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Biomedical subjects

A Ceci

Publications and source records attributed to A Ceci.

At least 55 records · Page 3Linked to original sources
PubMed1988

Tumor response and toxicity after single high-dose versus standard five-day divided-dose dactinomycin in childhood rhabdomyosarcoma.

This report deals with a randomized prospective multicentric clinical trial in childhood rhabdomyosarcoma (RMS) conducted to evaluate the toxicity and the effectiveness of dactinomycin (ACT-D) administered as high, single doses v five-day, divided doses administered in combination with vincristine (VCR) and cyclophosphamide (CYC). Fifty-five group III evaluable patients (pts) less than 15 years of age with tumor size greater than 5 cm in diameter, without high-risk features of CNS involvement, and 15 group IV RMS pts were randomized to receive VAC as primary chemotherapy (CT): VCR, 1.5 mg/m2 intravenously (IV) days 1 and 8; CYC, 275 mg/m2 IV days 1 through 5; and ACT-D, 0.45 mg/m2 IV days 1 through 5 every 28 days for three cycles (33 pts), or VAC-M: CYC, 150 mg/m2 intramuscularly (IM) days 1 through 7; VCR, 2.0 mg/m2 IV day 8; and ACT-D, 1.7 mg/m2 IV day 8 every 21 days for four cycles (37 pts). Major responses (complete plus partial responses [PR]) were obtained in 67% of the VAC pts and in 70% of the VAC-M pts. Toxic effects were low, and no increased toxicity was observed in pts treated with high, single-dose ACT-D. These results confirm the effectiveness and feasibility of single, high doses of ACT-D with the advantage of requiring less pt hospitalization.

Adolescent↗
PubMed1987

Neuroleptic-like effects of the l-isomer of fenfluramine on striatal dopamine release in freely moving rats.

l-Fenfluramine (l-F) was studied for its ability to release dopamine (DA) and its metabolites in freely moving rats through the trans-striatal dialysis technique. l-F's effect on striatal DA release was also studied in animals made tolerant to the effect of haloperidol by chronic treatment (1 mg/kg i.p. twice daily for 11 days and 48 hr wash-out) with the neuroleptic or pretreated with 300 mg/kg i.p. gamma-butyrolactone (GBL). Five and 10 mg/kg l-F dose-dependently increased the release of DA and its metabolites with a pattern of effects similar to that observed with neuroleptic drugs. The dose of 20 mg/kg l-F had the same effect as 10 mg/kg. Repeated haloperidol treatment reduced the basal release of DA and its metabolites and a much smaller amount of DA and metabolites was released by l-F (10 mg/kg i.p.) and haloperidol (0.1 mg/kg i.p.) in animals treated with haloperidol than in controls. GBL 300 mg/kg i.p. reduced basal DA release by about 50%. When 10 mg/kg l-F, 0.1 mg/kg haloperidol and 0.25 mg/kg d-amphetamine were injected i.p. 40 min after GBL, l-F and haloperidol did not significantly raise DA release in GBL-treated rats whereas a significant effect was observed at various times after d-amphetamine. The data show that l-F resembles haloperidol in its ability to release DA and its metabolites from the corpus striatum of freely moving rats. The cross-tolerance between haloperidol and l-F for their effect on DA release suggests that a common site is involved in the mechanism of these drugs.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Health status of young children with cancer following discontinuation of therapy.

This paper reports late effects and health status of 198 children who had cancer or leukemia diagnosed under 2 years of age and their therapies electively withdrawn. This series (92 neuroblastoma [NBL], 57 Wilms' tumor [WT], 46 acute lymphoblastic leukemia [ALL], and 3 non-Hodgkin's lymphoma) was followed for 1-12 years after discontinuation of therapy. Thirty-three children were diagnosed before 1973, 92 between 1973 and 1977, and 73 after 1977 in 16 Italian Pediatric Oncology Centers. As of December 1983, 176 children were reported to be alive and without evidence of primary cancer by physicians responsible for their care. One child died from a second primary tumor, two from late recurrences of the primary cancer, and three from other causes; eight were alive with evidence of primary cancer; and eight were lost to follow-up. Kyphoscoliosis was found in 22 children and other musculoskeletal anomalies in 8. Neurological sequelae were observed in 8 out 35 children with ALL treated with radiotherapy (RT) and intrathecal methotrexate. All but one were in continuous complete remission when they developed seizures (three cases), leukoencephalopathy (three cases), or intracerebral calcifications (two cases). One child had cardiomyopathy and subsequently died from cardiac failure: he had received doxorubicin (400 mg/m2) and mediastinal RT (13 Gy) for NBL. Growth impairments were observed in children with NBL and WT.

