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Biomedical subjects

L Munari

Publications and source records attributed to L Munari.

At least 19 recordsLinked to original sources
PubMed2004

Therapy with glatiramer acetate for multiple sclerosis.

BACKGROUND: Some clinical data have shown that glatiramer acetate (Copaxone), a synthetic amino acid polymer empirically found to suppress experimental allergic encephalomyelitis (EAE), an animal model of MS, might help improve the outcome of patients with multiple sclerosis (MS). OBJECTIVES: We performed a Cochrane review of all randomised, placebo-controlled trials of glatiramer acetate in MS, whatever the disease course. SEARCH STRATEGY: We searched the Cochrane MS Group trials register (June 2003), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2003), MEDLINE (PubMed) (January 1966 to June 2003), EMBASE (January 1988 to June 2003) and hand searching of symposia reports (1990-2002) from the neurological Associations and MS Societies in both Europe and America. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing glatiramer acetate and placebo in patients with definite MS, whatever the administration schedule and disease course, were eligible for this review. DATA COLLECTION AND ANALYSIS: Both patients with relapsing-remitting (RR) and chronic progressive (CP) MS were analysed. Study protocols were comparable across trials as to patient entry criteria and outcome definition. No major flaws were found in methodological quality. However, efficacy of blinding should be balanced against well-known side effects, including injection-site reactions in glatiramer acetate-treated patients. MAIN RESULTS: A total of 646 patients contributed to this review, as it is summarised in Table 01. Glatiramer acetate did not show any significant effect on disease progression, measured as a sustained worsening in the Expanded Disability Status Scale (EDSS). On the other hand, a slight decrease in the mean EDSS score, driven by a major study, should be considered in the light of the limited validity of this outcome measure. No benefit was shown in CP MS patients (progression at two years: RR=0.69, 95% CI [0.33 to 1.46]). The frequency of reported adverse events does not support any major toxicity associated with glatiramer acetate administration. The most common systemic adverse event was a transient and self-limiting patterned reaction of flushing, chest tightness, sweating, palpitations, anxiety (relative risk = 3.40 (95% CI [2.22 to 5.21], p <0.00001]). Local injection-site reactions were observed in up to a half of patients treated with glatiramer acetate, thus making a blind assessment of outcomes questionable. REVIEWER'S CONCLUSIONS: Glatiramer acetate did not show any beneficial effect on the main outcome measures in MS, i.e. disease progression, and it does not substantially affect the risk of clinical relapses. Therefore its routine use in clinical practice is not currently supported. More investigations are needed. Further research should also develop more reliable measures of patient disability over time and include quality of life among primary outcomes.

Glatiramer Acetate↗
PubMed2001

Interferon in relapsing-remitting multiple sclerosis.

BACKGROUND: Recombinant interferons have been shown to suppress both the clinical and magnetic resonance imaging (MRI) measures of disease activity in patients with relapsing remitting multiple sclerosis (RRMS). OBJECTIVES: We performed a Cochrane review of all randomised, placebo-controlled trials of recombinant interferons in RRMS. SEARCH STRATEGY: Of 208 articles identified by a predefined search strategy, seven of these, reporting randomised trials, met all the selection criteria and form the subject of this review. SELECTION CRITERIA: The trials selected were double-blind, placebo-controlled, randomised trials of RRMS patients who were treated with recombinant interferon, given by the subcutaneous or the intramuscular route. DATA COLLECTION AND ANALYSIS: The quality of the trials was variable, with substantial methodological inadequacies in allocation concealment, high proportion and incomplete description of dropouts and failure to adhere to the principles of intention to treat analysis. The baseline characteristics were largely comparable between treatment and placebo groups. Because of prominent treatment-associated side effects, which could be easily identified by patients, these trials could be considered as single blind rather than double-blind. MAIN RESULTS: Although 1215 patients were included in this review, only 919 (76%) contributed to the results concerning exacerbations and progression of the disease at two years. Specifically interferon significantly reduced the occurrence of exacerbations (RR =0.80, 95% CI [0.73,0.88], p<0.001) and progression of the disease (RR =0.69, 95% CI [0.55,0.87], p= 0.002) two years after randomisation. However, the correct assignment of dropouts was essential to the demonstration of efficacy, most conspicuously concerning the effect of the drug on disease progression. If interferon-treated patients who dropped out were deemed to have progressed (worst case scenario) the significance of these effects was lost (RR = 1.31, CI [0.60,2.89], p = 0.5). The evolution in magnetic resonance imaging (MRI) technology in the decade in which these trials were performed and different reporting of data among trials made it impossible to perform a quantitative analysis of the MRI results. Both clinical and laboratory side effects reported in the trials were more frequent in treated patients than in controls. No information was available regarding side effects and adverse events after two years of follow-up. The impact of interferon treatment (and its side effects) on the quality of life of patients was not reported in any trial included in this review. REVIEWER'S CONCLUSIONS: The efficacy of interferon on exacerbations and disease progression in patients with relapsing remitting MS was modest after one and two years of treatment. It was not possible to conduct a quantitative analysis beyond two years. Longer follow-up and more uniform reporting of clinical and MRI outcomes among these trials might have allowed for a more convincing conclusion.

