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Biomedical subjects

G Segni

Publications and source records attributed to G Segni.

At least 19 recordsLinked to original sources
PubMed2001

In vitro and in vivo antitumor activity of the novel trinuclear platinum complex BBR 3464 in neuroblastoma.

PURPOSE: BBR 3464 is a promising new trinuclear platinum complex that has been shown to circumvent the resistance to cisplatin in a panel of tumor cell lines and xenografts with acquired or intrinsic resistance to cisplatin. The in vitro and in vivo antitumor activity of BBR 3464 was evaluated and compared with that of cisplatin in neuroblastoma. METHODS: In in vitro studies, the short- and long-term cytotoxicities, cell cycle perturbations, the ability to induce apoptosis, the intracellular platinum accumulation and DNA platination were evaluated in three neuroblastoma cell lines exposed to appropriate drug concentrations for 1 h. In in vivo studies, BBR 3464 was administered i.v. at doses of 0.30 and 0.35 mg/kg three times at intervals of 4 days (q4dx3), and cisplatin was administered i.v. according to two different schedules (at 2 and 4 mg/kg three times at intervals of 4 days and at 6 and 12 mg/kg as single doses). RESULTS: In a short-term growth inhibition assay, BBR 3464 was shown to be up to 100-fold more potent than cisplatin and it was even more potent in a clonogenic assay. The difference in the antitumor effect of BBR 3464 on the different cell lines was evident in both assays, while cisplatin exerted a comparable antitumor activity in all lines tested. Cell cycle analysis demonstrated a longer-lasting block in G2/M phase induced by BBR 3464 without the early S phase accumulation induced by cisplatin. The higher potency of BBR 3464 appeared to be unrelated to the induction of apoptosis, that was lower or at most comparable to cisplatin. Cellular platinum accumulation and platinum-DNA adduct formation following BBR 3464 exposure was higher than following cisplatin exposure. These differences may have resulted from a different mechanism of action and may explain the lack of cross-resistance with cisplatin. In xenografts of neuroblastoma, BBR 3464 was confirmed to be very potent as compared to cisplatin (MTD 0.35 mg/kg and 4 mg/kg for BBR 3464 and cisplatin, respectively). The efficacy of BBR 3464 was superior to that of cisplatin when both drugs were administered on a fractionated schedule (q4dx3), while BBR 3464 appeared equally active to 12 mg/kg cisplatin administered as a single dose. CONCLUSIONS: Our findings indicate that BBR 3464 has a definite antitumor effect in neuroblastoma lines and may be a candidate for early clinical trials in children with neuroblastoma.

Animals↗
PubMed2001

The novel trinuclear platinum complex BBR3464 induces a cellular response different from cisplatin.

BBR3464 is a new platinum-based drug non cross-resistant with cisplatin. To characterise the cellular basis of BBR3464 cytotoxicity as opposed to cisplatin, we performed a comparative study of the two drugs in cisplatin-resistant neuroblastoma and astrocytoma cells. In both model systems, BBR3464 proved to be more potent than cisplatin and was able to overcome cisplatin resistance. The higher potency exhibited by BBR3464 correlated with an increased cellular platinum accumulation and DNA-adduct formation. At equitoxic doses, BBR3464 induced apoptosis to a lesser extent than cisplatin and failed to overcome the decreased susceptibility to cisplatin-induced apoptosis in cisplatin-resistant cells. Cell cycle analysis showed a dose-dependent G2/M arrest by BBR3464. In astrocytoma cells, cisplatin treatment resulted in the upregulation of p53, p21 and bax, while only p21 induction was observed after BBR3464 treatment. In cisplatin-resistant cells, the reduced sensitivity to cisplatin paralleled a resistance to the induction of p53/p21 pathway by cisplatin, while the same doses of BBR3464 induced p21 to a similar extent in the resistant cells as in the parental cells. In conclusion, BBR3464 induces a cellular response that is different from cisplatin, supporting the view that the two drugs act through different mechanisms. Our data indicate that BBR3464 may be a promising agent in the treatment of tumours unresponsive to cisplatin and with a non-functional p53.

