Search PubMed⌕ Search

Biomedical subjects

M Carli

Publications and source records attributed to M Carli.

At least 109 records · Page 6Linked to original sources

Effects of unilateral dorsal and ventral striatal dopamine depletion on visual neglect in the rat: a neural and behavioural analysis.

Rats were trained in a specially designed apparatus to detect brief, unpredictable visual stimuli presented to either side of the head. In one condition, rats reported the detection of the visual stimulus by removing their heads from a central location and responding in one of two adjacent side-holes where the visual stimulus had occurred. In the other condition, rats were trained to respond in the hole on the opposite side to where the visual stimulus had occurred. Following training all rats received striatal infusions of 6-hydroxydopamine leading to profound striatal dopamine depletion. One group received unilateral intra-nucleus accumbens 6-hydroxydopamine infusions. Two groups received 6-hydroxydopamine unilaterally into the caudate nucleus. Two other groups received two infusions of 6-hydroxydopamine, intra-accumbens and intra-caudate, on either the same side or on opposite sides. The results showed that all groups, except that receiving only intra-accumbens 6-hydroxydopamine, exhibited a significant bias in responding towards the side of the lesion which correlated with dopamine depletion in the head of the caudate nucleus, regardless of the type of discrimination or pre-operative strategy. These biased groups were also slower to initiate, but not to complete, contralateral responses. Detailed analysis of the behavioural evidence suggested that unilateral striatal dopamine depletion does not produce sensory loss or sensory inattention but rather an output type neglect, perhaps related to hemiakinesia or "intentional neglect". The bias recovered to preoperative levels by 7 weeks after surgery, but could be reinstated by pretreatment with alpha-methyl-para-tyrosine, thus suggesting the involvement of presynaptic mechanisms in recovery. Although unilateral dopamine depletion from the nucleus accumbens alone had no effects on visual neglect, it produced a lateralized bias in premature responding away from the side of the lesion, contrasting with the bias towards the side of the lesion seen in all of the other groups. These effects appeared to summate in this and in another condition in which a more eccentric response was required for stimulus detection, to suggest an interaction in function between the dorsal and ventral striatum.

Animals↗

Evidence that central 5-hydroxytryptaminergic neurones are involved in the anxiolytic activity of buspirone.

1. A two-compartment exploratory test was used to assess the role of central 5-hydroxytryptaminergic neurones in the anxiolytic activity of buspirone in rats. 2. Buspirone 0.1 mg kg-1, administered subcutaneously 15 min before testing, significantly increased black-white transitions (BWT) in control rats but had no effect in animals injected intracerebroventricularly one week before with 150 micrograms 5,7-dihydroxytryptamine (in 20 microliters). 3. Infusion of buspirone in the median raphe (but not in the dorsal raphe) significantly enhanced BWT, at doses from 1 micrograms to 10 micrograms (in 0.5 microliters). Buspirone 5 and 10 micrograms, but not 1 microgram, administered in the median raphe, significantly enhanced motor activity of rats during the first 10 min of testing in the activity cages. 4. The effect on BWT of 5 micrograms buspirone in the median raphe was completely antagonized in animals which had received either 5,7-dihydroxytryptamine intraventricularly, 150 micrograms (in 20 microliters), one week before or an infusion of 0.1 microgram (in 0.5 microliter) (-)-propranolol in the same area 5 min before. (-)-Propranolol infused in the median raphe did not modify the effect of buspirone on locomotion. 5. Infusion of 5 micrograms buspirone (in 0.5 microliter) in the median raphe significantly enhanced punished responses in a conflict test with no effect on unpunished responding. Buspirone infused in the dorsal raphe had no effect on punished or unpunished responding over a wide dose range. 6. The results indicate that at the relatively low dose used in the present study buspirone produces an anxiolytic effect by acting on central 5-hydroxytryptaminergic neurones. It is likely that activation of 5-hydroxytryptamine1A-receptors in the median raphe is involved.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Epidemiological features of Wilms' tumor: results of studies by the International Society of Paediatric Oncology (SIOP).

