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Biomedical subjects

S Bernasconi

Publications and source records attributed to S Bernasconi.

At least 163 records · Page 9Linked to original sources
PubMed1994

Soluble intercellular adhesion molecule-1 (ICAM-1) is released into the serum and ascites of human ovarian carcinoma patients and in nude mice bearing tumour xenografts.

We have demonstrated that patients with ovarian carcinoma have higher levels of soluble intercellular adhesion molecule-1 (ICAM-1) in their serum and ascitic fluids than serum from normal individuals and non-neoplastic gynaecological disease or ascites from patients with cirrhosis. In order to investigate the source of the ICAM-1, and to study the mechanisms which regulate ICAM-1 release in ovarian carcinoma, we have employed the nude mouse model system. Three different human ovarian carcinoma (HOC) cell lines were grown as ascitic tumours in the peritoneal cavity of nude mice. HOC xenografts harvested from nude mice expressed comparable levels of ICAM-1 on their cell surface. Human ICAM-1 was detected, with a species-specific ELISA, in serum and ascitic fluid of tumour-bearing mice, confirming that the tumours were the source of the ICAM-1. The three HOC xenografts showed different levels of ICAM-1 release, but within each xenograft model the level of ICAM-1 in serum and ascitic fluid correlated with the tumour burden. The level of ICAM-1 released by the HOC xenografts could be increased by in vivo treatment with interferon gamma (IFN-gamma). Interleukin 1 (IL-1), tumour necrosis factor (TNF) and IFN gamma increased the cell surface expression of ICAM-1 and caused the release of soluble ICAM-1 from HOC cells established in vitro. The nude mouse provides a useful system in which to study the effects of modulating ICAM-1 release on the progression of ovarian carcinoma and suggests that measuring ICAM-1 levels in the blood or ascites of patients may provide an indication of tumour burden.

Animals↗
PubMed1994

Inhibition of human monocyte adhesion to endothelial cells by the coumarin derivative, cloricromene.

1. The ability of the coumarin derivative cloricromene (8-monochloro-3-beta-diethylaminoethyl-4-methyl-7-ethoxy- carbonylmethoxycoumarin) to inhibit monocyte adhesion to human cultured umbilical vein endothelial cells (HUVEC) was investigated. 2. Cloricromene (10-200 microM) inhibited, in a concentration-dependent manner, the adhesion of both resting and activated monocytes to HUVEC. Significant inhibition was reached with drug concentrations ranging between 15 to 30 microM. 3. The inhibitory activity was, at least in large part, directed to monocytes since no inhibition was observed after selective preincubation of HUVEC with cloricromene and the drug maintained its effect also on monocyte adhesion to paraformaldehyde-treated HUVEC. 4. Inhibition was maximal after 1 min of exposure of monocytes to cloricromene and persisted even in the absence of the drug. 5. Both basal and chemoattractant-mediated monocyte adhesion was inhibited by cloricromene as it was by TS1/18, a monoclonal antibody (mAb) directed to beta 2 integrins; however, cytofluorimetric analysis showed that cloricromene was unable to modulate the expression of beta 2 integrins on the monocyte surface. 6. When monocyte adhesion was mediated by a large set of adhesive receptors, as obtained after treatment of HUVEC with either interleukin 1 beta (IL-1; 50 ng ml-1) or tumour necrosis factor-alpha (TNF; 100 u ml-1), the inhibitory effect of cloricromene was considerably reduced. 7. The results of this study show that cloricromene may regulate monocyte adhesion to HUVEC, an event relevant in vivo in the pathogenesis of inflammatory and atherosclerotic processes.

Antibodies, Monoclonal↗
PubMed1994

Final height in girls with central precocious puberty: comparison of two different luteinizing hormone-releasing hormone agonist treatments.

