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Biomedical subjects

L Bernardi

Publications and source records attributed to L Bernardi.

At least 37 records · Page 2Linked to original sources

[Interaction between respiration, autonomic function, and respiratory pattern in heart failure. New possibilities of rehabilitation intervention].

Some of the most invalidating symptoms in subjects with chronic heart failure, such as dyspnea and poor exercise tolerance, correlate poorly with indices of myocardial pump function, but are more related to alterations in autonomic nervous system, respiratory system, in addition to physical deconditioning. Increasing evidence suggests that in addition to pump function abnormalities, sympathetic and parasympathetic abnormalities, increased function of baro-, chemo- and ergoreflex control mechanisms play a pivotal role in the origin of symptoms in these patients, potentiating the mechanisms leading to physical deconditioning and further worsening of symptoms. This underlines the practical importance of studies focused on the possibility of modifying these control mechanisms. Recent evidence indicates that non-pharmacological interventions, such as general physical training, or, particularly, specific types of training of the respiratory pattern, may modify some of these reflex control mechanisms, including the chemoreflex response, and provide potential favorable effects in chronic heart failure.

Autonomic Nervous System↗

[Autonomic nervous system adaptation during physical exercise].

Physical exercise is a physiologic condition in which a variety of mechanisms and production/control systems combine and interact in order to accomplish the desired task (physical exercise) and preserve and/or restore body homeostasis. The autonomic nervous system provides a double response during exercise: at first a prevailing parasympathetic withdrawal followed, with the increase in duration and intensity of exercise, by a prevailing sympathetic activation. These modifications interact with the regulation of breathing, of body temperature, and of oxygen transport from the lungs to the body tissues through the modulation of the cardiac pump function and of the systemic and local vasoactivity and, at a tissue level, through the modulation of the local metabolism and the production of vasoactive and chemoactive substances. In the present review these aspects and the effects of physical training on the autonomic nervous system are examined in normal subjects and in patients with heart failure.

Autonomic Nervous System↗

Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor.

The lethal factor (LF) produced by toxigenic strains of Bacillus anthracis is a Zn(2+)-endopeptidase that cleaves the mitogen-activated protein kinase kinases (MAPKKs) MEK1, MEK2 and MKK3. Using genetic and biochemical approaches, we have extended the study of LF proteolytic specificity to all known MAPKK family members and found that LF also cleaves MKK4, MKK6 and MKK7, but not MEK5. The peptide bonds hydrolysed by LF within all MAPKKs were identified. Cleavage invariably occurs within the N-terminal proline-rich region preceding the kinase domain, thus disrupting a sequence involved in directing specific protein-protein interactions necessary for the assembly of signalling complexes. Alignment of the sequences flanking the site of cleavage reveals the occurrence of some consensus motifs: position P2 and P1' are occupied by hydrophobic residues and at least one basic residue is present between P4 and P7. The implications of these findings for the biochemical activity and functional specificity of LF are discussed.

Amino Acid Sequence↗

Yoga and chemoreflex response to hypoxia and hypercapnia.

We tested whether chemoreflex sensitivity could be affected by the practice of yoga, and whether this is specifically because of a slow breathing rate obtained during yoga or as a general consequence of yoga. We found that slow breathing rate per se substantially reduced chemoreflex sensitivity, but long-term yoga practice was responsible for a generalised reduction in chemoreflex.

Adult↗

Effects of breathing control on cardiocirculatory modulation in Caucasian lowlanders and Himalayan Sherpas.

This study was performed to investigate the influence of breathing control on the autonomic cardiac regulation at high altitude in adapted and non-adapted awake subjects. We recorded electrocardiogram and pulse oximetry in 14 short-term acclimatized lowlanders and 14 Himalayan Sherpas during resting conditions at an altitude of 5,050 m. Spectrum analysis was performed on synchronized 15 min periods of R-R intervals and the oxygen saturation of arterial blood (SaO2). Despite mean SaO2 being similar in lowlanders and Himalayan Sherpas [78.5 (SD 7.0)% compared to 79.4 (SD5.8)%, respectively], fluctuations in SaO2 were significantly increased in lowlanders compared to Sherpas, thus indicating an unstable regulation of respiration control in lowlanders. Regression analysis demonstrated a significant relationship between spectrum power of SaO2 and the relative power of R-R intervals in the frequency band between 0.01 and 0.08 Hz in lowlanders, but not in Sherpas. Our results demonstrate differences in respiratory and autonomic cardiac control between non-adapted lowlanders and Himalayan high-altitude residents and indicate that unstable breathing control during chronic hypobaric hypoxia is significantly correlated with the autonomic cardiocirculatory regulation.

