Patients who take NSAIDs have an increased risk of nonspecific ulceration of the small-intestinal mucosa. These ulcers are less common than ulcers of the stomach or duodenum, but can lead to life-threatening complications.

Thyroid hormones are required for human brain development, but data on local regulation are limited. We describe the ontogenic changes in T(4), T(3), and rT(3) and in the activities of the types I, II, and III iodothyronine deiodinases (D1, D2, and D3) in different brain regions in normal fetuses (13-20 wk postmenstrual age) and premature infants (24-42 wk postmenstrual age). D1 activity was undetectable. The developmental changes in the concentrations of the iodothyronines and D2 and D3 activities showed spatial and temporal specificity but with divergence in the cerebral cortex and cerebellum. T(3) increased in the cortex between 13 and 20 wk to levels higher than adults, unexpected given the low circulating T(3). Considerable D2 activity was found in the cortex, which correlated positively with T(4) (r = 0.65). Cortex D3 activity was very low, as was D3 activity in germinal eminence and choroid plexus. In contrast, cerebellar T(3) was very low and increased only after midgestation. Cerebellum D3 activities were the highest (64 fmol/min.mg) of the regions studied, decreasing after midgestation. Other regions with high D3 activities (midbrain, basal ganglia, brain stem, spinal cord, hippocampus) also had low T(3) until D3 started decreasing after midgestation. D3 was correlated with T(3) (r = -0.682) and rT(3)/T(3) (r = 0.812) and rT(3)/T(4) (r = 0.889). Our data support the hypothesis that T(3) is required by the human cerebral cortex before midgestation, when mother is the only source of T(4). D2 and D3 play important roles in the local bioavailability of T(3). T(3) is produced from T(4) by D2, and D3 protects brain regions from excessive T(3) until differentiation is required.

There is little evidence as to the fatty acid composition of the cerebellum in infancy and it remains uncertain whether milk diet can influence its composition. We therefore examined cerebellar gray and white matter of infants less than 6 month old who had died unexpectedly. The fatty acid content of 33 gray and 21 white matter specimens from infants born at term and 6 gray and 5 white matter specimens from preterm infants was assessed by gas chromatographic/mass spectrometric analysis. Infants were grouped according to whether they had received human or manufactured formula milk. Whereas cerebellar cortex docosahexaenoic acid (DHA, 22:6n-3) concentrations were significantly lower (P<0.01) in the formula-fed than breast-fed infants, no differences existed between the term (n = 10) and preterm (n = 5) Synthetic Milk Adapted [corrected] (SMA) formula-fed infants. Cerebellar white matter DHA concentrations were similarly lower (P<0.01) in the SMA formula-fed infants (n = 8) than in an age-matched breast-fed group. Low concentrations of cerebellar white matter lignoceric (24:0) and nervonic acid (24:1n-9) in two 7-wk-old preterm infants appeared to correlate with postgestational rather than chronological age. Dietary long-chain polyunsaturated fatty acids, particularly DHA, are probably essential for normal development of the infant cerebellum.

Stereologic methods are superior to model based techniques in estimating GBM thickness and should be regarded as the technique of choice in this area. GBM thickness was observed to increase during childhood with no gender effect demonstrable as a main effect or interaction.