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Biomedical subjects

G Bernini

Publications and source records attributed to G Bernini.

At least 19 recordsLinked to original sources

Endogenous digitalis-like factor and ouabain immunoreactivity in adrenalectomized patients and normal subjects after acute and prolonged salt loading.

The aim of our study was to evaluate whether adrenals are involved in the secretion of endogenous digitalis-like factor(s) with polarity similar to (or less than) that of ouabain (EDLF-1), and whether acute plasma volume expansion is a physiological releasing stimulus for this factor(s) in humans. For this purpose, we measured the concentration of this substance(s) by a human placenta radioreceptor assay (RRA) and by the Du-Pont-NEN ouabain-EIA (immunoreactive ouabain, I-Oua) in plasma C18-extracts of eight normotensives and six patients with bilateral adrenalectomy before and after acute salt loading (2 lt 0.9% NaCl/2 h). The study was repeated after 2 weeks of increased sodium intake (200 mEq/day). Under basal conditions, EDLF-1 by RRA and I-Oua were similar in adrenalectomized patients and in controls and were not significantly modified by saline infusion. After 15 days of high sodium intake, basal plasma EDLF-1 and I-Oua were not significantly different from prediet levels, both in adrenalectomized patients and controls and were likewise unaffected by saline loading. Saline infusion, by contrast, significantly (P < or = .05) suppressed hematocrit and PRA and increased ANP both in controls and in patients, either before or after prolonged high dietary sodium. Plasma aldosterone (ALD) was similarly reduced (P < .001) in controls and, as expected, was undetectable in adrenalectomized patients. Our data indicate that in adrenalectomized patients circulating levels of EDLF-1 and I-Oua are similar to those of controls and that, in both groups, acute saline loading before and after sodium repletion does not influence circulating levels of these compounds. These findings suggest that, at least in humans, adrenals are not the main source of endogenous digitalis-like factor(s) with polarity similar to (or less than) that of ouabain, and that plasma volume expansion may be not a sufficient stimulus for the release of this factor(s).

Adrenal Glands

G-CSF serum pharmacokinetics during peripheral blood progenitor cell mobilization: neutrophil count-adjusted dosage might potentially improve mobilization and be more cost-effective.

The optimal dosing schedule of G-CSF for peripheral blood progenitor cell (PBPC) mobilization is still under investigation although many centers use 10 microg/kg/day in a single subcutaneous dose. However, G-CSF clearance increases with increasing absolute neutrophil count (ANC). Hence a G-CSF dosage adjusted to ANC might be a reasonable approach. We measured G-CSF trough serum levels by sandwich ELISA assay at different ANCs in eight patients undergoing treatment with filgrastim at 10 microg/kg/day in a single subcutaneous dose. A total of 26 samples were analyzed, and a strong correlation between increasing ANC and decreasing G-CSF levels was found by linear regression analysis (P < 0.0003, r2 = 0.4199). For ANC values above 5000/microl the trough serum levels, ie 24 h after administration, were consistently below the level that provides maximal clonogenic precursor stimulation in vitro (10 ng/ml). Serial serum G-CSF measurements performed in three patients at 0, 3, 6, 9 and 24 h after G-CSF administration, showed a reduction of the area under the curve (AUC) with increasing ANC. For an ANC of 20000/microl or greater, the G-CSF serum level fell under the maximal in vitro stimulation threshold of 10 ng/ml within 12 h. This preliminary pharmacokinetic data seems to suggest that an ANC-adjusted G-CSF dosing schedule might improve the design of PBPC mobilization regimens.

Adolescent

Pediatric peripheral blood progenitor cell collection: haemonetics MCS 3P versus COBE Spectra versus Fresenius AS104.