In order to evaluate the effects of two long-acting luteinizing hormone-releasing hormone agonists on growth, bone maturation and final height in girls with central precocious puberty, we analyzed growth data from 40 girls (15 treated with buserelin intranasal spray (group A), 15 treated with triptorelin depot im every 28 days (group B) and 10 untreated (group C)). Patients in group A started treatment when chronological age (CA) was 7.7 +/- 0.9 years, bone age (BA) was 10.2 +/- 1.1 years and height was 131.9 +/- 5.0 cm. Patients in group B started therapy when CA was 7.6 +/- 0.5 years, BA 9.8 +/- 1.0 years and height 133.2 +/- 7.6 cm. The diagnosis of untreated patients (group C) was made when CA was 7.2 +/- 0.9 years, BA 9.6 +/- 2.2 years and height 130.2 +/- 8.6 cm. Both luteinizing hormone-releasing hormone agonists appeared to control precocious puberty. Final height in group B (160.6 +/- 5.7 cm) was significantly higher than that of group A (153.2 +/- 5.0 cm: p < 0.05) and group C (149.6 +/- 6.3; p < 0.01), whereas the difference between groups A and C was not statistically significant. In group B a positive difference was observed between final height (160.6 +/- 5.7 cm) and target height (157.6 +/- 5.9 cm) (ns); on the contrary, in groups A and C, final height was lower than target height (155.5 +/- 5.3 and 156.4 +/- 1.3 cm, respectively), but only in group C the difference was statistically significant (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1994

Turner's syndrome in Italy: familial characteristics, neonatal data, standards for birth weight and for height and weight from infancy to adulthood.

In 1990, the Italian Study Group for Turner's Syndrome (ISGTS) undertook a nationwide survey, involving the retrospective collection of cross-sectional data and longitudinal growth profiles of 772 girls with Turner's syndrome born between 1950 and 1990. The study was carried out in 29 pediatric endocrinological centers. In this first report, the familial characteristics and neonatal data of Turner girls are described, compared to those of the general population, and related to postnatal somatic development. Furthermore, charts for birth weight and growth standards for height and weight from infancy to adulthood are presented (these are the first charts based on a large sample from the Mediterranean area). The main findings were: (1) incidence of Turner births increases with parental age or parity; (2) most of the neonates are small for dates; (3) girls with normal birth weight tend to be both taller and heavier than girls with low birth weight during the whole growth period; and (4) a 10-cm difference in midparental height leads to a 6.5-cm difference in adult stature.

Adolescent↗
PubMed1994

Subcutaneous growth hormone administration in growth-hormone-deficient children. Continuous plus pulsatile overnight versus single daily injection: effects on growth rate velocity.

The aim of this study, performed in 10 children, was to verify if a treatment schedule, better reproducing the growth hormone (GH) physiological pattern, could achieve a greater growth response than daily s.c. administration in previously successfully treated children with an isolated idiopathic GH deficiency. A 1-month washout period was observed between the previous regimen and this study. GH (0.6 U/kg/week, the same as given previously) was administered weekly in 6 equal doses. Three children received the daily dose by a single s.c. administration (at 20.00 h) and the other 7 through a 27-gauge infusion needle inserted s.c., using a mini infusion pump permitting a constant delivery of 50% of the daily dose (20.00-08.00 h) and the administration of the other 50% through 3 equal pulses (at 20.00, 24.00, and 04.00 h). After 6 months each child changed regimen undergoing the other one with a 1-month washout interval. During the 12 months of therapy, the mean height increased from -3.2 (SE 0.45) to -2.8 (SE 0.37) SDS. When evaluating the circulating insulin-like growth factor-I pattern as well as the growth velocity and the ratio bone age increase/height age increase, no differences were noted between the two treatment regimens.

Body Height↗
PubMed1994

Rapidly alternating chemotherapy and hyperfractionated radiotherapy in the management of locally advanced head and neck carcinoma: four-year results of a phase I/II study.

