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Biomedical subjects

G Marini

Publications and source records attributed to G Marini.

At least 19 recordsLinked to original sources
PubMed2006

Behavioral and electrophysiological changes induced by acetyl-L-carnitine in aged freely-moving rats.

In chronically-implanted, drug-free, behaving aged Fischer rats, intracerebroventricularly (i.c.v.) and intraperitoneally (i.p.) acetyl-L-carnitine (ALCAR) injections powerfully enhanced motor behavior and head movements aimed at attention and exploratory activity. This effect was dose-dependent and associated with the abolition or substantial reduction of the incidence and duration of the spontaneous EEG generalized hypersynchronous patterns termed High Voltage Spindle (HVS), with an increase in EEG monitored theta activity. The results suggest that ALCAR may stimulate the motivational system and disrupt the hypersynchronous processes by inhibiting the GABAergic thalamic reticular neurons and/or activating the brain stem cholinergic reticular system (pedunculo pontine tegmental, PPT and laterodorsal tegmental, LDT nuclei).

Acetylcarnitine↗
PubMed2004

Supervised machine learning techniques for the classification of metabolic disorders in newborns.

MOTIVATION: During the Bavarian newborn screening programme all newborns have been tested for about 20 inherited metabolic disorders. Owing to the amount and complexity of the generated experimental data, machine learning techniques provide a promising approach to investigate novel patterns in high-dimensional metabolic data which form the source for constructing classification rules with high discriminatory power. RESULTS: Six machine learning techniques have been investigated for their classification accuracy focusing on two metabolic disorders, phenylketo nuria (PKU) and medium-chain acyl-CoA dehydrogenase deficiency (MCADD). Logistic regression analysis led to superior classification rules (sensitivity >96.8%, specificity >99.98%) compared to all investigated algorithms. Including novel constellations of metabolites into the models, the positive predictive value could be strongly increased (PKU 71.9% versus 16.2%, MCADD 88.4% versus 54.6% compared to the established diagnostic markers). Our results clearly prove that the mined data confirm the known and indicate some novel metabolic patterns which may contribute to a better understanding of newborn metabolism.

Algorithms↗
PubMed2004

Spontaneous K-complexes in behaving rats.

The K-complex (KC) is an electrographic rhythmic pattern present in human and cat sleep EEG. In long-term multisite videoEEG recordings in behaving Sprague-Dawley (SD) rats, well-defined spontaneous KCs were observed during sleep. Sprague-Dawley rats were implanted with multiple electrodes bilaterally along the antero-posterior axes at the locations F1, F2, F7, F8, T3, T4, P3, P4, all against a ground reference placed in the midline above the cerebellum. Multiple, closely spaced cortical electrodes allowed two-dimensional surface brain mapping of the power spectra distribution. Two silver wires were also inserted into nuchal muscles to record EMG activity. Each rat was monopolarly recorded from 0900 h to 1500 h in a natural dark-light rodents, we examined the patterns of appearance in various conditions, the progression through a full sleep-waking cycle, the shape, density, spectral components, and spatial distribution in power spectra. The rat KC appears to share similar features with the human and cat KC.

Action Potentials↗
PubMed2002

Thalamocortical dysrhythmia and the thalamic reticular nucleus in behaving rats.

OBJECTIVES: The aim of this study was to investigate the effects of bilateral chemical lesion of the rostral pole of the thalamic reticular nucleus on EEG activities in freely moving rats applying quantitative analysis and brain mapping of power spectra distribution. METHODS: Ketamine-sedated Sprague-Dawley rats were implanted to monitor behavioral states with frontoparietal electrodes in a first series of experiments and with multiple electrodes along the antero-posterior axis (F1, F2, F7, F8, T3, T4, P3, P4) in a second series. Monopolar and bipolar recordings were obtained in animals stereotaxically injected with ibotenic acid into both rostral poles of the thalamic reticular nucleus. Long-term video-EEG recordings and brain mapping based on quantitative spectral analysis were made. RESULTS: Two forms of dysrhythmia gradually emerged in the neocortical EEG at 12-24h post-injection: potentiation of theta waves and spontaneous high-voltage spindles (HVS) at 4.5-8Hz frequency. Brain mapping during these dysrhythmia shows highest power posteriorly (parietotemporal) for theta and mesiofrontally for HVS. CONCLUSIONS: Given the lack of inhibitory intrinsic interneurons in the rat thalamus, bilateral destruction of a small part of the solely GABAergic population may promote cortical dysrhythmia (probably by dis-inhibition). The topographic differences in power might indicate different involved structures.

