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Biomedical subjects

C Grassi

Publications and source records attributed to C Grassi.

At least 37 records · Page 2Linked to original sources

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AIDS-Related Opportunistic Infections

Possible modulation of auditory middle latency responses by nitric oxide in the inferior colliculus of anaesthetized rats.

Nitric oxide (NO) is a short-lived radical species endowed with intercellular signalling functions in the mammalian brain. In the present study we have investigated the effects of focal injection into one inferior colliculus of N omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, on the acoustic middle latency responses (MLRs) evoked by click stimuli and recorded from the auditory cortex in anaesthetized rats. Microinfusion of L-NAME (1.0 mM) did not alter the latency of MLRs nor did it affect the evoked brain stem responses (ABRs). By contrast, L-NAME reduced P1a-N1 amplitude of MLRs by 51.7 +/- 6.6% (mean +/- SEM; n = 5) and almost complete recovery to background amplitude was obtained 15-25 min after treatment. The less active isomer, D-NAME (1.0 mM; n = 5), failed to produce consistent effects on the evoked MLRs. A higher concentration of L-NAME (5.0 mM; n = 5) yielded a 69.0 +/- 13.3% inhibition whereas maximum inhibition produced by 0.5 mM (n = 3) L-NAME was approximately equal to 10% of control value. The inhibitory effect typically evoked by 1.0 mM L-NAME was prevented by treating rats with L-arginine (5.0 mM; n = 5), the endogenous precursor of NO synthesis. Reduction of MLR amplitude was also obtained in rats receiving intracollicular injection of dizocilpine (MK801; 1.0 microM) and LY274614 (1.0 mM), two selective N-methyl-D-aspartate (NMDA) receptor antagonists. In conclusion, the present data support a role for intracollicular NO in the processing and transmission of the acoustic input to the auditory cortex in the rat.

Acoustic Stimulation

A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy.

The natural course of idiopathic membranous nephropathy is variable, with some patients slowly progressing to renal failure while others maintain normal renal function over the entire time. Whether to treat this disease or not is controversial due to the lack of controlled data about the long-term effects of treatment. We updated at 10 years the results of a controlled trial in which 81 patients with idiopathic membraneous nephropathy and nephrotic syndrome were randomly assigned to receive symptomatic therapy (39 patients) or a treatment of six months with methylprednisolone and chlorambucil (42 patients). The probability of surviving without developing end-stage renal disease at 10 years was 92% in patients given methylprednisolone and chlorambucil versus 60% in controls (P = 0.0038). The slope of the reciprocal of plasma creatinine up to 10 years was significantly better in treated patients than in controls (P = 0.035). The probability of having a complete or partial remission of the nephrotic syndrome was significantly higher in treated patients (P = 0.000). Patients assigned to therapy spent significantly longer time without nephrotic syndrome than untreated patients (P = 0.0001). Four patients had to stop treatment because of reversible side-effects. In the long-term one treated patient developed diabetes and another one became obese. In conclusion, a six-month therapy with methylprednisolone and chlorambucil increases the probability of remission of proteinuria and protects from renal function deterioration even in the long-term. This treatment may avoid dialysis or death within 10 years to about one third of nephrotic patients with membranous nephropathy.

Adult

Ceftazidime monotherapy vs. ceftriaxone/tobramycin for serious hospital-acquired gram-negative infections. Antibiotic Study Group.

We compared ceftazidime monotherapy with ceftriaxone/tobramycin in a prospective, randomized clinical trial that included 580 patients with serious hospital-acquired infections. One-half of the patients had an underlying disease with a rapidly or ultimately fatal prognosis; 40% were nursed in intensive care units. Clinical response among patients with pneumonia (73% in the ceftazidime group vs. 65% in the ceftriaxone/tobramycin group), septicemia (73% vs. 59%), and complicated urinary tract infections (80% vs. 76%) showed that there were no significant differences in efficacy between the two regimens. Pseudomonas aeruginosa was the most prevalent pathogen and was effectively eradicated by both treatments. The odds of bacteriologic cure with either study regimen were equal. Mortality was similar in both treatment groups. Ceftazidime monotherapy was not associated with a higher incidence of development of resistance or superinfection. Both regimens were well tolerated; no patients receiving ceftazidime evidenced nephrotoxicity, compared with nine who received the combination. We conclude that ceftazidime may be used as monotherapy in the empirical treatment of patients with serious nosocomial infections.

Adult

Once-daily tobramycin therapy in lower respiratory tract infections.

