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M Losa

Publications and source records attributed to M Losa.

At least 55 records · Page 3Linked to original sources

The control on growth hormone release by free fatty acids is maintained in acromegaly.

Free fatty acids (FFA) physiologically regulate GH release via a negative feedback. The aim of this study was to examine whether such feedback is preserved in acromegaly, a condition in which alterations in other regulatory mechanisms of GH release occur. Eight acromegalic patients (group 1: five women and three men, 43.0 +/- 4.2 yr old, mean +/- SE) received per os on two different days, at a 3 day-interval, in a random order, placebo or 250 mg of acipimox, an inhibitor of lipolysis analogous to nicotinic acid, at 0700 and 1100 h. In both tests GHRH (1-29 NH2), 50 microg, was administered i.v. at 1300 h. Blood samples for GH, FFA, immunoreactive insulin (IRI), and glucose were taken from 0900 to 1500 h, and the time period considered for statistical analysis was 1200-1500 h, representative of steady-state condition for FFA, IRI, and glucose. Mean plasma FFA levels (1200-1500 h) were significantly lower after acipimox than after placebo (0.05 +/- 0.01 vs. 0.17 +/- 0.01 g/L, P < 0.01). In contrast, both mean basal GH levels (1200-1300 h) and the mean GH response to GHRH (GH delta area, 1300-1500 h) were significantly higher after acipimox than after placebo (12.0 +/- 1.9 vs. 7.8 +/- 1.2 microg/L, P < 0.01; 2937 +/- 959 vs. 1154 +/- 432 microg/L x 120 min, P < 0.01). The increase in both basal GH levels and GH delta area occurred in all eight patients. Acipimox also reduced mean serum IRI (83 +/- 12 vs. 112 +/- 14 pmol/L) and blood glucose (5.1 +/- 0.1 vs. 5.7 +/- 0.1 mmol/L) levels, as compared with placebo (P < 0.03 or less). Eight acromegalic patients (group 2: six women and two men, 46.6 +/- 5.7 yr old) underwent a constant i.v. 10% lipid infusion (150 mL/h), started at 0900 h and continued until 1500 h. Mean plasma FFA levels (1200-1500 h) were significantly higher during lipid infusion than after placebo (0.27 +/- 0.01 vs. 0.16 +/- 0.01 g/L, P < 0.02); in contrast, mean basal GH levels (1200-1300 h) were reduced by lipid infusion, as compared with placebo (9.9 +/- 3.1 vs. 16.6 +/- 4.4 microg/L, P < 0.01), and the same occurred for the GH delta area after GHRH (2498 +/- 1643 vs. 4512 +/- 1988 microg/L x 120 min, P < 0.01). Serum IRI and blood glucose levels were similar after placebo and during lipid infusion. These data indicate that, in acromegaly, the acute reduction of circulating FFA levels results in increased GH release, whereas the increase in circulating FFA levels is accompanied by a reduced GH release. Taken together, these findings suggest that, in acromegaly, the control of FFA on GH release is preserved.

Acromegaly↗

Galanin is released by adrenocorticotropin-secreting pituitary adenomas in vivo and in vitro.

