Biomedical subjects

L Fedeli

Publications and source records attributed to L Fedeli.

14 recordsLinked to original sources

PubMed1992

In vivo targeting of Hodgkin and Reed-Sternberg cells of Hodgkin's disease with monoclonal antibody Ber-H2 (CD30): immunohistological evidence.

The ability of the Ber-H2 (CD30) monoclonal antibody (mAb) to target in vivo Hodgkin (H) and Reed-Sternberg (R-S) cells was investigated in six patients with advanced Hodgkin's disease (HD). The patients were injected with scaled-up quantities of 'cold' Ber-H2 mixed-up to a small dose of 131I-labelled Ber-H2, and in vivo binding of the antibody to H and R-S cells was assessed by immunohistological analysis of tumour biopsies and immunoscintigraphy. Only 50% of tumour sites were imaged at scintigraphy by the 131I-labelled Ber-H2. In contrast, immunohistological studies on tissue biopsies, taken 24-72 h following the mAb injection, showed that H and R-S cells in all tumour sites, including those that were not imaged by immunoscintigraphy, were specifically and strongly labelled in vivo by the injected Ber-H2, at a dose as low as 30-50 mg of antibody. In vivo binding of a single dose of Ber-H2 mAb to H and R-S cells did not result in any anti-tumour effect. The excellent in vivo targeting of H and R-S cells with the Ber-H2 mAb may have been the result of multiple favourable factors, including: (a) the restricted expression of the CD30 antigen in normal human tissues; (b) the low level of soluble CD30 in the serum of our patients; and (c) the high affinity of the Ber-H2 mAb for the CD30 molecule. The immunohistological results presented in this study provide a strong argument for using the Ber-H2 mAb as a carrier for delivering cytotoxic agents (isotopes or toxins) to neoplastic cells of HD refractory to conventional therapy.

Adult↗

PubMed1989

Pharmacokinetics of vincristine in cancer patients treated with nifedipine.

The pharmacokinetics of vincristine (VCR) after an intravenous bolus dose of 2 mg were studied in patients with cancer with and without a concomitant treatment with the calcium-entry blocker nifedipine (NIF). VCR concentrations were determined by a sensitive radioimmunoassay. Pharmacokinetic data were analyzed by a nonlinear weighted least-square regression program (SAS-NLIN). A tri-exponential model fitted the raw data better than a bi-exponential model in five of 14 (35%) patients treated with VCR alone and in seven of 12 (58%) patients treated with VCR plus NIF (P = NS). The T1/2 alpha was shorter in NIF-treated patients, whereas the T1/2 gamma was longer in the NIF-treated group. The NIF-treated group showed an increase in the AUC O-infinity and AUC 1 to 96 hours, and a decrease in the AUC 0 to 1 hour. Total plasma clearance of VCR and 7-day urinary excretion of VCR was reduced in the NIF-treated patients. These data suggest that, when VCR is administered to NIF-treated patients with cancer, there is a decrease in VCR clearance from the body. Theoretically, a greater cytotoxicity may be anticipated.

Aged↗

PubMed1989

Thyroid function tests in acute viral hepatitis: relative reduction in serum thyroxine levels due to T4-TBG binding inhibitors in patients with severe liver cell necrosis.

Thyroid function tests were evaluated in 34 patients with acute viral hepatitis (AVH) and in 38 healthy controls (C). As expected, AVH patients displayed a significant increase in T4, rT3 and TBG serum levels with respect to C, while FT4 and TSH concentrations were similar. A positive correlation between TBG and T4 was evident in C, but not in AVH. In this group there was, instead, an inverse correlation between the sum of serum levels of GOT + GPT and T4 concentrations. When AVH patients were divided in "high necrosis" (HN, serum GOT + GPT greater than 2000 UI/l) and "low necrosis" (LN, serum GOT + GPT less than 2000 UI/ml) groups, we found a significant reduction in both T4 and T3 serum concentrations in HN with respect to LN, despite similar levels of TBG, albumin, FT4 and TSH. The hypothesis that thyroid-hormone binding inhibitors (THBI), released during severe liver cell injury, accounted for an impaired serum binding capacity in HN-AVH, was confirmed by the significant increase in FT4/T4 ratio and by the demonstration of THBI activity in pooled sera of these patients, with respect to LN subgroup. Our present finding may clarify the unexplained observation of reduced T4 levels in patients with fulminant hepatitis and the ominous prognostic significance of a "low T4 syndrome" in subjects with severe liver disease and/or other systemic illnesses.

