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Biomedical subjects

A Angeli

Publications and source records attributed to A Angeli.

At least 109 records · Page 6Linked to original sources
PubMed1995

Circadian variations of thyrotropin bioactivity in normal subjects and patients with primary hypothyroidism.

Circadian rhythm of TSH secretion is characterized by a pronounced nocturnal increment that is not followed by the expected rise of circulating thyroid hormone levels. These findings suggest that the nocturnal TSH surge may be constituted by molecules with reduced bioactivity. We, therefore, investigated TSH bioactivity (measured as cAMP accumulation in FRTL-5 cells) and its carbohydrate structure (by Concanavalin A affinity chromatography) in different blood pools taken during the day and night from seven normal subjects and from one patient with mild (mPH) and five with severe primary hypothyroidism (sPH). Patients with sPH were also studied during low dose L-T4 treatment. Cosinor analysis showed a significant TSH circadian rhythm in the control group and in L-T4-treated sPH patients. The nocturnal TSH surge was not followed by any increase in free thyroid hormone levels. In normal subjects, the daytime ratio of TSH bioactivity to immunoreactivity (TSH B/I) was higher than the nocturnal one [1.4 +/- 0.6 (+/- SD) vs. 1.1 +/- 0.6; P < 0.02]. The same pattern was observed in the only mPH patient (1.0 +/- 0.2 vs. 0.7 +/- 0.1; P < 0.01), but not in the sPH patients (0.8 +/- 0.3 vs. 0.7 +/- 0.1; P = 0.3). L-T4 administration to sPH patients caused the daytime TSH B/I to increase and restored the day/night difference in the TSH B/I (1.0 +/- 0.3 vs. 0.8 +/- 0.3; P < 0.02). Concanavalin A chromatography showed that a higher percentage of less mature forms of TSH are secreted during the night. These data indicate that TSH molecules secreted during the night are less bioactive and differently glycosylated than those circulating in the same individual during the day, thus explaining why thyroid hormone levels do not rise after the nocturnal TSH surge. In sPH patients, the TSH circadian rhythm is restored during L-T4 administration, and day/night differences in TSH B/I similar to those recorded in normal subjects are observed.

Adult↗
PubMed1995

Cytotoxic chemotherapy for adrenocortical carcinoma.

The efficacy of mitotane in providing objective tumour responses in patients with adrenocortical carcinoma (ACC), has been recently questioned. Experience with non specific chemotherapy is limited. Tumour responses have been reported with cisplatin administered as a single agent or in combination. Other reports however failed to show benefit from cytotoxic chemotherapy. The very low number of patients included in each study, mostly of them previously treated with mitotane, may account for these controversial results. The finding that multidrug resistance mediated by MDR-1/P-glycoprotein can be reverted by mitotane provides a rational basis for exploring the use of mitotane in combination with chemotherapeutic agents. In a multicenter cooperative (SWOG) phase II study, a combination of mitotane+cisplatin appeared active in advanced ACC, with 30% response rate in 37 eligible patients. These results prompted us to evaluate the activity of a combination chemotherapy of Eto-poside, Adriamycin and Cisplatin (EAP) in association with mitotane (4 g daily per os). Up to now we treated 6 patients, obtaining 3 partial responses. Recently, new drugs as suramin and gossypol have been show to have some activity in patients with surgically unresectable ACC, suggesting the need for further investigation. In conclusion, cytotoxic drugs+mitotane and new adrenocorticolytic/cytotoxic agents, should be explored as first line treatments in patients with advanced ACC. However, due to the extreme rarity of the disease, coordinated multicenter investigations should be highly encouraged.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Adrenal incidentaloma, a five year experience.

Since 1989, 45 patients 26 females and 19 males, aged 19-79 years (median 58) bearing incidentally discovered adrenal masses were studied. Endocrine work-up included determination of urinary catecholamines and their metabolites, measurement of plasma renin activity and aldosterone levels in clino- and orthostatic posture, basal and dynamic (dexamethasone-suppression, o-CRH stimulation) evaluation of hypothalamic-pituitary-adrenal (HPA) axis. The most frequent finding was the reduction of DHEA-S levels below the 3rd percentile of controls in 19 (42%) patients. As a whole group, DHEA-S levels were significantly lower in patients than in controls: 68 (5-1000) micrograms/dL vs 208 (34-326) micrograms/dL; p < 0.001. Three patients (7%) had high 24-h mean serum cortisol levels and 6 (14%) had blunted day-night amplitude of cortisol rhythm. Defective dexamethasone suppressibility was found in 15% of patients vs 8% of controls (p < 0.05). ACTH and cortisol responses after o-CRH did not significantly differ between patients and controls although blunted ACTH responses were found in 22% of cases. The above mentioned endocrine alterations could be accounted for by autonomous cortisol secretion by the adrenal nodule at a rate not sufficient to give clinical expression but able to inhibit to some extent the HPA axis. These results indicate that silent cortisol hypersecretion is frequently observed in patients with adrenal incidentaloma even if progression to overt Cushing's syndrome seems unlikely, at least in a short-term follow-up. From a mere cost-benefit ratio, the evaluation of DHEA-S levels and dex-suppression has sufficient sensitivity to identify the occurrence of silent hypercortisolism.