Anesthetics, Dissociative↗
PubMed2001

Effect of pregnancy on overall survival after the diagnosis of early-stage breast cancer.

PURPOSE: To evaluate the impact of subsequent pregnancy on the prognosis of patients with early breast cancer. PATIENTS AND METHODS: One hundred eight patients who became pregnant after diagnosis of early-stage breast cancer were identified in institutions participating in International Breast Cancer Study Group (IBCSG) studies. Fourteen had relapse of breast cancer before their first subsequent pregnancy. The remaining 94 patients (including eight who relapsed during pregnancy) formed the study group reported here. A comparison group of 188 was obtained by randomly selecting two patients, matched for nodal status, tumor size, age, and year of diagnosis from the IBCSG database, who were free of relapse for at least as long as the time between breast cancer diagnosis and completion of pregnancy for each pregnant patient. Survival comparison used Cox proportional hazards regression models. RESULTS: Overall 5- and 10-year survival percentages (+/- SE) measured from the diagnosis of early-stage breast cancer among the 94 study group patients were 92% +/- 3% and 86% +/- 4%, respectively. For the matched comparison group survival was 85% +/- 3% at 5 years and 74% +/- 4% at 10 years (risk ratio, 0.44; 95% confidence interval, 0.21 to 0.96; P =.04). CONCLUSION: Subsequent pregnancy does not adversely affect the prognosis of early-stage breast cancer. The superior survival seen in this and other controlled series may merely reflect a healthy patient selection bias, but is also consistent with an antitumor effect of the pregnancy.

Adolescent↗
PubMed2000

Cisplatin, dacarbazine, and fotemustine plus interferon alpha in patients with advanced malignant melanoma. A multicenter phase II study of the Italian Cooperative Oncology Group.

BACKGROUND: In a previous study, the authors tested the combination of fotemustine (FM) 100 mg/m(2) intravenously (i.v.) on Day 1, dacarbazine (DTIC) 250 mg/m(2) i.v. on Days 2-5, and interferon alpha (IFNalpha) 3 MIU intramuscularly three times per week in 43 patients with advanced melanoma. An overall response rate of 40% and a median survival of 40 weeks were obtained. To evaluate whether the addition of cisplatin (CDDP) to this regimen could improve these results, the authors conducted a preliminary Phase I study and concluded that CDDP 25 mg/m(2) i.v. for 2 days can be combined safely with DTIC, FM, and IFNalpha. Herein, the authors report the results of a Phase II trial with this regimen. METHODS: From June 1996 to February 1999, 64 patients with metastatic melanoma who were not amenable to surgery were enrolled in this study. Sixty eligible patients (32 males and 28 females; median age, 53 years) were treated with a combination of FM 100 mg/m(2) i.v. on Day 1, DTIC 300 mg/m(2) i.v. on Days 2-4, and CDDP 25 mg/m(2) i.v. on Days 3 and 4 recycled every 3 weeks. IFN alpha2b was administered at a dose of 3 MIU intramuscularly 3 times per week until disease progression. RESULTS: A total of 189 courses were administered, with a median number of 3 courses per patient (range, 1-8 courses per patient). Eleven complete responses and 12 partial responses were observed, for an overall response rate of 38.3% (95% exact confidence interval, 26.1-51.8%). The median survival was 36 weeks. Neutropenia and thrombocytopenia affected 85% of patients and 68% patients and was World Health Organization Grade 3-4 in 40% and 50%, respectively. The side effects attributable to IFN alpha2b were mild and manageable. The other side effects were moderate and well controlled by supportive therapy. CONCLUSIONS: The schedule used in this study demonstrated significant activity in patients with advanced, untreated melanoma. The addition of CDDP in the management of the patients in this series seemed to increase significantly both the proportion of patients who achieved a complete response and the probability of long term survival compared with a previous series of patients who were treated by the authors. However, considering the currently available therapies, this regimen does not seem to offer a special advantage in the treatment of patients with this disease. New agents and new protocols are needed.

