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E Ciccarelli

Publications and source records attributed to E Ciccarelli.

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Comparison between pituitary computed tomographic findings and tests of hypothalamo-pituitary function in 72 patients with hyperprolactinaemia.

To verify the diagnostic capacity of some dynamic tests of the prolactin (Prl) secretion, the findings obtained by high-resolution computed tomography (CT) were compared with results obtained from tests using nomifensine (NOM) domperidone (DOM) and thyrotrophin-releasing hormone (TRH) in 72 patients with pathological hyperprolactinaemia. None of the patients with tumours had a positive Prl response to NOM or to DOM administration; however, a positive response to these tests was present in only 24 and 41%, respectively, of the patients with normal CT picture. The results of TRH testing were similar to those obtained with DOM. Different neuroendocrine patterns were disclosed by comparing pituitary Prl and thyrotrophin (TSH) responses to DOM: 1) some subjects had a reduced Prl response together with an exaggerated or normal TSH response to DOM; they comprised patients with tumour, empty sella, and normal CT picture; 2) other patients with normal CT picture had a positive Prl and a normal TSH response to DOM. These results demonstrate that a negative Prl response to NOM and DOM characterizes all patients with adenoma; however, the tumour-like responses in patients with no visible tumours seem to reduce the diagnostic value of these tests, unless the latter may predate the radiological appearance of an adenoma. On the other hand, a positive Prl and a normal TSH response to DOM exclude the presence of a pituitary tumour. This diagnostic finding is strengthened by the positive response also to NOM. Whatever may be the diagnostic validity of dynamic tests, they provide sound information on the functional state of dopamine neurotransmission.

Adenoma↗

Growth hormone-releasing factor does not stimulate phosphoinositides breakdown in primary cultures of rat and human pituitary cells.

It has been reported that rat growth hormone releasing factor (rat GRF-43), similarly to the two human GRFs (GRF-40 and 44) stimulates adenylate cyclase activity in pituitary cells. Controversial findings have been presented by two different groups on the action of GRF on phosphoinositides (PI) metabolism, a phenomenon linked to Ca-- mediated intracellular mechanisms. In the work to be reported, we evaluated the accumulation of inositol phosphates induced by GRF exposure in primary cultures of rat and human pituitary cells. Addition of rat GRF-43 to rat pituitary cells at doses up to 1 microM had no effect on inositol phosphates accumulation, while already at a dose as low as 0.05 nM it increased growth hormone secretion in the incubation medium significantly. In the same cell system, TRH, a known activator of PI breakdown, significantly increased [3H]inositol phosphates. In primary cultures of human somatotrophs from acromegalic subjects as in rats, addition of hpGRF-40 and also of TRH did not elicit any modification in the accumulation of [3H]inositol phosphates. Consistent with in vivo findings, both peptides induced a significant release of GH in the medium. Our results show that the GH releasing effect of GRF does not involve the hydrolysis of phosphatidylinositol in normal rat as well as in tumoral human somatotrophs. In addition it appears that the anomalous response of TRH on adenomatous cells from acromegalic patients is differently mediated in respect to the action of the tripeptide on normal lactotrophs and thyrotrophs.

Acromegaly↗

Prolactin and thyrotropin response to blockade of dopamine synthesis by monoiodotyrosine in subjects with postpartum and pathological hyperprolactinemia.