Acute Disease↗

PubMed1988

Catecholamines and pituitary function. VII: Effects of acute and chronic dopamine-receptor blockade on pituitary response to TRH-GNRH in normal women and in patients with hyperprolactinemic amenorrhea.

To investigate whether an enhanced dopamine (DA) inhibition on pituitary thyrotrophs and gonadotrophs may account for the abnormal TSH and LH dynamics in pathological hyperprolactinemia, we examined the effect of an acute lysis of the putative DA overinhibition, as obtained with continuous domperidone (DOM) infusion, on both basal and TRH-GnRH stimulated PRL, TSH and LH release in both normal cycling women and patients with pathological hyperprolactinemia. The effect of TRH-GnRH administration was also examined in women with DA-antagonist induced hyperprolactinemia, in order to evaluate the effect of a chronic lack of the physiological DA inhibition on pituitary hormone dynamics. Patients with both pathological and DA-antagonist induced hyperprolactinemia displayed an evident TSH and LH hyper-responsiveness to TRH-GnRH. The PRL response was reduced in the former but enhanced in the latter group. Domperidone infusion resulted in a marked increase in serum PRL levels in normal cycling women, but not in patients with pathological hyperprolactinemia. The abolition of the putative DA-overinhibition at the pituitary level with DOM infusion in patients with pathological hyperprolactinemia was followed by a slight increase in basal TSH output but did not modify the TSH and LH hyperresponsiveness to TRH-GnRH. The similarities in TSH and LH dynamics between patients with pathological and DA-antagonist induced hyperprolactinemia and the ineffectiveness of DOM infusion in modifying the TSH and LH hyper-responses to TRH-GnRH in the former group, seem to exclude the widely accepted idea that endogenous DA overactivity is responsible for the abnormal thyrotroph and lactotroph dynamics in women with hyperprolactinemic amenorrhea.

Adult↗

PubMed1988

Radioisotopic method for nasal mucociliary function evaluation.

In 13 healthy young adults, nasal mucociliary transport velocity was measured by means of albumine microsphere labeled with Tc99m as a tracer. M + ISD of clearance velocity values and of the half time radioactivity (T1/2) resulted to be respectively 1.02 + 0.22 cm/min and 1.07 + 0.24 min. A significant correlation (P less than 0.05) between half time clearance (T1/2) values of the radioactive particles and the mucociliary velocity ones could be detected, making T1/2 a reliable and rapidly obtainable parameter for determining nasal mucociliary function. Advantages and disadvantages of the different techniques are discussed.

Adult↗

PubMed1987

Catecholamines and pituitary function. VI. Effect of different dopamine doses on TRH-induced prolactin release in women with pathological hyperprolactinemia.

The present study was designed to examine the effect of low-dose dopamine (DA) infusion rates (0.02 and 0.1 microgram/kg X min) on both basal and TRH-stimulated prolactin release in normal and hyperprolactinemic individuals. Sixteen normally menstruating women in the early follicular phase of a cycle and 23 hyperprolactinemic patients were studied. 0.1 microgram/kg X min DA was infused in 8 normal women and 15 patients with pathological hyperprolactinemia, while 8 normal controls and 8 patients received 0.02 microgram/kg X min DA TRH (200 micrograms, i.v.) was administered alone and at the 180th min of the 5-hour DA infusion in all controls and patients. A significant reduction in serum PRL levels, which was similar in normal women (-59.5 +/- 4.0%, mean +/- SE) and hyperprolactinemic patients (-48.2 +/- 5.5) was observed in response to 0.1 microgram/kg X min DA. In normal cycling women DA infusion significantly (P less than 0.02) reduced the PRL response to TRH with respect to the basal TRH test (delta PRL 45.0 +/- 7.0 vs. 77.9 +/- 15.4 ng/ml). On the contrary, the PRL response to TRH was significantly higher during 0.1 microgram/kg X min DA than in basal conditions in hyperprolactinemic patients, both in absolute (delta PRL 91.8 +/- 17.6 vs. 38.4 +/- 6.8, P less than 0.03) and per cent (198.5 +/- 67.6 vs. 32.1 +/- 7.5, P less than 0.02) values. A normal PRL response to TRH, arbitrarily defined as an increase greater than 100% of baseline, was restored in 11 out of 15 previously unresponsive hyperprolactinemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Dopamine↗

