Initial gastrointestinal endocrine cells (GIECs) likely appear at the proximal and distal sites of abdominal intestines and may take a close topographical relation with neural elements in the gut. We examined immunohistochemically-stained sections from 10 fetuses at approximately 8–18 weeks of gestational age (36–155 mm of crown-rump length). Irrespective of whether physiological herniation was present (early 5 specimens) or absent (the other 5), the duodenum and jejunum had well-developed mucosa with villi containing abundant flask-like chromogranin-positive cells. In the earlier 5 specimens, the rectum, standing up to a level of the umbilicus, had a lumen and villi with a few positive cells, but the colon carried neither the lumen or chromogranin-positive cells. The initial GIECs seemed to appear in the basal payer of the epithelium at the distal and proximal foci depending on double pathways of neural crest cell migration. Less number of the colic chromograninpositive cells, more than 5-times difference in density relative to small intestine, was seen in the larger 5 specimens. The appearance of GIECs was delayed at the anal transitional zone (a border area between the columnar and squamous epithelia).The reactivity of neuronal nitric oxide synthase was restricted in the myenteric plexus, whereas clusters of slender calretininpositive cells existed in the lamina propria or core of villi in the duodenum and colon. Relatively small, round or oval positive cells were also seen in the basal layer of the columnar epithelium. Therefore, calretinin-positive cells might exist closely to GIECs in the developing villi.

The patch test is the most reliable method for diagnosing a metal allergy. However, interpretation of patch test results depends on the experience of the investigator and on the conditions of the individual patient. In the case of patch tests for metal salts, irritant reactions such as pustular or follicular reactions are quite common. Therefore, one must be careful not to interpret irritant reactions as allergic responses, and objective standards to evaluate erythema in patch tests need to be established.In the present study, we attempted to objectively evaluate patch test results for metal salts using an erythema index meter. We used the Erythema Index Difference (EID) (patch test site erythema index (EI) minus the mean EI of healthy skin outside the patch test area and at the unit tape site) rather than the EI itself in order to eliminate the effects of the patch test unit and individual differences. We measured the EID over time in patients with suspected metal allergies to various metals. Significant differences in EID were observed among ++ assessments, + assessments and irritant reactions based on International Contact Dermatitis Research Group (ICDRG) standards. In considering changes in EID over time, allergic and irritant reactions can be discriminated with high sensitivity (73.3%) and specificity (91.2%).These results suggest that the measurement of erythema over time with an erythema index meter is useful for the objective assessment of metal patch test reactions.