BACKGROUND: An increasing number of apheresis machines are becoming available for peripheral blood progenitor cell (PBPC) collection in children. STUDY DESIGN AND METHODS: At the Children's Hospital of Florence (Italy), three apheresis machines were evaluated: MCS 3P (Haemonetics) (10 procedures in 4 patients, aged 10-12 years, weight 23.5-64 kg), Spectra, (COBE) (8 procedures in 3 patients, aged 4-17 years, weight 19-59 kg), and AS104 (Fresenius) (24 procedures in 9 patients, aged 2-16 years, weight 13.6-60 kg). For PBPC quantitative analysis, CD34 cytofluorimetry was employed. Relevant variables analyzed included efficiency of CD34+ cell extraction and enrichment, mononuclear cell purity and red cell contamination of the apheresis components, and platelet count decreases after leukapheresis. RESULTS: No significant differences in CD34+ cell-extraction abilities were found. However, the AS104 provided consistently purer leukapheresis components in terms of mononuclear cell and CD34+ cell enrichment (441 +/- 59%, vs. 240 +/- 35% and 290 +/- 42% for MCS 3P and Spectra, respectively). Postapheresis platelet counts dropped the least with the AS104. The smallest patient who underwent apheresis with MCS 3P (the only machine working on discontinuous flow and hence with greater volume shifts) weighed 23.5 kg and tolerated the procedure well, with no signs of hemodynamic instability. No significant complications were observed. CONCLUSION: All machines seem to have comparable PBPC extraction efficiency, but the AS104 seems to give the component with the greatest PBPC enrichment. This feature might be relevant for further ex vivo cell processing (CD34+ cell selection, expansion, and so on).

Adolescent

Neoadjuvant chemotherapy for extremity osteosarcoma--preliminary results of the Rizzoli's 4th study.

A neoadjuvant chemotherapy protocol (1/93-1/95) for extremity osteosarcoma preoperatively using high-dose methotrexate (HDMTX) as single agent per cycle and three different combinations of other drugs (CDP/IFO,CDP/ADM,IFO/ADM) is reported. The four drugs were used postoperatively as single agents. Treatment was uniform, but suspended earlier if total necrosis was attained. An improvement was found in the results of the previous study using only IFO postoperatively, with 16/119 patients (97%) avoiding amputation, and 38 (32%) attaining complete necrosis. At a 3-year (2-4 years) mean follow-up, 92 patients (76%) remained continuously disease-free, 2 died of chemotherapy-related toxicity and 25 suffered relapse. Projected 3-year DFS also improved (75% vs. 60%; p = 0.04). Despite limb salvage, local recurrences (6.3%) and infections were few, although postoperative chemotherapy was restarted within a week. Therefore, until new effective drugs are found, expertise in using the four known drugs may improve cure rate and help to avoid amputation in almost all patients.

Adolescent

Conn syndrome: 14 year's experience from two European centres.

OBJECTIVE: To evaluate the long term results of adrenalectomy for primary hyperaldosteronism. DESIGN: Multicentre retrospective cohort study. SETTING: Two university hospitals, UK and Italy. SUBJECTS: 55 patients who presented with a mean (SD) preoperative blood pressure of 181/110 (21/10) mmHg and a mean (SD) potassium of 2.8 (0.4) mmol/L (range 1.6-4) during the period October 1978 to October 1992. INTERVENTIONS: Unilateral adrenalectomy, usually by the extraperitoneal approach. Adrenalectomy was total in all but nine cases. MAIN OUTCOME MEASURES: Accuracy of preoperative investigations for the diagnosis and localisation of the lesions, histology, morbidity and mortality, long term outcome (mean follow up 8.8 years). RESULTS: Computed tomography gave a diagnostic accuracy for unilateral lesions of 88%, the postural stimulation test 80%, norcholesterol scintigraphy 84%, and ultrasonography 57%. Histological examination showed carcinoma (n = 1), diffuse hyperplasia (n = 2), nodular hyperplasia (n = 11) including 5 with macronodular hyperplasia, double adenoma (n = 1) and single adenoma (n = 40). No patient died, and 10 developed minor complications. At the latest follow-up 44/52 patients with benign unilateral lesions (85%) have been cured by adrenalectomy. CONCLUSIONS: Our results confirm the safety of the extraperitoneal approach, and suggest that the improvement in the accuracy of preoperative investigations has allowed a careful selection of patients with the consequent amelioration of the long term outcome of surgery for Conn's syndrome. As laparoscopic adrenalectomy is currently advocated as the operation of choice for surgically-remediable mineralocorticoid excess, its long term results will have to be comparable with these standards.

