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Biomedical subjects

G Marini

Publications and source records attributed to G Marini.

At least 55 records · Page 3Linked to original sources
PubMed1993

Diaphragm reinnervation by laryngeal motoneurons.

Inspiratory activity of the paralyzed diaphragm was restored by reinnervation with brain stem laryngeal motoneurons. In 10 anesthetized cats, the right recurrent laryngeal nerve (RLN) was cut and anastomosed to the distal stump of either one or both roots (C5-C6) of the ipsilateral phrenic nerve. Three to four months later, reinnervation was assessed under deep anesthesia by the reappearance in the paralyzed diaphragm of 1) direct electromyographic (EMG) responses after electrical stimulation of the RLN and 2) spontaneous inspiratory bursts. Serial radiography, performed on five animals, revealed diaphragmatic excursions of comparable amplitude on the normal and reinnervated sides. Six to twelve months after anastomosis, laparotomy (performed under Nembutal anesthesia) allowed inspection and EMG recording of the spontaneous inspiratory contractions of the reinnervated areas and their sustained responses to tetanic RLN stimulation. Inspiratory discharges showed a ramplike recruitment similar to that of the normal diaphragm. Although the RLN contains a number of expiratory axons, multiple-site recordings disclosed expiratory EMG discharges only once. Histological analysis confirmed the substitution of phrenic axons by regenerating RLN fibers.

Animals↗
PubMed1992

Effect of cholinergic tone on growth hormone-releasing hormone-induced secretion of growth hormone in normal aging.

Aging is associated with an impairment in the GH response to GHRH and to several other stimuli of GH secretion. We evaluated the effect of pyridostigmine (PD) or placebo pretreatment (Protocol A: placebo or 120 mg PD orally at 8 a.m.; Protocol B: placebo or 60 mg PD twice orally at 9 p.m. and 7 a.m.) on GH responsiveness to GHRH (1 micrograms/kg BW bolus i.v. at 9 a.m.) in 15 normal elderly males (65-92 years) and in 14 normal young adults (20-37 years). GH response to GHRH was significantly reduced in elderly subjects compared to young adults (p < 0.05). PD (Protocol A) increased GH release in both elderly and young subjects. In elderly men, PD enhanced GH response to GHRH. The phenomenon was more evident when PD was administered according to Protocol B (p < 0.01). The area under the curve of GH was significantly greater after PD plus GHRH than it was after placebo plus GHRH (p < 0.01). In young adults, PD induced an increase in GH responsiveness to GHRH when administered according to Protocol A (p < 0.05) but not Protocol B. Both GH peak and AUC of GH after PD plus GHRH (Protocols A and B) in elderly subjects were not significantly different from the same parameters found in young subjects after placebo plus GHRH. Our data confirm that pituitary somatotrophin responsiveness to GHRH in man changes with aging. PD restores GH responsiveness to GHRH in elderly subjects. The effect of PD on GH secretion suggests that cholinergic mechanisms may be involved in GH control in normal aging.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Enhancement of tonic and phasic events of rapid eye movement sleep following bilateral ibotenic acid injections into centralis lateralis thalamic nucleus of cats.

The excitotoxin ibotenic acid (1.2-2.6 microliters of 50 micrograms/microliters) was injected bilaterally into the thalamic centralis lateralis nucleus of chronically implanted cats in order to study the effects of tonic excitation followed by destruction of perikarya on the sleep-waking cycle and its electrographic correlates. Ibotenate injections were performed under mild ketamine anaesthesia. Immediately afterwards, the animals showed behavioural arousal accompanied first by ocular nystagmiform movements and then by pontogeniculooccipital waves. By 6-10 h post-injection, the numbers of rapid eye movement sleep episodes, but not their duration, increased compared to the preinjection control period. The injection sites were histologically confirmed using conventional Thionin stains. Additional control was provided by retrograde transport of wheat-germ agglutinin conjugated with horseradish peroxidase. The present results suggest that a population of neurons important for ocular saccades, pontogeniculooccipital waves, and the state of desynchronized sleep is present in the internal medullary lamina, in particular in the centralis lateralis nuclei.

Animals↗
PubMed1992

Potentiation of electroencephalographic spindles by ibotenate microinjections into nucleus reticularis thalami of cats.

