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M Losa

Publications and source records attributed to M Losa.

At least 73 records · Page 4Linked to original sources
PubMed1997

Nerve growth factor suppresses the tumoral phenotype of human prolactinomas.

We summarize here our data showing that various phenotypical characteristics distinguish prolactinoma cell lines obtained from responder and nonresponder patients, as defined by their responses to bromocriptine administration. Nonresponder cell lines have a higher degree of malignancy than responder cells and do not express D2 receptors for dopamine. Both cell lines express NGF receptors. Exposure of the most malignant nonresponder cell lines to NGF, both in vitro and when transplanted in vivo in nude mice, results in their differentiation into the responder phenotype reexpressing D2 receptors. Sequential administration of NGF and bromocriptine thus may be a promising therapy for patients refractory to bromocriptine.

Animals↗
PubMed1996

Surgical results in microadenomas.

Pituitary microadenomas are small tumors whose maximal diameter is less than 1 cm. The aim of surgical removal of microadenomas should be not only the reversal of hormone hypersecretion but also the preservation of normal anterior pituitary function. Our series includes 230 patients with a microadenoma who had their first operation in our department: 45 were GH-secreting, 92 were PRL-secreting, 90 were ACTH-secreting, and 3 were TSH-secreting. Remission of disease was achieved in 81%, 77%, 91%, and 100% of GH-, PRL-, ACTH-, and TSH-secreting adenomas, respectively. There was no perioperative mortality and only 5 patients experienced a major complication. A total of 7 patients had diabetes insipidus for at least 6 months after operation. Hypopituitarism, not present in any patients before operation, developed in 3.5% of the cases. Our experience confirms that patients with microadenomas have the best chances of a successful operation. Since tumor size should gradually increase with time, we underscore the need of early diagnosis and treatment in patients with pituitary adenomas.

Adenoma↗
PubMed1996

Proton magnetic resonance spectroscopy and intracranial tumours: clinical perspectives.

Proton magnetic resonance spectroscopy (1H-MRS) was applied to characterize intracranial tumours of different hystological types. Seventy patients with intracranial neoplasms were studied before receiving surgery, radiotherapy or chemotherapy. All tumours were characterized by reduced or absent N-acetylasparate and increased signal from choline-containing compounds. Distinctive patterns were observed only for primitive brain neoplasms; high-grade gliomas were differentiated from low-grade ones by higher levels of choline-containing compounds. The metabolic aspects of metastatic lesions were similar to high-grade gliomas. These results, together with the limitations of 1H-MRS and future applications are reviewed.

Adenoma↗
PubMed1996

Stereotactic radiosurgery of pituitary adenomas.

The first gamma knife (GK) treatment of a pituitary adenoma in 1967 was meant as an alternative to the primitive surgical approaches that prevailed at the time, with consequent unsatisfactory results. Surprisingly, pituitary adenomas still account for only 7.8% of the 27,000 cases treated in GK centers worldwide. Transnasosphenoidal surgery has greatly improved and surgeons are reluctant to give up a relatively safe and effective operative technique. Radiosurgery is not currently vying to be the primary method of "surgery", but has a definite role following failed pituitary surgery and for tumors that extend into the cavernous sinus. Of 300 patients treated in our GK service, 30 had pituitary adenomas and most had undergone surgery. To date, we have not noted any side effects in the pituitary group. Published information is also reviewed and divided, where possible, into the pre-computed tomography (CT) era and the era of CT-magnetic resonance imaging (MRI). Growth hormone (GH)-secreting adenomas and prolactinomas tend to be larger and cannot be treated with the high doses successful against corticotropin (ACTH)-secreting tumors in Cushing's disease. Radiation fall-off is steep in GK radiosurgery, with the 20% isodose curve being only millimeters away from the point of maximal radiation. The effective dose has mostly been decided on the basis of maintaining safe levels at the sensitive perisellar neural structures. The safety of GK treatment (with no mortality and no permanent morbidity) is compared with other radiosurgical techniques. Good patient response owes much to the cumulative experience of GK pioneers and also to recent advances in images and computers that have enabled increasingly precise stereotaxic targeting and dose planning.

Adenoma↗
PubMed1996

Surgical therapy of pituitary adenomas.