Galanin, a brain-gut peptide, is also synthesized and released by the pituitary. In man, galanin-like immunoreactivity and galanin messenger RNA have been detected specifically in normal and tumoral corticotropes, but little is known about the production and release of galanin by the human pituitary. We evaluated galanin release by 5 ACTH-secreting pituitary adenomas in culture and plasma galanin concentrations in the inferior petrosal sinuses (IPSs) of 15 patients with Cushing's disease before and after CRH administration. For comparison, the galanin response to CRH was evaluated in 8 normal controls. Galanin secretion by pituitary tumor cultures ranged from 30-230 pmol/4 h. Incubation with CRH induced an increase in galanin concentrations (100 pM CRH: 151 +/- 32%; 1 nM CRH: 232 +/- 43%; 10 nM CRH: 246 +/- 35%; and 100 nM CRH: 270 +/- 44% unstimulated levels at 24 h, P < 0.05). The stimulatory effect of CRH seemed to be dose-dependent. Basal and CRH-stimulated ACTH and galanin concentrations also exhibited a strong positive correlation in single tumor cultures. At IPS sampling, mean basal plasma galanin concentrations in the dominant IPS were somewhat higher than those registered at the periphery (18.6 +/- 1.94 vs. 15.8 +/- 1.60 pmol/L, P = 0.05). Administration of CRH induced a modest but significant increase in galanin concentrations at all three sampling sites. No correlations were found between ACTH and galanin levels in the IPSs and at the periphery. Different from what was observed in patients with Cushing's disease, CRH did not modify plasma galanin concentrations in normal subjects. In conclusion, this study demonstrates that galanin is released by human tumoral corticotropes and responds to CRH. The role of locally produced galanin is, as yet, unknown but may possibly be that of a autocrine/paracrine modulator.

Adenoma↗

Systemic administration of insulin-like growth factor decreases motor neuron cell death and promotes muscle reinnervation.

Neonatal sciatic nerve axotomy causes motoneuron death and muscle denervation atrophy. The aim of the present study was to determine whether insulin-like growth factor-I (IGF-I) administration promotes muscle reinnervation and counteracts motor neuron loss after such an injury. Six weeks after sciatic nerve axotomy performed in 2-day-old pups, the number of motor neurons, as assessed by retrograde transport of horseradish peroxidase injected into the extensor digitorum longus (EDL) muscle, was reduced from 52 +/- 3 to 26 +/- 3. Subsequent administration of IGF-I at the doses of 0.02 mg/kg or 1 mg/kg increased the number of motor neurons to 35 +/- 2 and 37 +/- 5, respectively. The effect on motoneuron survival was accompanied by improved muscle fibre morphometry and restoration of indirect EDL muscle isometric twitch tension, which was about 80 % of control values for both doses of IGF-I compared with 60% observed with saline treatment. Reinnervated EDL muscle from saline-treated rats cannot hold tetanic tension, which is, however, achieved after IGF-I treatment at either dose. Thus, both high and low doses of IGF-I counteracted motoneuron death and improved muscle reinnervation following neonatal sciatic nerve axotomy. IGF-I at 5 microg/kg failed to increase muscle reinnervation.

Animals↗

Dry lung syndrome: complete airway collapse mimicking pulmonary hypoplasia?

UNLABELLED: We observed a premature baby born after severe oligohydramnios who could not be ventilated efficiently even with very high pressures immediately after birth, but who, after cessation of resuscitation attempts, recovered spontaneous sufficient breathing during the following hour. After this experience we searched our case records for other newborns with dry lung syndrome using the following definition: (1) premature birth after prolonged leakage of amniotic fluid, (2) very high ventilatory requirement after birth, (3) dramatic improvement during the first 24 to 36 h and (4) respiratory distress syndrome and infection excluded. Among 93 prematures with rupture of membranes for 4 days or more we found 3, including the index case, matching this definition. CONCLUSION: Dry lung syndrome appears to be a distinct clinical entity that is possibly underrecognised but recognisable and that merits further study. Its pathogenesis may imply complete collapse of small airways to a degree that capillary forces impede distension by ordinary ventilatory pressures.

Female↗

Growth hormone and prolactin responses to corticotrophin-releasing-hormone in patients with Cushing's disease: a paracrine action of the adenomatous corticotrophic cells?