It is well known that the electroencephalogram of the cat in the early stages of slow wave sleep is mainly characterized by rhythmic wave activity at 7-14 Hz, termed spindles, which recur periodically with a slow rhythm of 0.1-0.2 Hz. From early stimulation, decortication and transection studies (see Ref. 14), spindle oscillations were thought to originate in the thalamus. The search for the anatomical substrate of thalamic spindling, however, moved from medial (intralaminar nuclei) to lateral thalamic nuclei, and recently focused on the extreme shell-shaped collection of GABA-ergic cells, the nucleus reticularis thalami. This proposition was based on its structural, hodological, and physiological aspects. There is accumulating evidence that the nucleus reticularis may act as a conditional pacemaker, synchronizing the activity of cortically projecting thalamic neurons. The introduction of glutamate analogues with excitotoxic properties such as ibotenic acid provided the opportunity of studying the immediate effects of chemical excitation of this nucleus on synchronized electroencephalographic activity. We found that, in cats, spindle density was dramatically increased following infusion of ibotenic acid into the rostral pole of the nucleus, supporting the role of this sector in spindle-related rhythmicity.

Animals↗
PubMed1992

Innervation of the paralyzed laryngeal muscles by phrenic motoneurons. A quantitative study by light and electron microscopy.

In the cat, inspiratory opening of the paralyzed glottis recovered after unilateral or bilateral reinnervation of the posterior cricoarytenoid (PCA) muscles by phrenic axons. The morphometric analysis of the regenerated recurrent laryngeal nerves (RLNs), showed that proliferation was abundant; 4 months after the nerve anastomosis, more than 500 myelinated axonal branches repopulated the RLNs. The mean diameter of motor axons (3.5 to 5.0 microns) was lower than in normal phrenic and RLN (8 to 10 microns), and the mean internode length was about half that of the normal RLN. Histochemical examination of the PCA muscle revealed that muscle fiber composition (44% type I and 56% type II muscle fiber) was fairly similar to that of normal PCA. The contraction time of the reinnervated muscles was as long as 60 msec at the time of movement recovery, but it shortened to 25 to 30 msec when the reinnervation time increased. These anatomical and functional results support the choice of the phrenic nerve for laryngeal reinnervation.

Adenosine Triphosphatases↗
PubMed1992

The effect of a met-enkephalin analogue on growth hormone, prolactin, gonadotropins, cortisol and thyroid stimulating hormone in healthy elderly men.

The aim of the study was to evaluate the effect of the guanyl derivative of the opioid analogue D-ala2,MePhe4-Met-enkephalin-(o)-ol (G-DAMME) on pituitary secretion in healthy elderly men. Nine healthy elderly men (65-88 years) and 10 young adults (20-30 years) were studied. GH, PRL, gonadotropins, cortisol (to evaluate the effect on ACTH) and TSH were measured after G-DAMME (0.25 mg iv) or placebo administration. In elderly men, the GH response to G-DAMME was reduced or absent, while prompt GH release was found in all young men. G-DAMME lowered LH levels in young men but not in elderly men. No significant variations in FSH levels after G-DAMME and placebo were noted in either group of subjects. A similar and significant rise in PRL and TSH, and a fall in cortisol, after G-DAMME was observed in both elderly and young adults. We have demonstrated that the sensitivity to opioid modulation by G-DAMME on PRL, TSH and cortisol secretion is unchanged with aging. On the other hand, the data indicate that LH and GH responsiveness to G-DAMME change with age.

Adult↗
PubMed1991

Mitomycin-C, adriamycin, 5-fluorouracil and leucovorin (L-FAM2) in the treatment of advanced gastric cancer: a phase II study.

Thirty previously untreated patients with advanced measurable gastric cancer were given a combination chemotherapy consisting of 5-fluorouracil, 400 mg/m2, and leucovorin, 200 mg/m2 iv on days 1 to 3, mitomycin-C, 10 mg/m2 on day 1 (every other cycle) and adriamycin, 40 mg/m2 on day 2, repeated every 21 days. The overall response rate was 46% (14/30; 95% confidence limits: 28%-64%) including 4 patients with a complete remission. Eight patients progressed. Median duration of remission (CR+PR) was 10 months, with a median survival of 13, 8 and 4 months for CR+PR, NC and PD, respectively. Main toxicities were leukopenia (WHO grade III-IV in 36% of the patients) and alopecia. One patient died from myocardial infarction after an adriamycin cumulative dose of 480 mg/m2. No other treatment-related death occurred. L-FAM2 is an effective combination for advanced gastric carcinoma. Further studies based on the association of leucovorin and 5-fluorouracil in combination with other active drugs are warranted.

Adult↗
PubMed1991

Open stereotactic neurosurgery: 57 cases.

The two main neurosurgical tools are the operative microscope and stereotactic apparatus. The operative microscope is essential in cisternal or ventricular surgery and the stereotactic apparatus is essential in approaching intracerebral lesions. Both given their best performance when the one aids the other. Small convexity lesions are best approach with stereotactic aid, and excellent microsurgical intracerebral lesions can be debulked with the operative microscope. Malignant tumours pursue their inevitable course but slow growing tumours and angiomas may have long survival even with one subtotal removal. The major problem in removing slow-growing tumors is the difficulty in distinguishing tumour from normal brain, but the stereotactic guide is useful in delimitating tumour volume. The results in 57 cases are described.

