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Biomedical subjects

G Marini

Publications and source records attributed to G Marini.

At least 73 records · Page 4Linked to original sources

5-Fluorouracil and dipyridamole in metastatic breast cancer: a pilot study.

In an attempt to increase the clinical activity of 5-fluorouracil (5-FU) by blocking the thymidine salvage pathway, 15 patients with refractory metastatic breast cancer (MBC) were treated with oral dipyridamole (D): 75 mg p.o. q.i.d. and 5-FU: 400 mg/m2 i.v. by bolus for 5 consecutive days, every 28 days. All the patients were pretreated with 5-FU and an anthracycline-based regimen. Toxicity was minimal, with 8 patients experiencing a D-related moderate headache. Although no objective responses were seen, two patients with 5-FU refractory disease showed tumor shrinkage. A different D schedule and the addition of folinic acid (FA) to 5-FU might provide better results and deserves further evaluation.

Adult↗

Phase II trial of 5-fluorouracil and high-dose folinic acid in advanced renal cell cancer.

Fourteen patients with metastatic renal cell carcinoma (RCC) were treated with high-dose folinic acid (HDFA): 200 mg/m2 i.v. and 5-fluorouracil (5-FU): 370 mg/m2 i.v. for 5 consecutive days every 28 days. Severe oral mucositis (WHO grade III-IV) was experienced by two patients, whereas hematological toxicity was mild. No complete or partial remission was observed. Short-lasting stable disease occurred in 8 patients (median = 5 months, range 2-11). This combination does not need further evaluation in patients with RCC.

Adult↗

Recovery of inspiratory abduction of the paralyzed vocal cords after bilateral reinnervation of the cricoarytenoid muscles by one single branch of the phrenic nerve.

The aim of this study was to provide the bilateral reinnervation of the posterior cricoarytenoid (PCA) muscles by the superior root of the right phrenic nerve. In six adult cats, the right phrenic root was anastomosed to the distal stump of the transected recurrent laryngeal nerve (RLN) on the same side. The RLN adductor branch was then cut and anastomosed to a nerve graft whose end was carried contralaterally and sutured to the left RLN or to the left PCA muscle. The phrenic fibers regrowing along the RLN abductor branch reinnervated the right PCA muscle and restored the inspiratory abduction of the right vocal cord in all the animals. In five of the six cats, the fibers regenerated through the RLN adductor branch and the graft reached the left PCA muscle and also restored the inspiratory opening of the larynx on the left side. Histological nerve examination revealed a fairly symmetrical distribution of the regenerated phrenic axons to the right and left PCA muscles.

Anastomosis, Surgical↗

Ibotenic acid lesions of the thalamic medialis dorsalis nucleus in the cat: effects on the sleep-waking cycle.

Bilateral ibotenic acid lesions of the thalamic medialis dorsalis nucleus in chronically implanted cats produced a significant reduction of slow wave sleep. Rapid eye movement sleep was also affected but in a less significant manner. The lesions were limited to the intermediate portion of the nucleus, which receives projections from the brainstem and prosencephalic structures implicated in sleep mechanisms. These results are consistent with the hypothesis that the medialis dorsalis nucleus plays an important role in the induction and maintenance of sleep.

Animals↗

Changes in sleep--waking cycle induced by lesions of medialis dorsalis thalamic nuclei in the cat.

Bilateral lesions of medialis dorsalis (MD) thalamic nuclei in chronically implanted cats disrupt the sleep-waking cycle by inducing a reduction of both slow-wave and desynchronized sleep and a corresponding increase of wakefulness. Bilateral lesions of the anterior thalamic group produce some postural deficits but no changes in the percentage of sleep and wakefulness. The hypothesis that MD lesions alter the sleep processes by interrupting an anterior forebrain-MD-cortical link has been put forward.

Animals↗

Brain stem expansive lesions: stereotactic biopsy for a better therapeutic approach.

CT diagnosed brain stem malignant lesions were in the past almost always treated with radiation therapy (RT). Eventually this turned out to be a grave mistake. With stereotactic serial biopsies of all brain stem expanding lesions we have been able to verify the histological nature in all cases but two and to prevent a blind therapeutic approach. In 24 patients bearing CT diagnosed expansive lesions into the brain stem 68 samples were taken during 24 stereotactic procedures. In 8 patients surgical removal of the expanding lesion was attempted after stereotactic biopsy.

Adolescent↗

Premarin priming before prednimustine, high-dose folinic acid and 5-fluorouracil as salvage chemotherapy for advanced breast cancer.