Adrenalectomy

High-sensitivity immunocytologic analysis of neuroblastoma cells in paired blood and marrow samples.

High-sensitivity immunocytochemistry was used to evaluate the relative frequency of neuroblastoma cells in bone marrow and peripheral blood in patients with neuroblastoma (NB). A total of 51 concomitant paired blood and marrow samples (102 total) from 35 patients with NB (age 4 months-31 years; stage 29 stage IV, 4 stage III, 2 stage IVS; 14 at diagnosis, 18 in relapse, 12 during treatment, and 7 off-therapy) were analyzed. Cytospins containing up to 10(6) cells each were prepared using the mononuclear cell (MNC) fraction. For immunocytologic staining, a primary mouse monoclonal anti-GD2 antibody (3F8), a secondary antimouse biotinylated antibody, and a streptavidin-alkaline phosphatase complex were used. A minimum of two cytospins containing a mean of 1.4 x 10(6) total MNCs was analyzed in addition to a negative and a positive control. No circulating tumor cells were detected when the concomitant marrow samples were negative or had <10 positive cells per 106 MNC (23 of 51 samples). Of the 18 marrow samples positive at 10-10,000 cells per 106 MNC, 6 had detectable NB cells in the corresponding blood sample, whereas for marrow samples with >10,000 NB cells per 10(6) MNC (1%), the concomitant blood sample was positive for 9 of the 10. When both marrow and blood samples were positive (15 BM-PB pairs), NB cell frequency was significantly lower in blood, with a mean difference of 2.14 logs (median 2.22, range -0.16-4.8, standard error 0.38). In patients with NB, circulating tumor cell frequencies seem to be substantially lower than in concomitant marrow samples, with a mean difference of >2 logs.

Adolescent

Endothelial dysfunction in hypertension is independent from the etiology and from vascular structure.

The aim of our study was to evaluate the relationships between endothelial function, small resistance artery structure, and blood pressure in patients with primary or secondary hypertension. Sixty subjects were included in the study: 9 patients with pheochromocytoma, 10 with primary aldosteronism, 17 with renovascular hypertension, and 13 with essential hypertension with 11 normotensive subjects who served as controls. Clinic and 24-hour ambulatory blood pressure (ABPM) were evaluated. All subjects were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on a micromyograph and the media/lumen ratio was calculated. A dose-response curve to acetylcholine was performed at cumulative concentrations from 10(-9) to 10(-5) mol/L. The vasodilator response to acetylcholine was similarly impaired in the four groups of hypertensive patients (ANOVA P<.05 versus normotensive controls), without any significant difference among them. In subcutaneous small arteries of patients with either primary aldosteronism or renovascular hypertension, a marked increase in media:lumen ratio was observed, while in patients with pheochromocytoma, the extent of vascular structural alterations was similar to that observed in essential hypertension. No significant correlation between media-lumen ratio or clinic blood pressure and maximum acetylcholine-induced vasodilatation was observed. On the contrary, a significant, albeit not very close, correlation between ABPM values and maximum acetylcholine-induced vasodilatation was observed (r=34, P<.05 with 24-hour systolic blood pressure, r=0.36, P<.05 with 24-hour diastolic blood pressure). In conclusion, endothelial dysfunction seems to be independent from the degree of vascular structural alterations and from the etiology of hypertension, and it is probably more linked to the hemodynamic load.

Acetylcholine

Endogenous estrogen and acetylcholine-induced vasodilation in normotensive women.