In a multicenter Italian study of 104 adult patients with severe bacterial lower respiratory tract infections, the safety and efficacy of a regimen of high dose, once-daily tobramycin alone or in combination with antipseudomonas betalactams was assessed. The overall bacteriological response was an elimination of the original pathogen in 70% of the patients while the overall clinical response mirrored the bacteriological results with a successful clinical outcome in 78% of patients. Adverse experiences were, in general, few and mild without oto- or nephrotoxicity. The once-daily, high dose regimen of tobramycin proved to be a safe and efficacious therapy for severe lower respiratory tract infections in adult patients.

Adult

Treatment of community-acquired pneumonia: a randomized comparison of sparfloxacin, amoxycillin-clavulanic acid and erythromycin.

The treatment of community-acquired pneumonia is empirical in most cases and must cover a wide range of potential pathogens, such as Streptococcus pneumoniae, including penicillin-resistant strains, Haemophilus influenzae and intracellular microorganisms. The objective of this double-blind, randomized, parallel group study was to compare the efficacy and safety of sparfloxacin (400 mg loading dose, followed by 200 mg o.d.) with that of oral amoxycillin-clavulanic acid (500/125 mg t.i.d.) or oral erythromycin (1 g b.i.d.), during 7-14 days in 808 patients with confirmed community-acquired pneumonia. The overall success rates for sparfloxacin (87%), amoxycillin-clavulanic acid (80%) and erythromycin (85%) were similar in evaluable patients, and the equivalence hypothesis used for the statistical analysis showed at least an equivalent efficacy for the three antibiotics tested. The analysis of microbiologically documented infections (40% of the patients) showed that overall success rates were similar for S. pneumoniae and H. influenzae infections. Treatment withdrawal was necessary in 3.5, 2.5 and 7.7% of the patients treated with sparfloxacin, amoxycillin-clavulanic acid and erythromycin, respectively. This study indicates that sparfloxacin was at least as effective as amoxycillin-clavulanic acid or erythromycin in the treatment of mild-to-moderate community-acquired pneumonia and that the adverse effects were similar in the three groups.

Adolescent

New drugs for tuberculosis.

Since the late 1960s, tuberculosis has been successfully cured with antibiotics. With the introduction of rifampin, "short course" regimens using isoniazid and rifampin together with either streptomycin, ethambutol or pyrazinamide, for 6-9 months, have been successfully adopted. The spread of drug resistant M. tuberculosis strains in large urban areas has made this armamentarium of drugs insufficient, calling for the development of new drugs. Among rifamycin derivatives, rifabutin is more active than rifampin in vitro and in experimental animals, and allows sputum conversion rats of 95-100%. It is effective in treating multidrug-resistant tuberculosis. Rifapentine is more active than rifampin in vitro and has a longer half-life, but it is not active against rifampin-resistant strains. Fluoroquinolones concentrate within macrophages, are effective against M. tuberculosis and act synergistically with rifampin and isoniazid. Ofloxacin, ciprofloxacin, sparfloxacin and lomefloxacin have been evaluated as antimycobacterial agents, and no cross-resistance with major antituberculous drugs has been found. Several other drugs, including new inhibitors of beta-lactamase and new beta-lactamase-resistant antibiotics, the aminoglycoside antibiotic, paromomycin, and the new nitroimidazole, 2-ethyl-5-intro-2.3-dihydro imidazo-oxazole, have been found to be active in vitro against M. tuberculosis.

Animals

Inhibition of low- and high-threshold Ca2+ channels of human neuroblastoma IMR32 cells by Lambert-Eaton myasthenic syndrome (LEMS) IgGs.

IgGs from two LEMS patients applied to human neuroblastoma IMR32 cells reduced the density of low- (LVA; T) and high-threshold (HVA; L and N) Ba2+ currents by different percentages: 36% (LVA) and 56% (HVA) for one and 48% and 45% for the other. A pharmacological assay of IgGs action based on the block of L-type channel by nifedipine and on the delayed activation of N-type channel by noradrenaline, indicated a preferential inhibition of the N-type current in IMR32 cells (55% and 47% for the two patients). The L-type current, contributing to approximately one-third of the total, was also depressed by LEMS IgGs but to a minor degree (49% and 30%). Except for an increase of single N-type channel inactivation, LEMS antibodies preserved the elementary properties of single HVA channels, suggesting that the macroscopic current reduction after IgGs treatment is likely due to a decrease in the number of active HVA Ca2+ channels.

Calcium Channel Blockers

Influence of aging on some specific and nonspecific mechanisms of the host defense system in 146 healthy subjects.