Humans↗
PubMed1992

Ventricular ectopic activity in physically trained hypertensive subjects.

Exercise training is currently recommended in the management of mild hypertension, but the relationship between training and ventricular arrhythmias has never been investigated in hypertensive subjects. Forty hypertensive sportsmen were studied by means of 24-h ECG Holter monitoring and the results were compared with those obtained in 40 sedentary hypertensives, 40 normotensive sportsmen and 40 normotensive sedentary subjects. Among the hypertensive sportsmen 82.5% exhibited at least one ventricular extrasystole and 32.5% complex forms of ectopy, a prevalence higher than that observed in the sedentary hypertensives (50% and 17.5%; P = 0.002). In the normotensive sportsmen the prevalence of ventricular arrhythmias (62.5% and 22.5%) was lower than that in the hypertensive sportsmen, but the difference was not statistically significant. During a training session the prevalence of ventricular ectopy was similar in the two groups of trained individuals. Among the hypertensive sportsmen no correlation was found between the severity of ventricular arrhythmias and the degree of left ventricular hypertrophy and performance. The results of the present study suggest that exercise training may enhance left ventricular vulnerability in hypertensive subjects. Whether subjects who manifest complex ventricular arrhythmias should continue to train remains a matter for individual judgement.

Adolescent↗
PubMed1992

[Sequential nimodipine-reduced glutathione treatment in alcoholic abstinence syndrome. Preliminary experience].

Alcohol abstinence syndrome (AAS) occurs in alcohol dependent patients a few hours after ceasing to drink, first in the form of gastrointestinal and dysvegetative signs, then with the involvement of neurological functions. The results obtained in 15 patients selected according to DSM III criteria, treated with nimodipine (calcium entry blocker) in the acute phase and with reduced glutathione in the subacute phase are presented. All patients who, during treatment, did not take other drugs, showed a definite, fast improvement in symptoms, especially in neurovegetative symptoms. Administration of nimodipine, which seems capable of reducing the catecholaminergic drive, was very well tolerated. Treatment with reduced glutathione is justified by the fact that the inadequate intake of alcohol is responsible for liver changes and, particularly, for a significant reduction in liver levels of glutathione, a condition that makes the cell more exposed to attack on the part of substances that activate lipoperoxidation processes. The results obtained seem to confirm a protective action on the part of reduced glutathione.

Acute Disease↗
PubMed1991

Natural history and postsurgical outcome of syringomyelia.

The surgical treatment of syringomyelia is still debatable and the result are often poor. Several surgical procedures, based on various proposed etiopathologies, have been developed but in many cases have proved completely ineffective. We have evaluated the follow-up of 69 syringomyelic patients, some operated on, some not, in the search for clues to the management of the disease. For this purpose we devised a rating system, which we describe. 31 patients underwent surgery while 38 received no treatment. We found that half of the patients deteriorated, whether they were operated on or not; only 1 in 5 improved and the rest remained stable. For surgical treatment to be successful, the disease must be in rapid evolution but without definite paraparesis.