In a series of approximately 1,000 patients with pituitary adenoma who were operated on at our institution from 1970 to 1994, 932 were operated on for the first time. Most microadenomas were corticotropin (ACTH)-secreting, whereas all nonfunctioning adenomas were macroadenomas, reflecting internal surgical policy. Only 48 of 932 patients (5.1%) had transcranial surgery. Using stringent criteria for the definition of a cure, we obtained remission of disease in 54.9%, 87.3%, 66.7%, and 46.2% of all patients with growth hormone (GH)-, ACTH-, thyrotropin (TSH)-, and prolactin (PRL)-secreting adenomas, respectively. The good result in patients with Cushing's disease is related to the higher percentage of microadenomas (approximately equal to 80%) in this group. Unfavorable prognostic characteristics for all adenomas are increasing tumor size, invasiveness, infiltration, and high serum levels of the hypersecreted hormone. The absence of a reliable tumor marker makes it difficult to assess the results of surgery in patients with nonfunctioning pituitary adenoma, but normalization or improvement of visual defects occurred in 72.4% of patients. Permanent worsening of vision was detected in 2.2%, mostly operated on through the transcranial approach, but they had large tumors and so were at greater risk. Accordingly, there was a higher death rate in patients who received the transcranial operation (two of 48; 4.2%) than in patients operated on through the trans-sphenoidal route (seven of 884; 0.8%). However, between 1970 and 1980, the mortality rate was 1.6% (six of 367 patients), while between 1981 and 1994, it was 0.5% (three of 565 patients), stressing the importance of surgical experience and perioperative medical management in improving the safety of pituitary surgery.

Adenoma↗
PubMed1996

Criteria of cure and follow-up of central hyperthyroidism due to thyrotropin-secreting pituitary adenomas.

The recorded number of patients with central hyperthyroidism due to TSH-secreting pituitary adenoma doubled in the last few years after the introduction of ultrasensitive TSH assays in the assessment of thyroid function; however, information about the results and the criteria for cure after pituitary surgery is scanty. Seventeen patients with a TSH-secreting adenoma, diagnosed on the basis of detectable TSH levels in the face of high free thyroid hormone concentrations and pituitary lesion at neuroimaging, underwent pituitary surgery. Hypersecretion of other pituitary hormones was diagnosed in 5 of 17 patients. Four patients were initially misdiagnosed and treated with thyroid surgery or radioiodine therapy. The majority (86%) of hyperthyroid patients normalized thyroid hormone concentrations and regained euthyroidism, although pituitary imaging, alpha-subunit, and alpha-subunit/TSH molar ratio normalized in only 47%, 54%, and 58% of patients, respectively. Moreover, TSH secretion was normally suppressed by T3 in 40% of the patients. Interestingly, the finding of undetectable TSH levels 7 days after surgery was highly predictive of successful outcome. During long term follow-up, there was one relapse of hyperthyroidism. Early diagnosis of TSH-secreting adenomas permits a high rate of remission of hyperthyroidism after surgery. However, normalization of thyroid function alone does not necessarily reflect complete removal of the tumor, and more comprehensive criteria of cure based on pituitary imaging, hormone measurement, and suppression of TSH during T3 administration should be used. Lastly, all patients need an accurate long term follow-up to monitor the possible recurrence of the adenoma.

Adenoma↗
PubMed1996

Nerve growth factor controls proliferation and progression of human prolactinoma cell lines through an autocrine mechanism.

Two different human prolactinoma phenotypes (responders and nonresponders), which are distinguished by different tumorigenic potential and different responsiveness to dopaminergic therapy, have recently been identified. Responders show low proliferation rate, low tumorigenic potential, and expression of D-2 receptors for dopamine (DA), while nonresponders are characterized by high proliferation rate, high tumorigenic potential, and lack of expression of DA D-2 receptors. In this study it has been shown that both gp140trk and gp75 components of nerve growth factor (NGF) receptor are expressed in responder prolactinoma cell lines. High levels of both NGF gene transcript and protein were also found in responders, and biologically active NGF was detectable in the media conditioned by these cells. Ablation of NGF production in responder cells by hybridization arrest of translation through NGF antisense oligonucleotides resulted in: 1) loss of secreted NGF; 2) loss of expression of gp75; 3) loss of expression of DA D-2 receptors; and 4) a remarkable increase in the cell proliferation rate. These results thus suggest that a NGF-mediated autocrine loop essential to control cell proliferation and to preserve some phenotypical characteristics of mammotroph cells is present in responder prolactinoma cell lines. Analysis of nonresponders showed that these cells express gp140trk but no detectable levels of gp75. In addition, no NGF mRNA or protein was detectable in nonresponders. Exposure of these cells to NGF resulted in the permanent expression of NGF mRNA and in the production and secretion of NGF protein, thus establishing the same NGF-mediated autocrine loop present in responders. As a result, it has been shown that nonresponder cells treated with NGF acquire and maintain most of the phenotypic characteristics of normal mammotroph cells. In conclusion, the present work reports that a NGF-mediated autocrine loop with an inhibitory role in the control of cell proliferation and tumor progression is active in the more differentiated DA-sensitive prolactinoma cell lines and is lost in the most malignant prolactinoma cells refractory to the dopaminergic therapy. Alterations in the expression of this autocrine loop thus may lead to cell transformation and tumor progression.