Adenoma↗
PubMed1994

Cyclic Cushing's syndrome due to ectopic ACTH secretion by an adrenal pheochromocytoma.

Pheochromocytoma is a rare cause of ectopic Cushing's syndrome. We report on such a patient in whom ectopic ACTH secretion displayed a cyclic pattern. A 35-year-old woman was referred to us with a diagnosis of ACTH-dependent Cushing's syndrome. A 3.3 cm left-sided adrenal mass was noted at abdominal computerized tomography. At admission, clinical and hormonal data were unrewarding, so it was decided to continue to observe the patient. Four months later, she became symptomatic with hypertensive and psychotic crises and glycemic decompensation. By that time, a full-blown Cushing picture was evident. Severe hypercortisolism was documented with urinary free cortisol ranging 1500-2200 micrograms/24 h, serum cortisol 143-160 micrograms/dl and plasma ACTH 167-218 pg/ml. Neither ACTH nor cortisol values were significantly modified after high-dose dexamethasone, oCRH or metyrapone. Urinary catecholamine and vanilyl mandelic acid excretion were moderately elevated. Chest CT and total body MIBG scan were negative and magnetic resonance of the sella region was inconclusive. No center to periphery ACTH gradient was observed by inferior petrosal sinus catheterization, whereas a significant left to right gradient was found on selective adrenal vein catheterization. A left adrenalectomy was performed and a 4 cm medullary neoplasia was removed. The cells were immunostained for ACTH, neuron-specific enolase and A chromogranin. Signs and symptoms of Cushing's syndrome resolved with normalization of basal and dynamic endocrine evaluations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1994

Steroid biochemistry and categorization of breast cyst fluid: relation to breast cancer risk.

Patients bearing macrocysts of the breast are at higher risk of later developing cancer. The fluid filling the cysts (breast cysts fluid, BCF) contains unusual amounts of steroid conjugates, first androgen and estrogen sulfates. Measuring BCF cations (K+,Na+) allows categorization of cysts into two major subsets (type I and type II) that are associated with a different degree and/or turnover of apocrine metaplastic cells in the lining epithelium. Type I cysts (high K+/Na+ ratio) accumulate hugh amounts of dehydroepiandrosterone sulfate, estrone sulfate, androstane-3 alpha,17 beta-diol glucuronide, androsterone glucuronide and contain more testosterone and dihydrotestosterone than type II. Conversely, type II cysts (low K+/Na+ ratio) contain more progesterone and pregnenolone. A cohort study was started in 1983 at the Cancer Prevention Center, Ravenna, Italy, with the aim of evaluating the relationships between the biochemistry of BCF and the incidence of breast cancer in women with gross cystic disease (GCD) of the breast. The bimodal distribution of the cationic pattern has been confirmed from data obtained in 798 patients aspirated. The risk of cyst relapse was significantly higher among women with type I cysts or with multiple cysts at presentation. Twelve incident cases of breast cancer have been diagnosed among women whose BCF was categorized. Eleven out of 12 cases had type I or multiple cysts. The cumulative incidence of breast cancer among patients bearing type I cysts was 2.5%. We conclude that women with GCD bearing type I cysts have an increased breast cancer risk when compared with the counterpart bearing type II cysts or the general population.

Adult↗
PubMed1994

Biochemical markers of bone and collagen turnover in acromegaly or Cushing's syndrome.