PubMed1987

Thyroid function tests in patients undergoing maintenance dialysis: characterization of the 'low-T4 syndrome' in subjects on regular hemodialysis and continuous ambulatory peritoneal dialysis.

Thyroid function tests were evaluated in 38 patients on regular hemodialysis (HD), in 36 on continuous ambulatory peritoneal dialysis (CAPD) and in 39 healthy controls. A significant reduction in total thyroxine (TT4), total triiodothyronine (TT3), reverse (rT3), and free T4 (fT4) mean levels and normal TSH, free T3, TBG and albumin concentrations was found in both HD and CAPD patients. A 'low-T4 syndrome' (serum T4 less than 5 micrograms/dl) was found in 9 CAPD (25%) and 20 HD (53%) patients, but none of them had fT4 levels below the normal laboratory range. The only striking difference between low-T4 HD and low-T4 CAPD patients was the significantly lower TBG and albumin serum levels in CAPD group. Low-T4 HD displayed normal TBG levels but enhanced fT4/TT4 and fT4/TT4 X TBG ratios. We concluded that: the abnormalities in thyroid function tests in patients on long-term dialysis (HD and CAPD) do not express the existence of a true hypothyroidism; a different pathogenesis of the low-T4 syndrome in the CAPD and HD groups may be hypothesized: in the former it could be attributed to a reduction in serum-binding capacity for thyroid hormones, in the latter the relative increase in fT4 percentage despite normal TBG levels suggests either the presence of T4-TBG-binding inhibitor(s), or structural abnormalities of thyroid-hormone-binding proteins.

Combined Modality Therapy↗

PubMed1986

Catecholamines and pituitary-function. V. Effect of low-dose dopamine infusion on basal and gonadotropin-releasing hormone stimulated gonadotropin release in normal cycling women and patients with hyperprolactinemic amenorrhea.

To verify the role of dopaminergic mechanisms in the control of gonadotropin secretion in normal and hyperprolactinemic women, we examined the gonadotropin response to GnRH (100 micrograms i.v.) administration in both basal conditions and during low-dose dopamine (DA, 0.1 microgram/kg/min) infusion. Hyperprolactinemic women, either with microadenoma or without radiological signs of pituitary tumor, showed significantly enhanced LH and FSH responses to GnRH in comparison with normal cycling women. 0.1 microgram/kg/min DA infusion did not result in any appreciable suppression of serum gonadotropin levels but significantly reduced the LH and FSH responses to GnRH in both normal and amenorrheic hyperprolactinemic women. Although both LH and FSH levels remained higher in hyperprolactinemic patients than in normal women after GnRH, the gonadotroph's sensitivity to DA inhibition was normal in the hyperprolactinemic group, as both control subjects and patients with hyperprolactinemic showed similar per cent suppression of GnRH-stimulated gonadotropin release during DA. These data confirm that hypothalamic DA modulates the gonadotroph's responsiveness to GnRH. The increased LH and FSH responses to GnRH in hyperprolactinemic patients and their reduction during low-dose DA infusion seem to indicate that endogenous DA inhibition of pituitary gonadotropin release is reduced rather than enhanced in women with pathological hyperprolactinemia.

Adenoma↗

PubMed1986

Catecholamines and pituitary function. IV. Effects of low-dose dopamine infusion and long-term bromocriptine treatment on the abnormal thyrotroph (TSH) dynamics in patients with pathological hyperprolactinaemia.