Animals↗
PubMed1995

Kartagener syndrome: an uncommon cause of neonatal respiratory distress?

We report a newborn with respiratory distress and situs inversus totalis. The diagnosis of primary ciliary dyskinesia was confirmed by both ultrastructural and functional investigations. The immotile cilia syndrome was suspected because of respiratory distress, situs inversus, abnormal nasal discharge and hyperinflated chest X-ray. We suggest that ultrastructural and functional investigations of the respiratory mucosa should be done in any newborn with respiratory distress without explanation for the respiratory problems. Establishment of the correct diagnosis at an early stage may allow to improve the prognosis provided prophylactic physiotherapy, vaccinations, and aggressive antibiotic treatment of intercurrent respiratory infections are instituted. CONCLUSION Despite its rarity, primary ciliary dyskinesia should be considered in unexplained cases of neonatal distress.

Bronchi↗
PubMed1995

Nerve growth factor and bromocriptine: a sequential therapy for human bromocriptine-resistant prolactinomas.

Nerve growth factor (NGF) administration to athymic mice with transplanted human bromocriptine-resistant prolactinoma, results in the expression of dopamine D-2 receptors in the tumour and restores sensitivity to subsequent treatment with bromocriptine, which then produces normalisation of plasma prolactin and tumour regression. Sequential administration of NGF and bromocriptine thus may be a promising therapy for patients refractory to bromocriptine.

Animals↗
PubMed1995

Changes in anterior pituitary response in patients with idiopathic hypothalamic hypogonadism caused by pulsatile GnRH therapy and testosterone replacement.

OBJECTIVE: This study evaluated in male patients with idiopathic hypothalamic hypogonadism the effect of pulsatile GnRH therapy or testosterone replacement on the response of all anterior pituitary hormones to adequate dynamic stimuli. PATIENTS AND DESIGN: In nine patients with idiopathic hypothalamic hypogonadism--mean age 21 +/- 1 (mean +/- SE)--a combined pituitary stimulation (CPS) with 200 micrograms TRH, 100 micrograms GnRH, 100 micrograms CRH and 100 micrograms GRH and an insulin tolerance-test (ITT) with 0.1 U insulin/kg body weight were performed. Both tests were repeated during pulsatile GnRH therapy and thereafter on testosterone replacement. MEASUREMENTS: Hormone levels were measured by immunometric assays. For statistical analysis the area under the curve (AUC) was used as a measure for hormone response. RESULTS: Testosterone levels did not differ significantly during GnRH therapy (16.6 +/- 2.1 nmol/L) and testosterone replacement (18.5 +/- 1.7 nmol/L). No significant differences were observed before and during the two treatment modalities for TSH and ACTH. PRL increase was significantly higher during GnRH therapy (AUC: 73580 +/- 8940) compared to the rise before treatment (AUC: 36161 +/- 5853; p < 0.01) and on testosterone replacement (AUC: 49995 +/- 6158; p < 0.01). The GH response to CPS and ITT was higher under testosterone replacement (AUC: 1826 +/- 353 and 1423 +/- 125) compared with the pretreatment situation (AUC: 727 +/- 115; p < 0.05 and 541 +/- 110; p < 0.01) and also more pronounced than under GnRH therapy (AUC: 1148 +/- 180 and 798 +/- 129; p < 0.05). FSH and LH after CPS rose significantly more during GnRH therapy (AUC: 864 +/- 122 and 2215 +/- 219) than before (AUC: 418 +/- 61 and 1424 +/- 277; p < 0.01) and on testosterone treatment (342 +/- 83 and 1153 +/- 323; p < 0.05). CONCLUSION: These results show that GnRH exerts a stimulatory effect on PRL secretion and may modulate GH secretion independently from sex steroids.

Adolescent↗
PubMed1995

Factors influencing the immediate and late outcome of Cushing's disease treated by transsphenoidal surgery: a retrospective study by the European Cushing's Disease Survey Group.