PURPOSE: Treatment of locally advanced head and neck carcinoma by surgery and/or radiotherapy is associated with a high recurrence rate, poor survival, and, often, limitation in speech and swallowing functions. Because prolonged time of treatment might be detrimental for tumor control, we designed a study to develop a schedule of alternating radiotherapy and chemotherapy that should be administered over the shortest period of time and with the highest dose of radiotherapy as possible. PATIENTS AND METHODS: Following four successive steps of schedule modifications, regimens alternating split hyperfractionated radiotherapy (2.0 Gy/d times three over 30 to 40 days, to a total of 48 Gy to 60 Gy) and chemotherapy (cisplatin 80 to 100 mg/m2 and fluorouracil 1,000 mg/m2 by continuous infusion for 3 to 4 days, +/- vindesine 8 mg/m2 for two cycles) were administered in 91 patients with advanced squamous cell carcinoma of the head and neck. Adenectomy was performed for residual nodes and major surgery for progression only. RESULTS: The overall response rate was 95.6% (95% confidence interval [CI], 89.1 to 98.8), with 69.2% complete and 26.4% partial responses. Among partial responders, two patients were converted into complete responders by resection of a residual node. With a median follow-up duration of 45 months, distant mestastases occurred in 18% and a second primary tumor in 7.7% of patients. The median overall survival (OS) and progression-free survival (PFS) durations were 24 months and 17 months, respectively. At 4 years, the survival rate was 40%. All of the locoregional recurrences occurred within the first 15 months, in 14% and 73% of the complete and partial responders, respectively. Mucositis was the dose-limiting toxicity, with a World Health Organization (WHO) grade III and IV rate of 81% at a 60-Gy dose of radiotherapy, compared with 65% at 48 Gy or 54 Gy, which precluded further dose escalation. Leukopenia was severe in the first two steps of treatment, with WHO grade IV toxicity occurring in 41% of patients; however, this decreased to 10% when vindesine was deleted from the chemotherapy regimen in the last two steps. Late toxicity in 29% of patients was not different from that expected with radiotherapy alone. Among patients with resectable tumors, a 64% rate of organ preservation was obtained. CONCLUSION: We demonstrated that a full dose of hyperfractionated radiotherapy alternated with chemotherapy over 40 days could produce high antitumor activity. Mucositis was the dose-limiting toxicity, but this resolved completely within a median period of 6 weeks.

Adult↗
PubMed1994

Isolated growth hormone deficiency type IA associated with a 45-kilobase gene deletion within the human growth hormone gene cluster in an Italian family.

An Italian family with three children presenting with isolated growth hormone (GH) deficiency type IA is described. Restriction endonuclease analysis revealed that the cause of hGH deficiency was a 45-kb gene deletion within the hGH-chorionic somatomammotropin (CS) gene cluster, encompassing the GH-1, CS-L, CS-A, and GH-2 genes. DNA sequence analysis and polymerase chain reaction amplification between two sequences located on each side of the deletion breakpoint accurately identified the deletion breakpoints and indicated that the regulatory sequences located upstream from the TATA box of the mutant CS-B belong to the GH-2 gene. Two of the affected children developed high-titer anti-hGH antibodies after recombinant hGH treatment with secondary growth arrest, whereas the third one maintained normal growth in the presence of very low-titer antibodies. This is the first report of a large deletional mutation within the hGH-CS gene cluster accompanied by phenotypic heterogeneity in terms of growth response and antibody formation in the different patients.

Base Sequence↗
PubMed1994

Effects of oral glucose administration on spontaneous and growth hormone (GH)-releasing hormone-stimulated GH release in children and adults.

