Adrenomedullin, a new vasoactive peptide, is increased in preeclampsia

Adrenomedullin is a novel peptide that elicits a long-lasting vasorelaxant activity. Recently, we found high concentrations of adrenomedullin in maternal and umbilical cord plasma and in amniotic fluid in full-term human pregnancy, indicating a role of this peptide during gestation. To investigate the possibility that adrenomedullin is involved in the pathophysiology of preeclampsia, we measured its concentration in maternal and fetoplacental compartments. We studied 12 normotensive nonpregnant women, 13 hypertensive nonpregnant subjects, 29 patients with preeclampsia, and 30 normotensive pregnant women. In all patients, plasma was collected from the cubital vein, and amniotic fluid samples were obtained by transabdominal amniocentesis or at elective cesarean section. Plasma samples from umbilical vein and placental tissues were collected at delivery. Adrenomedullin was assayed on plasma and amniotic fluid samples using a specific radioimmunoassay, and its localization and distribution on placental sections was determined by immunohistochemistry. Adrenomedullin concentrations were higher in hypertensive than in normotensive nonpregnant patients. Pregnant women had higher adrenomedullin levels than nonpregnant subjects, although maternal plasma adrenomedullin concentrations did not differ between normal pregnant and preeclamptic women. Preeclamptic patients showed higher concentrations (P<0.01) than normotensive pregnant women of adrenomedullin in amniotic fluid (252+/-29 versus 112+/-10 fmol/ micromol creatinine) and umbilical vein plasma (18.1+/-2.1 versus 8. 5+/-1.1 fmol/mL). Increased local production of adrenomedullin is associated with preeclampsia. The fetus seems to be responsible for the higher levels of this hormone. Increased adrenomedullin concentrations may be necessary to maintain placental vascular resistance and/or fetal circulation at a physiological level

Detection of HER2 Amplification Using the SISH Technique in Breast, Colon, Prostate, Lung and Ovarian Carcinoma

HER2 gene amplification was explored using the silver stain hybridization in situ (SISH) technique in colon, prostate, lung, ovarian and breast carcinomas. Clinical pathological features and immunohistochemical (IHC) expression were evaluated for HER2 in 225 carcinomas. All cases were subjected to SISH investigation. Statistical analysis revealed an association between HER2 protein expression and gene amplification in breast carcinoma. 14% of colon carcinomas (5 IHC score 0, 1 score 1+ and 1 score 2+), 2% of prostate carcinoma (IHC 2+), 4% of lung carcinomas (IHC 2+) and 16% ovarian carcinomas (IHC 3+) revealed gene amplification. SISH is an advantageous technique for the detection of gene amplification. The use of the SISH technique in breast carcinoma may be an alternative to other in situ hybridization (ISH) techniques however more detailed studies seem necessary to detect HER2 gene amplification in other human malignancies

Influence of labor on fetoplacental adrenomedullin concentrations

OBJECTIVE: Circulating adrenomedullin is increased in pregnancy, and placental and fetal membranes participate significantly in its secretion. Recent studies have suggested a potential role for this peptide in the regulation of fetoplacental circulation and placental hormonal secretion. Because adrenomedullin acts also as a uterorelaxant in rats, this study was designed to investigate whether fetoplacental adrenomedullin production changes with human labor, either at term or preterm. STUDY DESIGN: Eighty pregnant women grouped according to gestational age and presence of labor were studied. Adrenomedullin concentrations in plasma, amniotic fluid, and placental tissue extracts were measured by means of radioimmunoassay and immunohistochemistry. In addition, the ability of amnion and chorion-decidua to secrete adrenomedullin was investigated in vitro. RESULTS: Adrenomedullin concentrations in amniotic fluid were higher in preterm labor, whereas no differences were found in adrenomedullin expression or concentrations in tissues or in maternal and fetal plasma between vaginal delivery or elective cesarean section, both at term and preterm. During term labor (8 patients), maternal plasma adrenomedullin concentration decreased with advancing cervical dilatation, being 173 pg/mL at the beginning of the active stage of labor and 57 pg/mL at the time of delivery. Adrenomedullin concentration in the medium of amnion- and chorion-decidua-cultured cells was higher after vaginal delivery. CONCLUSION: These results suggest that a decrease in adrenomedullin production is not involved in the onset of labor in human subjects but rather that it may play a role other than that of a myometrial relaxant in human parturition

P53 as a marker of differentiation between hyperplastic and adenomatous parathyroids

