Early neurophysiology and MRI in predicting neurological outcome at 9-10 years after birth asphyxia.

OBJECTIVE: To assess whether early somatosensory evoked potentials (SEP) predict long-term neurodevelopmental outcome in normothermic, full-term infants with mild to moderate neonatal encephalopathy (NE), and to compare their predictive value to already available amplitude integrated EEG (aEEG) and magnetic resonance imaging (MRI). METHODS: Fifty-six infants with post-asphyxia NE were prospectively recruited, and their SEP, aEEG and MRI data were acquired during the first five days. Follow-up continued to 9-10 years for assessment of neuromotor and neurocognitive development. We analysed SEP latency (N1 component), normality of aEEG background pattern, as well as patterns of injury on the neonatal MRI. Neurological outcome measures at 9-10 years included conventional MRI, Movement-ABC and the WISC-III NL. RESULTS: A SEP latency <50 ms during the first five days was associated with a normal neuromotor outcome (p < 0.03), and a prolonged day 3 latency was associated with lower childhood IQ (p = 0.02). The presence of multiple seizures in aEEG, as well as a moderate or severe injury on the neonatal MRI was associated with a poor neuromotor score (p = 0.03 and p < 0.01, respectively). Combination of multiple techniques improved prediction of long-term outcome compared to single modality. CONCLUSION: Early SEPs provide information that is comparable to the already available aEEG and MRI paradigms in the prediction of long-term outcome of full-term infants with mild to moderate neonatal encephalopathy. SIGNIFICANCE: The present results call for further studies using early SEP to aid early assessment of infants treated with hypothermia.

Proteolytic degradation of human recombinant proinsulin/insulin by sera from acute pancreatitis patients and complete inhibition by Eglin-C.

Sera from patients of biliary, alcoholic, and idiopathic acute pancreatitis with severity scored from 1 to 5 based on the Ranson criteria were tested for proinsulin/insulin degrading activity. Proinsulin degrading activity by normal controls was 8 +/- 4% as compared with 22-78 +/- 17% with a mean of 45% by the patient sera. An order of magnitude increase of proinsulin degrading activity was accompanied by an order of magnitude increase of immunoreactive pancreatic cationic trypsin(ogen) and (pro)elastase-2 as determined by radioimmunoassay with day 1 sera. Proinsulin degrading activity also showed a negative correlation with the clinical time course and dropped to normal by 6 days after admission. The decrease of proinsulin degrading activity was concomitant with a decrease of serum immunoreactive pancreatic serine proteases. High-performance liquid chromatography analysis of the proteolysis products showed the appearance of insulin and smaller peptides with no proinsulin conversion intermediates. Ninety to ninety-eight percent of proinsulin degrading activity was inhibited by anti-alpha 2-macroglobulin (alpha 2-M) antiserum, or (Ac)Eglin-C(J141), and 52% by an elastase and chymotrypsin-specific inhibitor, MeOSuc-Ala-Ala-Pro-boroVal-pinacol. E64c, TLCK, alpha 1-protease inhibitor (alpha 1-PI), or Trasylol inhibited proinsulin degrading activity by 10-17%, and anti-cathepsin B antiserum by 9%. The observed proinsulin degrading activity did not correlate with the Ranson's scores, age, sex, etiology, total serum immunoreactive insulin, calcium, albumin or alpha 2-M but had a negative correlation with serum alpha 1-PI (r = -0.55) and a positive correlation with serum esterase activity (r = .62).(ABSTRACT TRUNCATED AT 250 WORDS)