Antineoplastic Agents↗
PubMed1987

Treatment of acute myelogenous leukemia in children: results of the Italian Cooperative Study AIEOP/LAM 8204.

One hundred thirty-three children with acute myelogenous leukemia (AML) entered the multicenter Pediatric Branch of the Italian Association Against Leukemia trial AIEOP/LAM 8204 between July 1982 and May 1986. Induction therapy consisted of two courses of daunomycin (DNM) plus cytosine arabinoside (Ara-C). Those patients who achieved remission were given four courses of consolidation with DNM, 6-thioguanine (6-TG) and escalated doses of Ara-C followed by six courses of sequential continuation therapy using monthly pairs: etoposide (VP-16)/Ara-C, Ara-C/6-TG, and DNM/Ara-C. Periodic intrathecal Ara-C was used for CNS prophylaxis. One hundred seven (80%) children achieved complete remission (CR). Kaplan-Meier estimates of 3-year disease-free survival (DFS) and event-free survival (EFS) are 41% and 33%, respectively. Relapses occurred in 34 patients after 5 to 97 weeks (32 marrow; 2 marrow plus CNS). Overall, 14 patients died of complications during treatment (nine during induction; five during the postremission phase), mostly from infection. Risk factor analysis showed that induction failures occurred predominantly in children with French-American-British (FAB) M5 and in those with elevated leukocyte counts; by step-up Cox analysis, only FAB subtype was predictive of remission success. None of the variables examined was significant for predicting the duration of remission. Hyperleukocytosis was predictive of a significantly worse EFS rate. These results are encouraging and further support the use of intensive chemotherapy programs for childhood AML.

Adolescent↗
PubMed1987

Therapeutic approach to primary malignant epithelial tumors of the liver in childhood: results of the Italian retrospective study and literature survey.

We analyzed the clinical features and treatment of 23 hepatoblastomas (HPBs) and 16 hepatocellular carcinomas (HPCs) occurring in patients less than 19 years old, admitted to the Italian retrospective multicentric study, conducted between 1983 and 1985, on childhood malignant hepatic tumors. The median ages of the patients with HPB and HPC at diagnosis were 22.34 months and 96.23 months, respectively, with a male/female ratio of 0.7 and 1.7, respectively. Fourteen HPBs (61%) and 5 HPCs (31%) achieved surgical complete remission (CR). Of these, 11 HPB and all 5 HPC are still in CR with a median follow-up of 36 months and 3.5 years, respectively. One HPB and 1 HPC became resectable after a primary course of cis-platinum alone in the case of HPB and used with VP-16 in the case of HPC. All of the 9 HPBs and 11 HPCs, who never achieved CR, died of disease at a median interval from diagnosis of 5 and 2 months, respectively. The published therapeutic approaches for these tumors were also reviewed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Phase II trial of cisplatin and etoposide in children with advanced soft tissue sarcoma: a report from the Italian Cooperative Rhabdomyosarcoma Group.

A phase II multicenter evaluation of cisplatin (90 mg/m2, Day 1) and etoposide (150 mg/m2, Days 2, 3, and 4) in 4-week cycles was carried out in 21 relapsed children with rhabdomyosarcoma (RMS) and six with non-RMS soft tissue sarcomas (NRSTS). Clinical responses were evaluated after four cycles. There were three complete responses (CRs) and four partial responses (PRs) among the 21 patients with RMS and no responses among the patients with NRSTS. The durations of the three CRs and the four PRs were 11, 9, and 8 months, and 5, 2, 2, and 1 month, respectively. Bone marrow and renal toxicity was cumulative and predictable, but not life threatening. The response rate (CR + PR = 33.3%) to cisplatin and etoposide warrants testing as front-line therapy for RMS.