OBJECTIVE: In patients with Cushing's disease multihormonal responses to ovine corticotrophin releasing hormone (oCRH) have been detected in blood from inferior petrosal sinuses. This finding has been explained by co-secretion of other hormones, in addition to ACTH, by the pituitary adenoma itself or by paracrine effects exerted by the adenoma on normal periadenomatous pituitary cells. To assess these hypotheses we compared the presence of a CRH induced GH and/or PRL response during inferior petrosal sinus sampling to the immunohistochemical detection of PRL and GH in adenomatous tissue removed from patients with Cushing's disease. PATIENTS AND MEASUREMENTS: Twenty-two patients with Cushing's disease and two patients with ectopic ACTH syndrome due to a bronchial carcinoid were studied; each patient had undergone preoperative inferior petrosal sinus sampling for diagnostic purposes with determination of GH and PRL in addition to ACTH, before and after administration of oCRH. Immunohistochemical studies for ACTH, GH and PRL detection were carried out on adenomatous tissue removed at surgery in the patients with pituitary dependent Cushing's disease and on the carcinoid tumours from the two patients with ectopic ACTH syndrome. RESULTS: All pituitary adenomas immunostained for ACTH, and four adenomas immunostained for GH or PRL in addition to ACTH. A PRL increase in the inferior petrosal sinus after oCRH administration was found in 11 of 22 patients, but none of their tumours immunostained for PRL. Immunostaining for PRL was found in the pituitary tumours from two patients but in neither patient was there a PRL response after oCRH. A GH response was found in 13 of 20 patients in whom it was sought; no patient showed immunostaining in their tumour. GH immunostaining was found in two tumours but in neither patient was there a GH response after oCRH. The oCRH-induced increase of GH and PRL was always recorded in the dominant inferior petrosal sinus. The ACTH response to oCRH was significantly higher in patients who showed oCRH induced increases in GH and/or PRL than in patients who did not, both in terms of area under the response-curve (22,032 +/- 9876 vs. 4371 +/- 2870 ng/l/10 min; P < 0.05) or mean percentage increase above baseline (754 +/- 229% vs. 147.2 +/- 67%, P < 0.02). A significant correlation was observed between ACTH and GH responses to oCRH. The two patients with ectopic Cushing's syndrome did not show ACTH, GH or PRL increases after oCRH administration and did not show immunostaining for GH or PRL in their tumours. CONCLUSIONS: The present data do not support the hypothesis of co-secretion of hormones by the pituitary adenoma as the cause of the GH and PRL responses to ovine corticotrophin releasing hormone observed in patients with Cushing's disease; it is suggested that a different mechanism, possibly involving an interaction between the ACTH secreting adenoma and the normal periadenomatous GH and PRL secreting cells, may be responsible.

Adenoma↗

Constitutively active Gs alpha is associated with an increased phosphodiesterase activity in human growth hormone-secreting adenomas.

Because phosphodiesterase (PDE) expression and activity are controlled by cAMP, we investigated whether activating mutations of Gs alpha gene that occur in human GH-secreting adenomas are associated with increased PDE activity. We studied 10 adenomas with wild-type Gs alpha (gsp-) and 8 with mutant Gs alpha (gsp+). Although, in the absence of PDE inhibitors, intracellular cAMP levels were similar in gsp+ e gsp- adenomas, the PDE blockade with 3-isobutyl-1-methylxanthine induced a marked increase in cAMP in all but one gsp+ adenoma (% increase: from 77 to 2900) and a slight rise in only 2 gsp-. Similar results were obtained with the PDE4 selective inhibitor 4-[3-(cyclopentyloxy)-4-methoxyphenyl)]-2-pyrrolidinone. In vitro GH release was significantly higher in gsp+ than in gsp- adenomas (315 +/- 158 vs. 82 +/- 53 micrograms/well; P < 0.01), and PDE blockade caused a further increase in 3 of 5 gsp+ adenomas but not in gsp- tumors. By direct measurement, PDE activity was about 7-fold higher in gsp+ than in gsp- adenomas (320 +/- 213 vs. 48 +/- 23 pmol/min.mg protein; P < 0.05) and was largely 4-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-pyrrolidinone sensitive. This study first demonstrates that activating mutations of the Gs alpha gene that naturally occur in pituitary adenomas is associated with an increased PDE activity that might, at least partially, counteract the constitutive activation of the cAMP-dependent pathway.