To better understand the state of dopamine (DA) neurotransmission in the tuberoinfundibular DA system (TIDA), monoiodotyrosine (3-iodo-L-tyrosine, MIT), a potent inhibitor of DA synthesis, was acutely administered to 8 normal women, 7 postpartum women, 8 women with pathological hyperprolactinemia and 5 women after successful removal of a prolactinoma. The effects on plasma prolactin (PRL) and thyrotropin (TSH) were compared to those induced in the same subjects by the DA receptor antagonist domperidone (DOM). MIT (1 gpo) and DOM (10 mg iv) induced qualitatively similar hormonal responses, although the PRL- and TSH-releasing effects of DOM were always greater than those of MIT. In control subjects, MIT treatment induced a consistent rise in plasma PRL (peak increment 45.2 +/- 13 ng/ml at 120 min); in the same subjects DOM induced a prompter and higher PRL response, (peak increment 147.8 +/- 26 ng/ml at 30 min). MIT failed to alter plasma TSH levels, while DOM induced a significant rise in plasma TSH. In postpartum women MIT induced a prompter and higher PRL rise than that occurring in controls (peak increment 180.3 +/- 20 ng/ml at 90 min), though also in this instance DOM proved to be a more potent PRL releaser (peak increment 345.7 +/- 88 ng/ml at 30 min) than MIT. MIT was unable to stimulate TSH secretion, while DOM induced a significant rise in plasma TSH. In women with pathological hyperprolactinemia MIT failed to alter baseline PRL levels while DOM slightly increased them (peak increment 14.7 +/- 3 ng/ml at 30 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

Defective regulation of prolactin secretion after successful removal of prolactinomas.

The PRL response to nomifensine (Nom), an indirect DA agonist; domperidone (Dom), a DA receptor antagonist; and TRH, which directly stimulates the PRL-secreting cells, was evaluated 2-53 months after surgery in 13 patients in whom successful removal of a prolactinoma had resulted in normal serum PRL levels and return of regular menses or libido and potency. In addition, the pattern of TSH secretion in response to Dom and the spontaneous rise in plasma PRL of 6 cured patients during pregnancy were evaluated. Nom induced an inconsistent decrease in basal PRL levels, a pattern contrasting with that in healthy women in whom plasma PRL was markedly suppressed after administration of the drug. Dom and TRH elicited a significant rise of basal PRL levels, but the rise was markedly lower than that occurring in the control group. The TSH increment after Dom treatment was lower than that before surgery, though higher than that in the controls. Evaluation of individual patients showed that only one patient had a normal PRL response to either Nom or Dom, while the TSH response to the latter returned to normal in five of seven patients. During pregnancy, plasma PRL rose inconsistently in the patients, and PRL levels were generally lower than those in normal pregnant women. These results suggest the presence of an abnormality in the dopaminergic mechanism(s) of PRL control before and after adenomectomy or, less likely, the existence of impaired pituitary function or reserve.

Adenoma↗

Natural killer activity in hyperprolactinemic patients.

Several pieces of evidence suggest the existence of a relationship between neuroendocrine and immune systems. Prolactin (PRL) has been demonstrated to modulate some immune responses and its influence seems to be permissive or inhibitory depending on its concentration. Previous studies have reported a reduced natural killer (NK) cell function in patients with hyperprolactinemia. In 36 patients (34 females and 2 males, aged 14-46 years) with hyperprolactinemia (mean +/- SEM PRL 142.2 +/- 42.1 micrograms/l) of tumorous (19 patients) and functional (17 patients) origins, NK activity of peripheral blood lymphocytes (PBL) was studied. Patients had NK cell activity against the K562 cell line which did not differ from that of lymphocytes from 36 age- and sex-matched healthy donors (mean +/- SEM lytic units (LU) 619.0 +/- 103.0 and 531.9 +/- 52.6 respectively). No correlation between PRL levels and LU values was found (r = 0.28). When patients with tumors or functional hyperprolactinemia were separately analysed no difference was found between these two groups (mean +/- SEM LU 690.0 +/- 117.7 vs. 606.0 +/- 148.8). In conclusion, our data demonstrate that neither the elevated PRL levels nor the PRL-secreting tumor per se interfere with the NK system of hyperprolactinemic patients.

Adolescent↗

[Social class, mode of admission, severity of illness and hospital mortality: an analysis with "All patient refined DRG" of discharges from the Molinette hospital in Turin].

