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.

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.

Carotid percutaneous angioplasty.

Clinical benefit from treatment of symptomatic severe carotid stenoses has been demonstrated recently. The safety profile of endarterectomy, however, justifies the development of alternative techniques as percutaneous transluminal angioplasty (PTA), at least in mild to moderate stenoses. Early results and follow-up data from our series of 44 carotid stenoses treated by PTA are reviewed in this paper, in comparison with other reports from literature. PTA may be beneficial as a therapy of symptomatic internal carotid stenoses, provided its cost/effectiveness has been evaluated by a valid method.

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.

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.

Preliminary data by cis-platin and etoposide using in primary glioblastoma.

In this preliminary study twenty-nine malignant glioma patients after surgery were treated using Cis-platin (CDDP) combined with etoposide (VP16). Superfractionated radiation therapy comes into chemotherapy. The time to tumor progression in GBM patients is encouraging result to continue in this treatment.

Intratumoral beta interferon and systemic chemotherapy. Preliminary data in GBM patients.

Doses and schedules for treatment of malignant glial tumors, using IFN are still uncertain and controversial. In this study preliminary results of treatment of 10 glioblastoma multiforme patients are shown. Six patients were treated with local injection of beta-IFN through an Ommaya reservoir: 4 with beta-IFN followed by systemic chemotherapy (CDDP-VP16); 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.

Adoptive immunotherapy with adherent lymphokine-activated killer (A-LAK) cells in glioblastoma multiforme.

Adherent lymphokine-activated killer (A-LAK) activity has been recently differentiated in recombinant interleukin-2 (rIL-2) activated PBL. A pilot study on A-LAK + rIL-2 injection into the post-surgical cavity of glioblastoma-operated patients is ongoing. Preliminary data support the feasibility of this technique, which may improve the antitumor response of the host.

Effect of a concomitant treatment with ethynylestradiol and ascorbic acid on bile secretion in female hamsters.

The administration of large doses (5 mg/kg b.wt./day) of ethynylestradiol to adult female hamsters did not induce cholestasis or modifications of bile lipid composition. These findings are in contrast with the data of other authors who in different experimental conditions described the sensitivity of hamsters to the estrogen-induced hepatobiliary toxicity. Ascorbic acid alone or added to ethynylestradiol did not impair bile secretion. However, it significantly increased the plasma levels of radioactivity tested 24 hours after the oral administration of a tracer dose of radiolabelled ethynylestradiol. These results confirm previous data showing in humans the capability of ascorbic acid to favour the rise of plasma concentrations of ethynylestradiol.

[Sequential nimodipine-reduced glutathione treatment in alcoholic abstinence syndrome. Preliminary experience]. / Trattamento sequenziale nimodipina-glutatione ridotto nella sindrome da astinenza alcolica. Esperienza preliminare.

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.

Pharmacologic evaluation of cardiovascular reflex responses in migraine patients: lack of central sympathetic modulation?

To characterize autonomic imbalance in migraine, we compared the cardiovascular reflex responses of 10 migraineurs and 10 healthy subjects after pharmacological noradrenergic stimulation or inhibition. A battery of 5 autonomic tests was administered on basal conditions as well as after pretreatment with drugs acting at different levels on the noradrenergic pathway: pseudoephedrine, clonidine, guanethidine, indenolol, prazosin. Our data confirm a predominantly sympathetic hypofunction in migraine and provide evidence for an impairment of the central autonomic control.

Cluster headache: lack of central modulation?

Activation of the SPergic pathway may be responsible for the starting of both painful and autonomic symptoms during a typical cluster headache (CH) attack. We utilized Brainstem Auditory Evoked Potentials (BAEPs) and Visual Evoked Potentials (VEPs) to evaluate the possibility of underlying asymmetries in central functions in CH attacks. We studied 14 CH (7 right and 7 left cluster) and 14 normal subjects. All the CH patients showed a significant VEP asymmetry; the mean P 100 amplitude was significantly reduced on the side of the pain and I-V latency of BAEP was increased on the symptomatic side. No check was made for any significant variation underlying asymmetries in the normal subjects. We postulate that such an asymmetry in VEP and BAEP responses could suggest a neurotransmitters disorder with a different manifestation in each hemisphere.

Cardiovascular reflex responses in cluster headache patients: basal autonomic alterations.

To investigate the involvement of the autonomic nervous system in Cluster Headache (CH) patients, we compared the cardiovascular reflex responses in a group of CH subjects and a group of controls. We considered five tests: 1) deep breathing test (DB); 2) lying to standing test; 3) heart rate response to Valsalva manoeuvre; 4) blood pressure response to standing; 5) blood pressure response to sustained handgrip. Our data confirm an autonomic dysfunction in CH, particularly regarding the parasympathetic system. Alternative interpretations of these results are discussed.

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.

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.

Ambulatory blood pressure versus casual pressure for the evaluation of target organ damage in hypertension: complications of hypertension.

In 122 patients aged between 14 and 58 years with different degrees of hypertension, mean 24-h ambulatory blood pressure (BP) and casual BP were measured to evaluate the relationship with hypertensive target organ damage. The following results were obtained: (1) In agreement with previous reports, this study found a better relationship between target organ damage and mean ambulatory BP than with causal BP, although the correlation coefficients were similar for both. (2) A higher degree of cardiovascular complications occurred in patients with higher variability in BP. These data emphasize the superiority of BP monitoring over causal BP for the study of hypertension and its complications.

Selective brain region activation by histamine H3 receptor antagonist/inverse agonist ABT-239 enhances acetylcholine and histamine release and increases c-Fos expression.

Histamine axons originate solely from the tuberomamillary nucleus (TMN) to innervate almost all brain regions. This feature is consistent with a function for histamine over a host of physiological processes, including regulation of appetite, body temperature, cognitive processes, pain perception and sleep-wake cycle. An important question is whether these diverse physiological roles are served by different histamine neuronal subpopulations. Here we report that systemic administration of the non-imidazole histamine H3 receptor antagonist 4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile (ABT-239, 3 mg/kg) increased c-Fos expression dose-dependently in rat cortex and nucleus basalis magnocellularis (NBM) but not in the nucleus accumbens (NAcc) nor striatum, and augmented acetylcholine and histamine release from rat prefrontal cortex. To further understand functional histaminergic pathways in the brain, dual-probe microdialysis was used to pharmacologically block H3 receptors in the TMN. Perfusion of the TMN with ABT-239 (10 µM) increased histamine release from the TMN, NBM, and cortex, but not from the striatum or NAcc. When administered locally, ABT-239 increased histamine release from the NBM, but not from the NAcc. Systemic as well as intra-TMN administration of ABT-239 increased c-Fos expression in the NBM, and cortex, but not in the striatum or NAcc. Thus, as defined by their sensitivity to ABT-239, histaminergic neurons establish distinct pathways according to their terminal projections, and can differentially modulate neurotransmitter release in a brain region-specific manner. This implies independent functions of subsets of histamine neurons according to their terminal projections, with relevant consequences for the development of specific compounds that affect only subsets of histamine neurones, thus increasing target specificity.