Acclimatization↗

Effects of controlled breathing, mental activity and mental stress with or without verbalization on heart rate variability.

OBJECTIVES: To assess whether talking or reading (silently or aloud) could affect heart rate variability (HRV) and to what extent these changes require a simultaneous recording of respiratory activity to be correctly interpreted. BACKGROUND: Sympathetic predominance in the power spectrum obtained from short- and long-term HRV recordings predicts a poor prognosis in a number of cardiac diseases. Heart rate variability is often recorded without measuring respiration; slow breaths might artefactually increase low frequency power in RR interval (RR) and falsely mimic sympathetic activation. METHODS: In 12 healthy volunteers we evaluated the effect of free talking and reading, silently and aloud, on respiration, RR and blood pressure (BP). We also compared spontaneous breathing to controlled breathing and mental arithmetic, silent or aloud. The power in the so called low- (LF) and high-frequency (HF) bands in RR and BP was obtained from autoregressive power spectrum analysis. RESULTS: Compared with spontaneous breathing, reading silently increased the speed of breathing (p < 0.05), decreased mean RR and RR variability and increased BP. Reading aloud, free talking and mental arithmetic aloud shifted the respiratory frequency into the LF band, thus increasing LF% and decreasing HF% to a similar degree in both RR and respiration, with decrease in mean RR but with minor differences in crude RR variability. CONCLUSIONS: Simple mental and verbal activities markedly affect HRV through changes in respiratory frequency. This possibility should be taken into account when analyzing HRV without simultaneous acquisition and analysis of respiration.

Arousal↗

Breast involvement in immunolymphoproliferative disorders: report of two cases of multiple myeloma of the breast.

Breast involvement by immunolymphoproliferative disorders is rare. Primary and secondary malignant lymphomas of the breast are much more common than multiple myeloma, of which only 16 cases have been described. We report two cases of patients with an established diagnosis of multiple myeloma in whom breast involvement appeared during the course of the disease. We underline diagnostic difficulties caused by the lack of clinical and radiological features which allow us to differentiate between breast carcinoma and breast involvement by lymphoproliferative disease. Only fine needle aspiration and/or excisional biopsy can differentiate between immunolymphoproliferative disorders and epithelial or mesenchymal tumors of the breast.

Adult↗

Comparison between different cell kinetic variables in human breast cancer.

Cell kinetics holds a prominent role among biological factors in predicting clinical outcome and response to treatment in neoplastic patients. Different cell kinetic variables are often considered as valid alternatives to each other, but the limited size of case series analysed in several studies and the lack of simultaneous determinations of all the variables on the same tumours do not justify this conclusion. In the present study, the correlation between [3H]thymidine labelling index ([3H]dT LI), flow cytometric S phase cell fraction (FCM-S) and Ki-67 immunoreactivity (Ki-67/MIB-1) was verified and the type of correlation with the most important clinical, pathological and biological patient and tumour characteristics was investigated in a very large series of breast cancer patients. Ki-67/MIB-1, FCM-S and [3H]dT LI were determined in 609, 526 and 485 patients, respectively, and all three cell proliferation indices were evaluated in parallel on the same tumour in a series of 330 breast cancer patients. All the cell kinetic determinations were performed within the context of National Quality Control Programmes. Very poor correlation coefficients (ranging from 0.37 to 0.18) were observed between the different cell kinetic variables determined in parallel on the same series of breast cancers. Moreover, Ki-67/MIB-1 and FCM-S showed a significant relationship with histological type, grade and tumour size, whereas statistically significant correlations were not observed for [3H]dT LI. In conclusion, the results show that the different cell kinetic variables provide different biological information and cannot be considered as alternatives to each other.

Adult↗

Dynamic cardiocirculatory control during propofol anesthesia in mechanically ventilated patients.