In order to gain further insight into the role of dopamine (DA) in the control of TSH release and to investigate whether an increased or defective DA inhibition on pituitary thyrotrophs may be considered responsible for the abnormal TSH dynamics in pathological hyperprolactinaemia, we examined the effect of low-dose DA infusion on TRH stimulated TSH secretion in normally cycling women and in patients with pathological hyperprolactinaemia. The effect of long-term bromocriptine therapy on TSH dynamics was also evaluated in a selected group of hyperprolactinaemic women. Fifty-two hyperprolactinaemic patients with no other signs of pituitary or thyroid dysfunction had significantly higher mean TSH serum concentrations and mean TSH peak values after TRH administration than 75 healthy controls. Furthermore, the TSH rises induced by the DA-synthesis inhibitor alpha-methyl-p-tyrosine (AMPT, 500 mg orally) were enhanced in both prolactinoma and 'idiopathic hyperprolactinaemia' patients as compared with controls. There was a positive correlation between the TRH- and AMPT-induced TSH rises in the hyperprolactinaemic group. Low-dose DA infusion (0.1 microgram/kg X min) reduced TSH response to TRH in both regularly cycling women and patients with hyperprolactinaemic amenorrhoea. Longterm bromocriptine therapy (2.5 mg tid over 60-150 days) not only normalized serum Prl levels, but also reduced the TSH response to TRH in 7 hyperprolactinaemic women who had presented exaggerated TSH responses to the basal TRH test.(ABSTRACT TRUNCATED AT 250 WORDS)

Bromocriptine↗

PubMed1985

Classification of idiopathic hypercalciuric patients by isotopic calcium absorption: a comparison with oral calcium tolerance test.

To test the accuracy of calcium tolerance test in estimating calcium absorption, we have measured the radioactive calcium absorption (expressed as Fx) in 27 patients with IH and renal calcium stones. The results of this test were compared with those of a standard oral calcium tolerance test. Although only seven of nine AH patients displayed normal fasting calcium excretion, they all displayed Fx values above normal and a normal parathyroid activity. Conversely, only 5 of our 18 RH patients demonstrated a hyperabsorption of radioactive calcium and an elevation in iPTH and cAMP above normal limits, yet all of them showed an increased calciuric response to an oral calcium challenge. Calcium absorption was inversely related to iPTH (r = -082; P less than 0.001) and cAMP (r = -064 P less than 0.05) in AH, but directly proportional to these parameters (r = 0.62 P less than 0.001 and r = 0.46 P less than 0.05, respectively) in RH patients. In view of these results, two ratios, iPTH/Fx and cAMP/Fx were used to discriminate between the two groups of patients. Both ratios were over normal limits in all RH patients and within normal range in all but one AH patient. Furthermore, no overlap was found between the two groups. Conversely, we were unable to completely separate AH from RH subjects on the basis of the oral calcium tolerance test, since in both groups the fasting and the absolute (or percentage) changes in urinary calcium, cAMP and blood iPTH levels following oral calcium loading, overlapped in each instance.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1985

Effect of N-acetylcysteine in subjects with slow pulmonary mucociliary clearance.

There is significant evidence that in the general population there are subjects either with fast or slow pulmonary mucociliary clearance rates. At the moment we do not know the physiological importance of such finding. Slow clearers should be regarded as a subpopulation at risk for bronchopulmonary diseases. Therefore, it would be of considerable interest if their mucociliary function could be stimulated by drugs for preventive purposes. Twelve apparently healthy subjects with slow mucociliary clearance rate, selected in an epidemiologic survey in a non-smokers population were given 0.6 g oral N-acetylcysteine/day/60 days in a double-blind cross-over randomized study. After treatment their mucociliary clearance rates increased by about 35% as compared with baseline values, and returned to pre-treatment values after the washout period. Subjects were unresponsive to placebo treatment. It would seem that slow clearers are protected against lung aggressions by prevention and/or mucus-active drugs.

Acetylcysteine↗

PubMed1985

Efficacy of two different doses of muzolimine in the treatment of mild hypertension.