Thirty patients with advanced and mainly pretreated breast cancer were treated with a combination of premarin, prednimustine, high-dose folinic acid and 5-fluorouracil. Among the 30 evaluable patients, 9 (30%) achieved an objective response (median duration: 9 months). Oral mucositis was the limiting toxicity, while myelosuppression was quite mild. In spite of considerable activity as salvage regimen, these results do not seem better than those achieved in our Institute with high-dose folinic acid and 5-fluorouracil alone.

Breast Neoplasms↗

Complete estrogen blockade with buserelin and aminoglutethimide for advanced breast cancer: a phase I-II study with long-term hormonal correlations.

We treated 21 patients with advanced breast cancer with buserelin, aminoglutethimide and cortisone acetate in an attempt to obtain a complete estrogen blockade both in premenopausal and postmenopausal patients. Ten patients (47%) obtained an objective response without any relevant side-effects. Dealing with hormonal data, it must be outlined that serum testosterone levels decreased significantly in postmenopausal patients, suggesting a possible explanation for the activity of luteinizing hormone-releasing hormone analogue in this group of patients.

Adult↗

Cortical and peripheral effects on single neurons of the lateral reticular nucleus in the monkey.

The aim of this study was to extend the anatomical study of the corticoreticular organization in the monkey by means of microelectrophysiological techniques. Considering the relatively modest projection (see companion paper, Wiesendanger and Wiesendanger, '87), it was surprising to see that over 70% of the investigated LRN neurons were influenced from at least one cortical stimulation site. Many neurons responded, however, with long latencies suggesting an indirect transmission line. In line with the anatomical tracing study, most short-latency responses were obtained from the motor cortex. Postcentral cortex and the SMA were, in general, less effective sites for evoking responses in the LRN. LRN neurons with similar cortical inputs tended to be clustered together suggesting that the corticoreticular projection is discretely organized with an "intermingled somatotopy". The majority of the 87 tested LRN neurons were not reactive to any peripheral stimulus (33%) or responded only to nociceptive peripheral stimulation (31%). Very large receptive fields were seen in 8% of the units. However, a significant proportion of LRN neurons (10%) had restricted receptive fields and reacted to gentle cutaneous stimuli, and others (17%) responded to discrete passive rotations of one or more joints. There was often a somatotopical correspondence between the peripheral and the cortical inputs. It is concluded that the LRN in monkeys is under the influence of the motor cortex, which, however, may be exerted to a major extent via indirect pathways. The electrophysiological data suggest a discrete rather than a diffuse relationship with the LRN.

Animals↗

Stereotactic computer graphic system with brain maps.

We have developed a stereotactic computer graphic system with brain maps that runs on a personal computer. This system consists of three parts: 1. firmware for dizitizing radiological films with a TV camera or scanner (when digital image is not directly obtained from floppy disks); 2. software for introducing or processing brain maps by matching them with CT or NMR images; 3. hardware. Our system is designed to: 1. recognize the relevant frame points and calculate targets, their volume and surgical instrument trajectory; 2. match between brain maps of an ideal brain and patient's CT or NMR images with visible and invisible pathology; 3. monitor during surgery the position of the surgical instrument or target modification. The whole procedure and processed images are stored in a data-base for further study.

Brain Mapping↗

Projections from lateral reticular nucleus neurons to trigeminal motor nucleus revealed by antidromic activation in rabbits.

In anesthetized rabbits, electrophysiological experiments were conducted to determine if neurons of the lateral reticular nucleus that modified their activity during masticatory movements project directly into the trigeminal motor nucleus. Of the 125 neurons tested, 50 responded to stimulation of the trigeminal motor nucleus; of these, 22 were antidromically excited. Among this last population, 9 were antidromically driven also by cerebellar stimulation. In these neurons the antidromic response evoked from one structure collided with the response antidromically evoked from the other, thus indicating that both potentials are from the same neuron projecting to the trigeminal motor nucleus and the cerebellum. The remaining 28 neurons responding to stimulation of the trigeminal motor nucleus were orthodromically activated with a wider range of latencies. The possible significance of these findings in the organization of the rhythmic masticatory movements is briefly discussed.

Action Potentials↗

Transcerebellar biopsy in the posterior fossa: 12 years experience.