Brain Neoplasms↗
PubMed1991

Differential control of in-phase and anti-phase coupling of rhythmic movements of ipsilateral hand and foot.

Rhythmic flexion-extensions of ipsilateral hand and foot are easily performed ("easy" association) when the two segments are moved in phase (isodirectionally), whereas great care and attention are required ("difficult" association) to move them in phase opposition. We searched for features distinguishing the two types of coupling by analyzing, on ten subjects: 1) the frequency limit in each association; and, 2) if coupling is modified by inertial or elastic loading of the hand. 1) Subjects were asked to oscillate hand and foot at various paced frequencies, in the easy or in the difficult association for one minute at least. In the easy coupling, the task was performed up to 2.0-2.5 Hz, the duration being thereafter shortened by muscular fatigue. In the difficult coupling when the frequency was increased above 0.7-1.7 Hz, the performance rapidly shortened, not because of fatigue but because of an inevitable reversal to the in-phase movement. The frequency-duration curve always followed a similar decay, although it covered different frequency ranges in the various subjects. 2) The effect of charging the hand with inertial or elastic loads was studied at the subject's preferred frequency, chosen when the hand was unloaded. Without loading, in the easy association the hand cycle slightly lagged the foot cycle while in the difficult one an almost perfect phase opposition was maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Aniracetam (Ro 13-5057) in the treatment of senile dementia of Alzheimer type (SDAT): results of a placebo controlled multicentre clinical study.

One hundred and nine elderly patients suffering from mild to moderate cognitive impairment fulfilling NINCDS-ADRDA criteria for probable dementia of the Alzheimer type were treated for 6 months with a new nootropic drug, aniracetam (Ro 13-5057) in a double-blind randomized study versus placebo. The two treatment groups were comparable at baseline for demographic and behaviourial parameters and symptomatology. Patients underwent clinical, behaviourial and psychometric evaluation every other month. The aniracetam group differed significantly from the placebo group by the end of the study and also showed a statistically significant improvement versus baseline in the psychobehavioural parameters, while in the placebo group a steady deterioration was observed. Tolerability to aniracetam was excellent.

Aged↗
PubMed1991

Fluorouracil, high-dose folinic acid, low-dose alpha-2b interferon and dipyridamole in the treatment of advanced colorectal cancer. A pilot study.

Twenty-six patients with advanced colorectal cancer were treated with a combination based on multimodal biochemical modulation of 5-fluorouracil by means of high dose folinic acid, low-dose alpha-2b interferon and dipyridamole. The overall response rate was 42% (95% confidence intervals = 23%. 61%) with four complete remissions (15%). The median duration of response was 9 months and the median survival for responders was 15 months (all patients = 12 months). Toxic side effects included oral mucositis (grade III-IV = 38%) and a generally mild flu-like syndrome. This regimen seems active and safe enough to be compared with the combination of fluorouracil and high-dose folinic acid.

Adult↗
PubMed1991

Growth hormone secretion in aging. Effect of pyridostigmine on growth hormone responsiveness to growth hormone-releasing hormone.

Recent studies in adults have shown that cholinergic enhancement by pyridostigmine (PD) has a stimulatory effect on growth hormone (GH) response to GH-releasing hormone (GHRH). PD probably reduces somatostatin release from the hypothalamus by increasing the central cholinergic tone. The aim of this study was to evaluate the effect of PD (120 mg orally) or placebo pretreatment on GH responsiveness to GHRH (1 micrograms/kg b.w. i.v.) or placebo in 10 normal elderly males (68-92 years). PD induced a significant increase in GH secretion (GH peak 7.3 +/- 1.8 micrograms/L, mean +/- SEM) over the basal value (0.9 +/- 0.2 micrograms/L; P less than 0.01) and enhanced GH response to GHRH (peak after GHRH: 17.0 +/- 3.8 micrograms/L; after PD plus GHRH: 42.6 +/- 12.2 micrograms/L; P less than 0.05). There was a significant difference in the secretory areas of GH among tests (P less than 0.05). The secretory area was greater after PD plus GHRH (2722 +/- 801 micrograms/L/120 min) than after GHRH (1185 +/- 206 micrograms/L 120 min; P less than 0.01). The effect of PD on GH secretion suggests that cholinergic mechanisms may be involved in GH control in normal aging. During the life-span cholinergic neurons and/or the somatostatin pathways could exert a differential effect on GH control.

Aged↗
PubMed1990

Effect of pulsatile luteinizing hormone-releasing hormone administration on pituitary-gonadal function in elderly man.