1-Methyl-3-isobutylxanthine↗

Laparoscopic bilateral adrenalectomy for persistent Cushing's disease after transsphenoidal surgery.

BACKGROUND: We performed bilateral laparoscopic adrenalectomies on four patients (three women and one man) with Cushing's disease (pituitary-dependent Cushing's syndrome) showing persistent hypercortisolism after transsphenoidal surgery. METHODS: The technique for bilateral transperitoneal laparoscopic adrenalectomy was derived from the one previously adopted by our group for unilateral adrenalectomy and previously described. Eight trocars were used, of which two were used for both left and right adrenalectomy. RESULTS: Bilateral laparoscopic adrenalectomy was performed in a one-stage procedure in the three women and, because of the abundant abdominal fat of the patient, in a two-stage procedure (after a 1-week interval) in the man. Operating times for the three women were 255 minutes, 230 minutes, and 220 minutes, and for the man 170 minutes for right adrenalectomy and 140 minutes for left adrenalectomy. No surgical or anesthesiologic complications were encountered. All patients were discharged from the hospital within 5 days after operation. At present, after follow-up periods of 23, 8, 6, and 18 months, all patients show remission of Cushing's disease and undetectable cortisol levels. CONCLUSIONS: Our experience suggests that bilateral laparoscopic adrenalectomy is a safe and effective procedure and a valid therapeutic option in patients with Cushing's disease showing persistent hypercortisolism after transsphenoidal surgery. However, the decision to remove both adrenal glands in such patients needs to be weighed against the risk of their having Nelson's syndrome or other long-term complications.

Adrenalectomy↗

Usefulness of markers of cell proliferation in the management of pituitary adenomas.

1. Pituitary adenomas are benign and slow-growing tumours whose clinical manifestations depend mainly on the secretory activity of the adenomatous cells. Except for prolactinomas, surgical removal of the tumour is the therapy of choice. 2. Despite extensive research on their clinical and pathophysiological aspects, few studies have explored the oncological characteristics of these rare lesions. Among these, the growth fraction of pituitary adenomas has been determined by different methods, of which the most useful are those performed in archival material. 3. The results reported in the literature show that adrenocorticotropic hormone-secreting tumours seem to be characterized by a higher proliferation index than the other types of pituitary adenomas, despite their usually small tumour size. 4. In small series of patients radiotherapy and medical treatment with dopaminergic drugs and octreotide were associated with a lower proliferation index than untreated tumours. Tumour size was not correlated with the growth fraction of the pituitary tumours, whereas invasiveness was correlated in most studies. 5. From a clinical point of view, however, the more promising utilization of the proliferation index seems to be in predicting the potential of recurrence of the tumour, thus allowing a more rational approach to follow-up and further treatment of patients with pituitary adenomas.

Adenoma↗

Cytogenetic study of pituitary adenomas.

We report the results of cytogenetic studies on 23 pituitary adenoma specimens, using both the direct and short-term tissue culture methods. The direct method was applied to all of the specimens and allowed a karyotype to be identified in 15 of the processed samples (65%). Four tumors were shown to have a hypotriploid chromosomal constitution, two of which also presented structural clonal rearrangements: an isochromosome 1q,i(1)(q10) and a der(1)t(1;3)(p22;q21) were observed in two PRL-secreting adenomas, one of which also had a telomeric association involving the short arms of chromosomes 14 and 19. Telomeric associations of the long arms of chromosomes 11, 19, and 22 were observed in a near-diploid, non-secreting tumor showing monosomy 13. One other adenoma showed trisomies 8 and 12, a finding that was confirmed by means of the FISH analysis of chromosome 8 and 12 centromeric probes in the more than 300 scored nuclei. An apparently normal chromosome constitution was observed in the remaining nine cases. Short-term cultures were set up in 21 of the 23 samples, allowing us to obtain a karyotype in 18 specimens (85%). The six tumors that could not be analyzed using the direct method showed a normal karyotype. A diploid chromosome constitution was observed in the four tumors shown to be hypotriploid by the direct method as well as in the tumor with monosomy 13. The trisomies 8 and 12 identified by the direct method in one tumor were still observed, but a clone with a normal karyotype was also found. To the best of our knowledge, this is the only report of the results of cytogenetic studies on pituitary adenomas performed using both direct preparation and short-term culture.