We evaluated serum bone Gla-protein (osteocalcin, BGP), carboxyterminal propeptide of type I procollagen (PICP) and aminoterminal propeptide of type III procollagen (PIIINP) in 15 patients with active acromegaly (6M aged 27-54, 4 PMF aged 39-51, 5MP aged 54-65 years), 12 with active Cushing's syndrome [(CS) 2M of 32 and 42 years; 4PMF aged 25-40; 6MF aged 50-64)] and controls evenly matched for age, sex and menstrual status. Patients with acromegaly were evaluated before and at regular intervals on octreotide treatment (50-150 micrograms t.i.d., s.c.); the duration of the follow-up was 5-49 months (median 28). Endocrine evaluation included measurements of serum GH, IGF-I, BGP, PICP and PIINP. In a case-control analysis, acromegalic patients showed increased BGP (14.3 +/- 2.1 vs 8.3 +/- 2.1 ng/ml p < 0.001) and PIIINP concentrations (4.8 +/- 1.4 vs 3.1 +/- 0.7 micrograms/l, p < 0.02). During octreotide treatment we observed a roughly parallel decline of GH, IGF-I and BGP. BGP and log-transformed 24-h mean GH concentrations were positively correlated (r = 0.48, p < 0.001) as was the case for BGP and IGF-I (r = 0.43, p < 0.001). Also PIIINP correlated with log-transformed GH (r = 0.58, p < 0.001) and IGF-I (r = 0.35, p < 0.05). Serum PICP did not differ in the two groups (152 +/- 55 vs 120 +/- 55 micrograms/l, NS) and did not correlate either with GH or IGF-I. Patients with CS were evaluated measuring serum and urinary cortisol (UFC), ACTH, BGP, PICP, PIIINP.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1994

Chemotherapy with dacarbazine and 5-fluorouracil in advanced medullary thyroid cancer.

BACKGROUND: Experience with chemotherapeutic agents in the management of advanced medullary thyroid carcinoma (MTC) is limited and controversial. However, since MTC is a neuroendocrine neoplasm, we considered the possibility that cytotoxic drugs previously used in the treatment of these tumours could also have activity in MTC. PATIENTS AND METHODS: Five patients (4 females and 1 male, aged 22-71 years) with locally advanced or metastatic MTC received 5 day intravenous courses of dacarbazine (DTIC) (250 mg/sqm) and 12 hour infusion 5-fluorouracil (450 mg/sqm), given every 4 weeks. Six cycles were administered to 4 patients and four to 1 patient. RESULTS: Three partial responses lasting 9, 10+ and 8+ months were observed; one patient had stable disease and one progressive disease. Toxicity was acceptable with grade I thrombocytopenia and grade II leukopenia occurring in one patient, and grade II nausea and vomiting in four patients. CONCLUSIONS: In our experience, treatment of advanced thyroid carcinoma with DTIC and 5-FU appeared to have significant activity and was well tolerated.

Adult↗
PubMed1994

Endocrine evaluation of incidentally discovered adrenal masses (incidentalomas)

Since 1989, 45 patients [pts; 26 females and 19 males, aged 19-79 yr (median, 58)] bearing incidentally discovered adrenal masses were studied. The aim of the study was to verify the prevalence of hormone activity in clinically silent adrenal masses. Endocrine work-up included determination of urinary catecholamines and their metabolites, measurement of PRA and aldosterone levels in clino- and orthostatic posture, and basal and dynamic [dexamethasone (dex) suppression and ovine CRH stimulation] evaluation of hypothalamic-pituitary-adrenal axis. The most frequent finding was the reduction of dehydroepiandrosterone sulfate (DHEA-S) levels below the third percentile of controls in 19 (42%) pts. DHEA-S levels were significantly lower in pts than in controls [68 (range, 5-1000) vs. 208 (34-326) micrograms/dL; 1.8 (0.1-27.1) vs. 5.6 (0.9-8.8) mumol/L; P < 0.001]. Three pts (7%) had high 24-h mean serum cortisol levels, and 6 (14%) had blunted day-night amplitude of cortisol rhythm. Defective dex suppressibility was found in 15% of pts vs. 8% of controls (P < 0.05). ACTH and cortisol responses to ovine CRH did not significantly differ between pts and controls, although blunted ACTH responses were found in 22% of the cases. The above-mentioned endocrine alterations could be accounted for by autonomous cortisol secretion by the adrenal nodule at a rate not sufficient to give clinical expression, but able to inhibit to some extent the hypothalamic-pituitary-adrenal axis. These results indicate that silent cortisol hypersecretion is frequently observed in pts with adrenal incidentaloma even if progression to overt Cushing's syndrome seems unlikely. Indeed, the size of the mass and the hormone pattern remained substantially unchanged in 9 pts followed up for 12 months. From merely a cost/benefit ratio, the evaluation of DHEA-S levels and dex suppression has sufficient sensitivity to identify the occurrence of silent hypercortisolism.

Adenoma↗
PubMed1994

Expression of the c-myc protooncogene product in cells infected with the hepatitis delta virus.