Adolescent↗
PubMed1986

Normal serotonin uptake by blood platelets and brain synaptosomes but selective impairment of platelet serotonin storage in mice with Chediack-Higashi syndrome.

The Chediack-Higashi syndrome (CHS) is an autosomal recessive disorder reported in man and in several animal species including the "beige mice" (bg/bg). Among several manifestations of this genetic trait, deficiency of secretable substances - including serotonin - normally stored in platelet dense granules is a characteristic feature. The animal model of Chediak-Higashi syndrome used in the present study provides a unique opportunity to compare the kinetics of serotonin (5-hydroxytryptamine, 5-HT) uptake in platelets and brain synaptosomes in conditions of selective reduction of 5HT concentration in the platelets. The kinetics of 5HT uptake, as measured in the present study, was normal in synaptosomes and platelets from the same animals. The lower intraplatelet 5HT levels in bg/bg animals as compared to normal synaptosomes levels in the presence of normal uptake offer an indirect proof that the 5HT defect described in the CHS is due to an impaired 5HT storage mechanism. This is supported by the observation that spontaneous release of 5HT was markedly increased in platelets from CH5 mice but was normal in synaptosomes from the same animals. Thus platelets are a reliable model to study 5HT uptake, but not 5HT storage and release in brain synaptosomes.

Animals↗
PubMed1986

Italian registry of patients off therapy after childhood acute lymphoblastic leukemia. Results after first phase of data collection.

The Italian Registry of Off-Therapy patients after childhood tumors now includes 760 subjects with acute lymphoblastic leukemia. These patients were all removed from treatment by December 31, 1981, and were followed in 35 different institutions. All the children have received multiple-drug treatment, combined, in 79.7% of the cases, with cranial irradiation. Thirty-nine (5%) experienced a relapse before treatment suspension. Total duration of antileukemic therapy ranges between 18 and 131 months (median, 38). At the last updating (December 31, 1981), 699 subjects were alive, 6 were lost to follow-up, and 55 had died. Life-table analysis shows that 90.8% were alive and 77% were alive in continuous complete remission at 36 months, whereas at 66 months, the cumulative proportions were 88% and 75.5%, respectively. One hundred thirty-six of 760 relapses after therapy suspension were reported: 83 in male patients and 53 in female patients (P less than 0.01). The longest interval between relapse and treatment suspension was 64 months. Six of 55 died in continuous complete remission 3 to 44 months after treatment suspension. Five births of apparently normal babies to female patients have been reported. A general outline of the project and the future program are given.

Actuarial Analysis↗
PubMed1986

Effect of long term amineptine treatment on pre- and postsynaptic mechanisms in rat brain.

The effect of amineptine and its two metabolites on monoamine uptake, release and receptor binding was studied in vitro. Amineptine and its two metabolites did not displace labelled ligands for known neurotransmitters and drug receptor sites. Amineptine and its two metabolites did not influence [3H]-5-hydroxytryptamine ([3H]-5-HT) uptake or release by rat brain synaptosomes. Amineptine inhibited [3H]-dopamine and [3H]-noradrenaline ([3H]-NA) accumulation, with IC50 values of 1.4 and 10 microM, respectively. The effect was retained, though with lower efficacy, by the two metabolites. Amineptine released [3H]-dopamine from preloaded synaptosomes. Metabolite 1 had no effect on catecholamine release, and metabolite 2 was about half as active as the parent compound on [3H]-dopamine release. The releasing effect of amineptine on [3H]-dopamine was potentiated by reserpine pretreatment, suggesting that the drug acts on the cytoplasmic neurotransmitter pool. Chronic treatment with amineptine (20 mg kg-1, twice daily for 15 days followed by a 3 days drug withdrawal period) resulted in a decrease of [3H]-spiperone binding sites in striatum, and of [3H]-dihyroalprenolol and [3H]-clonidine in cortex. Chronic treatment with amineptine reduced basal [3H]-dopamine accumulation in striatal synaptosomes, without affecting [3H]-NA or [3H]-5-HT accumulation. The adaptive changes in the pre- and postsynaptic dopamine mechanisms observed after long term treatment with amineptine are consistent with the drug acting as an indirect dopamine agonist. The down regulation of beta- and alpha 2-noradrenoceptors observed after long term amineptine treatment may play a role in the antidepressant activity of the drug.