Adenoma↗

Metastatic prostatic adenocarcinoma presenting as a pituitary mass: shrinkage of the lesion and clinical improvement with medical treatment.

BACKGROUND: Metastatic involvement of the pituitary gland is a very unusual presentation of prostatic cancer. We report a favorable response to medical treatment in such a patient. METHODS AND RESULTS: A 77-year-old man presented with blindness, ophthalmoplegia in his left eye, and mild impairment of memory and mental status. Neuroradiological studies showed a huge intra- and suprasellar lesion that destroyed the sellar floor and extended into the sphenoid sinus. Transsphenoidal biopsy of the lesion demonstrated a prostatic adenocarcinoma. Postoperative studies revealed an enlarged prostate gland and multiple lytic bone lesions. The patient was treated with a combination of leuprolide acetate plus flutamide. Four months later, the patient exhibited a marked improvement in his neurologic status and regained vision in the right eye (visual acuity 6/20). Repeat magnetic resonance imaging of the sellar region confirmed a striking shrinkage of the prostatic metastasis. The clinical status remained stable for 22 months, after which time the disease progressed and the patient died 25 months after beginning treatment. CONCLUSIONS: A favorable response to combined androgen blockade suggests that medical therapy should be considered the therapy of first choice when surgical removal of the metastatic lesion in the pituitary is impossible or too risky.

Adenocarcinoma↗

Indium-111 pentetreotide single-photon emission tomography in patients with TSH-secreting pituitary adenomas: correlation with the effect of a single administration of octreotide on serum TSH levels.

Few data are available on the visualization of somatostatin receptors in vivo in patients with thyrotropin (TSH)-secreting adenoma. We studied five patients with TSH-secreting adenomas using single-photon emission tomography (SPET) after administration of indium-111 pentetreotide. The intensity of 111In-pentetreotide uptake by the tumours was correlated with the degree of TSH suppression after a single administration of 100 microg octreotide s. c. Five patients (three women and two men) aged 27-46 years were investigated. Except for one patient with acromegaly, all had pure TSH-secreting tumours. One patient was previously untreated, while two had received octreotide, one antithyroid drugs, and one radioiodine. In all patients SPET demonstrated increased uptake of 111In-pentetreotide by the pituitary adenoma. The target to non-target ratio (T/nT) of 111In-pentetreotide uptake was higher than 10 in three patients. Administration of 100 microg octreotide s. c. caused a significant reduction in TSH levels from 4.8+/-1.4 mU/l to a nadir of 3.1+/-1.1 mU/l after 6 h (P<<0.001 by ANOVA). Suppression of TSH secretion ranged from 30% to 60% of the baseline value. The T/nT ratio showed a trend toward a direct relationship with the degree of TSH inhibition after acute octreotide administration (r=0.67; P=NS). Our study showed that 111In-pentetreotide scan visualized somatostatin receptors in all five of the patients with TSH-secreting pituitary adenomas, confirming the frequent presence of somatostatin receptors in these rare tumours, even though the correlation with the TSH inhibition after a single administration of octreotide did not reach significance.

Adenoma↗

Differentiation of clinically non-functioning pituitary adenomas from meningiomas and craniopharyngiomas by positron emission tomography with [18F]fluoro-ethyl-spiperone.