Adult↗
PubMed1991

Local immunotherapy (beta-IFN) and systemic chemotherapy in primary glial tumors.

Dosage and schedules for the treatment of malignant glial tumors using IFN (interferon) are still uncertain and controversial. In this study we give the preliminary results of treatment in 28 patients with glioblastoma multiforme (GBM). 6 patients were treated with local injection of beta-IFN through an Ommaya reservoir; 4 patients with beta-IFN followed by systemic chemotherapy (Cisplatin + Etoposide), and 18 patients with chemotherapy only. Two end points were evaluated: 1) Whether or not the patients responded to treatment. 2) Length of Time to Tumor Progression (TTP) after surgery. We found that IFN alone was ineffective. Results were improved when local immunotherapy was associated with systemic chemotherapy. New drugs and investigation of possible pharmacological synergism are needed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Cisplatin and etoposide combination therapy for primary glial tumors: preliminary results.

In this preliminary trial we studied 29 patients with primary malignant glial tumors to investigate the effectiveness of cisplatin combined with etoposide on these tumors. Hyperfractionated radiation therapy was given in the course of chemotherapy. The time to tumor progression in these glioblastoma multiforme (GBM) patients encouraged us to continue this treatment in a phase III study.

Adult↗
PubMed1990

Neuron specific enolase (NSE) and thymidine kinase (TK) as markers in biological fluids of brain tumor patients.

We studied the activity of two enzymes NSE and TK in the biological fluids of 104 patients with nervous system diseases, who fell into 4 groups. 20 subjects out of 35 in the tumor group had glial tumors. We fixed a cut-off value of NSE and TK activity at the 95th percentile of the control group, both in serum and in CSF. The aim of our investigation was to assess the reliability of TK and NSE assays in separating brain tumors from other neurological diseases. In our patients, most of the TK activity above the cut-off value was found in the tumor group. Serum TK seems to be a useful marker for following up cerebral tumors after surgery, but NSE is less useful for this purpose.

Biomarkers, Tumor↗
PubMed1990

The impact of maternal serum on development of enolase activity in fetal rat brain cell culture.

The effect of gestational age on serum-mediated changes in enolase activity was tested in a fetal rat brain cell culture. After 6 days exposure to graded concentrations (10 and 20%) of nonpregnant female rat sera, enolase activity in brain cell cultures increased from 2.83 +/- 0.03 to 3.74 +/- 0.19 mumol/min/mg protein, P less than 0.01. By contrast, similar concentrations of 20-day maternal serum progressively decreased enzyme activity from 1.52 +/- 0.14 to 1.19 +/- 0.08 mumol/min/mg protein. The inhibitory effect was apparent at 14 days gestation and became progressively greater during late gestation to reach a maximum at 20 days. Combining equal concentrations of 20-day pregnant with either nonpregnant or adult male serum neutralized the inhibitory activity. When serum from 20-day pregnant rats was partitioned by a dialysis membrane with a 50,000 MW pore size, inhibitory activity could be similarly neutralized by male or nonpregnant female serum. When 20-day maternal serum was passed successively through filters with a greater than 300,000, 100,000, and 50,000 MW exclusion, the inhibitory activity was apparent in all fractions excluded by a molecular weight of 50,000. No inhibition was apparent in fractions that were not excluded by 50,000 MW pore size. Inhibition of enolase activity was greatest in the fraction with MW greater than 300,000. Binding of IGF II could also be demonstrated in this fraction. Binding of IGF II was evident in the fraction greater than 100,000 MW but could not be demonstrated in fractions with a lower molecular weight. The presence of mRNA for IGF II in 20-day fetal rat brain cell cultures was evident when total cellular RNA was analyzed by an RNAase protection assay. It is proposed that a high-molecular-weight component of maternal serum in late gestation can bind endogenously generated IGF II. Such binding, by depleting the necessary growth factors, could inhibit in vitro growth and development of enolase activity.

Animals↗
PubMed1990

Intra-arterial blood pressure monitoring in the evaluation of the hypertensive athlete.