Adult↗
PubMed2000

Effects of bilateral microinjections of ibotenic acid in the thalamic reticular nucleus on delta oscillations and sleep in freely-moving rats.

The thalamic reticular nucleus (NRT) consists of a large pool of GABAergic neurons located on each side on the anterior, lateral, and ventral surfaces of the dorsal thalamus. The NRT is divided up into sectors. The aim of this study was to investigate the effects of bilateral lesions of the NRT on sleep and sleep oscillations. Only the results concerning delta oscillations will be reported here. As a first step we produced stereotaxically placed electrolytic lesions. The rats presented continuous circling behavior with electroencephalographic (EEG) theta and delta activity and subsequent sudden death. To avoid disruption of the bundles of fibers that pass through the NRT to and from the cerebral cortex, we used the excitotoxic ibotenic acid. Given its high toxicity, we concentrated on the rostral pole of the NRT, which is believed to have powerful effects on the synchronization of oscillatory activity during sleep. Immediately after surgery, the rats fell into a deep sleep during which there was an increase in EEG slow-wave activity and no spindles. On postoperative day 2, corresponding to the destruction period, the sleep/wake cycle partially recovered, but NREM sleep was quantitatively diminished and showed abnormalities (increased latency to sleep onset, sleep fragmentation, gradual elimination of the delta rhythm). It is concluded that the rostral pole of the NRT contributes to normal and pathological EEG synchronization and the organization of sleep in rats.

Animals↗
PubMed2000

Early start of adjuvant chemotherapy may improve treatment outcome for premenopausal breast cancer patients with tumors not expressing estrogen receptors. The International Breast Cancer Study Group.

PURPOSE: The proper time to commence adjuvant chemotherapy after primary surgery for breast cancer is unknown. An analysis of the International (Ludwig) Breast Cancer Study Group (IBCSG) Trial V at a median follow-up of 11 years suggested that early initiation of adjuvant chemotherapy might improve outcome for premenopausal, node-positive patients whose tumors did not express any estrogen receptor (ER). PATIENTS AND METHODS: We investigated the relationship between early initiation of adjuvant chemotherapy, ER status, and prognosis in 1,788 premenopausal, node-positive patients treated on IBCSG trials I, II, and VI. The disease-free survival for 599 patients (84 with ER-absent tumors) who commenced adjuvant chemotherapy within 20 days (early initiation) was compared with the disease-free survival for 1,189 patients (142 with ER-absent tumors) who started chemotherapy 21 to 86 days after surgery (conventional initiation). The median follow-up was 7.7 years. RESULTS: Among patients with ER-absent tumors, the 10-year disease-free survival was 60% for the early initiation group compared with 34% for the conventional initiation group (226 patients; hazard ratio [HR], 0. 49; 95% confidence interval [CI], 0.33 to 0.72; P =.0003). This difference remained statistically significant in a Cox multiple regression analysis controlling for study group, number of positive nodes, tumor size, age, vessel invasion, and institution (HR, 0.60; 95% CI, 0.39 to 0.92; P =.019). Conversely, early initiation of chemotherapy did not significantly improve disease-free survival for patients with tumors expressing ER (1,562 patients; multiple regression HR, 0.93; 95% CI, 0.79 to 1.10; P =.40). CONCLUSION: In premenopausal patients with ER-absent tumors, early initiation of systemic chemotherapy after primary surgery might improve outcome. Further confirmatory studies are required before any widespread modification of current clinical practice. In premenopausal patients with tumors expressing some ER, gains from early initiation are unlikely to be clinically significant.