Data available from the standard hospital discharge database (SDO) allow us to explore differences in health conditions according to different indicators of socioeconomic status (SES). We analysed all the patients aged 30-59, discharged from the S. Giovanni Battista (Molinette) hospital (the main general hospital in Turin, Italy) during three years (1996-1998) (n = 49949). Three health indicators were used as outcomes: a) emergency admission; b) severity of illness (according to the "All Patient Refined DRGs" subclasses); c) hospital mortality. Patients were compared for each outcome according to two different SES indicators: a) level of education; b) employment status. Logistic regression models (both conditional and unconditional) were used to adjust for several potential confounders. Patients with lower education (up to 5 years of schooling), compared to those with 13 or more years of schooling, showed a higher probability of being admitted through the emergency ward (29.1% vs 23.3%), with an odds ratio (OR) = 1.56-95% confidence interval (95% CI) = 1.45-1.68; of being classified in higher severity subclasses of illness (23.3% vs 17.7%, OR = 1.14; 95% CI = 1.07-1.22) and of dying in hospital (2.3% vs 1.6%). However, after adjustment for other prognostic factors (as severity of illness and specific expected mortality), this association disappeared (OR = 1.05, 95% CI = 0.84-1.32). Similar, but somewhat stronger, associations were observed when comparing the unemployed versus the employed. The corresponding figures (ORs; 95% CI) were 1.57 (1.42-1.74) for emergency admission; 1.31 (1.18-1.45) for severity of illness and 1.55 (1.10-2.16) for hospital mortality. In conclusion, this study showed that SES differentials in health are clearly measurable through routine hospital information systems, and documented that patients of low SES, particularly unemployed, experienced a delayed access to hospital, were admitted in poorer general health conditions and had a more unfavourable prognosis.

Catchment Area, Health↗

[Quality of data or quality of care? Comparison of diverse standarization methods by clinical severity, based on the discharge form, in the analysis of hospital mortality].

Using discharge abstract data, we analysed hospital mortality comparing four different methods of risk adjustment. All patients discharged from the S. Giovanni Battista (Molinette) hospital in Turin (Italy) between January 1996 and June 1999 (n = 169,746) were classified with All Patient Refined--Diagnosis Related Groups (APR-DRG). A first analysis evaluated the time trend of hospital mortality by semester. A second analysis compared hospital mortality during the last 12 months among eight units of internal medicine (n = 5592). All comparisons were made through logistic regression models. As the quality of discharge abstracts increased during time and showed variation among units with similar patients, all comparisons were repeated using four models, characterised by increasing predictivity and sensitivity to quality of data. In addition to crude comparisons (A), the other models included as risk factors: B) age and emergency admission; C) same as 'B' plus expected mortality by APR-DRG; D) same as 'B' plus expected mortality by APR-DRG and risk of death subclass. If no risk factors were considered (A), hospital mortality showed an increasing trend, with an odds ratio (OR) of 1.02 by semester, with a 95% confidence interval (CI) between 1.01 and 1.03. The association was weakened when age and mode of admission were taken into account (B) and disappeared when the APR-DRG expected mortality was also considered (C) (OR = 1.00; CI = 0.98-1.01). Finally, if the comparisons were adjusted also for the expected mortality by APR-DRG and risk of death subclass (D) a reversed trend appeared (OR = 0.95; CI = 0.94-0.97). The comparison among the units of internal medicine gave discordant results according to the method used to adjust for confounders. The most striking variations were detected for those units with the best and the worst clinical data. The unit with the poorer clinical data (average number of diagnoses per patient = 2.9) showed a crude OR of 1.38 (CI = 0.99-1.93) and an adjusted OR (D) of 1.71 (CI = 1.10-2.66); the unit with the best quality of data (average number of diagnoses per patient = 4.4) changed the OR from 1.55 (CI = 1.06-2.26) (A) to 0.66 (CI = 0.37-1.17) (D). In conclusion, these results confirm the high sensitivity of the APR-DRG classification to the quality of data and, more in general, suggest to be prudent when using powerful instruments like this to assess quality of care, especially if the quality of data among the units compared is less than optimal or not homogeneous.

Hospital Mortality↗