Hypercortisolism attributable to hypersecretion of ACTH by a pituitary adenoma is an uncommon and progressively lethal disease. Because of its rarity, it has been difficult to collect a large series of patients in order to identify the prognostic factors influencing the outcome after transsphenoidal surgery. We conducted a multicenter, retrospective analysis of the early and late results of surgical treatment of Cushing's disease. Files of patients with Cushing's disease who underwent transsphenoidal surgery between 1975 and 1990 were collected from 25 institutions throughout Europe. Data from 668 of 716 patients were suitable for statistical analyses. Surgical mortality was 1.9%, and major morbidity occurred in 97 patients (14.5%). Clinical and biochemical remission of Cushing's disease after surgery occurred in 510 cases (76.3%). Identification of the tumor by neuroradiological imaging or at operation with histopathological corroboration was associated with remission of hypercortisolism. Recurrence of the disease occurred in 65 (12.7%) of 510 patients in remission after surgery at a mean time of 39.3 months (range 6-104 months). The distribution of the recurrences did not show any apparent plateau or cluster throughout the follow-up period. Low postoperative steroid levels, absence of cortisol response to CRH, and the need for long-term glucocorticoid substitution therapy were all associated with a high probability of long-term remission. Our study demonstrates that transsphenoidal surgery is a safe and effective treatment for patients with Cushing's disease. However, after successful surgery there is a steady increase in the percentage of recurrences, which continues with time. Patients who after operation had hypoadrenocorticism and needed long-term glucocorticoid substitution therapy had the lowest risk of relapse.

Cushing Syndrome↗
PubMed1995

Assessment of growth hormone (GH) plasma clearance rate, half-life, and volume of distribution in acromegalic patients: the combined GH-octreotide infusion.

In acromegaly, high GH levels are primarily attributable to GH hypersecretion, but the contribution of GH clearance is still under debate and is difficult to assess. In the present study, GH plasma clearance rate (PCR), half-life (t1/2), and volume of distribution (VD) were assessed in seven acromegalic patients and seven normal lean subjects, after suppression of endogenous GH release by octreotide, with use of a constant GH infusion. An octreotide sc infusion was started the night before the day of the test (2100 h) and maintained throughout the study. On the day of the test, exogenous GH was constantly infused iv for 6 h (0900-1500 h) in order to achieve a new steady state of GH levels. After the cessation of GH infusion, the decay curve of serum GH levels was monitored for 1 h. In both groups, GH PCR was calculated from the steady state serum GH levels, and GH t1/2 was estimated from the monoexponential analysis of the GH disappearance curve. Estimates of VD were derived from PCR and t1/2. In acromegalic patients, GH PCR was 2.5 +/- 0.2 mL/kg.min-1, and GH t1/2 and VD were 15.7 +/- 1.0 min and 54.9 +/- 5.5 mL/kg, respectively. GH PCR and GH t1/2 of acromegalic patients were higher and lower, respectively, than those of normal subjects (PCR, 1.7 +/- 0.2 mL/kg.min-1, P < 0.02; t1/2, 18.4 +/- 0.6 min, P < 0.05). VD was not significantly different in the two groups. In summary, in acromegalic patients GH kinetic parameters can be reliably assessed by using a constant GH infusion after suppression of endogenous GH release by octreotide. Our results also indicate that the increased circulating GH levels observed in acromegaly are attributable only to GH overproduction and do not depend on an alteration in the processes of GH distribution or disappearance.

Acromegaly↗
PubMed1994

Acute effects of a single administration of dexamethasone on basal and growth hormone-releasing hormone stimulated GH secretion in acromegaly.

UNLABELLED: A single administration of dexamethasone causes both an early stimulatory and a late inhibitory effect on GH secretion in normal subjects. OBJECTIVE: We investigated the effects of a single administration of dexamethasone on basal and GH-releasing hormone-stimulated GH secretion in eight patients with active acromegaly. DESIGN: On three different days the patients received 4 mg i.v. dexamethasone, 1 microgram/kg body weight GH-releasing hormone 1-29, or matched placebos in different order. PATIENTS: Eight subjects with active acromegaly, five of whom had not been treated previously, while the other three had received octreotide therapy which was stopped at least 7 days before testing. MEASUREMENTS: Serum GH levels were measured in duplicate by a commercially available RIA kit. RESULTS: Dexamethasone administration caused a significant decline of mean +/- SE GH levels from 51.8 +/- 13.8 to 30.0 +/- 9.2 mU/I at 180 minutes, that was not influenced by placebo administration at 180 minutes. On the contrary, when GH-releasing hormone substituted placebo administration, GH levels increased from 34.0 +/- 9.8 mU/I at 180 minutes to 56.0 +/- 15.6 mU/I at 195 minutes. The GH increase was higher when GH-releasing hormone was given without dexamethasone pretreatment (from 52.4 +/- 13.0 mU/I at 180 minutes to 86.4 +/- 25.4 mU/I at 195 minutes). Analysis of the GH area under the curve confirmed the significant inhibition of GH secretion after dexamethasone administration and the significant reduction of the GH response to GH-releasing hormone in the study with dexamethasone pretreatment. CONCLUSIONS: At variance with data in normal subjects, acute i.v. administration of dexamethasone inhibits basal GH secretion and partially suppresses the GH response to GH-releasing hormone in acromegaly. Both alterations in the regulatory mechanism of adenomatous cells and perturbations of hypothalamic regulatory influences, induced by the state of chronic GH hypersecretion, are likely explanations of the different response to dexamethasone.