Acute exogenous estrogen administration enhances endothelial function in postmenopausal women. To evaluate the effect of endogenous estrogen on endothelium-dependent vasodilation, in 10 fertile normotensive women (age range 45 to 51 years) we studied the changes in forearm blood flow (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, 1.5 micrograms.100 mL-1.min-1), an endothelium-dependent vasodilator, or sodium nitroprusside (1, 2, 4 micrograms.100 mL-1.min-1), an endothelium-independent vasodilator, in basal conditions and within 1 month after ovariectomy. As control subjects, 10 matched healthy women were also evaluated. In basal condition, vasodilation to acetylcholine and sodium nitroprusside was similar in patients and control subjects. Ovariectomy was followed by endogenous estrogen deprivation (from 71.6 +/- 31.3 to < 12 pg/mL) and was associated with a significant (P < .01) reduction in acetylcholine-induced vasodilation compared with baseline (maximum percent increase in forearm blood flow: baseline 568.2 +/- 47.1%; ovariectomy 309.5 +/- 37.4%); the response to sodium nitroprusside was unaffected by ovariectomy (maximum percent increase in forearm blood flow: baseline 526.4 +/- 36.5%; ovariectomy 454.7 +/- 47.2%; P = NS). In 6 of 10 patients, the study was repeated after 3 months of estrogen replacement therapy (17 beta-estradiol, 50 micrograms/d by transdermal patches). Exogenous estrogen restored acetylcholine-induced vasodilation (maximum percent increase in forearm blood flow: 548.9 +/- 43.1%; P < .01 versus ovariectomy), which was no longer different from baseline, whereas the response to sodium nitroprusside was not affected (maximum percent increase in forearm blood flow: 480.2 +/- 39.3%; P = NS). These results suggest a protective role of endogenous estrogen on endothelium-dependent vasodilation in the forearm vascular bed of normotensive women.

Acetylcholine

Imaging of somatostatin receptors by indium-111-pentetreotide correlates with quantitative determination of somatostatin receptor type 2 gene expression in neuroblastoma tumors.

We reported previously that the relative level of gene expression for sst2, a subtype of somatostatin receptors, was positively related to patient outcome in the childhood tumor neuroblastoma (NB). Because sst2 binds with high-affinity octreotide and its scintigraphic derivative, 111In-pentetreotide, we tested the hypothesis of whether NB tumor imaging with 111In-pentetreotide gives similar information to ex vivo measurement of sst2 expression. We, therefore, studied simultaneously nine NB tumors with 111In-pentetreotide single photon emission computed tomography and competitive reverse transcription-PCR for sst2, along with other prognostic markers. To quantitate the relative abundance of 111In-pentetreotide binding to NB tumors, we developed a simple semiquantitative method, based on the mathematical analysis of 111In-pentetreotide association to cancer cell receptors at different time points (4 and 24 h). We indeed found that the ratio between the activity in a manually extracted region of interest from pathological (ROIT) and background (ROINT) area was increasing between early and late acquisition only in affected tissues. The rate of this pathological increase was quite different among patients and significantly (P < 0.01) related to the abundance of sst2 gene expression, as measured by competitive reverse transcription-PCR on ex vivo tumor samples. Because we demonstrated that in 26 NB patients the density of sst2 is strongly related to survival (P < 0.0005) and apparently independent from N-myc oncogene amplification (P < 0.05), we propose that NB tumor imaging with 111In-pentetreotide may have not only a diagnostic but also a prognostic value.

Adolescent

Menopause is associated with endothelial dysfunction in women.

To evaluate the effect of endogenous estrogens on endothelial function in humans, we examined whether menopause is associated with impairment in endothelium-dependent vasodilation in normotensive and essential hypertensive women. In 73 normotensive subjects (37 women, 36 men) and 73 hypertensive patients (36 women, 37 men), we studied endothelial function by measuring forearm blood flow modifications (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms/100 mL per minute), an endothelium-dependent vasodilator, and sodium nitroprusside (1,2, and 4 micrograms/100 mL per minute), an endothelium-independent vasodilator. Women younger than 45 years had normal menstrual cycles. In essential hypertensive patients, responses to acetylcholine but not to sodium nitroprusside were significantly (P < .001) reduced compared with responses in normotensive subjects. Moreover, in both groups, vasodilation to acetylcholine showed a marked negative correlation with advancing age (normotensive subjects: r = -.88, P < .001; hypertensive patients: r = -.87, P < .001). In contrast, vasodilation to sodium nitroprusside showed a less evident negative correlation with advancing age (normotensive subjects: r = -46, P < .01; hypertensive patients: r = -.48, P < .01). However, in normally menstruating normotensive women, no endothelial dysfunction was observed, and age-related impairment in endothelium-dependent vasodilation was evident only after menopause. In normally menstruating hypertensive women, aging was associated with endothelial dysfunction although the deterioration of endothelium-dependent vasodilation was less marked than that in men. In contrast, after menopause, the age-related endothelial dysfunction in hypertensive women was similar to that observed in men. Finally, no sex-related difference in the response to sodium nitroprusside was observed in either normotensive subjects or essential hypertensive patients. Age-related endothelial dysfunction is attenuated in premenopausal normotensive and hypertensive women compared with men, whereas no sex-induced difference is observed after menopause, suggesting a protective effect of endogenous estrogens on endothelial function.

