabolites are likely to be involved in the pathogenesis of renal failure during tumor lysis.

Nephrolithiasis in Childhood Inflammatory Bowel Disease

Summary:Six children with inflammatory bowel disease and nephrolithiasis are reported. Their mean age at the passage of the first stone was 12.5 years and the mean duration of active inflammatory bowel disease was 34.5 months. Four had ulcerative colitis and two had Crohns disease. In three patient

Fulminant hepatic failure

Fulminant hepatic failure is an infrequent, catastrophic illness that presents a formidable challenge. It is the result of massive hepatocellular injury and necrosis, usually without preexisting hepatic disease, and is complicated by the early development of hepatic encephalopathy. Hepatic insufficiency may also complicate chronic liver disease when progressive destruction leads to decompensation or when acute hepatopathy aggravates a chronic process. The prognosis is grave in both situations, although the patient without preexisting liver disease may recover. Viral hepatitis is the most common infectious cause of acute hepatic failure? Several drugs, including acetaminophen, 2. 3 isoniazid, methyldopa, and sodium valproate, 4 also cause liver failure. Tetracycline can result in a unique form of liver failure with extensive fatty replacement of the liver similar to that seen in fatty liver of pregnancy. A likely cause of fulminant liver failure can often be identified in infants with hepatic insufficiency (Table I), whereas the determinant tends to be elusive in the older child. Hepatic failure arising in the perinatal period is commonly related to a congenital viral infection. Metabolic disorders such as tyrosinemia, galactosemia, and fructose intolerance must be considered when severe hepatic dysfunction appears in the late perinatal period.

Hemorrhagic complications of Henoch-Schönlein syndrome.

Two patients are described with atypical manifestations of Henoch-Schönlein syndrome. One patient suffered severe intracranial hemorrhage and a subsequent massive gastric hemorrhage. The other patient developed an asymptomatic serosanguinous pleural effusion. Both had evidence of profound hypoprothrombinemia at the time of admission. Aggressive management of any coagulopathy accompanying Henoch-Schönlein syndrome is cardinal in order to prevent life-threatening complications such as gastrointestinal, intracranial, and pulmonary hemorrhage.

Spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis should be considered in the evaluation of any patient with acute abdominal complaints, especially in the presence of preexistent ascites. Paracentesis is indicated in all suspected cases of spontaneous peritonitis in order to obtain necessary studies, including microbial cultures. Broad-spectrum antibiotic coverage has become necessary because of the increasing incidence of gram-negative isolates. Ascitic pH and lactate may provide accurate information in the evaluation of spontaneous peritonitis, although increased clinical awareness remains the key to proper diagnosis.

Confirmation of serum salicylate levels in Reye's syndrome: a comparison between the Natelson colorimetric method and high performance liquid chromatography

Serum was obtained from 11 patients with Reyes syndrome at admission and analyzed for the presence of salicylates by the Natelson colorimetric technique and high performance liquid chromatography. Salicylate levels obtained by the Natelson method had a mean of 6.00 mg/dl +/- 4.58; the mean HPLC salicylic acid level was 5.09 mg/dl +/- 5.14. The correlation coefficient was 0.985 with a linear regression line y = 0.8788x + 1.527. No other salicylate metabolites nor interfering substances were identified. Once the accuracy of the Natelson method was confirmed, the charts of 82 patients were reviewed for admission salicylate levels. The overall mean was 8.63 mg/dl (survivors, 8.45 mg/dl +/- 8.56; fatalities, 9.28 mg/dl +/- 5.34). There was no correlation found between admission salicylate level and peak ammonia level, another important index of disease severity.

Dietary Fructose in the Management of Intractable Diarrhea of Infancy

Summary Carbohydrate digestion/absorption was evaluated in 11 infants with intractable diarrhea while they were receiving a carbohydrate-free soy-isolate formula. Seven patients were fed within 48 h of admission. Enteral feedings were initiated in the remainder after they had gained 1 kg while receiving parenteral nutrition. All feedings were initially administered by continuous nasogastric infusion. Nine patients were initially fed formula with polymeric glucose; two received fructose as the carbohydrate source, based on a documented history of polymeric glucose intolerance. Five of the nine developed watery, acidic stools while receiving polymeric glucose. All were switched to fructose, which resulted in improvement in stool pH and consistency. Glucose tolerance was normal 1 month after discharge in all seven fructose-requiring infants. Three of six infants have shown a persistent inability to hydrolyze sucrose. Several putative mechanisms of polymeric glucose intolerance are discussed, as well as the apparent association with primary sucrase-isomaltase deficiency in three of the patients. Fructose is an effective alternative carbohydrate source in infants unable to tolerate polymeric glucose, and early initiation of fructose may obviate the need for total parenteral nutrition and prolonged bowel rest.