Antineoplastic Agents↗
PubMed2001

Persistent spontaneous pneumothorax in an adolescent with Marfan's syndrome and pulmonary bullous dysplasia.

A 16-year-old boy with Marfan's syndrome was admitted with progressive dyspnea due to a large spontaneous pneumothorax. Bullous pulmonary dysplasia was confirmed and pleural tube drainage did not affect the air leak. Complete recovery required surgical resection of the bulla responsible for the ongoing air leak. This case report highlights the issue of management for severe spontaneous pneumothorax in general, showing that the choice of treatment should not depend on the presence of pulmonary bullous dysplasia but on the clinical evaluation of the individual patient.

Adolescent↗
PubMed1999

Bladder obstruction in Hunter's syndrome.

We report a case of bladder obstruction in a patient with Hunter's syndrome, presenting with acute painful symptomatology, due to the impossibility of voiding, which was diagnosed with ultrasonography and cystometrography. Intermittent catheterization with intravesical oxybutynin chloride lead to successful functional resolution of the obstruction.

Adult↗
PubMed1999

Italian multicentre open trial on DDAVP spray in nocturnal enuresis.

OBJECTIVE: The aim of the study was to compare the efficacy and safety of different doses of DDAVP spray treatment (20 to 40 mcg/day) in patients with primary monosymptomatic nocturnal enuresis (defined as three or more wet nights per week). MATERIAL AND METHODS: 237 patients (152 males, 75 females; age range 5-17 years), with no infections or organic abnormalities of the urinary apparatus and no neurological disorders, were admitted into the trial. The experimental design was planned as an "open study" with five different treatments schedules (5 groups). The daily doses of DDAVP at bedtime in groups 1 and 2 were 20 and 30 mcg, respectively, for 6 weeks. In groups 3 and 4 the daily doses for the first 2 weeks were 20 and 30 mcg, respectively, and then, after a washout period of 2 weeks, the daily doses for the two groups were 30 and 20 mcg, respectively. A dose-response study (20 to 40 mcg/day) was carried out in group 5. RESULTS: DDAVP spray therapy in primary monosymptomatic nocturnal enuresis was found to be resolutive in 70-75% of treated patients. No difference in response was found between the patients treated with the daily dose of 20 and those on 30 mcg. No important reactions were observed in patients treated with DDAVP spray at the different daily dose (20 to 40 mcg) or for different periods of time (up to 6 weeks). CONCLUSIONS: DDAVP spray therapy at a dose of 20 mcg/day was effective in 70-75% of primary monosymptomatic nocturnal enuretics. In non-responders the daily dose of DDAVP should be increased to 30 to 40 mcg.

Administration, Intranasal↗
PubMed1998

Cognitive impairment in school-age children with asymptomatic HIV infection.

Previous studies have shown that there is a positive correlation between clinical expression of HIV-1 disease and deficits in the cognitive and neuropsychologic abilities in afflicted children. To date there are few studies regarding analysis of the cognitive and neuropsychologic development of HIV-positive, asymptomatic nonprogressor children (6-12 years of age) (long-survivors). The purpose of this study was to explore the differences in neuropsychologic development of asymptomatic HIV-positive school-age children compared with a seroreverted group. Evaluation was conducted in 8 children with asymptomatic or mild clinical signs of HIV infection compared with 8 seroreverted children. All tests were administered in three sessions by a trained specialist in neuropsychologic observation. The results of neuropsychologic testing suggested the presence of some learning disorders, as well as major memory and perception deficit. Most of the children tended to have levels of performance that were below normal values. The impairment could likely be the expression of a greater biologic vulnerability of HIV-positive children. Additional studies are necessary to define the risk factors and, hence, the protective factors that might support normal development of HIV-positive children.

Child↗
PubMed1996

[Haemophilus influenzae disease in childhood. Comment about case reports of meningitis].