Acetylcholine

Severity grading of childhood poisoning: the Multicentre Study of Poisoning in Children (MSPC) score.

Scores for severity grading of childhood poisoning may be useful in comparing different causes of poisoning, in order to identify the main risks and their changes over time. The Multicentre Study of Poisoning in Children score is based on four levels of severity (1-mild, 2-moderate, 3-severe, 4-very severe) involving nine target groups: seven relating to organ systems (gastrointestinal, nervous, respiratory, circulatory, renal, hepatic, skin), one to metabolic abnormalities and one to injuries from corrosive substances. Each patient is classified by the highest level attributed to any one of the nine groups. The score has been prospectively tested in 644 symptomatic children, aged 0-13 years, admitted to six pediatric hospitals of Northern Italy from January 1, 1991 to December 31, 1993. Poisoning was categorized as mild (1) in 357 children (53.8%), moderate (2) in 285 (42.9%), severe (3) in 18 (2.7%) and very severe (4) in 4 (0.6%). No deaths occurred. Severity grading according to The Multicentre Study of Poisoning in Children score confirms the prevalence of mild and moderate poisonings in children; the score seems to be an objective method suitable for epidemiological studies in different countries. Its clinical usefulness deserves more investigation.

Adolescent

[Arterial hypertension in relation to life style and other cardiovascular risk factors. Epidemiologic study of a population of blood donors. Project AVIS].

The objectives of this research were to determine the prevalence of essential and borderline hypertension in a population of blood donors and their families and to determine if there is a correlation between blood pressure and lifestyle and/or other cardiovascular risk factors. The study was comprised of 1976 individuals, of whom 1290 were men and 686 were women, aged 18-65 years. The prevalence of essential hypertension was 15.1% for males and 12.5% for females: the prevalence of borderline hypertension was 22.3% for males and 15.7% for females. The population was divided into two groups: the first group included only subjects (1170 men, 543 women) who did not regularly use drugs that could modify the blood pressure and the heart rate, the second group included the entire population. In the first group, the multiple regression analysis indicated, in order of importance: age, BMI (body mass index), and heart rate. These variables were important in determining the systolic blood pressure in both sexes, uricemia for males and glycemia for females. The diastolic blood pressure was dependent on BMI, heart rate, and alcohol in both sexes, and glycemia, LDL cholesterol, and uricemia in the men. In the second group, primary and borderline hypertension are significantly correlated with age, BMI, and uricemia in both sexes and glycemia in females. A program of health and nutritional education could modify some factors related to blood pressure, such as obesity and alcohol consumption. The result would be a reduction of the prevalence not only of essential and borderline hypertension, but also of metabolic diseases such as dyslipidaemias, diabetes and hyperuricemia, with a global reduction of the cardiovascular risk.

Adolescent

Retroperitoneal seminoma secondary to 'burned out' testicular tumor in an acromegalic patient.

We report a case of an acromegalic patient with a retroperitoneal seminoma secondary to a testicular tumor which had completely disappeared. Testicular ultrasonography did not show any pathological mass and histological examination indicated that the normal testis had been totally replaced by fibrous tissue, without neoplastic cells. Our patient had high levels of growth hormone (GH) and prolactin (PRL), both hormones with high immunostimulating effect, and an increase of interleukin-2 receptor-positive lymphocytes, a finding supporting enhanced immunological activity. Thus, we cannot exclude that the immunological pattern of this acromegalic patient may have played some role in the tumoral destruction.

Acromegaly

Effect of fenfluramine on prolactin and thyroid-stimulating-hormone response to thyrotropin-releasing-hormone in obese and normal women.