The intrahepatic accumulation of the c-myc protooncogene product was observed on immunofluorescence in each of six patients with chronic hepatitis delta virus infection who exhibited the hepatitis D antigen in their livers. The c-myc product was stained in the same nuclei that contained the hepatitis D antigen. C-myc was not observed in acute hepatitis D or in cases of chronic hepatitis delta virus infection without expression of the hepatitis D antigen. The protooncogene product was detected in only 1 of 32 viral and nonviral liver disorders unrelated to hepatitis delta virus. To confirm these observations, we transfected HBsAg-positive (PCL/PRF/5) and HBsAg-negative (HepG2) transformed liver cell lines with a plasmid containing a hepatitis delta virus cDNA trimer under the control of the SV40 early enhancer/promoter sequences. Whereas baseline c-myc expression was barely detectable in mock-transfected PLC/PRF/5 or HepG2 cells, strong c-myc nuclear fluorescence was observed when these same cells were transfected with the hepatitis D antigen expression vector. Similar results were obtained after infection of HeLa cells with a recombinant vaccinia virus expressing the hepatitis D antigen. Detection of c-myc mRNA sequences by means of in situ hybridization suggested that the c-myc product accumulation was not due to increased amounts of its mRNA. The c-myc protein accumulates selectively in the livers of patients with chronic hepatitis delta virus infection and in the same nuclei that contain the hepatitis D antigen. The expression of c-myc in hepatitis D antigen-containing cells does not require the presence of hepatitis B virus infection.

Amino Acid Sequence↗
PubMed1993

Interplay in vitro between ACTH, beta-endorphin, and glucocorticoids in the modulation of spontaneous and lymphokine-inducible human natural killer (NK) cell activity.

Release of pro-opiomelanocortin (POMC)-derived peptides and glucocorticoids characterizes the activation of the hypothalamic-pituitary-adrenal (HPA) axis and represents a major adaptive response to stress. Both glucocorticoids and POMC-derived hormones are known to be crucial modifiers of the immune response. Natural killer (NK) cells are a lymphocyte subset deeply involved in immunosurveillance. Cortisol, the most important glucocorticoid hormone in humans, is a well-established inhibitor, whereas the two lymphokines, immune interferon (IFN-gamma) and interleukin-2 (IL-2), are important physiological stimulators. In the present study, physiological as well as superphysiological concentrations of two POMC-derived peptides, ACTH and beta-endorphin, were shown not only to affect in vitro spontaneous and lymphokine-inducible NK activity of peripheral blood mononuclear (PBM) cells, but also to modify cortisol-mediated inhibition. NK activity was measured in a 4-h cytotoxic assay using the cell line K562 as a target, after prior incubation with ACTH (10(-8)-10(-12) M) and beta-endorphin (10(-8)-10(-14) M) in the presence or absence of cortisol (10(-6) M), IFN-gamma (325 IU/ml), and IL-2 (25 IU/ml). ACTH was ineffective in changing spontaneous NK activity at all concentrations, whereas beta-endorphin enhanced NK cytotoxicity (p < .02). The concomitant exposure of PBM cells to the two POMC-derived peptides and IFN-gamma or IL-2 significantly enhanced the lymphokine-induced boosting of NK activity. Moreover, ACTH and beta-endorphin were able to significantly reduce the cortisol-dependent inhibition (p < .05). These data are compatible with the hypothesis that POMC-derived peptides have a role in the modulation of NK cell activity. It seems likely that in cases of activation of the HPA axis, ACTH and beta-endorphin may effectively counteract the negative effects of glucocorticoids on NK cell activity, and prevent, at least in some instances, any overshooting of the glucocorticoid-dependent effect on immune cells.

Adrenocorticotropic Hormone↗
PubMed1993

Serum levels of bone Gla protein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in acromegaly: effects of long-term octreotide treatment.

We measured serum concentrations of bone Gla-protein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in 14 patients with active acromegaly. Blood was collected at 0800 for measurement of bone Gla-protein (BGP), carboxyterminal propeptide of type I procollagen (PICP), and insulin-like growth factor I (IGF-I); growth hormone (GH) was then determined at 15-minute intervals for 3 hours and the integrated mean was calculated. The same protocol was repeated at regular intervals during treatment with the long-acting somatostatin analog, octreotide, 150-450 micrograms/day for 6-33 months (median 15). In a case-control analysis, serum BGP concentrations recorded in the acromegalic patients were significantly elevated (14.2 +/- 4.2 micrograms/liter versus 8.0 +/- 3.3 micrograms/liter, P < 0.001). Octreotide treatment induced a roughly parallel reduction in serum GH, IGF-I, and BGP. We found a significant positive correlation between BGP levels recorded before and during therapy and the logarithm of corresponding mean GH levels (r = 0.67, P < 0.001). Also IGF-I concentrations were positively correlated with BGP (r = 0.66, P < 0.001). On the other hand, PICP levels recorded in the acromegalics did not differ from control subjects (146 +/- 46 micrograms/liter versus 127 +/- 44 micrograms/liter, NS) and no correlation was found between either GH and PICP or IGF-I and PICP. To conclude, the present data are compatible with the view that GH and IGF-I play an important role in the control of BGP but not PICP production. It could be that BGP and PICP are submitted to different hormonal modulation.