This descriptive epidemiology study of 1,040 children with Wilms' tumor (WT) registered in the International Society of Paediatric Oncology (SIOP) clinical trials confirms the findings reported by the National Wilms' Tumor Study. The male:female rate was 0.89:1. The mean age at diagnosis of the 43 bilateral cases was significantly younger than children with unilateral renal involvement (32.4 vs 45 months). However, the mean ages of diagnosis for unilateral multicentric and for unicentric WT were very similar. On the other hand, the mean age at diagnosis of children with sporadic aniridia and hypospadias was younger than the mean age of patients with or without other congenital malformations. Thus aniridia as well as hypospadias could be indices of the first mutation, according to the Knudson and Stron hypothesis. WT was reported in two members of each of five families. However, these familial cases were comparable in terms of demographic and clinical features to the nonfamilial ones. These data suggest that the heritable fraction of WT is relatively small and that genetic and environmental factors interact in the development of WT.

Congenital Abnormalities↗

Neurochemical and behavioural studies with RU-24969 in the rat.

The regional brain synthesis of serotonin (5-HT) and dopamine (DA) was studied in rats after various doses of 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU-24969), a 5-HT1 receptor agonist. The potential anxiolytic and antidepressant properties of the compound were examined as well. RU-24969 0.62 mg/kg significantly reduced 5-HT synthesis in the nucleus accumbens and hypothalamus, while with 1.25 and 2.5 mg/kg the effect was also seen in striatum, hippocampus, brainstem and cortex. RU-24969 2.5 and 5 mg/kg had no effect on DA synthesis in the striatum, while 5.0 mg/kg significantly increased it in the nucleus accumbens. At doses of 2.5 and 5.0 mg/kg the drug increased the motor activity of rats measured during 1 h in activity cages while 0.625 and 1.25 mg/kg had no effect. Doses ranging from 0.62 to 2.5 mg/kg RU-24969 significantly reduced unpunished responding in a test of conditioned suppression of drinking. Doses of 1.25 and 2.5 mg/kg also reduced punished responding. Finally, of various doses only 2.5 mg/kg RU-24969 significantly reduced the duration of immobility of rats in the forced swimming test but the effects were due to running around the cylinder rather than to escape attempts. In conclusion, RU-24969 reduced 5-HT synthesis in all brain areas examined, with a preferential effect for the nucleus accumbens and the hypothalamus. At higher doses, there was also a specific increase in DA synthesis in the nucleus accumbens. The compound raised the level of activity of rats but no clear evidence of any potential anxiolytic or antidepressant properties has been obtained.

5-Hydroxytryptophan↗

Potential anxiolytic properties of 8-hydroxy-2-(di-n-propylamino)tetralin, a selective serotonin 1A receptor agonist.

The effects of a selective serotonin 1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), were studied in two animal models of anxiety. Peripherally injected 8-OH-DPAT in doses ranging from 0.125 to 2.0 mg/kg did not increase black-white transitions (BWT) and black square entries (BSE) in a two-compartment exploratory test or punished responding in a test of conditioned suppression of drinking. With 2.0 mg/kg 8-OH-DPAT BSE and unpunished responding were reduced. In an investigation of the drinking time of water-deprived rats, naive or habituated to the test environment, 1.0 and 2.0 mg/kg 8-OH-DPAT increased the drinking time of naive rats but 2.0 mg/kg 8-OH-DPAT reduced that of habituated animals. In animals deprived of water for 48 h or subjected to immobilization stress for 2 h, 1.0 mg/kg 8-OH-DPAT increased BWT and BSE values in the two-compartment exploratory test. Infusions of 5 micrograms/0.5 microliter 8-OH-DPAT in the nucleus raphe medianus increased BWT and BSE values in the exploratory test and punished responding in the test of conditioned suppression of drinking, whereas the same dose of 8-OH-DPAT injected in the nucleus raphe dorsalis had no effect on punished but suppressed unpunished responding. The effects of 8-OH-DPAT are only detectable in the appropriate experimental conditions. When injected systemically, the effects are evident when a state of arousal of the animals contributes to the overall behavioural output. 8-OH-DPAT shows effects comparable to those of established anxiolytics such as benzodiazepines and barbiturates when it is injected in the nucleus raphe medianus, but not in the dorsalis.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

An integrated approach to the assessment of family adjustment to acute lymphocytic leukemia in children.

This study evaluated psychological distress, social support and adjustment to the disease of 69 parents of 35 children suffering from acute lymphocytic leukemia. The study dealt with the initial phase of the disease. The following rating scales were used: the Symptom Distress Checklist-90, the Social Support Questionnaire and the Family Adjustment Scale. Psychological distress of the mothers was negatively correlated with their and their child's adjustment to the disease. A similar trend was found for fathers but the correlations reached statistical significance only for fathers' adjustment. Social support as evaluated by the 2 parents was positively correlated with their and their child's adjustment to the disease experience.