Primary hyperparathyroidism is the clinical result of parathyroid adenoma or hyperplasia, rarely of carcinoma. Clinical, serologic, and radiologic data are unable to discriminate a single parathyroid adenoma from an enlarged hyperplastic gland. Morphologic features also overlap in adenoma and small hyperplastic gland. Studying immunohistochemical expression of fatty acid synthase (FAS), p53, Ki67 and bcl-2, we found that among 21 adenomas 19 (90.5%) were positive for FAS, 12 (57.2%) for Ki67, 11 (52.4%) for p53, and 16 (76.2%) for bcl-2; among 12 hyperplasias, 12 (100%) were positive for FAS, 6 (50%) for KI67, 8 (66.7%) for p53, and 8 (66.7%) for bcl-2. Statistical analysis showed that FAS was associated with parathormone (PTH) (P = .001), Ki67 (P = .01), and p53 (P = .01). Moreover, FAS was associated with hyperplastic (P = .0001) and adenomatous glands (P = .0001). Ki67 was associated with both adenomatous (P = .02) and hyperplastic glands (P = .005). P53 protein were associated only with hyperplastic glands (P = .01). The different occurrence of p53 in parathyroids adenoma and hyperplasia may enable a different management and follow-up of the patients with primary hyperparathyroidism, stratifing them into two groups. The first, with a "false" adenoma having a high risk of relapse, may necessitate exams like serum calcium levels, PTH concentrations, urinary calcium levels for 24 hours, kidney functional tests, and radiology and ultrasound every 3 to 6 months, whereas the second with "true" adenoma, at low risk of relapse, may be checked less frequently with serum calcium levels and PTH concentrations. Copyright 2002, Elsevier Science (USA). All rights reserved

Revisione critica dei risultati colpo-istologici nella patologia cervicale.

The objective of this paper was to evaluate the role of squamous metaplasia in the determination of certain colposcopic appearances

High plasma levels of human chromogranin A and adrenomedullin in patients with pheochromocytoma

Aims and background: The aim of our study was to investigate the plasma chromogranin A (CgA) and adrenomedullin (AM) levels in patients with pheochromocytomas. Methods and study design: We collected blood samples for measurement of plasma CgA and AM in 21 patients with pheochromocytomas, 43 healthy subjects and 26 patients with solid non-functioning adrenocortical adenomas. In 11 patients with pheochromocytomas plasma CgA and AM were measured again four weeks after tumor removal. CgA and AM were measured by means of a novel solid-phase two-site immunoradiometric assay based on monoclonal antibodies (CgA-RIA CT, CIS bio international) and by a specific radioimmunoassay (RIA, Phoenix Pharm. Inc.), respectively. Results: The mean plasma CgA level (+/- SD) in patients with pheochromocytomas (204 +/- 147.9 ng/mL) was significantly higher (P < 0.001) than that in healthy subjects (41.6 +/- 10.7 ng/mL) and in patients with non-functioning adrenocortical adenomas (47.3 +/- 17.6 ng/mL). The mean plasma AM concentration (+/- SD) in patients with pheochromocytomas (27.5 +/- 10.4 pg/mL) was significantly higher (P < 0.001) than that in HS (13.8 +/- 4.5 pg/mL) and in patients with non-functioning adrenocortical adenomas (16.6 +/- 7.3 pg/mL). Plasma CgA levels correlated with plasma AM levels (r = 0.501; P < 0.02) and with plasma metanephrine levels (r = 0.738; P < 0.0001) in patients with pheochromocytomas. In 11 patients with pheochromocytomas plasma CgA and AM concentrations significantly decreased after tumor removal (P < 0.001 for both). Circulating CgA and AM had a sensitivity of 76.2% and 81%, a specificity of 97.7% and 90.7%, and an accuracy of 91% and 88%, respectively. Conclusion: This study demonstrates that circulating CgA and AM levels are increased in pheochromocytoma patients compared with healthy subjects and patients with non-functioning adrenocortical adenomas. Moreover, at the time of diagnosis plasma CgA levels correlated with plasma AM levels and with plasma metanephrine levels in all patients with pheochromocytomas. In conclusion, plasma CgA and AM concentrations may represent additional biochemical parameters for clinical monitoring of patients with pheochromocytomas

Adrenomedullin, a new peptide, in patients with insulinoma

It has been demonstrated that adrenomedullin, a newly discovered peptide, affects the release of insulin from pancreatic islets cells, suggesting a role in the insulin-regulating system. To investigate whether adrenomedullin secretion is modified in patients with insulin-secreting islet cell tumours. The study was performed in nine patients with surgically treated insulinoma. Circulating adrenomedullin was assayed using a specific radioimmunoassay and its localization and distribution in the tumour were determined by means of immunohistochemistry. Adrenomedullin concentrations were significantly greater in patients with insulinoma (6.6 +/- 3.2 fmol/ml) than in controls (2.1 +/- 1.1 fmol/ml). In six patients monitored before and after surgery, plasma adrenomedullin decreased from 6.3 +/- 2.9 fmol/ml to 3.0 +/- 1.6 fmol/ml. Immunoreactive adrenomedullin was localized exclusively in the tumours cells, whereas stroma, surrounding pancreas parenchyma and major ducts were negative for the peptide. Our findings indicate that circulating adrenomedullin is increased in insulinoma and that this increase is related to the neoplastic phenotype