In order to demonstrate the suggested failure of the serotoninergic system in human obesity and to evaluate the role of central serotoninergic activity in prolactin (PRL) and thyroid stimulating hormone (TSH) release in this condition, 13 euthyroid obese and 9 healthy women of normal weight were studied. A TRH test (200 micrograms i.v.) was performed before and after administration of fenfluramine (FF) 60 mg b.d. for 14 days. In the controls, FF did not modify the expected significant increase in PRL induced by TRH. In obese patients, however, the PRL levels was significantly increased after TRH, but the increase was less than in the controls. After FF, the PRL response to TRH was larger than in the pretreatment phase, with values similar to those observed in normal subjects. In neither group FF did change the TSH-stimulating effect of TRH, but the hormonal response in obese patients was greater than in the controls. The restoration of the responsiveness of PRL to TRH after central serotoninergic stimulation confirms the hypothesis that a failure of the serotoninergic system may occur in human obesity. Since FF does not interfere with the secretory pattern of basal and stimulated TSH in normal or obese subjects, the serotoninergic system does not seem to play a major role in the control of TSH secretion.

Adult

Hyperglycemia and prognosis of acute myocardial infarction in patients without diabetes mellitus.

The present study assessed the prognostic value of hyperglycemia--a common feature in the early phase of acute myocardial infarction (AMI)--in 330 nondiabetic patients. Seventy-nine known diabetics and 10 (3%) unknown diabetics--diagnosed before discharge by stable glycosylated hemoglobin greater than 6.9% and by oral glucose tolerance testing--were excluded. Thirty-three (10%) patients died. The mortality rate was higher in women, in patients with anterior AMI, in older patients (greater than 65 years) and in the presence of heart failure. It was highest in patients with cardiogenic shock (24/36 vs 9/294; p less than 0.0001). Admission plasma glucose was significantly higher in nonsurvivors than in survivors (163 +/- 60 vs 114 +/- 36 mg/dl; p less than 0.0001). Mortality rate increased with increasing admission plasma glucose: 3% in normoglycemic patients (less than or equal to 120 mg/dl) versus 15% in patients with borderline plasma glucose (121 to 180 mg/dl) versus 43% in hyperglycemic patients (greater than 180 mg/dl) (p less than 0.0001). Multiple regression (stepwise) analysis identified cardiogenic shock, infarct site and age as the major determinants of mortality, while admission plasma glucose failed to reach full statistical significance (p = 0.067). Hyperglycemia was related to all 3 of these independent prognostic factors; when age and infarct site were accounted for, hyperglycemia was significantly associated with heart failure only and this association was characterized by a remarkable mortality rate. In nondiabetic patients with AMI, hyperglycemia is a correlate of heart failure and, therefore, an important factor of prognosis.

Adult

Naloxone does not modify the antihypertensive effect of captopril in essential hypertensive patients.

It has been reported that endogenous opioid antagonism through naloxone (NAL) blunts the hypotensive effect of captopril (CAP) in normal man. For this reason a study was carried out to determine whether NAL interacts with the antihypertensive effect of CAP in patients with mild-to-moderate essential hypertension (n = 6; age 22-43 years). Patients received, according to a randomized code, placebo (PL) during saline infusion, CAP (25 mg orally) during saline infusion, PL + NAL (0.4 mg as a bolus followed by a continuous infusion of 4.0 mg/h for 2 h) and CAP + NAL at the same doses. Three-day intervals elapsed between each phase of the study. Blood pressure (BP) and heart rate (HR) were recorded before (-20 to 0 min) and every 15 min for the next 2 h after drug administration. Blood samples for plasma renin activity (PRA), noradrenaline (NA) and aldosterone (ALD) were collected before (time 0) and 120 min after drug administration. Neither PL nor NAL changed any of the parameters examined, while CAP alone reduced mean BP to a highly significant extent. Naloxone did not change the hypotensive effect of CAP to any significant extent. Captropril, either alone or associated with NAL, tended to reduce plasma ALD and increase PRA (P less than 0.05) without changing HR or plasma NA. These data indicate that, at least under the experimental conditions used, endogenous opioid antagonism does not interfere with the haemodynamic and humoral effect of CAP in essential hypertensive man. This suggests that endogenous opioids do not mediate the pharmacological actions of CAP.

Adult