UNLABELLED: We evaluated dynamic cardiovascular control by spectral analytical methods in 20 young adults anesthetized with propofol (2.5 mg/kg, followed by continuous infusion of 0.1 mg/kg/min) and in an awake control group during cyclic stimulation of the carotid baroreceptors via sinusoidal neck suction at 0.2 Hz (baroreflex response mediated mainly by vagal activity) and at 0.1 Hz (baroreflex response mediated by vagal and sympathetic activity). During anesthesia and mechanical ventilation at 0.25 Hz, major underdampened hemodynamic oscillations occurred at 0.055 +/- 0.012 Hz. The response of RR intervals to baroreceptor stimulation at 0.2 Hz was markedly decreased during anesthesia (median of transfer function magnitude between neck suction and RR intervals 3% of the awake control). Blood pressure response to baroreceptor stimulation at 0.1 Hz was significantly decreased during anesthesia to 26% (systolic blood pressure), and 44% (diastolic blood pressure) of the awake control. There was a significant delay in baroreflex effector responses during anesthesia. Our results demonstrate a markedly depressed vagally mediated heart rate response and an impaired blood pressure response to cyclic baroreceptor stimulation during propofol anesthesia in mechanically ventilated patients. The disturbed baroreflex control is accompanied by an irregular dynamic behavior of cardiovascular regulation, indicating a decreased stability of the control system. IMPLICATIONS: An irregular dynamic behavior of the cardiovascular control system, associated with an impaired baroreflex control of heart rate and blood pressure, can be observed during propofol anesthesia in mechanically ventilated subjects.

Adult↗

Expression, crystallization and preliminary X-ray diffraction studies of recombinant Bacillus anthracis lethal factor.

The lethal factor (LF) produced by Bacillus anthracis is a Zn(2+)-dependent endopeptidase which specifically cleaves the N-terminal tail of several MAP kinase kinases (MAPKKs). The recombinant expression, purification and crystallization of LF and of an inactive mutant consisting of a single amino-acid substitution in the conserved catalytic site are reported here. Both proteins crystallize in the cubic space group I432.

Bacillus anthracis↗

[Digital pacinian hyperplasia. Report of a case associated with foreign body reaction].

Digital Pacinian Hyperplasia is a non tumoral, very rare lesion. To date, only 31 cases have been reported, occasionally named Digital Pacinian Neuroma. Digital pain is usually associated to. Local trauma is reported in about half of the cases. We report a new case occurred in a 62 year-old male, associated with inflammatory and foreign body reaction. No recurrence was observed 6 months after surgical excision. Differential diagnosis and controversies about this lesion are discussed.

Fingers↗

Cardiocirculatory coupling during sinusoidal baroreceptor stimulation and fixed-frequency breathing.

The question of whether respiratory sinus arrhythmia (RSA) originates mainly from a central coupling between respiration and heart rate, or from baroreflex mechanisms, is a subject of controversy. If there is a major contribution of baroreflexes to RSA, cardiocirculatory coupling during breathing and during cyclic baroreflex stimulation should show similarities. We applied a sinusoidal stimulus to the carotid baroreceptors and generated heart rate fluctuations of the same magnitude as RSA with a frequency similar to, but different from, the breathing frequency (0.2 Hz, compared with 0.25 Hz), and at 0.1 Hz, in 17 supine healthy subjects (age 28-39 years). The data were analysed using discrete Fourier-transform and transfer function analysis. Respiratory fluctuations in systolic blood pressure preceded RSA with a time lag equal to that between baroreceptor stimulation and oscillations in RR interval (0.62+/-0.18 s compared with 0.57+/-0.28 s at 0.2 Hz neck suction). The response of systolic blood pressure to neck suction at 0.2 Hz was 5 times less than the respiratory blood pressure fluctuations. Neck suction at 0.1 Hz largely increased fluctuations in blood pressure and RR interval, whereas the spontaneous phase relationship between blood pressure and RR interval remained unchanged. Our results are not consistent with the hypothesis that the origin of RSA is predominantly a central phenomenon which secondarily generates fluctuations in blood pressure, but suggest that, under the condition of fixed-frequency breathing at 0.25 Hz, baroreflex mechanisms contribute to respiratory fluctuations in RR interval.

Adult↗

Clinical evaluation of arterial baroreflex activity in diabetes.

The clinical and prognostic relevance of the evaluation of the arterial baroreflex is now firmly established in clinical cardiology, where a number of important studies have shown that impairment of arterial baroreflex has independent adverse prognostic value. The results, applied to diabetes, have generated a new perspective in our understanding of autonomic neuropathy. Available data indicate that in diabetes, with or without overt autonomic neuropathy, a widespread abnormality in the baroreflex function is a common finding. This abnormality is evident not only at the cardiac level, but also at the vascular level, by using new techniques able to provide more complete information on the direct baroreflex modulation of the resistance vessels. The question of whether this abnormality is already the consequence of neural damage or only the consequence of a functional involvement remains unsettled, although animal studies and the presence of widespread baroreflex abnormalities even in asymptomatic subjects tend to support the view that baroreceptor function can be altered due to functional and, later, structural damages of efferent nerves, involving both branches of the autonomic nervous system.