Vitamin E sufficiency in children with cholestasis: A comparison between erythrocyte peroxide hemolysis and serum α-tocopherol

Vitamin E sufficiency was assessed in 19 children with chronic cholestasis by determining both erythrocyte peroxide hemolysis (EPH) and serum alpha-tocopherol (alpha-T) levels. Eight had normal alpha-T (1.19 +/- 0.67 mg/dl; normal greater than 0.5). The mean EPH in this group was 13.1 +/- 14.3% (normal less than 20%). The remaining 11 patients had low alpha-T levels (0.25 +/- 0.15 mg/dl) and elevated EPH (83.9 +/- 17.1%). Children found to be vitamin E deficient received either oral alpha-T (50-100 IU/kg per day) or parenteral alpha-tocopherol acetate in sesame oil every 2-4 wk (200-300 mg). This permitted serial monitoring of EPH and alpha-T. We found that normalization of the EPH was uniformly accompanied by normalization of the alpha-T level. However, normal alpha-T levels occurred with elevated EPH (between 20% and 80%) on 11 occasions. EPH greater than 80% correctly identified vitamin E deficiency in all cases. Hence, EPH is a satisfactory screening test of vitamin E sufficiently. When the EPH is less than 20%, the patient is vitamin E sufficient. Conversely, when the EPH is greater than 80%, the patient is vitamin E deficient. Serum alpha-T measurements are needed to determine vitamin E sufficiency when the EPH is greater than 20% and less than 80%.

630 FECAL CARBOHYDRATE ANALYSIS BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

Various techniques which assess carbohydrate (CHO) absorption are available. Determinations of stool pH and reducing substances are nonspecific, and oral CHO tolerance tests assume that gastric emptying and monosaccharide transport are normal. Breath hydrogen analysis quantitates intestinal bacterial degradation of unabsorbed CHO. We have developed a high performance liquid chromatographic (HPLC) technique to qualitate and quantitate unabsorbed CHO in feces. Individual dietary mono-saccharides and disaccharides can be identified. We can detect <1 mg CHO/g fresh stool. Mean recovery rates for fructose, glucose, galactose, sucrose and lactose were greater than 85% over a range of 15-70 mg CHO/g spiked stool. Only maltose demonstrated fecal degradation with 34% recovered as maltose and 50% as glucose. Four “normal” newborns less than two weeks of age had no detectable CHO in their stools. Twelve infants <1 year old with watery, acidic stools were evaluated; 7 had unabsorbed fecal CHO up to 173 mg/g stool. Six of the 12 were evaluated with CHO tolerance tests during convalescence; 3 patients with normal tolerance tests had no fecal CHO while the other 3 had flat tolerance tests and up to 15 mg CHO/g stool during the test. HPLC stool analysis identifies a variety of digestion/absorption defects. A single stool specimen is required and qualitative information is available in one hour.

NEPHROLITHIASIS IN CHILDHOOD INFLAMMATORY BOWEL DISEASE

Nephrolithiasis is an infrequent complication of inflammatory bowel disease (IBD) in children. Five patients have been managed at our institution since 1978. Their mean age at stone passage was 12.2 years and mean duration of active IBD was 33 months. The majority had ulcerative colitis, passed calcium phosphate stones, and developed nephrolithiasis during an acute exacerbation of IBD. Only one patient had a previous intestinal resection; no patient had a history of urinary tract infections. We have initiated a prospective evaluation of urinary crystalloid excretion in all newly diagnosed cases of IBD. Twenty-four hour urine determinations at diagnosis in 6 patients were within the normal range for calcium (mean = 151 mg), uric acid (338 mg) and oxalate (24 mg). One month after the initiation of therapy, there was an elevation in mean urinary calcium (222 mg) and uric acid (630 mg) excretion in 4 children receiving daily prednisone and salicylazosulfapyridine (SASP). These differences were not observed in 2 patients receiving SASP alone (calcium, 142 mg; uric acid, 374 mg). The effect of prednisone on calcium excretion is well described but its role in uric acid excretion is poorly understood. Further attention must be paid to the urinary excretion of various crystalline species throughout the course of IBD to prevent the complication of nephrolithiasis.