The influence of aging on some parameters of systemic host defense mechanisms, i.e. white cell counts, lymphocyte subpopulations, delayed-type hypersensitivity (DTH), polymorphonuclear and mononuclear leukocyte functions, was evaluated. One hundred and forty-six healthy volunteers (60 men and 86 women), aged 25-100 years, were enrolled. None of the subjects had taken any drug in the month before the study. Subjects were divided into three age groups: 25-45, 46-65 and 66-100 years. Groups were comparable in size, and sex distribution was similar throughout all age groups. Elderly people were 51 healthy volunteers between the ages of 66 and 100 years (mean age 79.2). Younger people were 41 subjects between the ages of 46 and 65 years (mean age 54.3) and 53 between the ages of 25 and 45 years (mean age 32.7). As for the comparison between sexes, no significant differences in the values of the studied parameters were found between males and females (p > 0.05). Only quantitative DTH data, i.e. the number of antigens producing positive reactions and the score (sum of positive reaction diameters), were significantly (p < 0.05) reduced in responsive females when compared to males. Aging did not affect white cell counts, lymphocyte subsets and many phagocytic functions, i.e. phagocytosis frequency and index, nitroblue tetrazolium reduction, superoxide production, microbicidal activity against bacteria and yeasts. A significant decrease (p < 0.05) in the chemotactic response to serum-derived chemotactic factors was observed in aged people in comparison to younger subjects. Anergy was more frequent in older (about 29%) than in younger (5-9.4%) healthy volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Non specific immunity in aged healthy subjects and in patients with chronic bronchitis.

We investigated the effects of aging on some functional activities (chemotaxis, phagocytosis, nitroblue tetrazolium reduction and candidacidal activity) of peripheral polymorphonuclear and mononuclear phagocytes in 96 healthy subjects and 89 patients with chronic bronchitis, aged 40 to 100 years. The subjects were divided according to age into younger (40-65 years) and older (66-100 years) individuals. No subject was taking any drug known to affect phagocytic functions. A few abnormalities in PMN and monocyte functions were observed in aged healthy subjects, in comparison to the younger ones; in fact, only the chemotactic response to complement-derived chemotactic factors was significantly impaired in elderly healthy individuals. On the contrary, multiple alterations of phagocyte activities, i.e., chemotaxis, phagocytosis, and candidacidal activity were observed in aged subjects with chronic bronchitis, compared to healthy adults. However, the results obtained in older and younger patients with chronic bronchitis were superimposable. The present data suggest that the decline in functional activities of phagocytes in the aged could depend on the effect of the underlying chronic bronchitis on the cellular components of the non-specific host defense system, rather than a direct effect of the aging process.

Adult

Cefepime: overview of activity in vitro and in vivo.

Cefepime is a novel methoxyimino-aminothiazolyl cephalosporin with a quaternized N-methyl-pyrrolidine moiety at the 3' position conferring zwitterionic properties. Because of this the molecule penetrates the outer cell membrane of Gram-negative bacteria rapidly. In addition it is resistant to degradation by several plasmid and chromosomally-mediated beta-lactamases, for which it also shows very low affinity and no inducing capacity. It has good affinity for PBPs 2 and 3 of Escherichia coli and for PBP 3 of Pseudomonas aeruginosa. Its broad-spectrum of activity includes Gram-positive and Gram-negative pathogens. It is more active than cefotaxime or ceftazidime, against Enterobacteriaceae. The MIC90 for P. aeruginosa is higher than that of ceftazidime, but lower than those of cefpirome, cefoperazone and latamoxef. Other Gram-negative organisms, Haemophilus influenzae, Neiserria meningitidis, Neiserria gonorrhoeae, Moraxella catarrhalis are highly susceptible to cefepime. Among Gram-positive species methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci, whether beta-lactamase producers or not, Streptococcus pneumoniae and Streptococcus pyogenes are susceptible. Cefepime is active against cefotaxime- and/or ceftazidime-resistant Enterobacteriaceae. Only strains of P. aeruginosa producing large amounts of beta-lactamase may be resistant to both ceftazidime and cefepime. In experimental infections such as meningitis, induced with various bacterial species in neonatal rats and chronic staphylococcal osteomyelitis in rabbits, cefepime has shown good efficacy.

Animals

Effect of sympathetic nervous system activation on the tonic vibration reflex in rabbit jaw closing muscles.

