Preimplantation human embryos and embryonic stem cells show comparable expression of stage-specific embryonic antigens.

Cell-surface antigens provide invaluable tools for the identification of cells and for the analysis of cell differentiation. In particular, stage-specific embryonic antigens that are developmentally regulated during early embryogenesis are widely used as markers to monitor the differentiation of both mouse and human embryonic stem (ES) cells and their malignant counterparts, embryonic carcinoma (EC) cells. However, there are notable differences in the expression patterns of some such markers between human and mouse ES/EC cells, and hitherto it has been unclear whether this indicates significant differences between human and mouse embryos, or whether ES/EC cells correspond to distinct cell types within the early embryos of each species. We now show that human ES cells are characterized by the expression of the cell-surface antigens, SSEA3, SSEA4, TRA-1-60, and TRA-1-81, and by the lack of SSEA1, and that inner cell mass cells of the human blastocyst express a similar antigen profile, in contrast to the corresponding cells of the mouse embryo.

A critical evaluation of transsphenoidal pituitary surgery in the treatment of Cushing's disease: prediction of outcome.

Twenty-eight patients underwent transsphenoidal pituitary surgery for Cushing's disease. Selective surgical procedures were performed in 26. In 19 patients pituitary adenoma was confirmed histologically and 5 had clumps or clusters of ACTH-staining cells. At follow-up after 22.3 (range 5-56) months 21 (75%) patients remained in clinical and biochemical remission. The 24-h urinary free cortisol performed between 1 and 4 weeks postoperatively while patients took replacement doses of dexamethasone (0.5 to 0.75 mg per day) was found to predict outcome. All patients with suppressed urinary free cortisol excretion have remained in remission, 3 with levels in the normal range have suffered late relapse after initial remission, and 4 with elevated urinary free cortisol excretion were regarded as having failed to remit. Furthermore, all patients with unsuccessful outcomes had no pituitary adenoma and 3 had features consistent with corticotrope nodular hyperplasia at histological examination compared to only 2 and 1, respectively, of patients still in remission. We conclude that 24-h urinary free cortisol performed at 1 to 4 weeks postoperatively whilst on low-dose dexamethasone and the histological findings may predict outcome following transsphenoidal pituitary surgery in Cushing's disease.

Inferior petrosal sinus sampling in acromegaly.

In view of the diagnostic value of bilateral simultaneous inferior petrosal sinus sampling (BSIPSS) in localising preoperatively the site of the microadenoma in pituitary dependent Cushing's disease, the clinical value of BSIPSS was evaluated in five acromegalic patients with equivocal or negative pituitary CT scans. Intersinus GH gradients were obtained for all patients (range 1.6-4.2) but in only one case was the gradient correctly localised to the side of the tumour. Gradients of several other pituitary hormones, particularly prolactin (range 1.6-4.0), also demonstrated gradients parallel to the GH intersinus gradients. Despite the paradoxical intersinus GH gradients, the surgeon was able to readily identify the tumour at the time of surgery. Thus BSIPSS is of little assistance to the surgeon for the preoperative radiological evaluation in acromegaly and these results caution against the universal adoption of the BSIPSS technique in the radiological assessment of all secretory pituitary microadenomas.

Multiple pituitary hormone gradients from inferior petrosal sinus sampling in Cushing's disease.

Pre-operative bilateral simultaneous inferior petrosal sinus sampling with assessment of ACTH levels in the left and right sinuses and the periphery was performed in 9 patients with pituitary dependent Cushing's disease who were subsequently found at surgery to have basophil microadenomata. The novel observation of this study was the pattern of secretion of other pituitary hormones so that significant inter-sinus gradients greater than or equal to 1.4:1 were seen for beta-endorphin (2.8 +/- 1.3, mean +/- SEM), PRL (4.2 +/- 1.3) and GH (6.9 +/- 2.4) as well as for ACTH (5.1 +/- 1.1). There was no inter-sinus gradient for LH, FSH and TSH. In these 9 patients with adenomata, the correlations between the inter-sinus gradients for ACTH and beta-endorphin were r = 0.95 (P less than 0.01), ACTH and PRL r = 0.90 (P less than 0.01) and for ACTH and GH r = 0.89 (P less than 0.05). This close association between the gradients for ACTH and other anterior pituitary hormones could be due either to co-secretion of beta-endorphin, PRL and GH by the ACTH-producing pituitary adenomata or to a paracrine effect of beta-endorphin from the tumours on adjacent pituitary tissue. By reflecting the central pituitary hormone milieu, petrosal sinus sampling can give information about pituitary function unobtainable from peripheral hormone levels.

Clinical spectrum of primary empty sella turcica.

Over recent years empty sella turcica has become more frequently diagnosed with high resolution computerized tomography and the associated clinical abnormalities have been better described. In this article the spectrum of clinical presentation is based on a review of 26 cases with six illustrative case reports. Recommendations for management and further assessment are presented. It is important for clinicians to be aware of the varying presentations of this syndrome, since it should not be considered simply as an incidental finding. A patient diagnosed with empty sella syndrome requires clinical and endocrine evaluation, and appropriate follow-up as determined by initial test results.

Modification of alpha-adrenoceptor agonist antinociceptive activity by nisoxetine: a selective inhibitor of noradrenergic uptake.

The alpha-adrenoceptor agonists, clonidine and xylazine, produced a dose-dependent antinociceptive effect in the mouse writhing assay as does morphine. Fluoxetine, a highly-specific inhibitor of serotonin uptake, enhanced the antinociceptive effect of morphine in this test but not that of clonidine or xylazine. In contrast, nisoxetine, a selective inhibitor of noradrenergic uptake, significantly potentiated the antinociceptive activity of morphine, clonidine, and xylazine. These findings strengthen the evidence for an involvement of a noradrenergic mechanism in the antinociceptive effects of alpha-adrenoceptor agonists.

The low intracranial pressure syndrome.

The syndrome of low intracranial pressure may develop in a variety of circumstances, e.g. after lumbar puncture, following head injury and intracranial operations. It sometimes occurs after viral meningitis. The case history is described of a woman in whom the disorder was unusually severe and persistent. Interesting radiological features were observed, the appearances being those of herniation of the brain towards the tentorial opening. Simple measures of treatment produced dramatic and lasting relief.