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Biomedical subjects

M Benedetti

Publications and source records attributed to M Benedetti.

At least 55 records · Page 3Linked to original sources
PubMed1989

Combination antibiotic treatment of chemotherapy-induced neutropenia in non-leukemic patients.

The use of more aggressive chemotherapies in the treatment of patients with some tumors has caused a higher frequency of neutropenia and subsequent serious infections. To verify the role in these patients of a combination therapy of amikacin (300 mg/m2 i.v. every 12 hours) plus ceftazidime (2 g/m2 i.v. every 8 hours) administered as initial empiric treatment, followed in non-responsive cases by a second-line therapy with clindamycin (300 mg/m2 i.v. every 8 hours), we conducted a prospective study in 45 febrile episodes (temperature greater than or equal to 38.5 degrees C) in neutropenic patients (neutrophils less than or equal to 500/ml). The patients' median age was 58 (range, 19-80); 29 were women and 16 were men. The median performance status was 50 (range, 30-90), and 71% of the patients had progressive tumoral disease. Before antibiotic therapy the median duration of fever was 12 hours (range, 4-48 hours). The median granulocyte count was 350/ml (range, 100-500 cells/ml), and the median peak temperature was 38.8 degrees C (range, 38.5-41 degrees C). The median time for neutrophils to rise towards 1000/ml was 4 days (range, 2-12), and the median duration of therapy was 8 days (range, 3-12). Documented bacterial infections were present in 28 patients whereas 17 had clinically possible infections or fever of unknown origin. The infection sites in microbiologically documented infections were: septicemia (12), multiple sites (4), tonsillitis (4), urinary tract (4), pneumonia (2) and fistula (2). Complete response to first-line therapy was obtained in 36 out of 45 episodes (80%; 95% confidence limits from 65% to 90%). Five out of 8 cases responded to second-line therapy with clindamycin for and overall recovery rate of 91%. The amikacin-ceftazidime combination followed by clindamycin in non-responsive cases is effective, with moderate toxicity in non-leukemic febrile neutropenic patients.

Adult↗
PubMed1989

Behavioural and electroencephalographic effects of excitatory amino acid antagonists and sigma opiate/phencyclidine-like compounds in rats.

The present work was a comparative study of the electrocortical and behavioural effects of phencyclidine-like drugs and sigma-opiate drugs and of some excitatory amino acid antagonists. Phencyclidine-like drugs and sigma-opiate drugs elicited three dose-dependent electrocortical patterns: 1. Increase of periods of cortical desynchronization 2. Increase of the amplitude of fast (20-30 Hz) cortical waves; 3. Appearance of typical cortical complexes consisting of slow-wave (0.5-2 Hz) sharp-wave complexes. These effects were accompanied by excitatory motor symptoms, such as stereotyped movements of the neck and limbs. The NMDA competitive antagonist D,L-2-amino-5-phosphonovaleric acid (D,L-AP5), administered intracerebroventricularly (0.25-2 mumol), elicited phencyclidine-like stereotyped behaviour and cortical desynchronization, but failed to elicit/sigma typical cortical complexes. The non-selective amino acid antagonist cis-2,3 piperidine dicarboxilic acid (cis 2,3-PDA), administered intraperitoneally (3.3 mmol) failed to elicit both stereotyped behaviour and typical phencyclidine/sigma cortical complexes. The results strongly suggest the hypothesis that a reduction of excitatory amino acid neurotransmission, utilizing N-methyl-d-aspartate (NMDA)-preferring receptors, may be involved in the genesis of phencyclidine/sigma-induced stereotyped behaviour.

2-Amino-5-phosphonovalerate↗
PubMed1989

Pharmacology of calcium-induced long-term potentiation in rat hippocampal slices.

A transient increase (10 min) in extracellular calcium concentration (4 mM) causes a long-lasting (greater than 2 hr) enhancement of population spike responses evoked by radiatum fibers to CA1 pyramidal neurons in rat hippocampal slices. This phenomenon is similar to tetanic long-term potentiation (LTP), and is also related to memory processes. The influence of various drugs was investigated on calcium-induced LTP. The NMDA antagonist 2 amino-5-phosphonopentanoic acid (AP5; 100 microM) was able to prevent the calcium-induced LTP, while atropine sulphate (10 microM), propranolol hydrochloride (10 microM) and verapamil hydrochloride (100 microM) were ineffective. The results suggest an involvement of the NMDA receptor in the development of calcium-induced LTP.

2-Amino-5-phosphonovalerate↗
PubMed1989

Selective depression of synaptic transmission by tetanus toxin: a comparative study on hippocampal and neostriatal slices.