It has been suggested that hypothalamic regulation of GH secretion in children may differ from that in adults. On the other hand, there is evidence that oral glucose administration affects GH secretion through hypothalamic mechanisms. Therefore, we investigated spontaneous and GHRH-stimulated (1 microgram/kg BW) GH responses after oral glucose administration (children, 1.75 g/kg BW; adults, 75 g) in peripubertal normal children (13 girls and 13 boys, aged 11.7 +/- 0.4 yr; range, 8-13) and healthy adults (12 males and 14 females, aged 25.7 +/- 1.2 yr; range, 18-39). Three studies were carried out. In study 1, serum GH levels in 8 children were suppressed (< 1 microgram/L) for 135 min after oral glucose administration. Afterward, there was a rise in serum GH levels. In 8 adults, the suppressive effect of glucose persisted throughout the 210-min study period, and no GH rebound appeared. In study 2, the GH responses to iv GHRH boli in 10 adults and 10 children were, respectively, inhibited, unchanged, or augmented by an oral glucose load administered 30, 60, or 120 min before GHRH challenge. In study 3, oral glucose administration to 8 adults greatly enhanced the GH response to GHRH given 180 min after the glucose, whereas in 8 children, the GH response to GHRH was unchanged. In conclusion, glucose affects basal and GHRH-stimulated GH release in a similar manner in adults and children, indicating that neuroregulatory influences of glucose on the GH axis may not differ in the two age groups. In children, however, the duration of both the initial inhibitory and subsequent stimulatory effects of glucose administration on GH secretion is shorter.

Administration, Oral↗
PubMed1993

Inhibition of cytokine production and endothelial expression of adhesion antigens by 5'-methylthioadenosine.

We investigated the activity of endogenous nucleoside 5'-deoxy-5'-methylthioadenosine (MTA) on both the production of inflammatory cytokines and the cytokine-dependent endothelial expression of adhesion molecules. The compound inhibited the production of tumor necrosis factor (but not interleukin-1) in lipopolysaccharide-activated macrophages. In addition, MTA selectively inhibited the expression of intercellular adhesion molecule-1 in endothelial cells activated with interleukin-1. This effect was paralleled by a reduction in endothelial adhesiveness for polymorphonuclear leukocytes. These data suggest that MTA might have anti-inflammatory activity.

Animals↗
PubMed1993

Type II interleukin-1 receptor is not expressed in cultured endothelial cells and is not involved in endothelial cell activation.

Interleukin-1 (IL-1) profoundly affects a number of functions of endothelial cells (EC). It was previously shown that EC express the type I 80-Kd IL-1 receptor (IL-1 RI). In this study we define the expression and functional significance of the type II IL-1R (IL-1 RII) in EC. Human umbilical vein EC did not express appreciable levels of IL-1 RII mRNA as assessed by Northern analysis or reverse transcription and polymerase chain reaction. Exposure to various cytokines (including IL-4, which augments IL-1 RII in neutrophils) failed to induce IL-1 RII mRNA. The binding of radiolabeled IL-1 beta to EC was blocked by antitype I (M4) but not by antitype II (M22) monoclonal antibodies (MoAbs). MoAbs directed against the IL-1 RI (M1 and M4) inhibited the induction of IL-6 and adhesion molecules in EC by IL-1, whereas an anti-IL-1 RII (M22) was inactive. The human IL-1 receptor antagonist (IL-1ra) preferentially interacts with IL-1 RI versus IL-1 RII in the mouse. IL-1 ra inhibited the response of mouse endothelial cells to IL-1. We conclude that EC selectively express the IL-1 RI and that this is involved in the response of this cell type to IL-1.

Animals↗
PubMed1993

[Retroperitoneal fibrosis and portal hypertension].

A patient is described in whom retroperitoneal fibrosis manifested itself by bleeding from ruptured varices and pain in the left flank and lumbar region. The clinical diagnosis was confirmed by axial computerized tomography and MRI, while the histology from a mesenteric biopsy taken during splenectomy was considered insufficiently consistent with the diagnosis of retroperitoneal fibrosis. Treatment with prednisone resulted in relief of lumbar and flank pain a well as in prevention of further digestive tract hemorrhage. A review of the literature since 1966 shows 16 articles describing the association of retroperitoneal fibrosis and portal hypertension manifesting itself by hemorrhage from bleeding varices.

Aged↗
PubMed1993

Divergent effects of interleukin-10 on cytokine production by mononuclear phagocytes and endothelial cells.