Utilizing the Leksell stereotactic system, the transcerebellar approach was used for posterior fossa biopsies. During a period of 12 years, a total of 29 patients were operated on by this technique, among them 12 children. In the adult, the procedure was carried out with the patient awake and sitting upright; the pediatric patients required general anesthesia and the head was supported either manually or by a clamp. Representative specimens were obtained in all cases but one, showing a wide diagnostic spectrum. As a rule, the procedures were performed smoothly, with no serious side effects. Stereotactic biopsies in the posterior fossa, hitherto seldom performed, open new diagnostic perspectives, one of which is for use in obscure brain stem lesions. The transcerebellar approach has been proven to be easy, direct, and safe provided an appropriate technique is used, such as that described in the present paper.

Adolescent↗

Role of aging on growth hormone and prolactin release after growth hormone-releasing hormone and domperidone in man.

Growth hormone (GH) and prolactin (PRL) secretion after GH-releasing hormone (GHRH) and domperidone (DOM), an antidopaminergic drug which does not cross the blood-brain barrier (BBB), was evaluated in 8 healthy elderly men (65-91 years) and in 7 young adults (23-40 years). All received in random order at 2-day intervals: GHRH(1-40) (50 micrograms i.v.) bolus, DOM (5 mg/h) infusion, GHRH(1-40) (50 micrograms i.v.) plus DOM (5 mg/h i.v.), saline solution. In elderly men GH increase after GHRH was significantly lower than in young men. DOM alone did not change GH secretion in either of these groups, whereas it increased the GH response to GHRH only in young adults. PRL levels increased in both young and elderly men during both DOM and GHRH plus DOM, but the PRL release was more marked in young than in elderly men. Both integrated secretion of GH after GHRH and of PRL after DOM were inversely correlated to chronological age. Our data show an impairment of GH rise after GHRH and of PRL after DOM in elderly adults. It is also stressed that peripheral blockade of dopamine receptors by DOM is unable to amplify the GH response to GHRH only in elderly men. A reduction in GH release after GHRH might be related to aging, perhaps through a reduction of dopaminergic tonus.

Adult↗

5-Fluorouracil and high-dose folinic acid as salvage treatment of advanced breast cancer: an update.

We report an update of our results of a trial of high-dose folinic acid (HDFA) and 5-fluorouracil (5-FU) in advanced breast cancer. Thirty-eight patients with advanced and mainly refractory breast cancer were treated with the following regimen: HDFA (200 mg/m2/day) and 5-FU (340, 370, 400 mg/m2/day) given immediately afterwards, for 5 consecutive days every 4 weeks. Of 36 evaluable patients, 3 achieved complete remission (8%) and 13 partial remission (36%) for an overall response rate of 44%, while 11 patients (30%) had stable disease. Thirteen out of sixteen responders (85%) were pretreated with some 5-FU-containing regimens. The median duration of response was 9.6+ months, the median survival for responders and for patients with stable or progressive disease was 19.9+, 18.8+ and 9 months, respectively. The overall toxicity was acceptable: while hematological toxicity was very mild, oral mucositis, diarrhea and conjunctivitis were major side effects. These results seem very promising and deserve further evaluation.

Antineoplastic Combined Chemotherapy Protocols↗

Clinical experience with 5-fluorouracil (5-FU) and high-dose folinic acid in solid tumors.

This paper reports experience with high-dose folinic acid (HDFA) and 5-fluorouracil (5-FU) in the treatment of 130 patients with various types of tumor. While the objective results obtained from gastrointestinal malignancies (response rate = 15%) are no better than those usually gained by 5-FU alone, impressive results were achieved in patients with advanced and mainly pretreated breast cancer (response rate = 44%). Haematological toxicity was generally mild, while oral mucositis, diarrhoea and conjunctivitis were major side effects. Our data suggest that HDFA and 5-FU seem a very promising combination and warrant further investigation.

Adult↗

Cisplatin, high dose folinic acid and 5-fluorouracil in squamous cell carcinoma of the esophagus. A pilot study.

We treated 20 patients with squamous cell carcinoma of the esophagus with the following regimen: cisplatin = 100 mg/m2 i.v. day 1, HDFA = 200 mg/m2 i.v. day 1 to 5, 5-fluorouracil = 370 mg/m2 i.v. day 1 to 5 repeated every 28 days. Among the 17 evaluable patients, 4 (23%) had a partial remission, 6 had stable disease while 7 progressed. The median survival for all patients was 6+ months. Grade III or IV toxicity included 2 patients with grade III leukopenia, 1 with grade III thrombocytopenia, 1 patient with grade IV and 3 patients with grade III oral mucositis, 3 patients with grade III diarrhea. The regimen did not seem particularly active in the treatment of squamous cell carcinoma of the esophagus and had manageable but substantial toxicity.

Aged↗