Adult↗
PubMed2000

Methadone dose and retention during treatment of heroin addicts with Axis I psychiatric comorbidity.

We studied 90 opioid-dependent subjects, 38 with one or more additional Axis I diagnosis and 52 with no psychiatric comorbidity. There were significant differences between these two groups regarding the methadone dose required for clinical stabilization, but not in the rate of retention in treatment. Dual Diagnosis patients, those with psychiatric comorbidity, required an average stabilization dose of 154 +/- 84 of methadone compared to 99 +/- 49 mg/day for patients whose only Axis I diagnosis was Opioid Dependence. In the 990-day period considered there were no differences between the two groups of patients in terms of retention in treatment.

Adult↗
PubMed1999

Descending projections arising from the parafascicular nucleus in rats: trajectory of fibers, projection pattern and mapping of terminations.

The organization of the descending projections from the intralaminar parafascicular nucleus was studied using biocytin as an anterograde tracer in rats. After biocytin injection into the lateral parafascicular nucleus, three bundles of fibers descending throughout the brainstem were seen. Terminal fields were found in several structures, for example the lateral geniculate nucleus, nucleus reticularis thalami, subthalamus, zona incerta, substantia nigra, red nucleus, periaqueductal gray, superior colliculus, reticular formation, raphe nuclei, pontine nuclei, trigeminal complex, and ventral horn of the spinal cord. Different types of labeled terminals (small terminal boutons, en passant varicosities, large claw-like terminals) were observed, particularly in the substantia nigra and reticular formation where the density of terminals was highest. The organization of these extensive descending connections to both motor and sensory structures does not allow functions to be conclusively attributed to the parafascicular nucleus neurons. Further investigations are required to resolve this question.

Age Factors↗
PubMed1998

Factors affecting baseline quality of life in two international adjuvant breast cancer trials. International Breast Cancer Study Group (IBCSG).

Quality of life (QL) is used to assess treatments in clinical trials but may be influenced by other factors. We analysed the impact of biomedical, sociodemographic and cultural factors on baseline QL indicators in two International Breast Cancer Study Group trials. Patients with stage II breast cancer were randomized within 6 weeks of primary surgery to various adjuvant treatments. They were asked to assess five indicators of QL at baseline. QL forms were available for 1231 (83%) of the 1475 premenopausal and 989 (82%) of the 1212 post-menopausal patients, who were from nine countries and spoke seven languages. Culture (defined as language/country groups) had a statistically significant impact on baseline QL measures. Premenopausal patients with poor prognostic factors showed a tendency to report worse QL, with oestrogen receptor status as an independent predictor for mood (P = 0.0005). Older post-menopausal patients reported better emotional wellbeing (P = 0.002), mood (P = 0.002), and less effort to cope (P = 0.0009) compared with younger post-menopausal patients. Co-morbidity, type of surgery, treatment assignment and sociodemographic factors showed a statistically significant impact in post-menopausal patients only. Cultural and biomedical factors influenced baseline QL and should be considered when evaluating the impact of treatment on QL in international breast cancer clinical trials.

Adult↗
PubMed1998

Abolition of the neocortically monitored theta rhythm after ibotenic acid lesion of the parafascicular nucleus in behaving rats.

Seven adult Sprague-Dawley rats, chronically implanted with standard electrodes to monitor frontoparietal electroencephalographic (EEG) and nuchal electromyographic (EMG) activity, received, under deep anesthesia, unilateral or bilateral microinjections of ibotenic acid in the lateral part of the parafascicular nucleus of the thalamus. Four days after the injections (corresponding to the period of neuronal destruction), obliteration of the oscillatory activity in the theta range was found on the side ipsilateral to the injection, while on the intact hemisphere the rhythm was well developed. The asymmetry between the two hemispheres was particularly evident during REM sleep but was also seen during attentive but immobile alertness. In bilaterally injected rats, the neocortical theta rhythm was abolished on both hemispheres. These results suggest that in freely-moving rats the lateral parafasciculus neurons are part of the network on which the emergence of the theta rhythm relies.