Tetanus toxin reduces the release of neurotransmitters in several brain areas. We have studied the effects of this toxin on the intrinsic and synaptic activity of CA1 hippocampal neurons and of neostriatal cells in the rat by utilizing intracellular and extracellular recordings from slice preparations. Tetanus toxin (10 micrograms/ml) applied by bath produced an increase of the field potentials evoked by the orthodromic stimulation of the CA1 region coupled with the disappearance of the inhibitory period following the first conditioning stimulus. Orthodromically and antidromically activated postsynaptic hyperpolarizing potentials were also decreased and spontaneous bursting activity was observed following the application of tetanus toxin. At this concentration the toxin did not alter excitability in neostriatal cells and in these neurons even 30-50 micrograms/ml of the toxin produced only a slight increase of excitability. Higher concentrations (100 micrograms/ml) of tetanus toxin reduced the excitatory synaptic transmission in the hippocampus as well as in the neostriatum. The toxin (10-100 micrograms/ml) did not alter membrane potential, input resistance or directly evoked firing in both these structures. We conclude that, although the toxin's mechanisms of action in the neostriatum are similar to those operating in the hippocampus (i.e. decrease of inhibitory and/or excitatory inputs), the local synaptic circuits produce differential electrophysiological effects in these two structures.

Action Potentials↗
PubMed1988

Comparative influence of calcium blocker and purinergic drugs on epileptiform bursting in rat hippocampal slices.

Caffeine (50 microM) increases the amplitude of the basal field potential (BFP) due to orthodromic stimulation of CA1 pyramidal neurons in rat hippocampal slices. This effect is absent if (1) the adenosine agonist L-phenyl-isopropyladenosine (L-PIA) (0.5 microM) is added to the perfusion with caffeine, and (2) low calcium (0.1 mM)-high magnesium (5mM) solutions are used. The calcium blocker verapamil (0.05-0.2 mM) does not modify the caffeine-induced effects. Higher concentrations of caffeine (0.2-0.5 mM) elicit the appearance of an epileptiform bursting, whose duration is inhibited at almost the 50% by 0.5 microM of L-PIA and unaffected by verapamil (0.2 mM) and nifedipine (0.05-0.10 mM). 5 microM of L-PIA, low calcium (0.1 mM)-high magnesium (5 mM) solution and verapamil (0.2 mM) are able to inhibit at almost the 50% the epileptiform bursting duration due to the potassium blocker 4-aminopyridine (4-AP). Nifedipine (0.05-0.1 mM) does not affect the 4-AP effects. L-PIA (0.5-2 microM) but not verapamil (0.2 mM) and nifedipine (0.1 mM) inhibits at almost the 50% the penicillin (1 mM) epileptiform bursting duration. The data indicate a different antagonistic influence of purinergic drugs and verapamil, on different models of epilepsy in rat hippocampal slices. In addition, the lack of antagonism between purinergic drugs and verapamil suggests different sites of action of the drugs.

Adenosine↗
PubMed1988

Depletion of catecholamines reveals inhibitory effects of bromocryptine and lysuride on neostriatal neurones recorded intracellularly in vitro.

Intracellular recordings were obtained from slices of striata from naive and catecholamine-depleted rats. Depletion of catecholamines was obtained by: (i) acute treatment with reserpine (5 mg/kg i.p., 12 hr before sacrifice); (ii) chronic treatment with reserpine (2-3 mg/kg i.p. die for 5 days) and (iii) electrolytic lesion of the homolateral substantia nigra. The ergots, bromocryptine and lysuride (0.1-1 microM), D2 dopamine agonists, did not have detectable effects on the striatal cells of naive animals, but produced a dose-dependent decrease of the excitatory synaptic potentials evoked intrastriatally and recorded from slices depleted of DA; this inhibitory effect was not coupled to changes in membrane potential and input resistance. Lysuride was more potent than bromocryptine. In 78% of the cells recorded, these ergots also produced a decrease in the intrinsic membrane excitability. The inhibitory effects of the ergots were antagonized by the D2 antagonist sulpiride (1 microM), but not by the D1 antagonist SCH 23390 (1 microM). It is concluded that treatments causing depletion of catecholamines, by up-regulating striatal D2 receptors, reveal inhibitory effects of bromocryptine and lysuride.

Animals↗
PubMed1988

Anticonvulsant activity of carbamazepine and N6-L-phenylisopropyladenosine in rabbits. Relationship to adenosine receptors in central nervous system.