Animals↗

Stenting of the extracranial internal carotid artery for dissecting aneurysm.

Symptomatic dissecting aneurysms of the extracranial internal carotid artery are not frequent. Medical treatment of these lesions can be ineffective and surgical options present high morbidity. We describe a case successfully treated with endovascular therapy, using a self-expanding stent. The advantages of the endovascular treatment and the rationale of the use of self-expanding stents are discussed.

Adult↗

Autonomic control of the cerebral circulation during normal and impaired peripheral circulatory control.

OBJECTIVE: To determine whether oscillations in the cerebrovascular circulation undergo autonomic modulation in the same way as cardiovascular oscillations. DESIGN: Cardiovascular and cerebrovascular oscillations were monitored at rest and during sympathetic stimulation (head up tilt). The association with and transmission of the oscillations in the sympathetic (low frequency, LF) and respiratory (high frequency, HF) bands was assessed. SUBJECTS: 13 healthy volunteers, 10 subjects with vasovagal syncope, and 12 patients with complicated non-insulin dependent diabetes mellitus. MAIN OUTCOME MEASURES: Power spectrum analysis of cerebral blood flow velocity, arterial blood pressure, and heart rate. Coherence analysis was used to study the association between each pair of oscillations. Phase analysis showed the delay of the oscillations in the cardiovascular signals with respect to the cerebrovascular signals. RESULTS: The power in the sympathetic (LF) components in all the oscillations increased during head up tilt (p < 0.01) in the controls and in the subjects with vasovagal syncope, but not in patients with diabetes. Significant coherence (> 0.5) in the LF band was present between cerebrovascular and cardiovascular oscillations in most of the controls and in subjects with vasovagal syncope, but not in the diabetic patients (< 50% of the patients). In the LF band, cerebrovascular oscillations preceded the cardiovascular oscillations (p < 0.05) at rest in all groups: the phase shifts were reduced (p < 0.05) during head up tilt for all cardiovascular signals in healthy and syncopal subjects, but only for heart rate in diabetic patients. CONCLUSIONS: The cerebrovascular resistance vessels are subject to autonomic modulation; low frequency oscillations in cerebral blood flow velocity precede the resulting fluctuations in other cardiovascular signals. Autonomic neuropathy and microvascular stiffness in diabetic patients reduces this modulation.

Adult↗

Effect of beta-blockade on baroreceptor and autonomic function in heart failure.

Although beta-adrenoreceptor antagonists appear to be beneficial in chronic heart failure there is little information on their effects on autonomic and baroreceptor function which may have important prognostic implications. We sought to determine first whether beta-adrenoreceptor blockade will improve baroreceptor function and vagal tone in chronic heart failure, and second whether there were any differences between standard therapy with metoprolol and the second-generation vasodilating beta-blocker celiprolol. In this double-blind randomized placebo-controlled study 50 patients with stable chronic heart failure received either celiprolol 200 mg daily, metoprolol 50 mg twice daily or placebo for 12 weeks after a 4-week dose titration period. Thirty-five healthy normal subjects were also studied. Baroreceptor gain was assessed non-invasively by cross-spectral analysis of R-R and systolic blood pressure low- and high-frequency components (the alpha angle) during controlled respiration. High-frequency power was used as a measure of vagal modulation. Satisfactory recordings for analysis were obtained in 31 patients with heart failure. The results showed that at baseline baroreceptor gain (alphaHF) was significantly depressed in patients with heart failure compared with the normal control group (4.95+/-0. 55 versus 11.73+/-1.32 ms/mmHg, P<0.0001). After 12 weeks of treatment with metoprolol baroreceptor gain improved significantly whether measured while supine (P=0.03) or standing (P=0.009), and this was associated with a significant increase in R-R HF power (P=0. 008). There were no significant changes after treatment with celiprolol or placebo. We conclude that metoprolol but not celiprolol therapy restores baroreceptor gain towards normal and increases vagal tone in chronic heart failure. The ancillary properties of celiprolol do not appear to provide any advantages over metoprolol for the restoration of autonomic and baroreceptor function in heart failure.

Adrenergic beta-Antagonists↗