Animals↗
PubMed1985

Acute changes in blood-CSF barrier permselectivity to serum proteins after intrathecal methotrexate and CNS irradiation.

Ten children affected by acute lymphoblastic leukaemia without CNS involvement were treated with a CNS prophylaxis protocol. Intrathecal methotrexate and CNS irradiation (60Co) administered at different times both induced an increase in blood-CSF barrier permeability to serum proteins (albumin, IgG, alpha 2 macroglobulin). The relationship between permeability coefficients of proteins was analysed by theoretical porous or vesicular blood-CSF barrier models. The analysis indicated that both therapeutic procedures affect endothelial pinocytosis. An increase in radius of pinocytotic vesicles from 400 to 1500 A seemed the most relevant change. The damage of endothelial barrier permselectivity could be involved in acute and late delayed toxic effects of intrathecal methotrexate and of CNS irradiation.

Acute Disease↗
PubMed1984

Stimulation of serotonin synthesis in rat brain after antiepilepsirine, an antiepileptic piperine derivative.

Piperine and two of its derivatives, antiepilepsirine (AE or 3,4-methylendioxycynnamoylpiperine) and compound 7448 (N-isopropyl 3 (4 chloro-phenyl) propenoylamide) are very effective in stimulating serotonin (5HT) synthesis. AE raises the ratio of free-to-bound tryptophan (TP) in plasma and induces a long-lasting increase of this aminoacid in brain. At the same time in striatum and limbic area it causes a lasting increase in 5 hydroxyindolacetic acid (5HIAA) a 5HT metabolite and to a lesser extent, an increase in the levels of the monoamine itself. Together with this action on 5HT metabolism we found that AE caused release of 3H-5HT from an in vitro synaptosomal preparation. It thus appears that piperine and its derivatives AE and compound 7148 affect the central serotonergic system.

Animals↗
PubMed1984

Diazepam increases membrane fluidity of rat hippocampus synaptosomes.

Diazepam in vitro produced a concentration-dependent increase of membrane fluidity in crude synaptic membranes from rat hippocampus, but not cerebellum. Similar effects were obtained with higher concentrations of Ro 15-1788 and PK 11195, while zopiclone was completely inactive. In vivo acute treatment with diazepam and Ro 15-1788 gave results similar to those in vitro. The specific benzodiazepine antagonist also significantly increased membrane fluidity and was not able to reverse diazepam's effect. The data are discussed in terms of a possible role of protein kinase inhibition by the drugs not mediated by the 'central' or 'peripheral' type of benzodiazepine receptors.

Animals↗
PubMed1984

Early deaths in acute lymphoblastic leukemia (ALL): results of the Italian Pediatric Cooperative Group for Therapy of Acute Leukemia (AIL-AIEOP).

In this retrospective multicentric study, we report on early deaths (ie, those that occurred during the first month of treatment) in a total of 943 newly diagnosed ALL pediatric patients registered from 1976 to 1981 at 21 centers of the AIL- AIEOP . Objectives of this study were as follows: (1) to verify the incidence and the cause of early death in a wide population of children with ALL and (2) to elucidate factors associated with early death and therefore to identify "high-risk" groups of patients. Out of the 943 ALL patients, 39 (4.1%) early deaths were registered. Main causes were infection, 20 patients (51.3%); hemorrhage, 11 patients (28.3%); uric acid nephropathy, 2 patients (5.1%); cardiac failure, 3 patients (7.6%); syndrome of inappropriate antidiuretic hormone secretion, 1 patient. Two patients died during the first week of unknown cause. Thirteen factors measured at diagnosis and possibly influencing the early death rate were analyzed. Using the chi-square test, only three of these factors (age, mediastinum status, surface markers) appear to have any significant influence on the early death rate. We also tried to determine how therapy influences this process by analyzing variations in the early death rate, other factors being equal. Significant differences in the early death rates were encountered in AIEOP protocols using different induction regimens.