The differential diagnosis among various types of non-functioning sellar and parasellar tumours is sometimes difficult using currently available methods of morphological imaging. The aim of this study was to define whether assessment of the uptake of [18F]fluoro-ethyl-spiperone (FESP) with positron emission tomography (PET) could be helpful for the differential diagnosis of pituitary adenomas and other parasellar lesions, and for establishing the appropriate therapeutic approach. The population examined comprised 16 patients with the diagnosis of primary tumour of the sellar/parasellar region who were waiting to undergo surgical treatment. The results demonstrated that PET with [18F]FESP is a very specific method for differentiating adenomas from craniopharyngiomas and meningiomas. The visual interpretation of images allows such differentiation at approximately 70 min after tracer injection. Semiquantitative analysis of the dynamic PET data confirmed the results of visual interpretation, demonstrating that the uptake of [18F]FESP was consistently (i.e. throughout the series) at least two- to threefold higher in non-functioning adenomas than in other parasellar tumours as early as 70 min after tracer injection, and that it increased still further thereafter. It is concluded that PET with [18F]FESP might be of clinical value in those cases in which the differential diagnosis among various histological types of sellar tumour is uncertain with conventional methods.

Adenoma↗

Immunodetection of glycoprotein hormone subunits in nonfunctioning and glycoprotein hormone-secreting pituitary adenomas.

While it is established that nonfunctioning pituitary adenomas (NFPA) produce a spectrum of glycoprotein hormones, the ability of glycoprotein hormone-secreting adenomas to synthesize hormones other than those in vivo hypersecreted has been poorly investigated so far. In this study the immunolocalization of the beta-subunits of LH, FSH, CG and TSH and the common alpha-subunit was investigated in 10 NFPA, 3 gonadotropin-secreting adenomas (Gn-omas, 1 LH-oma, 1 FSH-oma and 1 LH/FSH-oma) and 3 TSH-secreting adenomas (TSH-omas) using an immunohistochemical technique with specific antibodies to glycoprotein subunits. The percentage of positive cells was determined observing at least 5 photograph fields containing about 50 cells. Nine of the 10 NFPA were positive for FSH beta with a high percent of positive cells (> or =30%), 6 for LH beta and 5 for TSH beta with a lower number of labelled cells (from 5 to 30%). Of the 8 NFPA tested, 5 showed a marked positivity for CG beta. In Gn-omas, tumors were positive for the gonadotropin that was in vivo hypersecreted (10-60% positive cells) and negative for either TSH beta or CG beta. Similarly, in TSH-omas TSH beta was detected in a variable proportion of cells (10-30%) with no immunoreactivity for either LH beta or FSH beta or CG beta. This study indicates that the coexpression of FSH beta, LH beta, CG beta and TSH beta molecules is characteristic of NFPA since Gn-omas were negative for CG beta and TSH beta and TSH-omas were negative for FSH beta, LH beta and CG beta. Moreover, the biological events that make NFPA 'silent' glycoprotein hormone-secreting adenomas remain unclear since the positivity for gonadotropins and TSH showed by NFPA was similar to that observed in Gn-omas and TSH-omas, respectively.

Adenoma↗

Generation of nitrogen dioxide during nitric oxide therapy and mechanical ventilation of children with a Servo 900C ventilator.

