Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia.

A compound identified as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) was found in higher concentrations in urine samples of children with autism compared to age and sex appropriate controls and in an adult with recurrent diarrhea due to Clostridium difficile infections. The highest value measured in urine samples was 7500 mmol/mol creatinine, a value 300 times the median normal adult value, in a patient with acute schizophrenia during an acute psychotic episode. The psychosis remitted after treatment with oral vancomycin with a concomitant marked decrease in HPHPA. The source of this compound appears to be multiple species of anaerobic bacteria of the Clostridium genus. The significance of this compound is that it is a probable metabolite of m-tyrosine (3-hydroxyphenylalanine), a tyrosine analog which depletes brain catecholamines and causes symptoms of autism (stereotypical behavior, hyperactivity, and hyper-reactivity) in experimental animals.

Necrotizing enterocolitis: diagnosis with CT examination of urine after enteral administration of iodinated water-soluble contrast material.

PURPOSE: To develop a new method for diagnosing necrotizing enterocolitis with use of computed tomography (CT). MATERIALS AND METHODS: Urine specimens from 22 neonates were obtained 8-12 hours after iohexol was administered enterally. Twelve neonates had suspected (n = 5) or definite (n = 7) necrotizing enterocolitis, and 10 neonates without necrotizing enterocolitis underwent routine upper gastrointestinal study. Urine from another 13 neonates without necrotizing enterocolitis who did not receive iohexol was collected. The attenuation coefficient of each urine specimen was determined with CT. RESULTS: The mean CT attenuation coefficient of urine from neonates who did not receive iohexol was 5.6 HU +/- 3.9, and that from neonates without necrotizing enterocolitis who underwent upper gastrointestinal study was 6.7 HU +/- 3.2. The mean CT attenuation coefficient of urine from patients with suspected necrotizing enterocolitis was 26.0 HU +/- 3.4, and that in patients with definite necrotizing enterocolitis was 71.0 HU +/- 18.8. The mean CT attenuation coefficients in neonates with necrotizing enterocolitis were significantly different from that in patients without necrotizing enterocolitis who underwent upper gastrointestinal study. CONCLUSION: Urine from neonates with necrotizing enterocolitis show significantly higher CT attenuation coefficients than those from patients without necrotizing enterocolitis. CT examination of urine may allow early detection of necrotizing enterocolitis.

Effect of necrotizing enterocolitis on urinary epidermal growth factor levels.

The pattern of urinary epidermal growth factor/creatinine levels in necrotizing enterocolitis was examined in 75 infants (in 28 infants the diagnosis of necrotizing enterocolitis was considered; 47 infants were studied for effect of surgery or nutrition on epidermal growth factor levels). There was a consistent and significant increase in epidermal growth factor/creatinine values at the time of diagnosis of necrotizing enterocolitis compared with baseline values. Epidermal growth factor levels in infants without necrotizing enterocolitis and in early nutrition remained unchanged. These results suggested that urinary epidermal growth factor/creatinine levels may differentiate stage II and III necrotizing enterocolitis from stage I disease. The increased epidermal growth factor/creatinine levels may be related to the absorption into the circulation of preexisting gastrointestinal tract epidermal growth factor through damaged tissue or to increased synthesis by the gastrointestinal tract in response to the injury caused by necrotizing enterocolitis.

Enhanced urinary immunoreactive thromboxane in neonatal necrotizing enterocolitis. A diagnostic indicator of thrombotic activity.

Urinary thromboxane B2 levels increased threefold to 20-fold in infants with neonatal necrotizing enterocolitis compared with healthy infants and infants with benign causes of heme-positive stools. Increased urinary thromboxane B2 levels were detected coincidently with the initial signs of necrotizing enterocolitis, and values paralleled the course of the illness. Infants with serious illnesses other than necrotizing enterocolitis had increased urinary thromboxane B2 levels but with lower values than those of infants with necrotizing enterocolitis. Indomethacin therapy appeared to reduce urinary thromboxane B2 levels and reduce their usefulness as a marker of illness. Another product of platelet activation, beta-thromboglobulin, was increased in the urine of infants with necrotizing enterocolitis. Decreased platelet counts in infants with necrotizing enterocolitis correlated inversely with urinary thromboxane. Results of beta-thromboglobulin and platelet studies are consistent with the concept that platelet consumption due to ischemic thrombosis was the source of enhanced thromboxane excretion.

Urinary D-lactate excretion in infants with necrotizing enterocolitis.

Urinary D-lactate excretion, expressed as the molar D-lactate/creatinine ratio, was measured serially in nine term and premature infants with necrotizing enterocolitis, 15 healthy term infants, and eight term and premature infants sick but without NEC. The mean (+/- SD) uDL/CR of the infants with NEC was 1.63 +/- 1.09, significantly greater than the mean uDL/CR of the healthy infants (0.16 +/- 0.04) or the sick infants without NEC (0.43 +/- 0.32). The uDL/CR of infants with NEC rose coincident with the onset of disease, reached peak values at an average of 5.8 days, and subsided to baseline levels on recovery. Seven of the nine infants with NEC reached or exceeded a peak uDL/CR of 1.47; no infant without NEC reached this ratio. We conclude that uDL/CR is increased in infants with NEC and demonstrates the increased enteric bacterial activity in this disease.