Interleukin-10 (IL-10), a product of T helper type 2 (TH2) cells and monocytes, inhibits cytokine production in mononuclear phagocytes. Given the similarities and interrelationship between cells of the monocyte-macrophage lineage and endothelial cells, we examined the effects of IL-10 on vascular endothelium. Murine IL-10 induced low levels of IL-6 production and amplified induction of IL-6 by lipopolysaccharide (LPS) or IL-1 in the murine tEND.1 endothelioma line, used for these studies because it retains properties of normal endothelium. The effect was more evident after prolonged (48-72 h) exposure to IL-10. IL-10 had similar activity on other endothelioma lines, whereas it inhibited IL-6 production by peritoneal macrophages. Induction and amplification of cytokine production by IL-10 was associated with higher levels of mRNA, which were maintained longer (up to 48 h) than in controls. In addition to IL-6, murine IL-10 induced or amplified expression of the chemoattractant cytokines monocyte chemotactic protein-1 (MCP-1) and KC. Human IL-10 inhibited IL-6 release by LPS-stimulated human peripheral blood mononuclear cells, whereas it did not interfere with cytokine production by LPS- or IL-1-stimulated human umbilical vein endothelial cells. The selective inhibitory action of IL-10 on mononuclear phagocytes versus endothelial cells may play a role in the pathophysiology of TH2-directed responses.

Animals↗
PubMed1993

Combined treatment with growth hormone and luteinizing hormone releasing hormone-analogue (LHRHa) of pubertal children with familial short stature.

We evaluated the 12 month growth of 18 pubertal children with familial short stature randomly assigned to clinical follow-up (group A), GH treatment alone (group B) and GH+LHRH analogue (LHRHa) treatment (group C). Height velocity increased significantly compared to baseline in groups A and B (4.7 +/- 0.4 vs 6.6 +/- 0.6 and 4.4 +/- 0.3 vs 8 +/- 1 respectively), but not in C (5 +/- 0.5 vs 6.5 +/- 0.4). Moreover in group B height and height prognosis standard deviation score SDS) also were higher (-2.2 +/- 0.2 vs -1.7 +/- 0.2 and 1.8 +/- 0.3 vs -1 +/- 0.2, respectively). Comparisons among the groups showed a significant increase in group B vs the other groups of height velocity SDS (3.9 +/- 1.3 vs 0.4 + 1 and 0.3 +/- 0.7) and of height prognosis SDS (-1 +/- 0.2 vs -2.4 +/- 0.3 and -2.4 +/- 0.3). In conclusion, after one-year treatment, GH seems to be more effective in stimulating growth than GH +/- LHRHa, even if studies of longer duration and/or follow-up are needed.

Adolescent↗
PubMed1993

Adrenal steroid and adrenocorticotropin responses to human corticotropin-releasing hormone stimulation test in adolescents with type I diabetes mellitus.

To determine whether abnormalities of hypothalamic-pituitary-adrenal axis function occur in type I diabetes mellitus, corticotropin, cortisol, 17-hydroxyprogesterone (17-OHP), androstenedione (D4-A), dehydroepiandrosterone (DHEA), and DHEA sulfate (DS) levels were measured after an intravenous (IV) injection of 1 microgram/kg human corticotropin-releasing hormone (CRH) in diabetic adolescents and normal age-matched subjects. CRH produced a consistent increase in corticotropin blood levels that was comparable in the two groups. In contrast, both baseline and stimulated cortisol concentrations were greater in diabetic patients. Levels of 17-OHP increased after CRH administration, and the magnitude of increase was similar in all subjects. Stimulation with CRH determined an attenuated integrated DS response in diabetics compared with normal subjects with a different pattern of the hormone secretion, whereas no differences in D4-A concentrations were detected between the two groups. DHEA serum levels of subjects from both groups underwent similar changes following administration of CRH. In conclusion, patients with type I diabetes have a discrete response of adrenal steroids to CRH stimulation that appears to be independent of corticotropin secretion. This phenomenon might be related to a direct effect of insulin on enzyme systems involved in the biosynthetic pathway of adrenal steroids or, alternatively, to an intra-adrenal CRH/corticotropin mechanism acting on the adrenal cortex in a paracrine manner.