To compare the blood pressure (BP) changes during a long-distance run with those during bicycle ergometry, nine normotensive and 18 hypertensive joggers were studied by means of ambulatory intra-arterial monitoring. In all subjects the ergometric test caused a progressive increase in systolic and little change in diastolic BP. Exertional BP levels were closely related to pre-exercise baseline values (P less than 0.001). A different BP pattern was observed during track running, as a sharp rise in systolic BP reaching maximum values 2-4 min after the start was recorded. Subsequently, systolic BP progressively declined throughout the run, only to increase again during the final sprint. Diastolic BP fell markedly at the onset of the run and then remained substantially stable throughout. A poor relationship was observed between the BP values at peak exercise and baseline levels (P less than 0.05) as the normotensives showed a significantly higher BP response than the hypertensives. On the contrary, during the ergometric test a parallel increase in BP was recorded in the normotensive and the hypertensive joggers. No correlation was found between the BP response to track running and to bicycle ergometry. These results indicate that the BP response to a standard stress test is not predictive of the BP changes determined by a long-distance run. The BP increase with strenuous effort seems to be reduced in hypertensive individuals, probably because of latent impairment of cardiac performance.

Adolescent↗
PubMed1989

Beats modulate blood pressure during running.

Blood pressure (BP) changes during running were studied in 25 subjects with intraarterial monitoring. Periodic pulse pressure variations ranging from 20 to 200 mm Hg were recorded throughout the exercise. To prove that these pressure oscillations were due to a "beat" phenomenon 10 athletes ran with a Teruflex container filled with saline: pressure changes up to +/- 62 mm Hg were recorded in the container. These pressure waves were added by computer to the sphygmic waves recorded intraarterially in the same subject during bicycle ergometry: the resultant tracing showed a beat-shaped pattern similar to that recorded during running.

Adolescent↗
PubMed1989

Blood pressure changes during heavy-resistance exercise.

To study the mechanisms of the blood pressure changes during weight-lifting, three hypertensive and five normotensive body-builders underwent continuous intra-arterial monitoring. In two subjects (one normotensive and one hypertensive), intrathoracic and intra-abdominal pressures were also measured. Extremely high blood pressure elevations of up to 345/245 mmHg were observed during the lifts. Squatting caused the highest pressure rises and single-arm curls the lowest. Both the intrathoracic and the intra-abdominal pressures increased greatly during each lift and closely paralleled the changes in intra-arterial pressure. A close correlation was found between the blood pressure increase during the exercise and during a hand-grip test (r = 0.95, P less than 0.001). These results suggest that a pronounced increase in intra-thoracic and intra-abdominal pressures is a major determinant of the blood pressure elevations occurring during weight-lifting. The pressor reflex which accompanies static contractions and the individual baseline blood pressure levels also seem to affect the height of the pressure peaks.

Adult↗
PubMed1989

Blood pressure changes during running in humans: the "beat" phenomenon.

In 20 runners the intra-arterial blood pressure changes determined by a long-distance run and by a maximal bicycle ergometric test were recorded by means of the portable Oxford system. A peculiar pattern of the phasic waves was observed throughout the run: continuous rhythmic pulse pressure oscillations ranging in frequency between 4 and 28/min and unrelated to respiration were detected. The shape of these oscillations prompted us to investigate whether they were due to a "beat" phenomenon, that is, to the combined effect of two waves with a nearly equal frequency. To test this hypothesis, during the run 10 athletes carried a fluid-filled container around the chest. The pressure waves recorded in the container were added by computer to those recorded intra-arterially during bicycle ergometry. The resultant harmonic showed a pattern similar to that recorded in the athlete's radial artery during running. Conversely, by subtracting the pressure waves recorded in the container from those simultaneously recorded at the radial artery during running, nearly flat tracings were obtained. The source of the beat phenomenon has therefore been identified in the wave, which generates inside the aorta and the great vessels at each foot-strike shock.

Adolescent↗
PubMed1988

Blood pressure changes during physical exercise (the beat phenomenon).