The present work deals with an EEG and behavioral study on the effects of carbamazepine (CBZ) and N6-L-phenylisopropyladenosine (L-PIA) against the convulsions due to caffeine and pentylenetetrazole (PTZ) in rabbits. Pretreatment with L-PIA (1, 3 and 4 mg/kg) caused a dose-related inhibition of the motor convulsions and the EEG "grand mal" ictal seizure induced by caffeine (75 mg/kg IV). On the contrary, L-PIA given at the high dose of 5 mg/kg IV partially inhibited the EEG and motor seizures elicited by PTZ (20 mg/kg IV). CBZ completely antagonized the EEG and motor convulsions induced by caffeine, while exerted only a protective action towards the EEG and motor convulsions due to PTZ. The administration of an ineffective dose of CBZ (5 mg/kg IV) was able to enhance the protective action of L-PIA towards caffeine-induced convulsions. This synergistic action between CBZ and L-PIA is also present towards the spike-and-wave complexes elicited by PTZ (10 mg/kg). These results confirm that the purinergic system plays an important role in the regulation of the CNS excitability. They suggest therefore, that the anticonvulsant properties of CBZ may be at least partially explained by an influence of this drug on the purinergic system.

Adenosine↗
PubMed1988

Endogenous dopamine and dopaminergic agonists modulate synaptic excitation in neostriatum: intracellular studies from naive and catecholamine-depleted rats.

Intracellular recordings from slices of rat neostriatum were utilized to study the effects of endogenous dopamine and of exogenous dopaminergic agonists on the excitatory synaptic potentials evoked by the local stimulation of the slice. D-Amphetamine (0.1-5 microM), as well as dopamine, produced a dose-dependent decrease of the excitatory synaptic potentials. This effect was blocked by membrane hyperpolarization. The blockade of potassium channels by intracellular cesium or by extracellular 4-aminopyridine (0.5-1 mM) did not block the voltage-dependent effect of dopamine. The effects of D-amphetamine were antagonized by (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7 -ol (SCH 23390) (0.1-1 microM), an antagonist for D1 dopaminergic receptors, but not by sulpiride (0.1-1 microM), an antagonist for D2 receptors. Pretreatment of the animals with alpha-methyl-p-tyrosine (200 mg/kg) or with reserpine (5 mg/kg) blocked the amphetamine-induced effect on the synaptic potentials. In reserpinized animals, the hyperpolarization of the membrane potential did not block the dopamine-induced decrease of the synaptic excitation. After reserpine pretreatment bromocryptine and lysuride, D2 agonists which in control conditions were ineffective, also mimicked the effects of dopamine. In reserpinized rats, the inhibitory effects of the dopaminergic agonists were antagonized by sulpiride, but not by SCH 23390. We conclude that in naive animals endogenous dopamine mimics the voltage-dependent reduction of synaptic excitation produced by D1 activation, while in catecholamine-depleted rats dopamine lacks its voltage-dependent effect and interacts with "supersensitive" D2 receptors.

4-Aminopyridine↗
PubMed1988

Safety profile of ofloxacin in elderly patients.

In clinical trials co-ordinated in Italy by Glaxo S.p.A. from May 1984 to February 1988, 553 patients aged over 65 years (376 men and 177 women), suffering from different infectious diseases (mostly LRTI and UTI), were treated with ofloxacin, a new broad-spectrum quinolone. Of the patients studied, 75% presented one or more concurrent diseases and 72.3% were receiving one or more concurrent therapies. Daily dose of the drug varied, in most cases, between 400 and 800 mg in two oral administrations. In all, 21 adverse events were recorded in 19 patients (3.44%): 13 gastrointestinal events (gastric pain, nausea, vomiting), 3 cutaneous events and 5 others. The severity of the events was judged as mild in 56.3% of the cases and moderate in 43.7%. The treatment was stopped because of adverse events in three patients (0.54%). Abnormal laboratory parameters, probably related to the drug, were observed in four patients. In conclusion, ofloxacin appears to be a very safe drug in the treatment of bacterial infections in elderly patients.

Aged↗
PubMed1987

Modulatory action of purinergic drugs on high potassium-induced epileptiform bursting in rat hippocampal slices.

Increase of the potassium concentration up to 8 mM in the superfused solution of rat hippocampal slices leads to the development of an epileptiform bursting. The derivative agonist L-phenyl isopropyl adenosine (L-PIA) (0.05-0.5 microM) is able to block the potassium induced epileptiform activity. The adenosine antagonist caffeine (100 microM) reverts the antiepileptic effect of L-PIA. Our data show a modulatory action of the purinergic transmission in a model of experimental in vitro epilepsy, and point out about a control of endogenous adenosine in the development of focal epileptiform activity. The relationships between the purinergic influence on the release of neurotransmitters, and the convulsant-anticonvulsant effects of the drugs are discussed.

Animals↗
PubMed1987

Use of ceftazidime in the treatment of otorhinolaryngoiatric bacterial infections.