Adolescent↗
PubMed1993

Early down-regulation of TNF production by LPS tolerance in human monocytes: comparison with IL-1 beta, IL-6, and IL-8.

We studied the effect of a 4-hr preexposure to LPS on the ability of human monocytes to respond to a subsequent stimulation with LPS in terms of cytokine production. LPS-preexposed monocytes did not produce TNF on LPS restimulation, but they retained the ability to produce IL-1 beta, IL-6, and IL-8. LPS-tolerant monocytes were still capable of producing TNF when restimulated with zymosan. Down-regulation of TNF by LPS tolerance was also evident at the mRNA level. To investigate the possible mechanisms underlying this phenomenon, we also studied the effect of LPS preexposure on membrane CD14, which was suggested to be an LPS receptor, and on intracellular cAMP, an inhibitor of TNF production. LPS induced a 50% decrease in CD14 expression. On the other hand, the increase in cAMP levels by LPS was not affected by preexposure to LPS. In conclusion, (a) TNF is more rapidly down-regulated than IL-1 beta, IL-6, and IL-8 during LPS tolerance in vitro; (b) early LPS tolerance is associated with decreased CD14, which might partially explain the decreased LPS response; and (c) a feedback mechanism controlling TNF synthesis, cAMP elevation, is not down-regulated in LPS tolerance.

Antigens, CD↗
PubMed1993

[Retroextraperitoneal laparoscopic nephrectomy].

The authors describe a new technique of laparoscopic nephrectomy; the retroextraperitoneal approach has been successfully performed in 4 patients with the following indications: 2 non functioning hydronephrotic kidneys, 2 atrophic chronic pyelonephritic kidneys. The patient was put in a proneoblique position after the retrograde placement of a ureteral catheter up to the renal pelvis, through which the contrast medium was injected. The Veress needle is inserted under fluoroscopic guidance into the perirenal fatty space which was insufflated with CO2. One 12 mm and three 10 mm Trocars were inserted into the cavity created by gas in the trapezoid area whose boundaries are: the 12th rib, the iliac crest, the posterior axillary line and the sacrospinalis muscle. The kidney was progressively dissected free with the traditional laparoscopic instruments (forceps and scissors). The artery has always been closed with clips. In two patients the vein has been stapled and cut with EndoGIA. After the section of the clipped ureter the kidney was removed en block by pulling it out through the 20 mm Kleiber Trocar in two cases and in the other two cases by extending to a length of 4 cm the port of one Trocar. The average total operating time was 4.35 hours and blood loss < 200 cc. The patients were all discharged on the fourth postoperative day. The advantages of the retroextraperitoneal approach with respect to open surgery are synthetically the following: a less traumatic and a more accurate dissection almost always bloodless; a shorter hospitalization period; an almost painless postoperative course.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Ligation of the internal spermatic vein through 2 laparoscopic ports].

Thirty-three two port laparoscopic internal spermatic vein ligations have been performed in 31 patients in our Department. The procedure carried out through two 10 mm ports in a mean time of 25 minutes decreases both the invasivity of intervention and the costs when reusable instruments are used. The technique is feasible with an operative laparoscope (working channel diameter 4 mm) through which a grasp can be maneuvered. The two port procedure is as safe as the three port procedures. Preliminary follow up indicated only one recurrence of varicocele (4%). Out of the 19 patients treated for male subfertility who have at least a 6 month follow up, eleven reported an improvement in seminal quality. All the patients but one were discharged on the first postoperative day. Laparoscopic internal spermatic vein ligation provides a real alternative to different surgical techniques decreasing postoperative pain and shortening period of convalescence with immediate return to full activity. The advantages of laparoscopic internal spermatic vein ligation are increased with the two port procedure.

Adolescent↗