We have previously reported that blood pressure during running shows a peculiar pattern attributable to the beat phenomenon. To elucidate the mechanism behind this phenomenon in 10 amateur athletes, intra-arterial blood pressure was continuously recorded using the Oxford technique. During the run, each athlete carried on his chest a container filled with saline kept under pressure, connected to a second transducer. In the container, pressure waves ranging in amplitude from +/- 10 to +/- 62 mmHg were recorded. Their frequency was equal to that of the athletes' strides. When these waves were added by computer to the blood pressure tracing recorded during a bicycle ergometric test, the resultant harmonic proved to be similar to the tracing observed during running. The present results demonstrate that the running-induced blood pressure pattern is the sum of the accessory wave generated by the rhythmic aortic shocks produced by running locomotion and the normal sphygmic wave.

Adolescent↗
PubMed1987

Effect of endurance training on Q-T interval and cardiac electrical stability in boys aged 10 to 14. Ventricular arrhythmias in trained boys.

In 30 highly trained boys aged 10-14 the prevalence of ventricular ectopic beats and Q-T interval duration were studied. In trained boys ECG Holter monitoring showed a higher even though not significantly different prevalence of ventricular arrhythmias than in 30 age-matched untrained controls. Ventricular ectopy was on the contrary lower than in a group of 30 adult athletes. Q-T corrected (Q-Tc) interval in the trained boys was longer than in the sedentary controls (p less than 0.001), while it was as long as in the adult athletes. No correlation was found between the degree of severity of ventricular ectopic beats and Q-Tc interval duration, heart rate or echocardiographic dimensional and functional findings. The clinical and prognostic importance of complex ventricular arrhythmias detected in healthy athletes remains to be elucidated.

Adolescent↗
PubMed1987

[Behavior of arterial pressure during sports activity: track running].

In 6 normotensive and 14 borderline or mild hypertensive runners the intraarterial blood pressure (BP) changes determined by a maximal bicycle ergometric test and by an exhaustive run performed in outdoor conditions were recorded by means of the portable Oxford system. During running systolic BP attained higher values than during bicycle ergometry, while diastolic BP decreased during running and remained unchanged during ergometry. The highest BP values were recorded soon after starting running, then they progressively declined to increase once again during the final sprinting. Beat to beat analysis of the pressure tracings showed a peculiar pattern of the phasic waves throughout the run: continuous cyclic oscillations of pulse pressure were detected, as the variations of systolic blood pressure were not paralleled by those of the diastolic. The frequency of these rhythmic oscillations varied from 6-7 to 24-27/minute and was not related to respiration rate. The shape of these oscillations prompted us to investigate whether they were due to the "beat" phenomenon, that is to the combined effect of two waves with a nearly equal frequency. To verify this hypothesis 10 athletes during the run carried around the chest a Teruflex container filled with saline. The amplitude of the BP changes recorded in the container ranged from +/- 10 to +/- 50 mmHg. They were added by means of a computer to the BP tracing recorded during bicycle ergometry. The resultant wave was similar to that recorded in the radial artery during running.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

[Validity of the dynamic exertion test for the diagnosis of arterial hypertension. The exertion test in hypertension].

To assess the role of dynamic stress test in hypertension three normotensive and ten borderline or mild hypertensive subjects were studied by means of the intraarterial Oxford technique. In all of the subjects the intraarterial monitoring lasted for 12 hours; during the recording a graded maximal bicycle exercise test was performed. Five patients considered hypertensive on the basis of their office blood pressure readings showed normal average 12-hour intraarterial recordings. Systolic blood pressure increase during ergometry ranged from 22 to 57 mmHg; exertional pressure readings were strictly related to average 12 hours intraarterial blood pressure (r = 0.92; p less than 0.001). No correlation was found between resting blood pressure and the exertional pressure taken with the auscultatory method. These data indicate that the level that blood pressure attains during ergometry primarily depends on the resting blood pressure values, and therefore do not justified the separation between normo and hyperreactive subjects as some authors have done. In conclusion, dynamic exercise may be a useful diagnostic test for hypertension but has no predictive value for either the development of high blood pressure or the progression from borderline to more severe forms of hypertension.

Adolescent↗