The effect of short-term pulsatile LHRH administration was studied in 8 healthy subjects ranging from 60 to 81 yr to see if the decrease of pituitary gonadal function could be in part due to changes in the discharge of LHRH from the hypothalamus. Gonadotropin and testosterone (T) secretion was evaluated two weeks before and during LHRH (122-160 ng/kg bw every 120 min sc) infusion. In addition, a bolus dosage of LHRH (50 mu iv) was given both at the beginning and at the end of pulsatile LHRH administration in order to test gonadotrophs sensitivity. A significant increase in gonadotropin levels from day 0 to day 4 was found, and was followed by a subsequent decrease from day 7 to day 14. A slight significant increase in T levels was observed during LHRH administration (p less than 0.01). LH pulses were identified in 5 out of 8 subjects on day 0. On day 14, all the exogenous LHRH pulses were followed by significant LH bursts. There was not a significant decrease in the pituitary LH responsiveness to LHRH test from day 0 to day 14. Our study seems to indicate that pituitary - gonadal unit in normal elderly men can be modulated by pulsatile administration of LHRH. A pulse frequency of LHRH which is probably similar to the physiological one, could induce a slight increase in T levels via qualitative changes in LH activity. We can assume that clinical changes in gonadal activity might also be connected to some disturbances in endogenous LHRH pulsar.

Aged↗
PubMed1990

Mitomycin-C, vinblastine, and lonidamine as salvage treatment of advanced breast cancer. A pilot study.

Thirty-two patients with advanced breast cancer were treated with mitomycin-C 10 mg/m2 IV and vinblastine 6 mg/m2 IV every 21 days in combination with lonidamine 450 mg/day P.O. and prednisone 15 mg/day P.O. given continuously. Among the 29 evaluable patients (all but three pretreated with an anthracycline-based regimen), one complete remission (CR) and six partial remissions (PR) (response rate, 24%) were seen. The median duration of response was 14 months (range, 4-30 months). Median survival for responders was 18 months (range, 4-30 months). Hematological toxicity was uncommon; the main lonidamine-related side effects were myalgia, abdominal cramps, and reversible deafness; these side effects were severe in two, one, and one patients, respectively. The regimen seems to have a reasonable degree of activity and toxicity in advanced, refractory breast cancer. The role of lonidamine in the treatment of this disease warrants further evaluation.

Adult↗
PubMed1989

Changes in EEG spindle activity induced by ibotenic acid lesions of medialis dorsalis thalamic nuclei in the cat.

The injection of an excitotoxin into medialis dorsalis thalamic nuclei (MD) elicited a short-term increase followed by a depression on EEG spindle waves in chronically implanted cats. This biphasic action provides further evidence to the hypothesis that MD plays a crucial role in transferring and inducing spindling on frontal cortex. In addition, retrograde horseradish peroxidase transport from previously lesioned MD labeled subcortical structures such as basal forebrain, anterior hypothalamus, reticular thalamic nucleus, ventral tegmental area, and locus coeruleus.

Animals↗
PubMed1989

Brain stem expanding lesions: stereotactic diagnosis and therapeutical approach.

In most cases of brain stem expansive lesion a surgical approach is possible, but in each patient it must be evaluated if the surgical risk is proportional to the therapeutic result. Sometime surgery is limited to a biopsy sample, particularly in malignant lesions. We started stereotactic serial biopsy sampling in all CT or NMR intraaxial brain stem expansive lesions as a preliminary diagnostic procedure. The aim is to look for benign well delimited lesions that we consider for surgical removal or to drain haematomas and abscesses. 35 patients with brain stem expansive lesions were submitted to 47 surgical procedures: 35 stereotactic biopsies (one each patient) and, among them, 12 were major surgical procedures (with craniotomy) for microsurgical removal of the expansive lesions. 15 patients were in paediatric age. Suboccipital transcerebellar approach was performed in 25 mesencephalic, pontine, bulbar expansive lesions and frontal approach was limited to 10 thalamo-mesencephalic lesions. There was no mortality. Two patients were stereotactically drained and definitively cured.

Adolescent↗
PubMed1989

Cyclophosphamide, epirubicin, high-dose folinic acid and 5-fluorouracil (super-FEC) as first-line chemotherapy for advanced breast cancer: preliminary results.

Forty patients with metastatic breast cancer were treated with a new combination regimen consisting of cyclophosphamide, epirubicin, high-dose folinic acid and 5-fluorouracil (super-FEC). A major objective response was observed in 32 patients (80%). Among these, 11 patients (27%) experienced a complete remission. The median duration of response was 10+ and 12+ months for CR and PR, respectively. The most common side-effect was oral mucositis (Grade III = nine patients; grade IV = two patients), while haematological toxicity was virtually absent. Considering the high-risk characteristics of the vast majority of the enrolled patients (75% had dominant visceral disease), these preliminary results suggest that super-FEC has a powerful activity in poor-prognosis metastatic breast cancer with an acceptable degree of toxicity.

Adult↗