UNLABELLED: A report is given on the effects of oral therapy with muzolimine (M) in patients with mild hypertension. SUBJECTS AND METHOD: 21 untreated patients, aged 35 to 69 (mean 53.1 yrs) with orthostatic diastolic BP between 100 and 115 mmHg were randomly assigned to either group A (10 mg M/day) or group B (20 mg M/day) in a single blind study for a period of two weeks. Clinostatic and orthostatic systolic and diastolic BP and heart rate were recorded at weekly intervals. PRA, aldosteronemia, ECG and blood chemistry were analyzed at the beginning and at the end of the study. Student's t-test was used for the statistical evaluation and p values below 0.05 were considered significant. RESULTS: Both clinostatic and orthostatic diastolic BP were significantly reduced in group A whereas only orthostatic diastolic BP was decreased in group B (Fig. 1). PRA and aldosteronemia values and blood chemistry showed no statistically significant changes. No side effects were noted. We conclude that 10 mg/day of muzolimine is more effective than 20 mg/day in reducing orthostatic diastolic BP (A vs. B p less than 0.02). Although these results are only preliminary data and further investigations are required, they suggest that muzolimine may be safely used, in combination with other antihypertensive agents, particularly in cases of renal failure.

Adult↗

PubMed1984

Does the hypothalamic tyrosine-hydroxylase inhibition mediate the positive feedback of progesterone on gonadotropin release in women?

Neuropharmacological studies suggest a common inhibitory role for the hypothalamic dopaminergic pathway on gonadotropin and prolactin pituitary release, in humans. As a consequence, it has been hypothesized that the inhibition of hypothalamic tyrosine-hydroxylase and the subsequent fall in dopamine synthesis is involved in the positive feedback of progesterone on LH and PRL pituitary release in estrogen-primed hypogonadal women. The aim of our study was to verify whether an inhibition of tyrosine-hydroxylase may really account for the progesterone action on gonadotropin and prolactin secretion. For this purpose, we compared the effect of a specific tyrosine-hydroxylase inhibitor (alpha-methyl-p-tyrosine, AMPT) with the effect of progesterone on gonadotropin and prolactin release in estrogen-primed postmenopausal women. Progesterone induced a marked release of LH (delta: 129.7 +/- 16.5 mlU/ml, mean +/- SE) and a slight increase in FSH (delta: 39.4 +/- 11.6 mlU/ml) and PRL (delta: 15.3 +/- 2.8 ng/ml) serum levels. Acute or two-day administration of AMPT was followed by a marked rise in PRL serum levels (delta: 82.9 +/- 13.8 and 88.3 +/- 8.2 ng/ml, respectively) while there were no significant increases in serum LH (delta: 5.4 +/- 2.6 and 3.3 +/- 4.6 mlU/ml) and FSH (delta: 3.4 +/- 0.9 and -0.4 +/- 2.9) concentrations. The ineffectiveness of a specific tyrosine-hydroxylase inhibitor in simulating the progesterone effect on gonadotropin secretion seems to negate the hypothesis that a reduction in hypothalamic dopaminergic activity mediates the positive feedback of progesterone on gonadotropin release.

Aged↗

PubMedDate not supplied

[Visualization of carotid and femoral atherosclerotic lesions using autologous lipoprotein reinjection containing apo-B marked with 131I: preliminary data].

Atherosclerotic lesions can be detected by several methods, such as angiography, B-mode ultrasonography, computed tomography and magnetic resonance. Radioisotopic techniques, recently introduced by using radiolabelled platelets and LDL (low-density lipoproteins), can give more informations about the "metabolic activity" of atherosclerotic lesions. The aim of this study was to detect atherosclerotic lesions in 7 hyperlipemic patients using autologous apo-B containing lipoproteins labelled with 131I in order to evaluate different functional patterns of these lesions. Carotid and femoral accumulations of this radiocompound were detected in the majority of patients. The method appears promising for evaluating the "in vivo" relationships between lipoproteins, which are involved in the pathogenesis of atherosclerosis, and the vessel wall.

Adult↗