Acromegaly↗
PubMed1993

Nerve growth factor suppresses the transforming phenotype of human prolactinomas.

The most effective therapy of human prolactinomas is represented by dopamine D-2 receptor agonists; there is, however, a population of nonresponder patients who require surgical intervention. In the present study, we report that prolactinomas totally resistant to pharmacological therapy have a high potential of both growing in soft agar and forming tumors in nude mice and lack D-2 receptors for dopamine. These tumors express the receptors for nerve growth factor (NGF) and are sensitive to its differentiating activity. After exposure to NGF for 4 days, prolactinoma cells decreased their proliferation rate, lost their capability to form colonies in soft agar, lost their tumorigenic activity in nude mice, and reexpressed the lactotroph-specific D-2 receptor protein inhibiting prolactin release. These effects were permanent after NGF withdrawal and were reproducible in vivo in nude mice transplanted with the tumors. NGF in fact remarkably and lastingly depressed tumor growth and induced expression of D-2 receptors when injected intravenously once a day for 5 days into prolactinoma-bearing nude mice. These data suggest that NGF may induce a long-lasting switch of gene expression in human prolactinomas, modifying their transforming phenotype and reverting them to more differentiated, less malignant, dopamine-sensitive lactotroph-like cells. The possibility thus arises that short-term treatment with NGF may restore the refractory patients to conventional pharmacological therapy with D-2 agonists.

Animals↗
PubMed1992

[New faces, forgotten diseases:border medical examination of asylum seekers' children 1990-1991].

Hitherto there has been no epidemiologic basis for the extent of initial medical examination (IME) of children of refugees. In Switzerland little data is published on the incidence of diseases among refugees; in particular information on their children is scarce. We report the results of IME in these children in the Canton of Zürich from 1 July 1990 to 30 June 1991. The Federal Refugees Office assigned 1487 children to the Canton of Zürich. 920 children (61.9%) were registered, 259 (17.4%) at Zürich Children's Hospital and 661 with local physicians (44.5%). The current IME included a tuberculin skin test only, with additional hepatitis B screening of children from high risk countries. At the Zürich Children's Hospital the IME was extended: every child was examined clinically and a history was taken. The findings in the children examined at the Zürich Children's Hospital were as follows: 171 (66%) were healthy. 5 children (2%) had tuberculosis, 2 (0.8%) vitamin D deficiency rickets, 5 (2%) had iron deficiency anemia, 9 had hepatitis B (all recovered), 25 (9.7%) had various skin diseases and in 51 a variety of diseases of differing clinical significance were diagnosed. The local physicians found a similar incidence of tuberculosis, vitamin D deficiency rickets, iron deficiency anemia and skin diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hypochromic↗
PubMed1992

Solitary plasmacytoma of the sphenoid sinus involving the pituitary fossa: a case report and review of the literature.

A rare case of solitary plasmacytoma of the sphenoid sinus involving the pituitary fossa is reported. A 50-year-old woman with a history of diplopia and a mass in the sphenoid sinus and the sellar region, documented by computed tomography, was referred to our department with a presumed diagnosis of nonfunctioning pituitary adenoma. The clinical and biochemical characteristics were unrevealing, but magnetic resonance imaging examination demonstrated the extrapituitary origin of the lesion. The patient was operated on by the transsphenoidal approach, and the lesion was histologically diagnosed as a plasmacytoma. Review of the literature disclosed 11 previously described cases of myelomatous disease presenting clinically as a pituitary adenoma. Our case demonstrates that magnetic resonance imaging investigation may help in distinguishing the extrapituitary origin of a mass involving the pituitary fossa.

Adenoma↗