The authors describe a series of Haemophilus influenzae meningitis in childhood, obtained with a retrospective analysis of the cases of bacterial meningitis admitted to Isolamento Pediatrico department of "A. Gemelli" Polyclinic in Rome, from January 1, 1970 to December 31, 1994. Haemophilus influenzae resulted the second agent in frequency (first was Neisseria meningitidis). Main features were: no patient was older than 5 years, and most of them were less than 2 years old; clinical feature was aspecific in the first year of life, it was typical of bacterial meningitis in older children; blood culture and detection of bacterial antigens in cerebrospinal fluid (CSF) were useful for etiological diagnosis, supporting CSF culture; clinical course was characterized by many complications, but no case was lethal and incidence of sequelae at discharge was low; C reactive protein was effective as index of inflammation and as indicator of arising complications; chosen antibiotics were efficacious, but frequency of antibiotic resistance, especially to beta-lactams, was found to be increasing; results of dexamethasone therapy were not of univocal interpretation. The authors are in favour of spreading of vaccination against Haemophilus influenzae in Italy, too, in order to eradicate this disease, as experiences in other countries are successful, and of setting up of the combined vaccines, in order to increase parents' compliance to vaccinal practices.

Child, Preschool↗
PubMed1994

[Neonatal abstinence syndrome and maternal toxicological profile].

Neonatal abstinence syndrome (NAS) is one of the most frequent manifestations in the neonates of drug-addicted mothers. It is caused by the abrupt interruption of the transplacentar passage of drugs from the mother to the fetus. The aim of this study was to evaluate the correlation between drugs taken during pregnancy and NAS. Data were examined relating to 223 neonates born during 1975-1992 to drug-addict mothers. Neonates were subdivided into four groups according to the maternal toxicological profile. It was thus possible to observe that there is a greater prevalence of NAS in cases of polypharmacomania and that it gradually diminishes in the children of heroin addicts and those receiving methadone treatment. Moreover, the intensity of the syndrome is correlated to the high doses of methadone and/or heroin. In the group of neonates whose mothers had complied with the methadone treatment protocol, the severity of NAS was proportional to the dose taken by the mother. In conclusion, the management of pregnant drug addicts following a controlled methadone treatment programme is accompanied by improved obstetric help and is the most suitable way of reducing perinatal complications and the prevalence of NAS.

Dose-Response Relationship, Drug↗
PubMed1993

Costello syndrome: further clinical delineation, natural history, genetic definition, and nosology.

In 1977 Costello described two unrelated children with poor postnatal growth, mental retardation, curly hair, coarse face of similar appearance, and nasal papillomata, suggesting the existence of a previously undescribed syndrome of uncertain familial nature [Costello, Aust Paediatr J 13: 114-118, 1977]. The existence of this syndrome as a separate entity was substantiated several years later by two additional reports by Der Kaloustian et al. [Am J Med Genet 43:678-685, 1991] and Martin and Jones [Am J Med Genet 41:346-349, 1991]. More recently Borochowitz et al. [Am J Med Genet 43:678-685, 1992] described a new "multiple congenital anomalies/mental retardation syndrome with facio-cutaneous-skeletal involvement." Whether this condition should be considered separately from the Costello syndrome is currently a matter of debate. We present three cases, two of whom are sibs, who support the identity of the two syndromes. Our aim is to better redefine the diagnostic criteria, describe the natural history, and confirm the genetic cause of the Costello syndrome, whose pattern of inheritance is most likely autosomal recessive.

Abnormalities, Multiple↗
PubMed1992

[Familial Mediterranean fever and electroencephalographic changes. A clinical case].

The Authors describe the case of a non-Hebrew Italian girl suffering from short-lasting fever episodes, associated with abdominal colic, since the age of 3. The occurrence of acute arthrosynovitis during the last episode, at 12 years of age, clinically confirms the diagnosis of familial mediterranean fever, as previously supposed. The increase in urinary coproporphyrins, with normal values of delta-aminolevulinic acid and porphobilinogen poses the problem of the differential diagnosis between hereditary coproporphyria and secondary coproporphinuria. The importance of this case lies in the presence of electroencephalographic alteration since the first years of life, suggesting a temporal epilepsy for which the patient was at length submitted to anti-epileptic treatment. Electroencephalographic alterations, of different type and uneasy interpretation, are described in the literature with a frequency which does not seem accidental. Renal biopsy does not show amyloid, nor the RMN reveals cerebral abnormalities. The anti-epileptic therapy being withdrawn, the patient was treated with daily administrations of colchicine (1 mg/die); 18 months after, she is disease free.