Adaptation, Psychological↗

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↗

Localized neuroblastoma. Surgical and pathologic staging.

Sixty-five children with neuroblastoma without evidence of distant metastases underwent initial tumor resection. Seventeen with no evidence of lymph node involvement in whom tumor resection was complete (Group 1) received no further antitumor therapy. One child died postoperatively; disease recurred in the bone marrow of one child at 52 months, the child subsequently died. Fifteen were alive without disease, giving an 82% actuarial five year survival. Forty-eight children with minimal residual tumor and/or regional lymph node involvement (Group 2) received two 5-day courses of Peptichemio (1.2 mg/kg/d) and the 29 children in this group who were older than 1 year of age at diagnosis were randomized to receive either radiotherapy to the tumor bed in addition or no radiotherapy. In Group 2, ten of the 48 have relapsed: six of 17 with initial lymph node involvement, three of four with tumor rupture at operation, and one of eight with tumor extension to the intervertebral foramen. No relapses were seen in the 19 children with minimal residual tumor confined to the tumor bed. Only one of the 18 Group 2 children who were younger than 1 year of age at diagnosis relapsed. Of the 29 Group 2 children who were older than 1 year of age at diagnosis, five relapses occurred in the 14 who received radiotherapy and four relapses in the 15 who did not receive radiotherapy. All six children with disseminated relapse died. Actuarial 5-year survival in Group 2 is 87%, and actuarial relapse-free survival, 76%.

Child↗

Undifferentiated (embryonal) sarcoma of the liver in childhood: results of a retrospective Italian study.

The clinical features and the treatment of undifferentiated (embryonal) sarcoma of the liver in 8 patients younger than 19 years old were analyzed. All these cases were registered in the retrospective multicentric study on childhood malignant tumors of the liver, conducted between 1983 and 1985 by the Italian Association of Pediatric Hematology Oncology. The age of the patients ranged from 94 to 190 months (median = 113.5 months); all children were males. An abdominal mass was the common presenting features. Abnormalities in hemogram and common liver tests were rarely reported. Angiography revealed various degrees of vascularization in these tumors. Two patients achieved a surgical complete remission (CR) at diagnosis; one patient achieved surgical CR after primary chemotherapy with vincristine, adriamycin, cyclophosphamide and 5-fluorouracil, which reduced the tumor volume and permitted surgical resection. Two of these patients are still in CR at 14 and 60 months after diagnosis; the third patient died of liver failure without evidence of recurrence 6 months after diagnosis. All of the other patients, who never achieved CR, died of disease. One was lost to follow-up, and one surgical death occurred. Reports of childhood undifferentiated sarcoma are reviewed.

Child↗

Cancer mortality among relatives of children with soft-tissue sarcoma: a national survey in Italy.

Information was obtained on the living status or cause of death of 2223 close relatives of 195 children with soft-tissue sarcomas (STS) diagnosed under age 15. Three-hundred nine relatives had died, from all causes, before STS diagnosis in the index child. The expected figure estimated from age- and sex-specific mortality rates in Italy was 293.3. Cancer was reported as cause of death in 76 relatives (75.1 expected). Seven grandmothers, 2 aunts, 1 uncle and 0 mothers died from breast cancer vs. 4.6, 0.9, 0.0 and 0.2 expected. Three siblings died from cancer (0.2 expected, P less than 0.01), i.e. STS, ependymoma and non-Hodgkin lymphoma. These results confirm and expand previous observations that STS in children are associated with other cancers, particularly childhood and breast cancer, in members of the same family.

Adolescent↗

The monitoring of optimal experience. A tool for psychiatric rehabilitation.

This article illustrates the use of quantitative time-sampling data in developing a psychology of "optimal experience" to help in the psychiatric development of adequate rehabilitation approaches. The Experience-Sampling Method was used on a sample of 47 Italian adolescent students to measure fluctuations in their experience. We found that the ratio of subjectively experienced challenges and skills was a fundamental parameter that predicted optimal experience as well as boredom and anxiety. In contrast, "low" experience in daily life was viewed as a risk factor that could be minimized to increase the quality of life. Monitoring fluctuations in optimal and low experience may therefore be an important tool in developing personalized psychiatric rehabilitation plans.

Activities of Daily Living↗

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↗

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↗