Within the framework of an investigation into otorhinolaryngoiatric bacterial infections in Italy conducted in 1159 patients (607 with otitis media, 354 with pharyngo-tonsillitis and 198 with sinusitis), 124 ceftazidime-treated subjects (92 with otitis media, 22 with pharyngo-tonsillitis and 10 with sinusitis) were observed. The authors report the examination of a number of microbial isolates obtained in the various forms of otorhinolaryngoiatric bacterial infection. Gram-negative organisms were found as causative agents in such diseases, particularly in otitis media. Bacterial resistance to ceftazidime was assessed in all 1159 cases and proved relatively infrequent (3.6%) and markedly less than the detected resistance to other antibiotics (10.7% resistance to cefotaxime, 35% resistance to ampicillin, 43% resistance to penicillin). Ceftazidime, used mainly in otitis media, showed very substantial clinical efficacy with positive results in as many as 97% of cases treated, which is particularly significant, if one considers that roughly 64% of the infections were caused by "difficult" gram-negative bacteria (49% by Pseudomonas).

Adolescent↗
PubMed1987

Early indicators of nephrotoxicity: comparison of two antibiotics.

The aim of the study was the evaluation of the clinical efficacy and the kidney tolerance of ceftazidime in comparison with netilmicin in pediatric patients. Forty subjects, ranging from six months to ten years of age were randomly allocated in two groups and treated either with ceftazidime (80-100 mg/kg/day) or netilmicin (6 mg/kg/day). A control group of twenty subjects was selected in order to establish the normal values of beta 2-microglobulin and urinary enzymes excretion. beta 2-microglobulin, enzymuria, cylindruria and urinary osmolability were estimated, as well as hematological parameters. Ceftazidime was as efficacious as netilmicin in the clinical outcome and in addition it did not cause any pathological change in early markers of tubular damage.

Ceftazidime↗
PubMed1987

Efficacy and tolerance of ceftazidime in the treatment of post-operative respiratory tract infections.

Ceftazidime proved particularly effective in the treatment of acute respiratory tract infections arising in the immediate post-operative period, affording complete clinical cures in 88.8% of cases and a substantial improvement in the pathological picture in the other 11.2% of cases treated. The authors also draw attention to the excellent tolerance of the antibiotic, as evaluated on the basis of liver and kidney function and blood chemistry parameters and the total absence of adverse reactions.

Adult↗
PubMed1987

Ceftazidime in antibiotic prophylaxis for emergency cesarean section: a randomized prospective study.

The efficacy of two randomized antibiotic prophylactic schedules with ceftazidime (group A: single preoperative 2 g intramuscular dose; group B: 3 perioperative 1 g intramuscular doses every 6 h) was evaluated in 200 pregnant women undergoing cesarean section. Postoperative complications were observed in 9 cases (4 in group A and 5 in group B; p = NS). Analysis of possible risk factors revealed 1) a relationship between postoperative morbidity and overweight (body mass index above 30) in group A only; 2) a possible contributory effect of duration of labor (more than 6 h) in group A; and 3) a possible effect of duration of rupture of the membranes (more than 6 h) in group B only. The results obtained lead to the conclusion that single-dose prophylaxis with ceftazidime is as effective as short-term 3-dose ceftazidime prophylaxis in preventing post-cesarean complications.

Adult↗
PubMed1987

Combination of amikacin and ceftazidime as empiric treatment of febrile leukopenic patients affected by solid tumors.

A combination of amikacin and ceftazidime was used as initial empiric therapy for the treatment of 25 evaluable febrile episodes (temperature greater than or equal to 38.5 degrees C) in leukopenic adult patients (wbc less than or equal to 1,000/mm3) with solid tumors, characterized by poor prognosis because of low performance status (median Karnofsky score: 50) and progressive disease (76% of cases). Nineteen (76%) of the 25 episodes responded to the initial empiric antibiotic combination. In the microbiologically documented infections, there was no significant difference in the response rate between bacteremia (67%) and localized infections (81%). The response in localized infections caused by gram-negative organisms (81%) was similar to that obtained in gram-positive organisms (82%), whereas gram-positive bacteremia responded better than gram-negative (100 vs 50%). No serious side effects were observed. Reversible nephrotoxicity occurred in 12% and hypokalemia in 20% of the patients treated. This antibiotic combination is a safe and efficacious empiric therapy for infections in leukopenic patients with solid neoplasia.

Adult↗
PubMed1987

[Pseudoaneurysm of a branch of the internal mammary artery in a case operated on for aortic coarctation].

False aneurysm of the internal mammary artery (IMA) is a rare complication of closure of median sternotomy by peristernal wiring. In this report a case of a false aneurysm of a branch of the internal mammary artery following a surgical repair of a complex cardiac anomaly in a patient with a previously dilated mammary artery system for pre-existing coarctation of the aorta is described. In our opinion a special attention has to be given to the course of the IMA and its collaterals whenever a median sternotomy is required to treat an aortic coarctation or its associated diseases, considering the possibility of ligation of vessels at risk of being damaged by the sutures used for closure of the sternal and rectus sheath incisions.

Adult↗