Animals↗
PubMed1998

[Hydrocephalus and rebleeding in subarachnoid hemorrhage].

The main features of rebleeding and post-haemorrhagic hydrocephalus in case of subarachnoid haemorrhage following the rupture of an intracranial aneurysm are presented. In both cases frequency, causes, clinical events, prevention and therapy are discussed.

Humans↗
PubMed1997

High-dose chemotherapy with autologous stem cell transplantation is feasible and safe in a regional hospital. A 6-year experience in southern Switzerland.

High-dose therapy with bone marrow (BM) or blood stem cell (BSC) support is a high-technology technique usually administered in specialized tertiary centers. The use of BSC has made this technique simpler and accessible also to smaller hospitals. We retrospectively analyzed the data of patients with lymphoma, leukemia and other tumors who received high-dose therapy and BM or BSC transplantation in our district hospital, looking at the type of procedure performed, complications, use of growth factors, and progression-free and overall survival. A total of 40 patients were transplanted over 6 years. No procedure-related deaths and no permanent organ toxicities were seen. The use of BSC brought about a great reduction in the duration of hospital stay, septic complications and transfusion of blood components. For patients with lymphoma (n = 20) the probabilities of progression-free survival and of overall survival at 2 years are 48% (95% C.I. 28-68%) and 68% (95% C.I. 46-84%), respectively. Based on these data, we believe that ABMT and BSC transplantation are feasible and safe in a peripheral hospital when the appropriate human and technical conditions are present. Treatment outcome is then comparable to that of specialized centers.

Adolescent↗
PubMed1997

Paclitaxel, ifosfamide, and carboplatin for the treatment of stages IIIB and IV non-small cell lung cancer: preliminary results.

We have treated 26 consecutive chemotherapy-naive patients with stage IIIB/IV non-small cell lung cancer with an innovative regimen based on a 1-hour infusion of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 125 to 250 mg/m2, ifosfamide 3 g/m2 (with mesna), and carboplatin dosed to an area under the concentration-time curve of 5, every 21 days for a total of six cycles in responding or stabilized patients. Among 22 fully evaluable patients, 14 (64%) achieved a partial remission, six had disease stabilization, and two had disease progression. Hematologic toxicity was remarkably mild; only one patient had grade 3 neutropenia (on day 21). Arthralgias/myalgias (grade 3 in nine patients, grade 4 in one patient) and neurologic toxicity (a cumulative sensory neuropathy of grade 3 or 4 in five patients) were the most common side effects and seem to be dose related. To date, few patients are fully evaluable and survival data are clearly immature. Nevertheless, this regimen seems highly active and quite well tolerated, and deserves further evaluation.

Adult↗
PubMed1996

[Paraplegia following intrathecal chemotherapy].

The occurrence of major neurologic disturbances is a rare complication of intrathecal cytotoxic drug administration. We describe the case of a 30-year old man with relapsed lymphoblastic lymphoma and CNS involvement who was treated by systemic chemotherapy (ESHAP) and intrathecal injections of methotrexate, cytarabine, thiotepa and hydrocortisone. Thereafter he developed persistent paraplegia with sensory and sphincteric insufficiency. The role of the drug in causing this syndrome was suspected when more common causes, such as a meningeal carcinomatosis, had been excluded by means of CNF analysis and radiological examinations. We review this and other published cases and discuss the possible pathogenesis, as well as the clinical and paraclinical findings in paraplegia following intrathecal chemotherapy. Patients particularly at risk are those who receive intrathecal chemotherapy for over CNS disease rather than as prophylaxis, those who receive several injections and patients who are concomitantly treated with radiotherapy to the brain or systemic high-dose methotrexate or cytarabine.

Adult↗