Acromegaly↗
PubMed1993

Evening administration of melatonin enhances the pulsatile secretion of prolactin but not of LH and TSH in normally cycling women.

OBJECTIVE: The aim of the study was to evaluate the effects of exogenous melatonin on the spontaneous pulsatile release of PRL, TSH and LH in normal women. DESIGN: A double blind placebo-controlled protocol was designed to study seven subjects in the mid follicular phase of two non-consecutive cycles. Two mg of exogenous melatonin or placebo were given at 1600 and 2000 h, and blood samples were collected every 10 minutes from 1800 to 2400 h for hormone determination. RESULTS: Melatonin treatment caused a significant upward resetting of the pulsatile pattern of PRL in six out of seven subjects. Average maximal peak height was significantly increased (median 716 mIU/l (range 198-1433) on melatonin vs 324 mIU/l (212-688) on placebo, P < 0.001), nadir value (572 mIU/l (148-1084) vs 216 mIU/l (54-580), P < 0.001) and area under the peak (26352 mIU/l min (5904-93672) vs 12096 mIU/l min (2340-33552), P < 0.001), whereas peak number, amplitude and interpeak interval did not change significantly. TSH pulsatility was unaffected by melatonin administration in four out of six subjects. Distribution of LH patterns after melatonin was inhomogeneous: level of pulsatility was higher in two cases and reduced in three; group analysis did not therefore show significant variation of pulsatility parameters. CONCLUSIONS: Exogenous melatonin has a stimulatory effect on PRL release without affecting the temporal pattern of its pulsatile secretion in normal women. Melatonin has minor, if any, effect on TSH secretion whereas the effect on LH may depend on individual sensitivity.

Adult↗
PubMed1992

Favorable response of metastatic adrenocortical carcinoma to etoposide, adriamycin and cisplatin (EAP) chemotherapy. Report of two cases.

The usefulness of non-specific chemotherapy for advanced adrenocortical carcinoma (ACC) is controversial. We report on 2 young female patients (25 and 19 yr) who presented with a clinical picture of Cushing's syndrome due to histologically confirmed ACC. The first patient underwent radical surgery, but after a disease-free interval of 6 months a local recurrence was apparent. She was reoperated and treated with 6 courses of cisplatin and etoposide chemotherapy. Mitotane (8 g daily) was begun, but 2 months later debulking surgery was again performed. A second-line chemotherapy with the etoposide, adriamycin, cisplatin (EAP) scheme attained a partial remission lasting 7 months, then metastatic spread to the brain led to death of the patient. The survival time was 30 months. The second patient underwent radical surgery and adjuvant mitotane (4 g daily), but multiple lung and mediastinal metastases were diagnosed after an interval of 29 months. Chemotherapy with the EAP regimen (6 courses) without interrupting mitotane attained a partial remission lasting 21+ months. We suggest that the EAP scheme is active in advanced ACC and that its association with mitotane is feasible.

Adrenal Cortex Neoplasms↗
PubMed1992

Association of cyst type with risk factors for breast cancer and relapse rate in women with gross cystic disease of the breast.

The concentration of potassium (K+) and sodium (Na+) was measured in breast cyst fluid (BCF) from 611 cysts greater than 3 ml aspirated in 520 women with gross cystic disease of the breast. These women were enrolled, from 1983 on, in a cohort study aimed at assessing the relationship between cyst type, as defined by the K+/Na+ ratio in BCF, and the risk of breast cancer. The inverse relationship between K+ and Na+ and the bimodal distribution of the K+/Na+ ratio in BCF were confirmed. Type I cysts were defined as cysts with a K+/Na+ greater than 1.5 in BCF. Among women with type I cysts, a higher proportion of women with one or no births, of women with a history of apocrine cysts, of current smokers, and of women who do not drink coffee was found, as compared to women with other types of cysts. The risk of cyst relapse was significantly higher among women with type I cysts than among women with other types of cysts and among women with multiple cysts at presentation. These findings indicate that type I BCF is a marker of "active" gross cystic disease of the breast and suggest that it may be associated with increased breast cancer risk.

Abortion, Spontaneous↗