From childhood migraine headache to pheochromocytoma.

Pheochromocytoma may have multiple clinical manifestations including paroxysmal hypertension, tachycardia, sweating, nausea, and headache (Phillips et al., 2002). Migraine has some of the manifestations seen with pheochromocytoma. We describe a patient who had a history of migraine headaches since childhood and was found to have pheochromocytoma. Resection of her tumor significantly improved her headache. The diagnoses of pheochromocytoma subsequently lead to diagnosing her with medullary thyroid cancer (MTC) and multiple endocrine neoplasia type 2A (MEN-2A).

Urothelial mesh--a new technique of cell culture on biomaterials.

INTRODUCTION: Urogenital malformations, trauma or tumours may demand surgical reconstruction in children. Cell culture is an important technology in biomaterial research and tissue engineering. Tissue-engineering of urothelial organs is of interest in children, because the number of complications and re-operations may be reduced. Actually, monolayer cultures of urothelium are used for tissue engineering and biocompatibility testing. A culture system that more closely mimics the physiologic environment of the urothelium would be of interest. The aim of this study was to determine the biological and mechanical characteristics of urothelial mesh cultured in vitro. METHODS: Meshes containing urothelium, lamina propria, and submucosal tissue were generated using a skin mesh graft cutter. Meshes were cultured in 6-well plates, on collagen I/III, polydioxanone/polylactic acid and silicone matrices. Cell morphology was examined by inversion microscopy, histology, and scanning electron microscopy. It was compared to urothelium cultured by methods reported in the literature. To define the basic mechanical properties, meshes were extended longitudinally by a servohydraulic testing machine and strain diagrams generated. RESULTS: Urothelium was reproducibly cultured from meshes. Cell growth could be induced onto fibrillary collagen, polydioxanone-polylactic acid matrices and shaped polyurethane surfaces. Cells formed confluent layers of flat cells, resembling native urothelium. The meshes have unique mechanical properties, allowing for stable fixation, surgical handling and mechanical stimulation. CONCLUSIONS: Meshes can be used for cell culture on biomaterials. They maintain epithelial-stromal integrity and mechanic stability. The small size of tissue bridges allows in vitro culture for long periods with many potential advantages for tissue engineering and biologic research. Applications are possible both in vitro and in vivo.

An adrenal cyst associated with 19-nor-deoxycorticosterone excess and low renin hypertension.

Adrenal cysts are rare, but they have been disproportionately associated with hypertension. This report describes a hypertensive patient with increased levels of 19-nor-deoxycorticosterone (19-nor-DOC), a potent mineralocorticoid. The patient was a thirty year old man with hypokalemia, moderately severe hypertension, suppressed PRA, and low aldosterone secretion. Following surgical removal of a 10 cm adrenal cyst, the hypertension improved, the hypokalemia resolved, and the PRA and the aldosterone secretion normalized. Urinary 19-nor-DOC pre-op was elevated 4.6 microgram per day (normal less than 1.0 microgram/day and subsequently became normal at 0.7 microgram per day following surgery. The adrenal cyst was a fibrous walled structure containing mucinous straw-colored fluid. Pericystic adrenocortical tissue demonstrated increased 19-OH-DOC production (a 19-nor-DOC precursor) which may have been responsible for the 19-nor-DOC excess. We hypothesize that compressive adrenal damage from the cyst may produce a form of adrenal regeneration hypertension which is known to be associated with 19-nor-DOC excess.

Identification of 19-hydroxy-progesterone in human placenta.

We have tentatively demonstrated the presence of a 19-hydroxylated C21 steroid, 19-hydroxy-progesterone, in normal human placenta. A 19-hydroxylated steroid such as 19-hydroxy-progesterone, if produced by the placenta, could serve as a precursor for such hypertensinogenic 19-nor-steroids as 19-nor-deoxycorticosterone and 19-nor-progesterone. Freshly delivered, homogenized placental tissue was extracted and subjected to thin layer chromatography. A steroid corresponding to standard 19-hydroxy-progesterone was subsequently purified in HPLC, where authentic 19-hydroxy-progesterone and the sample had the same retention time. The identity of the sample was further confirmed by repeat HPLC after acetylation and mass spectrometry. Our experiment indicates that 19-hydroxy-progesterone is present in term placental tissue, where it appears to be synthesized.

Elevated urinary 19-Nor-deoxycorticosterone glucuronide in Cushing's syndrome.

Hypertension is a common finding in patients with Cushing's syndrome (CS), but the cause is unknown. One possibility is excess production of nonaldosterone mineralocorticoids, such as 19-nor-deoxycorticosterone (19-Nor-DOC). To evaluate this possibility we measured urinary 19-Nor-DOC glucuronide in normal subjects (n = 14) and patients with essential hypertension (n = 10), pituitary-dependent CS (n = 8), and adrenal tumors producing CS (n = 6). The subjects were admitted to a metabolic unit where 24-h urine samples were collected while they ate an isocaloric diet (128 meq Na+ 80 meq K+/day). 19-Nor-DOC glucuronide was purified by extraction and chromatography and measured by RIA. Urinary 19-Nor-DOC glucuronide excretion was significantly higher in patients with both pituitary CS and adrenal CS compared to that in normal subjects, while the values in the two CS groups were similar. The patients with essential hypertension also had elevated urinary 19-Nor-DOC glucuronide excretion, although the values were lower than those in either CS group. These results demonstrate that a nonaldosterone mineralocorticoid, 19-Nor-DOC, is produced in excess in patients with either pituitary or adrenal CS and, thus, suggest a possible role for 19-Nor-DOC in the pathogenesis of some hypertensive disorders.