OBJECTIVE: To determine the combinations of nitric oxide (NO), oxygen (O2), minute ventilation (MV) and total gas flow (TGF) which generate toxic concentrations of nitrogen dioxide (NO2) during mechanical ventilation with a Servo 900C ventilator. DESIGN: The measurement of NO2 generated with NO (20, 40, 60, 80, 100 ppm) and O2 [fractional inspired oxygen (FIO2) 0.21, 0.4, 0.6, 0.9] during mechanical ventilation with MVs of 2.5, 5.0 and 7.5 l/min and TGFs from 2 to 14 l/min. SETTING: Laboratory of intensive care unit in paediatric tertiary hospital. RESULTS: Toxic concentrations of NO2 (> 5 ppm) were generated in the ventilator circuit when NO was 80 ppm or 100 ppm in FIO2 of 0.6 or 0.9 with MVs of 2.5, 5.0 and 7.5 l/ min; and with 80 ppm NO in FIO2 of 0.6 at all TGFs from 2.0 to 13.6 l/min and MVs of 2.5, 5.0 and 7.5 l/min (TGF/MV 0.3-5.4). NO2 1.5-2.6 ppm was generated with 40 ppm NO in FIO2 of 0.6, TGFs 2.1-13.7 l/ min, and MVs 2.5, 5.0 and 7.5 l/min (TGF/MV 0.3-5.5). NO2 0.9-0.6 ppm was generated with 20 ppm NO in FIO2 of 0.6, TGFs 2.5-13.8 and MVs 2.5, 5.0 and 7.5 (TGF/MV 0.3-5.5). NO2 generation was not affected significantly by the TGF/MV ratio. CONCLUSIONS: The generation of NO2 in the ventilator circuit is directly proportional to concentration of NO and O2 and inversely proportional to the TGF and MV but uninfluenced by the TGF/MV ratio. NO 80 ppm, but neither 20 nor 40 ppm in FIO2 of 0.6, generates toxic NO2 irrespective of TGF, MV or the TGF/MV ratio.

Child↗

[Combined neuronal and endocrine tumors of the sellar region].

Gangliocytomas or gangliogliomas of the sellar region are very rare tumors. In a great proportion of those cases an adenoma of the anterior pituitary develops from the cell type that is hyperstimulated by the releasing hormone produced from the gangliocytoma. Five GHRH secreting gangliocytomas are reported. Four of these were localized adjacent to a GH secreting adenoma. In one case, no adenoma tissue was found beside the ganglicytoma. As only the adenomas can secrete GH, the adenomas and not the gangliocytomas are directly responsible for acromegaly so that such an adenoma has to be present in cases of acromegaly. A CRH secreting gangliocytoma was combined with an ACTH cell adenoma that had induced Cushing's disease. A ganglioglioma of the posterior pituitary had led to an inappropriate secretion of Vasopressin. The morphology of the different tumors is presented.

Acromegaly↗

Oestrogen receptors in meningiomas: a correlative PET and immunohistochemical study.

There have been a number of indications that sex hormones can affect the rate of growth of meningiomas during pregnancy. The presence of oestrogen or progesterone receptors in meningiomas and the influence of sex hormones upon cell cultures derived from human meningiomas have been extensively investigated. The results have been controversial, with most of the discussion centring upon the presence and possible role of oestrogen receptors. The aim of the present study was to assess oestrogen receptors in human meningiomas with 16alpha[l8F]fluoro-17beta-oestradiol ([18F]FES) and positron emission tomography (PET). With this purpose in mind, we measured the regional brain uptake of [18F]FES in six patients with a neuroradiological and histological diagnosis of meningioma, comparing the in vivo PET data with the immunohistological analysis of oestrogen receptors performed on formalin-fixed, paraffin-embedded tissue obtained at surgery. Two analyses were used for the in vivo measurement of [18F]FES binding to oestrogen receptors: the ratio of tumour activity to that of normal tissue (T/NT), calculated 90 min after tracer injection, and the ratio between the equilibrium distribution volume (DV) in normal and pathological tissues, calculated by means of a graphical kinetic analysis. PET studies demonstrated a marked uptake of [18F]FES by the tumour in four of the six patients. Immunohistochemical assay using a manual staining method capable of detecting oestrogen receptors at a level of > 10 pmol mg(-1) of protein detected only sparse immunostaining in one of the six meningiomas. Distinct albeit weak immunostaining was demonstrated in five of the six meningiomas when the sensitivity of the immunohistochemical assay was increased to < 10 pmol mg(-1) of protein by use of an automated staining method (Bioteck 1000). Comparison of the in vivo and immunohistochemical results showed a correlation in five of the six patients, thus indicating the high sensitivity of [18F]FES for the in vivo evaluation of oestrogen receptor expression.

Adult↗