Biochemical Phenomena↗
PubMed1991

Immunodeficiency and plasma zinc levels in children with Down's syndrome: a long-term follow-up of oral zinc supplementation.

To evaluate the possible effect of zinc treatment on immune disorders in children with Down's syndrome (DS), 38 noninstitutionalized DS children were investigated. Twenty-four patients (63.2%) had plasmatic zinc levels lower than 0.70 microgram/dl ("hypozinkemic," LZn) and 14 patients (36.8%) had levels higher than 0.75 microgram/dl ("normozinkemic," NZn). No correlation was found between the zinc deficiency and recurrence and/or intensity of infections. The absolute numbers of peripheral lymphocytes, the percentages of B lymphocytes, total T cells, and serum IgG, IgA, and IgM levels did not differ between the DS children and the controls. Eight (21%) patients had CD4+ T cell counts below the lowest value for the controls. Seventeen (44%) DS patients had increased levels of CD8+ T cells. The mean percentage of Leu 7+ cells in DS subjects (22.8 +/- 12.9%) was significantly higher than that in controls (15.8 +/- 4.8%) (P less than 0.01). Notably, Ig levels and numbers of lymphocytes in each subset did not show any significant difference in NZn and LZn trisomic subjects. On the contrary the peripheral blood mononuclear cells (PBMCs) from LZn DS children showed a significantly lower proliferative response to phytohemagglutinin (PHA) (S.I. = 23.4 +/- 22.4) than that of PBMCs from NZn DS children (S.I. = 46.1 +/- 21.5, P less than 0.01). A significant increase in DNA synthesis was obtained after oral administration of zinc sulfate (20 mg/kg/day, for 2 months). The lymphocyte response to PHA appeared to be normal in all patients up to 6 months after the end of the zinc treatment and it became low in half of the patients 22 months after therapy.

Administration, Oral↗
PubMed1988

Birth defects in the Seveso area after TCDD contamination.

A study on the frequency of birth defects was conducted in the area around Seveso, Italy, which was contaminated by 2,3,7,8-tetrachlorodibenzo-p-dioxin in July 1976; this has been the largest population ever exposed to dioxin. From Jan 1, 1977, to Dec 31, 1982, a total of 15,291 births (still and live) were examined, and malformations were reported to an ad hoc birth defects registry. In the most highly contaminated area, 26 births were observed. None of these infants had any major structural defect. Two infants had mild defects. The frequencies of major defects detected in the areas of low or very low contamination were 29.9/1000 and 22.1/1000, respectively. A frequency of 27.7/1000 was registered in the control area. Relative risks were calculated for specific categories of birth defects and for grouped malformations. Although the data collected failed to demonstrate any increased risk of birth defects associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin, the number of exposed pregnancies was not big enough to show a low and specific teratogenic risk increase.

Accidents, Occupational↗
PubMed1988

Relationship between maternal parity, basal prolactin levels and neonatal breast milk intake.

Basal serum levels of prolactin (PRL) in 21 nursing mothers were measured by radioimmunoassay on the 2nd, 3rd and 4th days of the puerperium. The quantity of breast milk suckled during the 4th day of life was also evaluated by calculating the difference in the baby's weight before and after each feeding. During the first postpartum days, mean basal levels of PRL did not change. However these levels were noted to be significantly lower in the multiparas (p less than 0.05) than in the primiparas. In addition, the milk intake in neonates of multiparous mothers was significantly greater (p less than 0.05) than that in neonates of primiparous mothers. The author's hypothesis, based on the results of animal experimentation described in the literature, is that initiation of breast-feeding is facilitated in multiparas by the increased number of occupied PRL receptors in the mammary glands reflected by the lowered serum levels of the hormone.

Female↗