Adolescent↗
PubMed1983

Differences between d-fenfluramine and d-norfenfluramine in serotonin presynaptic mechanisms.

The abilities of d-fenfluramine (d-F) and that of d-norfenfluramine (d-NF) to inhibit [3H]serotonin ([3H]5-HT) accumulation in normal and reserpinized synaptosomes were compared to establish to what extent the serotonin-releasing activity of the two drugs might contribute to reduced accumulation of [3H]5-HT. The results indicate that the inhibitory action of (d-NF) on [3H]5-HT accumulation is due principally to its ability to release [3H]5-HT. In contrast, the interference of release in accumulation studies does not seem to play an important role for d-F, suggesting that release from the granular pool and true uptake inhibition are two different mechanisms by which d-F affects serotonin neurons in vitro.

Animals↗
PubMed1982

Effect of peptichemio in nonlocalized neuroblastoma.

PTC, a mixture of oligopeptides of m-L-sarcholysin, acting primarily as an alkylating agent, was utilized as initial therapy following diagnosis in 80 children with nonlocalized neuroblastoma. Of the 67 evaluable patients (21 Stage III, 41 Stage IV and five Stage IV-S), 51 had measurable lesions allowing to evaluate PTC activity; objective tumor responses to the drug were recorded in 45 of these 51 cases (88.2%); 5/5 Stage III, 37/41 Stage IV, 3/5 Stage IV-S. Complete responses were obtained in seven patients (13.7%), partial responses in 32 (62.7%), objective improvement in six (11.8%). Four patients (7.8%) had either no tumor change, or tumor progression. There have been two early drug-related deaths (3.9%). Stage III and IV patients responding to PTC were then treated by irradiation + VCR, followed by cycles of a combination of ADriamycin, vincristine, and cyclophosphamide. Stage IV-S patients received no further therapy. Thirteen of 21 Stage III (61.9%), five of 41 Stage IV (12.2%) and four of five Stage IV-S (80%) are presently alive from 19-48 months (median, 27 months). PTC is an effective agent in advanced neuroblastoma. However, the results of this report do not indicate that its addition to a "standard" treatment, at least in the schedule adopted in this protocol, has improved the final outcome of children with nonlocalized disease.

Adolescent↗
PubMed1982

The outcome of Wilms' tumor in infants. Italy 1970-79.

Thirty-four infants under 1 year of age with Wilms' tumor were diagnosed and treated in 14 Italian pediatric oncology units during 1970-79. The 3-year survival rates decreased with higher group unilateral tumors: 95% in group I Wilms' tumor, 75% in group II and 20% in group III. The survival rates for children with group I and II Wilms' tumor were similar for those who were treated with surgery and chemotherapy and those who also received postoperative radiotherapy. During 1975-79 fewer patients with group I Wilms' tumor received radiotherapy (1 of 11) than during 1970-74 (4 of 6, p less than 0.05). All these children are alive at this writing.

Female↗
PubMed1982

Congenital self-healing histiocytosis.

In a typical case of congenital self-healing histiocytosis of the Hashimoto-Pritzker type, the results of an ultrastructural examination of a nodule of a 30-day-old patient showed that about 25% of the cells contained unique phagosomes but no regularly laminated bodies. This case of congenital self-healing histiocytosis is an example of concurrent proliferation of two types of histiocytes (one with and one without Langerhans' granules). Since transitional forms were not observed, this finding might indicate the existence of congenital, self-healing forms of histiocytosis X.

Cytoplasm↗