1. In precollicular decerebrate rabbits we investigated the effect of sympathetic stimulation, at frequencies within the physiological range, on the tonic vibration reflex (TVR) elicited in jaw closing muscles by small amplitude vibrations applied to the mandible (15-50 microns, 150-180 Hz). The EMG activity was recorded bilaterally from masseter muscle and the force developed by the reflex was measured through an isometric transducer connected with the mandibular symphysis. 2. Unilateral stimulation of the peripheral stump of the cervical sympathetic by the TVR, and a marked decrease or disappearance of the ipsilateral EMG activity. No significant changes were detected in the EMG contralateral to the stimulated nerve. Bilateral CSN stimulation reduced by 60-90% the force reflexly produced by the jaw closing muscles and strongly decreased or suppressed EMG activity on both sides. This effect was often preceded by a transient TVR enhancement, very variable in amplitude and duration, which was concomitant with the modest increase in pulmonary ventilation induced by the sympathetic stimulation. 3. During bilateral CSN stimulation, an increase in the vibration amplitude by a factor of 1.5-2.5 was sufficient to restore the TVR reduced by sympathetic stimulation. 4. The depressant action exerted by sympathetic activation on the TVR is mediated by alpha-adrenergic receptors, since it was almost completely abolished by the I.V. administration of either phentolamine or prazosin, this last drug being a selective antagonist of alpha 1-adrenoceptors. The sympathetically induced decrease in the TVR was not mimicked by manoeuvres producing a large and sudden reduction or abolition of the blood flow to jaw muscles, such as unilateral or bilateral occlusion of the common carotid artery. 5. The effect of sympathetic stimulation was not significantly modified after denervation of the inferior dental arch and/or anaesthesia of the temporomandibular joint, i.e. after having reduced the afferent input from those receptors, potentially affected by CSN stimulation, which can elicit either a jaw opening reflex or a decrease in the activity of the jaw elevator muscle motoneurons. 6. These data suggest that, when the sympathetic nervous system is activated under physiological conditions, there is a marked depression of the stretch reflex which is independent of vasomotor changes and is probably due to a decrease in sensitivity of muscle spindle afferents.

Animals

Magnetic resonance imaging in cervical spinal cord compression.

In patients with cervical spondylotic myelopathy MRI sometimes shows increased signal intensity zones on the T2-weighted images. It has been suggested that these findings carry prognostic significance. We studied 56 subjects with cervical spinal cord compression. Twelve patients showed an increased signal intensity (21.4%) and a prevalence of narrowing of the AP-diameter (62% vs 24%). Furthermore, in this group, there was evidence of a longer mean duration of the symptoms and, in most of the patients, of more serious clinical conditions. The importance of these predisposing factors remains, however, to be clarified since they are also present in some patients without the increased signal intensity.

Adult

Modulation of the jaw jerk reflex by the sympathetic nervous system.

The effect of sympathetic stimulation on the jaw jerk reflex has been studied in precollicular decerebrate rabbits. This reflex was elicited by a downward mandibular movement applied to the lower jaw through a servo controlled puller. Unilateral stimulation of the cervical sympathetic nerve at 10/s consistently induced a decrease in the JJR, i.e. a marked reduction of the EMG activity in the ipsilateral masseter muscle, accompanied by a 30-40% decrease in the reflexly developed force. In these trials EMG of the contralateral muscle, recorded as control, was not significantly affected. Bilateral stimulation of cervical sympathetic nerve strongly reduced or suppressed the EMG activity in both sides and produced a parallel decrease in the developed force which reached values ranging from 12.5% to 37.0% of controls (with an average of 28.9% +/- 8.9, S.D.). The effect of sympathetic stimulation was also tested on the contraction of the masseter muscle elicited by direct electrical stimulation. Sympathetic activation induced a modest increase in both amplitude and duration of muscle twitch, thus showing that the reduction in the reflex response can not be attributed to an action exerted by the adrenergic mediator on the muscular contraction. All these effects were almost completely abolished by the blockade of alpha-adrenergic receptors. They were proved not to be secondary to the sympathetically-induced vasomotor changes. Therefore the marked JJR reduction produced by activation of the sympathetic nervous system is suggested to be due to the sympathetically-induced decrease in neuromuscular spindle sensitivity to muscle length changes, previously reported.

Adrenergic alpha-Antagonists

Bioavailability of isoniazid, rifampicin and pyrazinamide (in free combination or fixed-triple formulation) in intermittent antituberculous chemotherapy.

A study was carried out in six human volunteers, to assess the blood kinetics of isoniazid, rifampicin and pyrazinamide, administered in a fixed-triple combination intended for use in intermittent chemotherapy of tuberculosis. The formulation employed contained 125 mg of isoniazid (H), 100 mg of rifampicin (R) and 375 mg of pyrazinamide (Z) per tablet; six tablets were administered to every subject, giving a total dosage of 750 mg of isoniazid, 600 mg of rifampicin and 2,250 mg of pyrazinamide. In each subject, the same dose of each drug was administered individually in separate sessions and the results compared. The results indicated that, at the level of dose of the intermittent tablet, no negative interactions between the drugs were observed.

Adult